10-Day versus 14-day bismuth quadruple therapy for first-line eradication of Helicobacter pylori infection: a randomised, open-label, non-inferiority trial.

Background: Bismuth quadruple therapy is currently consensus recommendation for first-line Helicobacter pylori (H. pylori) treatment; however, the optimal duration is unknown. We compared the efficacy of 10-day bismuth quadruple therapy with that of 14-day bismuth quadruple therapy for first-line eradication. Methods: For our multicentre, parallel randomised, open-label, and non-inferiority study, we recruited H. pylori treatment-naïve patients from one medical centre and one teaching hospital in Taiwan. Patients were randomly assigned (1:1) to receive 10-day (PBMT-10) or 14-day (PBMT-14) bismuth quadruple therapy. The primary outcome was the eradication rate as determined by intention-to-treat (ITT) and per-protocol (PP) analyses. The eradication rates between the two groups were compared using a one-sided α value of 0.025 and a non-inferiority margin of 7%. The secondary outcomes were the rate of adverse effects. The trial is registered with ClincialTrials.gov (NCT04527055). Findings: From August 3, 2020 to April 28, 2023, 313 H. pylori treatment-naïve patients (PBMT-10 = 157; PBMT-14 = 156) were enrolled. 35 patients were excluded from PP analyses. The eradication rates (95% CI) for PBMT-10 and PBMT-14 were respectively 92.4% (88.2%-96.5%) and 92.9% (88.9%-97.0%) by ITT analyses, and 97.9% (95.5%-100.0%) and 99.3% (97.8%-100.0%) by PP analyses. The eradication rates for PBMT-10 were non-inferior to those for PBMT-14 (absolute difference [lower boundary of the one-sided 97.5% CI] -0.6% [-6.7%], PNI = 0.020 in ITT analyses, -1.4% [-5.8%], PNI = 0.007 in PP analyses). The rates of overall adverse effects (54.1% versus 57.1%, P = 0.604) were similar between the two groups; nevertheless, the rates of dizziness (18.5% versus 34.0%, P = 0.003) and vomiting (4.5% versus 12.8%, P = 0.008) were lower in PBMT-10 than in PBMT-14. Interpretation: The 10-day bismuth quadruple therapy was non-inferior to the 14-day therapy as a first-line treatment for eradicating H. pylori infection and had no different rates of overall adverse effects, but less serious adverse events in terms of dizziness and vomiting. Funding: The National Science and Technology Council and Ministry of Health and Welfare, Taiwan.

The nonadherence and risk factors of eradication failure by sequential therapy as first-line anti-Helicobacter pylori treatment in real-world clinical practice.

BACKGROUND: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. MATERIALS AND METHODS: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. RESULTS: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). CONCLUSIONS: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.

In situ real-time dataset as compared to the predicted thermal wheel performance of an energy recovery system.

The data article refers to in situ real-time dataset of a rotary desiccant wheel system and description of its experimental design. The original research paper was published in Heliyon, "Optimization of a rotary desiccant wheel for enthalpy recovery of air-conditioning in a humid hospitality environment" [1]. Supplementing to this data article are eight dataset files pertaining to ambient conditions and dehumidified process air outputs, as well as comparisons of experimental and numerical outputs under various operating conditions. Physical implementation of the experiments for numerical validation of transient responses included step changes to the regeneration air temperature, wheel speed, and airflow rate (i.e. fan speed). Finally, the data article provides insights to optimal performance of thermal wheel operation for HVAC practitioners and academic researchers.

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Optimization of a rotary desiccant wheel for enthalpy recovery of air-conditioning in a humid hospitality environment.

Excessive condensation on cooling coils can be costly energy-wise due to humid process air streams. An innovative desiccant cooling system is introduced into an existing hotel in Taoyuan, Taiwan, where the ambient is humid year-round. Rejected heat from the existing cooling system is used as the energy source to heat the regeneration airstream for dehumidification of the process airstream via a rotary desiccant wheel. The paper develops and validates a numerical model for the heat and mass (moisture) transfer of the rotary desiccant wheel. The validated numerical model is used to simulate the expected performance of the rotary wheel under various conditions and operating strategies. The desiccant wheel's performance includes the steady-state moisture removal capacity (MRC) and the transient response time to reach steady-state. The examined factors include the ambient temperature and humidity, air flow rate, rotational speed of the wheel, wheel-split, and regeneration airstream temperature. From the simulation results, the paper offers the optimized control strategies for the operation of the rotary desiccant wheel system in the hotel.

