Five-Year Impacts of Antithrombotic Therapy Based on 10-Year Clinical Outcomes of Cypher™ Stent Implantation.

INTRODUCTION: Few researchers have investigated the optimal long-term antithrombotic therapy regimen, especially after first-generation drug-eluting stent (DES) use. This study aimed to evaluate the impact of mid-term antithrombotic therapy on long-term outcomes in patients treated with the first sirolimus-eluting coronary stent (Cypher™). METHODS: Between 2004 and 2009, 1021 patients underwent Cypher™ implantation at our institute; among them, 567 patients had available data on antithrombotic therapy at year 5. We assessed patients' antithrombotic therapy at year 5 post Cypher™ implantation and examined their association with adverse events from year 5 to year 10 post Cypher™ implantation. RESULTS: Patients with dual-antiplatelet therapy (DAPT) at year 5 had significantly lower risk of stent thrombosis (ST) than those with single-antiplatelet therapy (SAPT) (hazard ratio [HR] 0.24, p = 0.034). The HR of major bleeding in DAPT, compared to SAPT, was high, but the difference was not significant (HR 1.72, p = 0.26). Risk of major bleeding was significantly higher in patients on oral anticoagulants (OAC) than in those in other groups (OAC/SAPT; HR 5.31, p = 0.0048, OAC/DAPT; HR 3.08, p = 0.022), without significant reduction in the risk of cardiovascular events. CONCLUSIONS: The incidence of ST after Cypher™ implantation in patients with DAPT at year 5 was significantly lower than that in SAPT. However, the risk of bleeding was higher with DAPT than with SAPT. Moreover, the risk of major bleeding was significantly higher in patients on anticoagulant therapy than in other patients. New options for the use of antithrombotic drugs after percutaneous coronary intervention warrant further studies on the optimal antithrombotic therapy for first-generation DES.

Fragmented QRS on far-field intracardiac electrograms as a predictor of arrhythmic events.

BACKGROUND: Studies suggest that fragmented QRS (fQRS) can predict arrhythmic events in various cardiac diseases. However, the association between fQRS recordings on intracardiac electrogram (EGM) and ventricular arrhythmic events remains unknown. METHODS: We enrolled 51 patients (age, 62 ± 12 years; 40 men) with an implantable cardioverter-defibrillator (ICD) and structural heart disease and evaluated surface electrocardiogram (ECG) and EGM measurement of fQRS and the association between fQRS and arrhythmic events. RESULTS: fQRS was detected on surface ECG and ICD-EGM in 12 (23.5%) and 15 (29.4%) patients, respectively. fQRS was detected more frequently on ICD-EGM in patients with fQRS on surface ECG than in patients without fQRS (7/12 [58.3%] vs 8/39 patients [20.5%], P = .01). Appropriate ICD therapies were documented in 16 patients. Among these patients, fQRS was detected more frequently on surface ECG and ICD-EGM in patients with appropriate ICD therapies (8/16, 50.0%; P = .001 and 11/16, 68.9%; P < .001). Nonsustained ventricular tachycardia was significantly more frequent in patients with appropriate ICD therapies (15/16, 93.8%; P = .04). Multiple logistic regression analysis showed that fQRS on ICD-EGM was a predictor of arrhythmic events (P = .03). Kaplan-Meier survival analysis revealed that ICD therapies were significantly more frequent among patients with fQRS on both surface ECG and ICD-EGM than among those without fQRS (66.7% vs 6.6%, P < .001). CONCLUSION: The presence of fQRS on ICD-EGM can be a predictor of arrhythmic events in ICD patients. Surface ECG and ICD-EGM measurement may help predict ventricular arrhythmic events.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

[The practical assessment of H. pylori eradication].

