C. Pagnini

Eczema and food allergy in an Italian pediatric cohort: No association with TLR-2 and TLR-4 polymorphisms

Recent studies have indicated that Toll-like receptor polymorphisms or their impaired signalling, specifically TLR-2 and TLR-4, were correlated with a higher risk for allergy. The purpose of this study is to evaluate the associations of TRL-2 and TRL-4 single nucleotide polymorphisms (SNP) and atopic traits in a cohort of 159 Italian allergic children (102 affected by eczema and 57 by IgE-mediated food allergy) and 147 healthy controls recruited in Rome, Italy. DNA was isolated from the peripheral blood and TLR-2 R753Q/TLR-4 D299G polymorphisms were determined by TaqMan MGB probes using Real-Time PCR technique. In the control group, the TLR-2 polymorphism R753Q had a prevalence of 2.5% while the frequency of the TLR-4 D299G was 12%. None of the 159 allergic patients showed the R753Q SNP. By contrast, 7/57 patients with food allergy (12%) and 6/102 subjects with eczema (6%) carried the TLR-4 mutation. In our cohort, no evidence of correlation between TLR-2 or TLR-4 polymorphism and eczema and food allergy incidence and/or severity was found. Further studies are needed to clarify the possible role of TLR-2 and TLR-4 polymorphism in allergic disease, in Italian children.

IL-1β-511 and IL-1RN*2 polymorphisms in inflammatory bowel disease: An Italian population study and meta-analysis of European studies

BACKGROUND Several studies have tried to find possible associations between genetic polymorphisms and inflammatory bowel disease prevalence and/or phenotype. Our objectives were to test the frequency and phenotypic association of two polymorphisms of the interleukin-1 pathway, IL-1beta-511 and IL-1RN*2, in inflammatory bowel disease patients and controls from an Italian population, and to compare our data with previously published similar studies in Europe. METHODS We screened 290 inflammatory bowel disease patients (178 ulcerative colitis and 112 Crohns disease) and 106 controls for IL-1beta-511 and IL-1RN*2 polymorphisms by polymerase chain reaction (PCR)-based methods. The prevalence of the IL-1beta-511 and IL-1RN*2 polymorphisms in European inflammatory bowel disease patients was calculated by a meta-analysis of previously published studies using the Mantel-Haenszel method. RESULTS No correlation between the IL-1 polymorphisms and inflammatory bowel disease prevalence was found in our study population. Crohns disease patients with the IL-1beta-511 mutation had a higher rate of complicated disease. A trend for an association between the IL-1RN*2 mutation and a higher risk for inflammatory bowel disease has been found only in studies with Northern European populations. CONCLUSIONS The IL-1beta-511 mutation can be associated with complex disease behaviour in Italian Crohns disease patients. The IL-1RN*2 mutation may play a role in Northern European people with inflammatory bowel disease.

Probiotics in experimental and human inflammatory bowel disease: Discussion points

In recent years, novel insights have been made into the role of bacterial microflora in health and disease. Commensal flora manipulation by probiotic bacteria has been investigated in human and experimental inflammatory bowel disease (IBD). In particular, animal models of IBD offer the opportunity to address important issues regarding indication, therapeutic efficacy and mechanism of action of the probiotic bacteria. Despite the appealing results of many published studies, fundamental questions still remain unanswered. Further studies on appropriate animal models are needed in order to better clarify our knowledge about probiotic bacteria and their potential application as a valid therapeutic option in IBD patients.

Outcome and risk of recurrence for endoscopic resection of colonic superficial neoplastic lesions over 2 cm in diameter

BACKGROUND Large colorectal superficial neoplastic lesions are challenging to remove. This study aimed to assess the outcomes of routine endoscopic resection of large (≥2 cm and <3 cm) and giant (≥3 cm) lesions. METHODS From 4587 endoscopic resections, 265 (5.7%) large and giant lesions were removed in 249 patients. We retrospectively analyzed 125 patients (141 endoscopic mucosal resection, 73 large and 68 giant lesions) with a follow-up of 6-12 months. Rate of en bloc and piecemeal resection, recurrence and risk factors were analyzed. RESULTS En bloc was performed in 92 cases (65.2%) and piecemeal resection in 49 (34.8%). A complete endoscopic resection was achieved in 139 cases (98.5%) with radical resection in 84/139 cases (60.4%). Argon plasma coagulation was applied in 18/141 lesions (12.8%). A recurrence occurred in 16/139 lesions (11.5%). The risk of recurrence at one year was significantly higher for giant than large lesions (p=0.03). The recurrence risk was higher in treated than in non-argon plasma coagulation treated lesions (p=0.01). CONCLUSIONS endoscopic mucosal resection is a safe and effective routine treatment for large superficial neoplastic lesions. The risk factors for recurrence include giant size, non-protruding morphology, piecemeal technique and argon plasma coagulation.