An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding.

BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen.

PURPOSE: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. METHODS: We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. RESULTS: The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025). CONCLUSION: Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Spasmolytic polypeptide-expressing metaplasia associated with higher expressions of miR-21, 155, and 223 can be regressed by Helicobacter pylori eradication in the gastric cancer familial relatives.

BACKGROUND AND AIMS: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a preneoplastic gastric cancer lesion related to epigenetic microRNA (miRNA) expression. This study elucidated whether Helicobacter pylori-infected first-degree relatives of patients with gastric cancer (GCF) are susceptible to have SPEM and correlated with miR-21, 155, and 223 expressions. We also validated whether SPEM and these miRNAs can be regressed after H pylori eradication. METHODS: We prospectively enrolled 148 GCF and 148 nonulcer dyspepsia (NUD) subjects without gastric cancer familial history as controls. Each case had received a panendoscopy to determine H pylori status and gastric histology, including SPEM. The cases with SPEM were followed after H pylori eradication to determine SPEM regression. The total RNA was extracted to analyze tissues miR-21, 155, and 223 before and after eradication. RESULTS: GCF subjects had a higher prevalence of H pylori infection (73% vs 32%) and SPEM (42% vs 14%, P < 0.01) than controls. The tissue miR-21, 155, and 223 in antrum were higher in cases with SPEM than in those without SPEM (P <= 0.05). There was similar SPEM reversibility after H pylori eradication between GCF subjects and controls (72% vs 69%, P = 0.852). In the SPEM regressed cases, tissue miR-21, 155, and 223 decreased after H pylori eradication (P < 0.05). CONCLUSION: The H pylori-infected GCF subjects were prone to have SPEM with higher tissues miR-21, 155, and 223 expressions. H pylori eradication can result in a 70% SPEM regression, accompanied by a decline in miR-21, 155, and 233 expression levels.

Helicobacter pylori eradication improves glycemic control in type 2 diabetes patients with asymptomatic active Helicobacter pylori infection.

AIMS/INTRODUCTION: Helicobacter pylori infection is associated with insulin resistance and glycemia in non-diabetes. However, the relationship between H. pylori infection and glycemia in diabetes remains inconclusive. Therefore, we explored the effect of H. pylori infection status and its eradication on glycemic control and antidiabetic therapy in type 2 diabetes patients. MATERIALS AND METHODS: A total of 549 diabetes patients were recruited for sequential two-step approach (immunoglobulin G [IgG] serology followed by 13 C-urea breath test [UBT]) to discriminate "active" (IgG+ and UBT+) from "non-active" (UBT- or IgG-) H. pylori infection, and "past" (IgG+ but UBT-) from "never/remote" (IgG-) infection. The differences in hemoglobin A1c (A1C) and antidiabetic regimens between groups were compared. In the "active" infection group, the differences in A1C changes between participants with and without 10-day eradication therapy were compared after 3 months. RESULTS: Despite no between-group difference in A1C, the "active" infection group (n = 208) had significantly more prescriptions of oral antidiabetic drug classes (2.1 ± 1.1 vs 1.8 ± 1.1, P = 0.004) and higher percentages of sulfonylurea use (67.3% vs 50.4%, P < 0.001) than the "non-active" infection group (n = 341). There were no differences in A1C and oral antidiabetic drug classes between "past" (n = 111) and "never/remote" infection groups (n = 230). Compared with the non-eradication group (n = 99), the eradication group (n = 98) had significant within-group (-0.17 ± 0.80%, P = 0.036) and between-group (-0.23 ± 0.10%, P = 0.024) improvements in A1C. CONCLUSIONS: Diabetes patients with active H. pylori infection need higher glycemic treatment intensity to achieve comparable glycemia. Furthermore, H. pylori eradication decreases A1C, and thus improves glycemic control.

Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use.

