[Show abstract][Hide abstract] ABSTRACT: Excessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn’s disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression.
Microarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva.
Our results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy.
Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by (13)C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial.
Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (eg, susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group.
These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains.
Trial registration number:
Gut 09/2015; DOI:10.1136/gutjnl-2015-309900 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis.
Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto.
All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection.
A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Gut 07/2015; 64(9). DOI:10.1136/gutjnl-2015-309252 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigated the performance of the tissue resonance interaction method (TRIM) for the non-invasive detection of colon lesions.
We performed a prospective single-center blinded pilot study of consecutive adults undergoing colonoscopy at the University Hospital in Sassari, Italy. Before patients underwent colonoscopy, they were examined by the TRIMprobe which detects differences in electromagnetic properties between pathological and normal tissues. All patients had completed the polyethylene glycol-containing bowel prep for the colonoscopy procedure before being screened. During the procedure the subjects remained fully dressed. A hand-held probe was moved over the abdomen and variations in electromagnetic signals were recorded for 3 spectral lines (462-465 MHz, 930 MHz, and 1395 MHz). A single investigator, blind to any clinical information, performed the test using the TRIMprob system. Abnormal signals were identified and recorded as malignant or benign (adenoma or hyperplastic polyps). Findings were compared with those from colonoscopy with histologic confirmation. Statistical analysis was performed by χ(2) test.
A total of 305 consecutive patients fulfilling the inclusion criteria were enrolled over a period of 12 months. The most frequent indication for colonoscopy was abdominal pain (33%). The TRIMprob was well accepted by all patients; none spontaneously complained about the procedure, and no adverse effects were observed. TRIM proved inaccurate for polyp detection in patients with inflammatory bowel disease (IBD) and they were excluded leaving 281 subjects (mean age 59 ± 13 years; 107 males). The TRIM detected and accurately characterized all 12 adenocarcinomas and 135/137 polyps (98.5%) including 64 adenomatous (100%) found. The method identified cancers and polyps with 98.7% sensitivity, 96.2% specificity, and 97.5% diagnostic accuracy, compared to colonoscopy and histology analyses. The positive predictive value was 96.7% and the negative predictive value 98.4%. Among the 281 non-IBD subjects, there were 7 cases with discordant results (2.5%) between TRIMprob and the reference standard including 5 false positive results (1.8%) and 2 false negative (0.7%) results. The main limitation of the TRIMprob system is the need for trained operators.
The study confirmed that TRIM provides rapid, accurate, convenient and noninvasive means to identify individuals most likely to benefit from colonoscopy.
[Show abstract][Hide abstract] ABSTRACT: Bismuth triple therapy was the first effective Helicobacter pylori eradication therapy. The addition of a proton pump inhibitor helped overcome metronidazole resistance. Its primary indication is penicillin allergy or when clarithromycin and metronidazole resistance are both common. Resistance to the primary first-line therapy have centered on complexity and difficulties with compliance. Understanding regional differences in effectiveness remains unexplained because of the lack of studies including susceptibility testing and adherence data. We discuss regimen variations including substitutions of doxycycline, amoxicillin, and twice a day therapy and provide suggestions regarding what is needed to rationally and effectively use bismuth quadruple therapy.
Published by Elsevier Inc.
Gastroenterology clinics of North America 06/2015; 44(3). DOI:10.1016/j.gtc.2015.05.003 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over the past 50 years, the prevalence of Helicobacter pylori infection has fallen as standards of living improved. The changes in the prevalence of infection and its manifestations (peptic ulcer disease and gastric mucosal lesions) were investigated in a large cohort of Sardinians undergoing upper endoscopy for dyspepsia. A retrospective observational study was conducted involving patients undergoing endoscopy for dyspepsia from 1995 to 2013. H. pylori status was assessed by histology plus the rapid urease test or 13C-UBT. Gastric mucosal lesions were evaluated histologically. Data including non-steroidal anti-inflammatory drugs (NSAIDs) use and the presence of peptic ulcers were collected. The prevalence of H. pylori was calculated for each quartile and for each birth cohort from 1910 to 2000. 11,202 records were retrieved for the analysis (62.9 % women). The overall prevalence of H. pylori infection was 43.8 % (M: 46.6 % vs. F: 42.0 %; P = 0.0001). A dramatic decrease in the prevalence of infection occurred over the 19-year observation period. The birth cohort effect was evident in each category (quartile) reflecting the continuous decline in H. pylori acquisition. Over time, the prevalence of peptic ulcers also declined, resulting in an increase in the proportion of H. pylori negative/NSAID positive and H. pylori negative/NSAID negative peptic ulcers. The prevalence of gastric mucosal changes also declined despite aging. The decline in H. pylori prevalence over time likely reflects the improvement in socioeconomic conditions in Sardinia such that H. pylori infection and its clinical outcomes including peptic ulcer are becoming less frequent even among dyspeptic patients.
Internal and Emergency Medicine 03/2015; DOI:10.1007/s11739-015-1218-4 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most gastric cancers are caused by infection with the common human bacterial pathogen, Helicobacter pylori. It is now accepted that gastric cancer can be prevented and virtually eliminated by H. pylori eradication and this knowledge was responsible for country-wide H. pylori eradication combined with secondary cancer prevention for those with residual risk that was introduced in Japan in 2013. Korea is a high H. pylori prevalence and high gastric cancer incidence country and a good candidate for a gastric cancer elimination program. The presence of an H. pylori infection is now considered as an indication for treatment of the infection. However, antimicrobial drug resistance is common among H. pylori in Korea making effective therapy problematic. Country-wide studies of the local and regional antimicrobial resistance patterns are needed to choose the most appropriate therapies. H. pylori and gastric cancer eradication can be both efficient and cost effective making it possible and practical to make Korea H. pylori and gastric cancer free. There is no reason to delay.
The Korean Journal of Internal Medicine 03/2015; 30(2):133-139. DOI:10.3904/kjim.2015.30.2.133 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori (H. pylori) is a major human pathogen which causes progressive gastroduodenal damage. Guidelines recommend that, unless there are compelling reasons to delay, treatment is indicated for all patients in whom the infection is diagnosed. The rapid urease test (RUT) is a popular diagnostic test in that it is a rapid, cheap and simple test that detects the presence of urease in or on the gastric mucosa. The sensitivity and specificity are generally high and many versions have been approved for use in humans. Best results are obtained if biopsies are obtained from both the antrum and corpus. The tissue sample embedded in the RUT gel can also be utilized for other tests such as for molecular based tests of microbial susceptibility or for host factors. False-positive results are rare if the RUT contains an antibacterial agent to prevent growth of urease-containing contaminants and the tests are discarded at 24 hours. The use of antimicrobial drugs and proton pump inhibitors as well as the presence of intestinal metaplasia may result in false-negative results. A negative test should not be used as the criteria for cure or in cases where accuracy is important for patient management such as in upper gastrointestinal bleeding. Interpretation of the test should take into account the pretest probability and the prevalence of H. pylori in the population. The test can also be used to provide an informal assessment of the accuracy of the histopathology result and discrepancies should prompt a review of the histopathology and discussions with the pathologist.
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections.
[Show abstract][Hide abstract] ABSTRACT: Background:
Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection.
We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection.
Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection.
NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.
The Journal of Infectious Diseases 01/2015; 212(3). DOI:10.1093/infdis/jiv053 · 6.00 Impact Factor