Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study.

BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.     

A Randomized Comparison of Fixed Power and Temperature Monitoring During Slow Pathway Ablation in Patients With Atrioventricular Nodal Reentrant Tachycardia

Temperature monitoring may be helpful for ablation of accessory pathways, however its role in ablation of atrioventricular nodal reentrant tachycardia (AVNRT) using the slow pathway approach is unclear. Therefore, the purpose of this study was to prospectively compare slow pathway ablation for AVNRT using fixed power or temperature monitoring. The study included 120 patients undergoing ablation for AVNRT. Patients were randomly assigned to receive either fixed power at 32 watts, or to temperature monitoring with a target temperature of 60°C. The primary success rate was 72% in the fixed power group and 95% in the temperature monitoring group (p=0.001). The ablation procedure duration (35±29 min vs 35±30 min; p=0.9), fluoroscopic time (32±17 vs 35±19 min; p=0.4), mean number of applications (10.2±8.1 vs 8.4±7.9; p=0.2), and coagulum formation per application (0.2% vs 0.5%; p=0.6) were statistically similar in the fixed power and temperature monitoring groups, respectively. The mean temperature (47.3±4.8°C vs 48.6±3.8°C; p<0.01), and the temperature associated with junctional ectopy (48.2±3.8°C vs 49.3±3.6°C, p<0.01) were less for the fixed power than the temperature monitoring group. In the temperature monitoring group, only 31% of applications achieved an electrode temperature of 60°C. During follow up of 6.6±3.6 months there were two recurrences in the fixed power group and one in the temperature monitoring group (p=1.0). In summary, power titration directed by temperature monitoring was associated with an improved primary procedural success rate. Applications of energy were associated with a temperature of approximately 50°C with both techniques, suggesting that there is a low efficiency of heating in the posterior septum.     

High-intensity focused ultrasound ablation:An effective bridging therapy for hepatocellular carcinoma patients

AIM:To analyze whether high-intensity focused ultrasound(HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma(HCC).METHODS:From January 2007 to December 2010,49 consecutive HCC patients were listed for liver transplantation(UCSF criteria).The median waiting time for transplantation was 9.5 mo.Twenty-nine patients received transarterial chemoembolization(TACE) as a bringing therapy and 16 patients received no treatment before transplantation.Five patients received HIFU ablation as a bridging therapy.Another five patients with the same tumor staging(within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison.Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores,tumor size and number,and cause of cirrhosis.RESULTS:The HIFU group and TACE group showed no difference in terms of tumor size and tumor number.One patient in the HIFU group and no patient in the TACE group had gross ascites.The median hospital stay was 1 d(range,1-21 d) in the TACE group and two days(range,1-9 d) in the HIFU group(P < 0.000).No HIFU-related complication occurred.In the HIFU group,nine patients(90%) had complete response and one patient(10%) had partial response to the treatment.In the TACE group,only one patient(3%) had response to the treatment while 14 patients(48%) had stable disease and 14 patients(48%) had progressive disease(P = 0.00).Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list(P = 0.559).CONCLUSION:HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis.It may reduce the drop-out rate of liver transplant candidate.     

Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment

Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic hepatitis B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long‐term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have been described with clevudine and telbivudine use. Both adefovir and tenofovir are associated with dose‐dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia have been described with the use of NAs, although the overwhelming studies have been with human immunodeficiency virus‐infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs, with telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.     

VDD vs DDD Pacemakers: A Meta-analysis

Background

Dual-chamber (DDD) and VDD pacing are recognized alternatives for patients with advanced atrioventricular (AV) conduction abnormalities and spared sinus node function. The comparative data between these 2 modes are limited.

Methods

A literature search was performed using multiple major databases. Outcomes of interest were (1) adverse events including incidence of atrial fibrillation (AF) and (2) procedural parameters. Odds ratio (OR) was reported for dichotomous variables and standardized mean difference (SMD) for continuous variables.

Results

Eight controlled studies (7 cohorts and 1 randomized controlled trial: total 1942 patients) were included. VDD mode was used in 922 patients. Mean follow-up period for the VDD group was 51 ± 24 months. There was a trend toward lower overall adverse events in the VDD group (9.6% vs 11.6%; OR, 0.74 [95% confidence interval (CI), 0.51-1.05; P = 0.09]). Shorter implantation and fluoroscopy times were noted with VDD pacing (46.2 ± 12 vs 65.9 ± 20 minutes; SMD, −0.96 [95% CI, −1.26 to −0.66; P < 0.0001] and 4.6 ± 1 vs 9.3 ± 0.4 minutes; SMD, −0.83 [95% CI, −1.38 to −0.29; P = 0.003], respectively). Mean P-wave amplitude was significantly lower in VDD (1.5 ± 0.8 mV vs 3.1 ± 0.9 mV; P = 0.02). The incidence of AF was lower in the VDD group but it did not reach statistical significance (7.5% vs 13.0%; OR, 0.7; 95% CI, 0.39-1.27; P = 0.24).

