Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has ...been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
Inflammatory bowel disease (IBD) encompasses 2 independent but related entities: ulcerative colitis (UC) and Crohn's disease. Crohn's disease is characterised by transmural patchy inflammation which ...can involve any portion of the gastrointestinal tract. UC is characterised by superficial inflammation that begins in the rectum and extends proximally along the colon. In Europe, approximately 2.2 million people have a diagnosis of IBD. The aetiology of IBD is unknown, however, immune, environmental and genetic factors are thought to be involved. Individuals with IBD are at risk of developing osteoporosis. In line with this, there are clear guidelines that recommend vitamin D supplementation for IBD patients to prevent bone disease, especially when undergoing steroid treatment. Despite an established role for vitamin D in IBD, deficiency is common. More novel effects of vitamin D beyond bone are emerging. It is now well established that vitamin D is an important regulator of the immune system which may have implications for the development, severity and management of immune related disorders such as IBD. The efficacy of vitamin D as an immune modulator in IBD remains to be proven. This review aims to evaluate the evidence implicating vitamin D deficiency in IBD pathogenesis, to examine vitamin D's anti-inflammatory mechanisms and to explore its therapeutic potential, optimal serum levels and dietary intakes which may support immune function in this disease.
A hyper-responsive adaptive immunologic response to a variety of microbial antigens has been described in Crohn's disease (CD) patients and elevated levels of a number of antibodies have been ...identified in the sera of CD patients. To date, the serological profiles of an Irish CD population have not been characterized.
The aim of this study is to determine the serological profile of Irish patients with CD. Second, we aim to assess the correlation, if any, between serological profile and disease phenotype within this cohort.
A total of 179 consecutive adults with CD attending a specialist inflammatory bowel disease clinic at a university hospital were recruited. Blood samples were taken and sera were analysed for the expression of pANCA and Crohn's related antibodies.
pANCA was present in 47/179 (26.3%), anti-OmpC antibodies were present in 49/179 (27.4%), anti-Saccharomyces cervisiae (ASCA) in 64/179 (35.75%), ASCA IgA in 56/179 (31.28%) and ASCA IgG in 37/179 (20.67%), and anti-CBir antibodies in 97/179 (54.18%). The presence of ASCA IgA (P=0.031), ASCA IgG (P=0.007) and anti-CBir antibodies (P=0.003) were all significantly associated with small bowel involvement. Anti-OmpC, ASCA IgA and anti-CBir antibodies' positivity were all associated with complicated disease behaviour, whereas ANCA positivity was associated with inflammatory disease.
Our study supports previous findings of an association between serological profiles and disease behaviour and a corresponding association with increased need for surgery. In this genetically homogenous Irish CD study group, the levels of specific antibody responses to commensal gut flora are lower than reported previously in other European and American populations.
Introduction
Helicobacter pylori selectively infects the human stomach, being the most prevalent chronic infection in the world. H pylori presence causes chronic gastritis in 100% of infected ...patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease, and gastric cancer; it is for this reason that from a public health standpoint, it is considered a high‐impact pathogen, responsible of a significant morbidity and mortality. Nowadays, there are consensus and clinical guidelines regarding the infection management at a European level and in most of European countries, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs.
Aim
To register the diagnosis, management strategies, and treatment of H pylori‐infected adult patients in the Digestive Services outpatient clinics throughout Europe.
Methods
Noninterventionist prospective multicentre international Registry promoted by the European Helicobacter and Microbiota Study Group. National Coordinators will select recruiting gastroenterologists in their country that will register the H pylori‐related routine clinical practice consultations they receive in an electronic case report form (e‐CRF) provided by AEG‐REDCap. Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation, and outcome data. The database will allow researchers to perform specific subanalyses after approval by the Scientific Committee of the study.
Treatment of Helicobacter pylori Infection 2013 O'Connor, Anthony; Molina-Infante, Javier; Gisbert, Javier P. ...