Disease Extension Matters in Endoscopic Scores: UCEIS Calculated as a Sum of the Single Colonic Segments Performed Better than Regular UCEIS in Outpatients with Ulcerative Colitis

We have read with great interest the article by Corte et al .1 Indeed, the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] provides an accurate evaluation of the mucosal appearance together with high intra- and inter-observer agreement.2,3 Nonetheless, it considers just the more inflamed colonic segment, not including the disease extension. This could from one side allow the calculation of the score even from a rectum-sigmoidoscopy, thus avoiding complete colonoscopy that may be contraindicated in particular settings such as acute severe ulcerative colitis [UC]. From the other side, this may represent a potential limitation, in particular in outpatients where total colonoscopy may be the most appropriate examination.4 We retrospectively analysed data of 80 UC outpatients, between 2009 and 2013, at S. Andrea Hospital in Rome, Italy. We included patients who had, within a 1-month period, …

Safety considerations when using anti-TNFα therapy to treat Crohn's disease.

Introduction: Over the past decade, the introduction of a new class of anti-TNFα drugs has dramatically changed the approach taken to the management of Crohn’s disease (CD). An increasing number of patients are receiving treatment with these advanced biological therapies, and the risk of adverse events that may be associated with their use must be carefully evaluated. Areas covered: Safety data about the three anti-TNFα drugs currently approved for use in CD patients (infliximab, adalimumab, and certolizumab pegol) is critically evaluated, including data coming from randomized clinical trials and post-marketing reports. Possible side effects of anti-TNFα agents are presented as drug-, class- and disease-specific adverse events. Management strategies to minimize the occurrence of side effects are summarized. Expert opinion: The safety profile of the three anti-TNFα drugs approved for clinical use in CD patients appears to be comparable among drugs. Data from clinical trials and a growing body of information from post-marketing surveillance indicate that anti-TNFα agents are generally safe, and that most of the observed side effects are mild and easily manageable. Nonetheless, serious short- and long-term adverse events may occur. Accurate selection of patients, careful pre-treatment evaluation, and regular follow-up during therapy could potentially reduce the rate of adverse events related to the use of anti-TNFα drugs.

Natalizumab in the treatment of Crohn’s disease patients

ABSTRACT Introduction: Amongst the available therapies for moderate to severe Crohn’s disease (CD) patients who are refractory to conventional therapy, anti-TNF blockers are the most effective biological treatment option. However, many patients experience a primary or secondary non-response to anti-TNF therapy, creating the need for alternative biological drugs that target different mechanisms of action and inflammatory pathways. Natalizumab, the first non-anti-TNF biological drug to be approved for treatment of CD patients, is a recombinant humanized antibody that targets the α4-subunit of both α4β1 and α4β7 integrins, thus preventing activated leukocyte homing to the intestinal mucosa. Areas covered: This article summarizes the pathophysiological background and the efficacy and safety data of natalizumab, as well as the regulatory issues surrounding it. Expert opinion: Natalizumab represents an effective therapy for refractory CD patients. However, the rare but serious event of progressive multifocal leukoencephalopathy occurrence has compromised its widespread use. The subsequent advent of more specific anti-integrin drugs (i.e. vedolizumab) that carry a more favorable safety profile further reduces the clinical indications for natalizumab. The regulatory process for natalizumab distribution and monitoring in the US may provide a forum for discussion on how to optimally manage use of drugs that offer clinical benefits to patients, while minimizing associated risks.

CARD15 and Toll-like receptor 4 mutations in Italian patients with inflammatory bowel disease

ylori, Borrelia burgdorferi and Chlamydia psittaci, respectively [3,5]. t remains unknown however whether long-term persistence of . jejuni in the intestine is needed to trigger IPSID or if a shorter hedding is sufficient. It is also possible that C. jejuni persistently olonizes the small intestinal mucosa without detectable faecal hedding. This is to our knowledge the first case of IPSID associated with . jejuni since the association was originally reported. It shows otential regression following C. jejuni eradication and further trengthens the link between infectious agents and immunoproiferative diseases. This case also provides the first WCE illustration f IPSID, confirming in this patient in whom no surgery was perormed, the jejunal extension of the disease.