Helicobacter pylori (H. pylori) gastritis has been approved by Ministry of Health, Labour and Welfare as an additional indication for H. pylori eradication in Japan on Feburary 21, 2013. Diagnostic methods of H. pylori infection have been divided into direct (invasive) and indirect (non-invasive). Invasive tests requiring endoscopic biopsy include culture, histology and rapid urease test (RUT). Non-invasive tests not requiring endoscopic biopsy include measurement of H. pylori antibody(serum, urine), urea breath test(UBT) and stool antigen test. Assessment of the efficacy of H. pylori eradication therapy should be performed at least 4 weeks after the completion of treatment. UBT and monoclonal stool antigen test are both recommended for the assessment of H. pylori eradication. When the results obtained is doubtful for assessment of H. pylori eradication, it is preferable to perform another test or follow-up.

[Gastric hyperplastic polyps and H. pylori infection, their relationship and effects of eradication therapy].

Gastric hyperplastic polyp is frequently found in the stomach. The polyp almost never occurs in normal gastric mucosa and is most commonly associated with chronic gastritis induced by H. pylori infection. Most gastric hyperplastic polyps disappear after eradication of H. pylori. Eradication therapy is safe, non-invasive, and reduces medical cost in comparison with polypectomy. It is now expected that H. pylori infection rate may decrease in the future, and H. pylori eradication treatment in Japan may become more common. Therefore, cases of gastric hyperplastic polyp and gastric cancer may decrease.

[Helicobacter pylori eradication therapy for gastric ulcer in elderly].

Sixty-five-years or older person accounts for 23% of the population in Japan. Hence, Helicobacter pylori (H. pylori) eradication therapy is performed in many elderly patients. Urea breath test and H. pylori stool antigen test for diagnosis of H. pylori infection before and after eradication therapy are recommended from the point of being a noninvasive test and providing accurate diagnosis. H. pylori eradication therapy in Japan consists of the PPI/AMPC/CAM as the first therapy, and PPI/AMPC/MNZ as the second therapy. Eradication therapy rate and adverse effect rate of H. pylori eradication therapy for elderly patients are the same as for young people. It is not necessary to avoid H. pylori eradication therapy merely because of high age in elderly patients. However, it is necessary to be careful regarding drug interactions in patients who are taking multiple drugs.

[The present status and problems of Helicobacter pylori first-line eradication therapy].

The widespread of eradication therapy for H. pylori has lead to an increase in antibiotic resistant strains. The combination of a proton pump inhibitor, amoxycillin and clarithromycin (PPI/AC) has been one of the most popular regimens and has shown satisfactory results. Clarithromycin (CAM)-resistance of H. pylori is a clinical problem because it reduces the efficacy of PPI/AC regimen. We investigated the rate of acquisition of H. pylori resistance against CAM before triple therapy. The rate of CAM-resistant strains was 0% in 1985, 14.6% in 1996-99, 21.2% in 2001-04, and 24.1% in 2005-08, respectively. Tokyo H. pylori Study Group consisting of eleven institutions assessed the eradication rate of PPI/AC regimen from 2001 to 2008 in Tokyo metropolitan area. Intension-to-treat based eradication rate for PPI/AC regimen was decreased gradually from 70% to 60% level. The reduction in eradication rate of H. pylori consisting of PPI/AC was recognized. Furthermore, when the increase in CAM-resistant strains results in a decrease in eradication rate for H. pylori, new alternative first-line treatment combination should be considered in Japan.

Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota.

Antibiotic associated diarrhea due to human intestinal microbiota abnormalities is a side effect of H. pylori eradication therapy. We examined intestinal microbiota changes during H. pylori eradication therapy and the preventive effect of CBM588 as a probiotic agent. Nineteen patients with gastro-duodenal ulcer were randomly divided into three groups: group A (without probiotics), group B (with regular doses of CBM588) and group C (with double doses of CBM588). The incidence of diarrhea and soft stools during H. pylori eradication therapy was 43% in group A and 14% in group B, while none of the patients in group C reported diarrhea or soft stools. Both bacterial counts and detection rates of bifidobacteria and/or obligate anaerobe were decreased by eradication therapy. However, bacterial counts of obligate anaerobes in group C were significantly higher than in group A (P < 0.05). Additionally, during eradication therapy C. difficile toxin A was detected in both group A and group B but not in group C. In conclusion, these results indicate that H. pylori eradication therapy induces antibiotic associated diarrhea due to abnormalities in intestinal microbiota and/or C. difficile. However, these side effects might be prevented by probiotics.