Conclusions

This meta-analysis suggests that VDD is a reasonable alternative to DDD pacemakers with lower pneumothorax risk and shorter implantation and fluoroscopy times. More high-quality data are required to definitively compare the 2 strategies.     

Good longterm survival after primary living donor liver transplantation for solitary hepatocellular carcinomas up to 8 cm in diameter

Objectives

There is controversy over whether hepatocellular carcinoma (HCC) should be primarily treated with living donor liver transplantation (LDLT) if liver resection (LR) can be effective. This retrospective study was conducted to compare survival outcomes in patients treated with either modality for solitary HCC measuring ≤8 cm in diameter.

Methods

Outcomes in patients with solitary HCC primarily treated by LDLT were analysed. Patients with solitary HCC of similar sizes with or without microvascular invasion primarily treated with LR were selected at a ratio of 6 : 1 for comparison.

Results

In-hospital mortality amounted to 0% and 1.3% in the LDLT (n = 50) and LR (n = 300) groups, respectively (P = 0.918). Complication rates were 34% and 20% in the LDLT and LR groups, respectively (P = 0.027). Rates of 1-, 3-, 5- and 10-year overall survival were 98%, 94%, 89% and 83%, respectively, in the LDLT group and 95%, 85%, 76% and 56%, respectively, in the LR group (P = 0.013). Rates of 1-, 3-, 5- and 10-year disease-free survival were 96%, 90%, 87% and 81%, respectively, in the LDLT group and 81%, 64%, 57% and 40%, respectively, in the LR group (P < 0.0001).

Conclusions

Living donor liver transplantation surpassed LR in survival outcomes, achieving a 10-year overall survival rate 1.5 times as high and a 10-year disease-free survival rate twice as high as those facilitated by LR. However, it entailed more complications, in addition to the inevitable risks to the donor.     

Nonsteroidal Antiinflammatory Drugs Could Reverse Helicobacter pylori-Induced Apoptosis and Proliferation in Gastric Epithelial Cells

It remains controversial whether the harmfuleffects of Helicobacter pylori (Hp) and nonsteroidalantiinflammatory drugs (NSAIDs) are additive. We studiedthe effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, onapoptosis and proliferation of gastric epithelial cellsin nonulcer dyspepsia (NUD) patients. Forty-four (25Hppositive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who hadtaken continuously NSAIDs for more than three monthswere recruited for this study. Another 41 (20Hp-positive and 21 Hp-negative) NUD patients not on anyNSAIDs were included as controls. All patientsunderwent a gastroscopy examination and gastricbiopsies. Hp infection was confirmed by CLOtest, anti-HpELISA, and [¹³C]urea breath test. The CagAstatus was determined by the anti-CagA antibody assay. The degree ofgastritis, apoptosis, and proliferation indices weredetermined with H&E staining, terminal uridinedeoxynucleotidyl nick end-labeling (TUNEL), andproliferating cell nuclear antigen (PCNA) immunostainingmethods, respectively. A significantly higher apoptosiswas observed in subjects who had Hp infection or hadbeen consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hpinfection were shown to have significantly enhanced cellproliferation. However, the increased apoptosis andproliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was foundbetween apoptosis and proliferation in all the studygroups. There was no association found between CagAexpression or degree of gastritis with cellproliferation or apoptosis. It was demonstrated at thecellular level that NSAIDs could abrogate apoptosis orproliferation effects induced by Hp. Furthermore, thelatter effects appeared not to be influenced by the virulent nature of the Hp strains.     

Letter recognition reveals pathways of second-order and third-order motion

How are second-order (texture-defined) and third-order (pattern-tracking) motions processed in our brains? As shown here in the context of an ambiguous motion task involving a nominal second-order stimuli first devised by Werkhoven et al., [Werkhoven, P., Sperling, G. & Chubb, C. (1993) Vision Res. 33, 463–485.], the observers fell into two distinct groups based on the direction of perceived motion. The differences were interpreted in terms of the algorithms used to extract motion: one group by using a second-order motion process and the other by using a third-order motion process. This was investigated further using a dual-task paradigm in which the interference between two tasks indicated the nature of processing involved. Observers who used third-order motion processing experienced interference with letter recognition and a more severe interference in dual third-order motion tasks. Observers who used second-order motion processing experienced interference with another second-order motion detection but not with letter recognition. Insofar as task interference implies the need for attention, the complex interference effects and the apparently paradoxical interference effects of second-order motion perception imply that there are multiple forms of attention. Whether two tasks interfere depends on whether they require the same form of attention. Insofar as spatio-temporal processing is assumed to be carried out in the dorsal stream and pattern recognition in the ventral stream, the interference patterns suggest that second-order motion may be computed entirely in the dorsal stream, and third-order motion may involve two computational processes, one of which shares computational resources with the letter recognition task in the ventral stream.