BACKGROUND/PURPOSE: Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. METHODS: The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding. RESULTS: The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05). CONCLUSION: Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083).

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long-term ulcer rebleeding: A 3.5-year prospective longitudinal study.

BACKGROUND AND AIM: Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long-term outcomes deserve follow-up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5-year longitudinal cohort. METHODS: Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding. RESULTS: The proportion of patients with rebleeding during the 3.5-year follow-up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5-fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person-year, P = 0.012, log-rank test). CONCLUSIONS: Patients with Rockall scores ≥6 are at risk of long-term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5-fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6.

Male non-insulin users with type 2 diabetes mellitus are predisposed to gastric corpus-predominant inflammation after H. pylori infection.

BACKGROUND: Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. METHODS: A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. RESULTS: The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11-4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15-0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus. CONCLUSIONS: Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection. TRIAL REGISTRATION: ClinicalTrial: NCT02466919 , retrospectively registered may 17, 2015.

Ten days of levofloxacin-containing concomitant therapy can achieve effective Helicobacter pylori eradication in patients with type 2 diabetes.

BACKGROUND: This study investigated whether levofloxacin-containing concomitant therapy can effectively eradicate Helicobacter pylori infection in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 797 T2DM patients were screened for anti-H. pylori IgG antibodies, and the presence of H. pylori infection was confirmed by 13C-urea breath test. We prospectively randomized 114 of these patients to receive either 10 d of levofloxacin-concomitant therapy (n = 55) or sequential therapy (n = 59). Antimicrobial resistance of H. pylori isolates collected from the patients with T2DM (n = 109) and dyspeptic controls without DM (n = 110) was determined using the E-test. This study was approved by our Institutional Review Board (A-BR-103-021). RESULTS: The H. pylori eradication rates with concomitant therapy were higher than sequential therapy in both intention-to-treat (96.4% versus 81.4%, p = 0.012) and per-protocol (100% versus 85.4%, p = 0.006) analysis. The adverse effects in both groups were similarly mild. In the patients who received sequential therapy, clarithromycin resistance was significantly associated with eradication failure (p = 0.02). There were no significant differences in the antibiotic-resistant rates to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin between the patients with and without T2DM. CONCLUSIONS: Ten days of levofloxacin-containing concomitant therapy is an effective and well-tolerated treatment to eradicate H. pylori infection for T2DM patients. Key messages Ten days of levofloxacin-containing concomitant therapy is well tolerated and superior to clarithromycin-containing sequential therapy for first-line H. pylori eradication in patients with type 2 diabetes. Clarithromycin resistance to H. pylori is the main factor associated with eradication failure in clarithromycin-containing sequential therapy in diabetic patients.

Serum Level of Trefoil Factor 2 can Predict the Extent of Gastric Spasmolytic Polypeptide-Expressing Metaplasia in the H. pylori-Infected Gastric Cancer Relatives.

BACKGROUND & AIMS: Gastric cancer has familial clustering in incidence, and the familial relatives of gastric cancer sufferers are prone to have spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM) after H. pylori infection. This study tested whether serum pepsinogen I/II and trefoil factor family (TFF) proteins can predict SPEM or IM in the H. pylori-infected relatives of patients with gastric cancer. METHODS: We prospectively enrolled 119 H. pylori-infected relatives of gastric cancer patients of noncardiac gastric cancer patients, who then received panendoscopy to obtain gastric biopsy to define the presence of corpus gastritis index (CGI), SPEM, and IM. The advanced SPEM in histology was defined by TFF2 immunohistochemistry. Each patient also had checkups of serum TFF2, TFF3, and pepsinogen I/II by enzyme-linked immunosorbent assay (ELISA). RESULTS: The 119 H. pylori-infected relatives included 61 with SPEM, and 34 with IM. The presence of either IM or SPEM was not related to the serum TFF2, TFF3, and pepsinogen I/II levels (p > .05). Serum TFF2 levels were higher in relatives with CGI who also had advanced SPEM (p = .032). For relatives without CGI, the elevated serum TFF2 levels correlated with higher H. pylori density and more severe gastritis in antrum (p = .001). CONCLUSION: The serum TFF2 level cannot predict SPEM or IM in H. pylori-infected relatives of patients with gastric cancer. For H. pylori-infected relatives with CGI, serum TFF2 levels may predict the advanced severity of SPEM. Elevated serum TFF2 levels may indicate severe H. pylori-related inflammation, at risk of development or progression of SPEM in relatives without CGI.