Detection of mixed clarithromycin-resistant and -susceptible Helicobacter pylori using nested PCR and direct sequencing of DNA extracted from faeces.

The major cause of chemotherapy failure in patients with chronic gastritis and peptic ulcers caused by Helicobacter pylori is clarithromycin (CAM) resistance due to a mutation in the 23S rRNA gene. This study describes a non-invasive and accurate method for the detection of mixed CAM-resistant and -susceptible H. pylori by sequencing of the H. pylori 23S rRNA gene. Faeces were crushed with beads and the 23S rRNA gene was amplified using a nested PCR on the extracted DNA. Mutation analysis of this gene using this method showed that 20.4 % of patients carried mixed CAM-susceptible (wild type) and -resistant (A2142G or A2143G mutant) H. pylori. Furthermore, it was found that 66.6 % of patients who had been treated unsuccessfully carried one of these mutations in the 23S rRNA gene (including the mixed type), whilst standard culture detected CAM-resistant isolates in only 22.2 % of patients with unsuccessful treatment. These data suggest that, for successful therapy, the diagnosis method described here would more accurately detect CAM-resistant H. pylori, including mixed infections.

Lactobacillus reuteri tablets suppress Helicobacter pylori infection--a double-blind randomised placebo-controlled cross-over clinical study.

UNLABELLED: We studied the effect of Lactobacillus reuteri strain SD2112 Tablets Reuterina (ERINA Co., Inc.), in suppressing H. pylori urease activity and to use the urea breath test (UBT) as a marker for the burden of infection. Method 1: Assessment of UBT and H. pylori density. Subjects were 33 H. pylori-positive patients from whom were obtained gastric biopsy specimens by upper gastrointestinal endoscopy. The correlation between UBT and H. pylori density was investigated. Individual UBT was established for each patient. Patients were divided by H. pylori density was 3 groups: Group I (low-density), Group II (moderate-density), and Group III (high-density). The individual UBTs were then correlated to the established H. pylori quantity. Method 2: Assessment of suppressive effect of L. reuteri on H. pylori urease activity. Subjects were 40 asymptomatic volunteers with an UBT exceeding 15 per thousand, randomly allocated to four groups: Subjects in Group A underwent active treatment for 4 weeks (period 1) and placebo treatment for the following 4 weeks (period 2). These in Group B underwent treatment in reverse order. Those in Group C underwent placebo. Group D consisted of volunteers with negative UBT undergoing active treatment for the full 8 weeks. Result 1: UBT was 11.6+/-2.0 per thousand, 22.1+/-2.6 per thousand, and 35.4+/-7.6 per thousand in Groups I, II, and III, showing UBT that increased significantly (I vs. II: p< 0.01 and I vs. III: p<0.05) based on H. pylori density. Result 2:Significant differences were seen in the decrease in UBT before versus after medication in Groups A and B. In Group A, lower UBT was maintained until the end of the full 8-week period. The overall decrease in UBT due to medication with L. reuteri Tablets was 69.7+/-4.0% (p<0.05). CONCLUSION: Administration of L. reuteri Tablets [Reuterina (ERINA Co.,Inc.)] significantly decreased UBT in H. pylori-positive subjects, demonstrating that L. reuteri suppresses H. pylori urease activity and H. pylori density.

[Generalization of Helicobacter pylori eradication therapy and its future in Japan].