Helicobacter (Cambridge, Mass.),
09/2013, Volume:
18, Issue:
s1
Journal Article
Peer reviewed
Open access
This review summarizes important studies regarding Helicobacter pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last ...year, highlighting the role of bismuth and nonbismuth quadruple regimen as first‐line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first‐line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the “concomitant” therapy over the “sequential” regimen. “Hybrid” therapy, a combination of sequential and concomitant therapy, has also shown advantage over sequential therapy. Levofloxacin‐based therapies appear to be useful and versatile in second‐ and third‐line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth‐based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth‐line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial.
Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the ...genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.
Background
There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a ...three‐in‐one single‐capsule formulation.
Objective
To evaluate the effectiveness and safety of the single‐capsule bismuth quadruple therapy.
Methods
Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention‐to‐treat and per‐protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line.
Results
Finally, 2100 patients were prescribed single‐capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention‐to‐treat effectiveness of 92% was achieved. Eradication was over 90% in first‐line treatment (95% modified intention‐to‐treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention‐to‐treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention‐to‐treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases.
Conclusions
Single‐capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real‐world clinical practice, both as a first‐line and rescue treatment, with good compliance and a favourable safety profile.
Key Summary
The development of a three‐in‐one single‐capsule formulation has led to a resurgence in the use of bismuth quadruple therapy (BQT) to treat Helicobacter pylori infection.
In the largest study carried out to date, the effectiveness of single‐capsule BQT was optimal both as a firstline and as a rescue therapy.
Compliance was the factor most closely associated with treatment effectiveness.
Single‐capsule BQT eradicates H. pylori in approximately 90% of patients in real‐world clinical practice, with a favourable safety profile.
Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the ...polyp-adenoma-carcinoma sequences well described in medical literature 1, 2. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.
A number of double, triple, and quadruple therapies have been proposed as first-line empiric treatments for Helicobacter pylori infection. However, knowledge of their worldwide and regional ...comparative efficacy is lacking. We examined the comparative effectiveness of all empirically used first-line regimens tested against standard triple treatment using a network meta-analysis of published randomized controlled trials.
Data extracted from eligible randomized controlled trials were entered into a Bayesian network meta-analysis to investigate the comparative efficacy of H pylori infection empiric first-line regimens and to explore their effectiveness rank order. The ranking probability for each regimen was evaluated by means of surfaces under cumulative ranking values.
Sixty-eight eligible randomized controlled trials were included, giving a total of 92 paired comparisons with 22,975 patients randomized to 8 first-line regimens. The overall results showed that only vonoprazan triple therapy and reverse hybrid therapy achieved cure rates of >90%. Levofloxacin triple therapy performed best in Western countries (eradication rate 88.5%). The comparative effectiveness ranking showed that vonoprazan triple therapy had the best results, whereas standard triple therapy was the least efficacious regimen (surfaces under cumulative ranking 92.4% vs 4.7% respectively; odds ratio, 3.80; 95% credible interval, 1.62–8.94).
For first-line empiric treatment of H pylori infection, vonoprazan triple therapy and reverse hybrid therapy achieved high eradication rates of >90%. Levofloxacin triple therapy achieved the highest eradication rates in Western countries. Standard triple therapy was the least efficacious regimen in this network meta-analysis.
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This network meta-analysis, examining the comparative effectiveness of Helicobacter pylori first-line dual, triple, and quadruple therapies showed that vonoprazan-based triple therapy was the most effective worldwide and standard triple therapy was the least efficacious.
Background
Internationally, colorectal cancer screening participation remains low despite the availability of home‐based testing and numerous interventions to increase uptake. To be effective, ...interventions should be based on an understanding of what influences individuals’ decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)–based colorectal cancer screening uptake.
Methods
Regression modeling of data from a cross‐sectional survey within a population‐based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake.
Results
Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of “deny immediacy to be tested” (OR, 0.53; 95% confidence interval CI, 0.43–0.65; p < .001) and “self‐exemption” (OR, 0.80; 95% CI, 0.68–0.96; p < .001) independently predicted nonuse of FIT‐based screening.
Conclusions
This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT‐based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self‐exempting oneself from screening, may be promising targets for future interventions to improve uptake.
Defensive information processing, in the form of suppression, is associated with lower fecal immunochemical test‐based colorectal cancer screening uptake. Two suppression barriers, denying the immediacy to be tested and self‐exempting oneself from screening, are promising targets for future interventions.
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