Letter: investigating the intestinal mucosa-associated microbiota – relevance and potential pitfalls

SIRS, We read with great interest the paper from Shanahan et al. We completely agree with the authors about the relevant role of an accurate evaluation of the mucosal-associated microbiota, which represents the part of the intestinal flora directly interacting with the host. Most of the studies in the literature, to date, have evaluated the faecal microbiome, since faecal sample collection do not require invasive examination and could be easier to collect for both patients and researchers. Nonetheless, evidence is mounting about profound differences between faecal bacteria and the mucosal-associated microbiota. 3 Considering that molecular crosstalk between enteric bacteria and intestine takes place at the mucosal surface (i.e. pattern recognition receptors/ pathogen-associated molecular patterns interaction), and giving the spatially heterogeneous distribution of different bacterial species throughout the gut, the analysis of only the faecal microbiome could be misleading. In our institution, we are focusing our research on the evaluation of the mucosal-associated microbiota in different clinical scenarios. We have already demonstrated that the mucosal-associated microbiota is consistently altered in colonic adenomatous polyps’ mucosa, compared with adjacent normal mucosa, with a profound reduction in total bacteria concentration that is coupled with an increased production of antibacterial molecules (a-defensins) in adenomas’ mucosa. We are currently investigating the mucosal adhesion of probiotic bacteria species in different colonic segments as a target for a possible specific therapeutic utilisation in particular clinical conditions (unpublished data) via real-timepolymerase chain reaction quantification. Although direct evidence is lacking, it is reasonable to speculate that the issue raised by Shanahan et al., i.e. the possible cross-contamination of bioptic samples with luminal bacteria, may be more relevant for upper gastrointestinal tract biopsies than for ileal and colonic ones. Indeed, for the latter, the bowel-cleansing regimen that precedes the colonoscopy may represent the real confounding factor to take into account. In fact, while bowel preparation can represent, from one side, a negative factor by inducing changes in the mucosal bacteria composition per-se, on the other hand, it may be a positive factor by reducing luminal bacteria concentration and therefore the potential risk of cross-contamination during biopsy collection. In line with that, the same article by Dave et al., cited by the authors, failed to show significant differences in the microbial diversity of samples obtained using sheathed vs. unsheathed forceps. Nonetheless, the utilisation of the device proposed by Shanahan et al., and the comparison with standard bioptic forceps for ileal and colonic biopsies, could be of interest. Even more remarkable, the better characterisation of bowel cleansing effect on mucosal-adherent bacteria, and the identification and utilisation of cleansing regimens with lower impact on the mucosa-associated microbiome, would help the progress of the research in the intestinal microbiota field.

Elevated C-Reactive Protein in Asymptomatic Crohnʼs Disease Patients: Listen to the Sound of Silence

To the Editor: Bhattacharya et al1 confirmed and extended their previous finding2 indicating that “silent” Crohn’s disease (CD) patients (i.e., asymptomatic patients with elevated C-reactive protein [CRP] level) are a subgroup of patients at the higher risk of hospitalization and of more disabling disease. We completely agree with the relevant role of CRP in asymptomatic CD management, and we conducted a cross-sectional observational study at our institution that showed that such patients are at the higher risk, even in the short time, of clinical flare. In fact, from an electronic database of prospectively collected data of patients visited at the Inflammatory Bowel Disease Outpatient Clinic of S. Andrea Hospital in Rome, Italy, we evaluated a cohort of CD patients at regular follow-up visit, from January 2013 to December 2014. Inclusion criteria were firm diagnosis of CD, availability of clinical (age, sex, disease location and duration, presence of extraintestinal manifestation, smoking status) and biochemical (CRP, hemoglobin level) data, Harvey–Bradshaw index # 4 (clinical remission), and 1 year of recorded follow-up from the index visit. From a total of 97 CD patients with complete data reports, 64 fulfilled inclusion criteria for the study. Among those, 15 (23%) had a CRP level at least 2-fold above the normal laboratory-reported value (“silent” CD patients). Thirteen (20%) of 64 CD patients in clinical remission experienced a clinical flare of disease (empirically defined by the onset of clinical symptoms related to CD [abdominal pain and/or diarrhea] that required a medical consultation). In that group, 6 patients (46%) required steroids administration, and no hospitalization was recorded. In a multivariate analysis, only elevated CRP value showed independent association with disease flare onset at 1 year of follow-up (P , 0.05). Patient with “silent” CD had a significantly lower remission rate at 1 year compared with those with normal CRP (60% versus 86%; log-rank test, P , 0.05), with a 4-fold higher risk of flare (odds ratio, 4; 95% confidence interval, 1.0829–14.7754; P 1⁄4 0.038; Fig. 1). In conclusion, despite the fact that the relevance of CRP in the monitoring of CD patients has been recognized from a long time,3 CRP is not currently indicated as a treatment target.4 Nonetheless, because assessing bowel inflammation burden could be challenging, we believe that the results of the study of Bhattacharya et al, further confirmed by the present retrospective investigation, underline the important role of CRP as a “surrogate”marker in CD management, even in the absence of clinical symptoms. For the future, those findings may open the door to the consideration of specific treat-to-target trials to evaluate possible influence on disease course of treatment optimization aiming to normalize CRP level in CD patients.