After official acceptance of eradication therapy for Helicobacter pylori infected peptic ulcer disease in 2000, this treatment has been generalized as ulcer therapy in Japan. In 2003 the consensus statement of the Japanese Society for Helicobacter Research (JSHR) for Helicobacter pylori infection was presented. According to this statement MALT lymphoma was recommended to treat H. pylori infection because of the efficacy of its out come. Atrophic gastritis was also advised to treat H. pylori infection for the purpose of preventing gastric cancer development. The extra alimentary disease such as idiopathic thrombocytopenic purpura was still under evaluation. In diagnostic method the importance of drug susceptibility test is rising because of the increase of drug resistant H. pylori strain in Japan. The false positive case of urea breath test, the accuracy of new Japanese original serology tests and the stool antigen test are also under investigation. The standard regimen of H. pylori eradication therapy in Japan is proton pomp inhibitor (PPI) + amoxicilin (AMPC) + clarithromycin (CAM). The problem of this regimen is the decrease of eradication rate. The reason of this trend might be increase of CAM resistant strain. JSHR recommended a rescue regimen as PPI + AMPC + metronidazole for the patient whose first eradication therapy was unsuccessful result. The eradication of this second line regimen was reported as about 90%.

[Evaluation of 13C-urea breath test to confirm eradication of Helicobacter pylori].

This study aimed to evaluate the effectiveness of the 13C-urea breath test (UBT) for assessment of Helicobacter pylori eradication after treatment. One hundred twenty six patients were enrolled with 85 receiving proton pomp inhibitor based triple therapy. They were underwent upper gastrointestinal endoscopy with biopsies for diagnosis and assessment of H. pylori infection using culture, histology, rapid urease test (RUT) and 13C-UBT. Assessment of eradication needs to be performed 4 weeks or more after completion of treatment. Breath samples were taken 15 minutes after the ingestion of 100 mg 13C-urea. Breath samples were analyzed on a mass spectrometer system. The gold standard for H. pylori infection was a positive culture or positive histology + positive RUT; negative for infection was defined as negative results of all three biopsy tests. Based on ROC curves, the most appropriate cut-off value for diagnosis of H. pylori infection was identified as 2.5/1000, which provided 96.2% sensitivity, 100% specificity, and 96.8% accuracy as judged by the gold standard. However, when confirming the eradication of H. pylori, it was 3.5/1000, which provides for 100%, 95.8%, and 96.5%, respectively. Ten patients (11.8%) had delta13C values that were 2.5-5.0/1000 4-12 weeks after therapy. Eight patients were considered cured of H. pylori infection, and 2 were considered to still have H. pylori infection following 13C-UBT, serology, and H. pylori specific antigen test. The false-positive rate of 13C-UBT was 9.4% (8/85). When the grey zone of 13C-UBT was set at a level of 2.5 to 5.0/1000 (2.5 > : negative, 5.0 < or = : positive) after eradication therapy, the sensitivity and specificity of 13C-UBT was 100% and 98.4% compared to the gold standard. It was concluded that to avoid false-positive results of 13C-UBT, the grey zone of 13C-UBT needs to be set at a level of 2.5 to 5.0/1000; thus improving the accuracy of test for the assessment of eradication of H. pylori infection.

Amoxicillin resistance in Helicobacter pylori: studies from Tokyo, Japan from 1985 to 2003.

BACKGROUND: Previous reports revealed no resistant strains of amoxicillin (AMPC), which is usually used in eradication therapy for H. pylori infection. However, the frequency and evolution of natural AMPC-resistant strains in the Japanese population remains unknown. AIM: To assess the prevalence of H. pylori resistance against AMPC in the Tokyo area, a collection of 648 H. pylori strains isolated from patients with GI diseases from 1985 to 2003 was tested for their sensitivity to AMPC. METHODS: The susceptibility of the strains was assessed by determination of the minimal inhibitory concentration (MIC) using the E-test and/or the Dry-plate method. The susceptibility breakpoints of AMPC for H. pylori were: sensitive (AMPC-S); MIC < 0.04 microg/ml, intermittent resistance (AMPC-I); 0.04-1, resistant (AMPC-R); > 1. RESULTS: No AMPC-R strains were detected in the strains isolated between 1985 and 1996, while the rate of resistance was determined to be 1.1%, 2.1%, 5.4%, 5.6%, 0%, 8.8%, and 1.5% every year, respectively, from 1997 to 2003. The percentage of AMPC-I strains increased from 2000 to 2003. The total eradication rate of H. pylori in the patients who received triple therapy containing AMPC was 81.4% (214/263). Classified as above, the rates of AMPC-S, AMPC-I, and AMPC-R were 84.6%, 77.8%, 25%, respectively. CONCLUSION: H. pylori resistance to AMPC is still rare in Japan, although the percentage of AMPC-I strains has increased over the last 4 years. The frequency of isolation of strains showing true resistance to AMPC may increase in the future, along with an increase in the frequency of isolation of AMPC-I strains.

