Marco Astegiano

Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells

We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand β-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) γ strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by β-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor β, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4+ T cells, IL-1β, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference

BACKGROUND Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <−1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

Side-to-Side Stapled Anastomosis Strongly Reduces Anastomotic Leak Rates in Crohn’s Disease Surgery

PURPOSEAnastomotic configuration may influence anastomotic leak rates. The aim of this study was to determine whether a side-to-side stapled ileocolonic anastomosis produces lower anastomotic leak rates than those with a handsewn end-to-end ileocolonic anastomosis after ileocecal or ileocolonic resection for Crohn’s disease.METHODSA series of 122 consecutive patients underwent elective ileocecal or ileocolonic resection with ileocolonic anastomosis for Crohn’s disease from January 1998 to June 2003: 71 had handsewn end-to-end anastomosis and 51 had side-to-side stapled anastomosis. The choice between the two anastomoses was left to the surgeon’s preference. A retrospective analysis was performed to assess if there was any difference in anastomotic leak rates.RESULTSThe two groups were comparable in terms of age, gender, preoperative presence of abscess or fistula, history of smoking, and albumin levels. More patients were taking steroids in the handsewn group than in the stapled group. In the handsewn group there were 10 anastomotic leaks (14.1 percent) and in the stapled group there was 1 anastomotic leak (2.0 percent) (risk difference, +12.1 percent; 95 percent confidence interval, 1.7–22.2; P = 0.02). Anastomotic configuration was the sole variable that influenced anastomotic leak rates at univariate analysis. Mortality was 1.4 percent in the handsewn group and 0 percent in the stapled group. Complications other than anastomotic leak developed in 11 patients in the handsewn group and in 6 patients in the stapled group. Mean postoperative hospital stay was 12.3 days in the handsewn group and 9.7 days in the stapled group (P = 0.03). Excluding those patients who had an anastomotic leak, the difference was still present (handsewn group, 10.1 days; stapled group, 9.1 days; P = 0.04).CONCLUSIONAlthough confirmation from randomized, controlled trials is required, side-to-side stapled anastomosis seems to substantially decrease anastomotic leak rates in surgical patients with Crohn’s disease, compared with handsewn end-to-end anastomosis. Postoperative hospital stay decreased in the stapled anastomosis group, and this was not entirely a result of decreased anastomotic leak rates.

The natural history of ulcerative proctitis: a multicenter, retrospective study

Abstract OBJECTIVE: The aim of this study was to evaluate the clinical features and the long term evolution of patients with a well defined initial diagnosis of ulcerative proctitis. METHODS: Patients with an original diagnosis of ulcerative proctitis who had been seen at any of 13 institutions from 1989 to 1994 were identified. Data on disease onset and subsequent evolution were recorded. In addition, 575 patients with more extensive disease, treated in the same centers, were used as controls. RESULTS: A total of 341 patients satisfied the inclusion criteria. The percentage of smokers in these patients was slightly lower than in controls; no differences were found in the other clinical/demographic variables evaluated. A total of 273 patients entered long term follow-up (mean, 52 months). Proximal extension of the disease occurred in 74 of them (27.1%). The cumulative rate of proximal extension and of extension beyond the splenic flexure was 20% and 4% at 5 yr and 54% and 10% at 10 yr, respectively. The risk of proximal extension was higher in nonsmokers, in patients with >3 relapses/yr, and in patients needing systemic steroid or immunosuppressive treatment. Refractory disease was confirmed as an independent prognostic factor at multivariate analysis. CONCLUSIONS: Proximal extension of ulcerative proctitis is frequent and may occur even late after the original diagnosis. However, the risk of extension beyond the splenic flexure appears to be quite low. Smoking seems to be a protective factor against proximal extension, whereas refractoriness is a risk factor for proximal extension of the disease.

Safety and efficacy of azathioprine in the maintenance of ciclosporin‐induced remission of ulcerative colitis

It has been shown that azathioprine prolongs the response to ciclosporin of steroid‐refractory ulcerative colitis, but no specific data are available concerning its toxicity in this indication.

Controlled trial of oral 5‐aminosalicylic acid for the prevention of early relapse in Crohn's disease

Recent data indicate that 5‐aminosalicylic acid (5‐ASA) is most effective in preventing relapse of Crohns disease in patients with a short duration of remission before enrolment.

Abdominal pain and bowel dysfunction : diagnostic role of intestinal ultrasound

Background Abdominal pain and irregular bowel habits are common among young people. Irritable bowel syndrome is frequent in the general population and has important economic and social costs. Inflammatory bowel diseases are chronic processes with an acute or indolent onset in young people. Differential clinical diagnosis between irritable bowel syndrome and inflammatory bowel disease can be difficult since symptoms and signs are often non-specific. Objective To evaluate the role of intestinal ultrasound, a non-invasive, simple and cheap diagnostic tool, in the differentiation between organic and functional bowel diseases. Methods Abdominal and intestinal ultrasound examinations were performed on 313 consecutive outpatients presenting with abdominal pain and irregular bowel habits lasting more than 3 months. These patients had no symptoms or signs indicative of organic disorders and no previous diagnosis of organic disease. An intestinal wall thickness of more than 7 mm was considered diagnostic for inflammatory bowel disease. Subsequently, we compared the ultrasound results with diagnoses obtained following the traditional criteria (radiological and endoscopic examinations). Results Intestinal ultrasound for the diagnosis of inflammatory bowel disease showed 74% sensitivity, 98% specificity, a positive predictive value of 92% and a negative predictive value of 92%. Conclusions In our experience, intestinal ultrasound seems important as a first diagnostic tool in young patients without clear symptoms or signs of organic diseases, and can be used as an indication that subsequent invasive tests are required.

A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life.

A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fishers exact, P < 0·001; test for trend, P < 0·001) or positive EMA (Fishers exact, P = 0·001; test for trend, P = 0·018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD.

Analysis of the CARD15 variants R702W, G908R and L1007fs in Italian IBD patients

CARD15 on chromosome 16 is the only IBD susceptibility gene identified among several mapped loci. Its recurrent variants R702W, G908R and L1007fs have shown significant association with Crohns disease (CD), but not with ulcerative colitis (UC), in different Caucasian populations. We analysed these three variants in 184 CD and 92 UC Italian patients and in 177 healthy controls. L1007fs and G908R were independently associated with CD, while R702W showed a nonsignificant increase. After combining the three variants together, 32.6% of CD patients were positive vs 18.6% of the controls. The association was stronger for homozygotes and compound heterozygotes, OR 13.9 (1.8–108), and weaker but still significant for simple heterozygotes, OR 1.7 (1.0–2.9). An excess of homozygotes/compound heterozygotes also resulted from the comparison with Hardy–Weinberg expectations. Phenotype–genotype correlations were analysed first by univariate logistic regression and then by multivariate analysis, the effect of CARD15 positivity being adjusted according to the status of smoking, familiarity and sex, so as to focus on the predictivity of genetic and environmental risk factors on the clinical phenotype. Significant risk estimates of the CARD15 genotype were obtained for stricturing vs inflammatory behaviour, OR 2.76 (1.2–6.3), and for penetrating behaviour, 2.59 (1.0–6.6), and marginally significant for ileal vs colic location, OR 3.0 (0.9–9.8). Our findings indicate that the association of the CARD15 genotype with behaviour and location of disease holds also for the Italian population.