Risk factors determining the need for second-look endoscopy for peptic ulcer bleeding after endoscopic hemostasis and proton pump inhibitor infusion.

BACKGROUND AND STUDY AIMS: The need for routine second-look endoscopy in cases of peptic ulcer bleeding remains uncertain. We investigated risk factors related to the need for second-look endoscopy after endoscopic hemostasis and proton pump inhibitor (PPI) infusion. PATIENTS AND METHODS: We prospectively enrolled 316 patients with peptic ulcer bleeding after endoscopic hemostasis. Second-look endoscopy was scheduled after 72-hour PPI infusion (Day-3 subgroup) or one day early (Day-2 subgroup). If early rebleeding developed within 3 days, emergent second-look endoscopy was conducted. Risk factors for early rebleeding (use of E2(nd) score to predict the need for early second-look endoscopy) and persistent major stigmata in the Day-3 subgroup (use of R2(nd) score to predict the need for routine second-look endoscopy) were analyzed using univariable and multivariable regression. RESULTS: Excluding 10 of 316 patients with early rebleeding, the rate of persistent major stigmata was lower in the Day-3 subgroup than in the Day-2 subgroup (4.8 % vs. 15.4 %, P  = 0.002). Endoscopic epinephrine-injection monotherapy and hypoalbuminemia < 3.0 g/dL were two independent risk factors for early rebleeding (P  ≤ 0.05). The Forrest Ia-Ib type and hypoalbuminemia < 3.5 g/dL were two independent risk factors for persistent major stigmata on the day-3 second-look endoscopy (P  < 0.05). The E2(nd) score was highly accurate for prediction of early rebleeding (AUROC 0.86; 95 % CI, 0.73~0.99), and the R2(nd) score could predict persistent major stigmata at second-look endoscopy (AUROC 0.84; 95 % CI, 0.69~0.99). CONCLUSIONS: For patients with peptic ulcer bleeding, E2(nd) and R2(nd) scores can indicate the need for early and routine second-look endoscopy, respectively (Trial registration identifier: NCT02197039).

Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study.

BACKGROUND: Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. OBJECTIVE: To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. DESIGN: We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores <6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. RESULTS: Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores <6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002). CONCLUSIONS: Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. TRIAL REGISTRATION NUMBER: NCT01591083.

Long-term celecoxib can prevent the progression of persistent gastric intestinal metaplasia After H. pylori eradication.

BACKGROUND AND AIM: Intestinal metaplasia (IM) has overexpressions of COX-2. Short-term 8-week celecoxib, a selective COX-2 inhibitor, exerts a preliminary hint to improve regression in part for persistent IM after Helicobacter pylori eradication. This study further validated whether or not a prolonged duration of celecoxib of up to 1 year can be safe and effective. METHODS: One hundred and forty patients, with persistent IM after H. pylori eradication for 1 year, were included with half of them receiving celecoxib 200 mg/day for 12 months and the other half serving as controls. Each patient received serial checkups of blood creatinine levels every 4 months. After the 1-year follow-up, panendoscopy was repeated to assess the IM regression. The serial gastric specimens, taken before and after celecoxib therapy, were immunochemically stained for COX-2. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) analyses to the rates of IM regression were higher in the celecoxib group than in the controls (ITT: 44.3% [31/70] vs 14.3% [10/70], p < .001; and PP: 51.7% [31/60] vs 16.1% [10/62], p < .001). All enrolled patients had no renal impairment during follow-up. Even in the patients without IM regression, the mean IM scores and COX-2 expressions were significantly more decreased in the celecoxib group than in the controls (p < .005). CONCLUSION: One year 200-mg celecoxib daily be safely administered to improve the regression or prevent the progression of persistent IM after H. pylori eradication.

Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan.

BACKGROUNDS: The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. MATERIALS AND METHODS: Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) > 1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. RESULTS: All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05). CONCLUSION: Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.