[Helicobacter pylori stool antigen test].

In Japan, Helicobacter pylori stool antigen(HpSA) test was opened for diagnosis of H. pylori infection before and after eradication therapy form Nov. 1, 2003. We can use two kinds of HpSA kits, Premier Platinum HpSA(Meridian Bioscience, USA) and Testmate pylori antigen EIA(Wakamoto Pharmaceutical Co., Ltd., Japan). We evaluated the diagnostic accuracy of the HpSA test(Premier Platinum HpSA) compared with diagnosis based on endoscopic biopsy-based methods. In 136 patients, the sensitivity and specificity of the HpSA test before therapy were 98.3% and 95.0%, respectively. In 54 patients, the sensitivity and specificity of the HpSA test after eradication therapy were 90% and 97.7%, respectively. Therefore, it is concluded that the HpSA test is a useful method for the diagnosis of H. pylori infection before and after eradication therapy.

Evaluation of Helicobacter pylori stool antigen test before and after eradication therapy.

BACKGROUND AND AIM: The Helicobacter pylori stool antigen (HpSA) test is useful for initial diagnosis of H. pylori infection, but there is disagreement regarding its diagnostic accuracy after eradication therapy. The aim of the present study was to evaluate the diagnostic accuracy of the HpSA test before and after eradication therapy. METHODS: One hundred and thirty-six patients underwent upper gastrointestinal endoscopy with biopsies for the diagnosis of H. pylori infection using culture, histology and the rapid urease test. Fifty-four H. pylori-positive patients were treated with 1-week triple therapy. Six to 10 weeks after the end of therapy, the patients underwent re-endoscopy and received the same biopsy-based methods. In addition, the 13C-urea breath test was performed. The HpSA test was performed before and 6-10 weeks after the end of therapy. In 23 patients, the HpSA test was also performed at the end of therapy. RESULTS: Before therapy, the sensitivity and specificity of the HpSA test was 98.3% (95% confidence interval (CI): 95.9-100%) and 95.0% (95% CI: 75.1-99.9%), respectively. At the end of therapy, the HpSA tests were all negative both for eradication and non-eradication patients. The sensitivity and specificity of the HpSA test after eradication therapy were 90% (95% CI: 55.5-99.7%) and 97.7% (95% CI: 93.3-100%), respectively. CONCLUSIONS: The HpSA test is a useful method for the diagnosis of H. pylori infection before and after eradication therapy.

Helicobacter pylori and acetylsalicylic acid synergistically accelerate apoptosis via Fas antigen pathway in rabbit gastric epithelial cells.

The mechanism for gastric epithelial cellular apoptosis by both H. pylori and NSAIDs remains unknown. Normal gastric epithelial cells, collected from rabbit stomach, were cultured with viable H. pylori and/or an acetylsalicylic acid for 24 hr as an in vitro model of gastric epithelial cell injury. The Fas antigen expression rate in the gastric epithelial cells was measured using a FACScan. In group E, in which H. pylori inoculation of epithelial cells was followed by treatment with an NSAID, the rate of Fas antigen expression was significantly higher than the rate observed after treatment with either H. pylori or NSAID alone. Despite the fact that drug treatment alone did not significantly increase the Fas expression rate vs control cells. The results suggest that H. pylori and NSAID induce gastric cell injury as apoptosis via the Fas antigen pathway in a synergistic manner and that this effect is particularly strong when NSAID treatment follows H. pylori infection.