Elisa Liverani

How to predict clinical relapse in inflammatory bowel disease patients

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohns disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse.

Clinical application of faecal calprotectin in ulcerative colitis patients.

Objective Faecal calprotectin (FC) is the most relevant noninvasive biomarker for monitoring inflammatory status, response to treatment and for predicting clinical relapse in ulcerative colitis (UC). The aim of this study was to evaluate the role of FC in predicting both clinical/endoscopic activity and clinical relapse in a large UC patient cohort. Patients and methods A two-phase prospective study was carried out. In the first phase, the relationship between FC and clinical/endoscopic activity was evaluated. In the second phase, a cohort of asymptomatic patients with endoscopic mucosal healing was followed up using clinical and FC level determinations. Results One hundred and twenty-one UC patients were enrolled. The FC concentrations were directly correlated with both clinical and endoscopic activity (r=0.76 and 0.87, respectively, P<0.05) and were capable of differentiating between different degrees of endoscopic severity (P<0.01). An FC cut-off value of 110 &mgr;g/g was highly predictive (95%) of endoscopic activity. Seventy-four patients in clinical remission with mucosal healing were followed up for a year or until relapse and 27% developed a clinical relapse. The FC concentration of nonrelapsed patients (48 &mgr;g/g) versus relapsed patients (218 &mgr;g/g) was significantly different (P<0.01). An FC cut-off value of 193 &mgr;g/g had an accuracy of 89% in predicting clinical relapse. High FC levels were associated with clinical relapse using survival analysis and multivariate analysis. Conclusion Our data strongly support the use of FC for staging the activity of disease, predicting relapse and leading decision-making in a UC setting.

The Pharmacokinetic Profile of a New Gastroresistant Capsule Preparation of Eicosapentaenoic Acid as the Free Fatty Acid

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohns disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10–16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the “universal donor” with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance.

The Imbalance between n-6/n-3 Polyunsaturated Fatty Acids and Inflammatory Bowel Disease: A Comprehensive Review and Future Therapeutic Perspectives

Eating habits have changed dramatically over the years, leading to an imbalance in the ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) in favour of n-6 PUFAs, particularly in the Western diet. Meanwhile, the incidence of inflammatory bowel disease (IBD) is increasing worldwide. Recent epidemiological data indicate the potential beneficial effect of n-3 PUFAs in ulcerative colitis (UC) prevention, whereas consumption of a higher ratio of n-6 PUFAs versus n-3 PUFAs has been associated with an increased UC incidence. The long-chain dietary n-3 PUFAs are the major components of n-3 fish oil and have been shown to have anti-inflammatory properties in several chronic inflammatory disorders, being involved in the regulation of immunological and inflammatory responses. Despite experimental evidence implying biological plausibility, clinical data are still controversial, especially in Crohn’s disease. Clinical trials of fish-oil derivatives in IBD have produced mixed results, showing beneficial effects, but failing to demonstrate a clear protective effect in preventing clinical relapse. Such data are insufficient to make a recommendation for the use of n-3 PUFAs in clinical practice. Here, we present the findings of a comprehensive literature search on the role of n-3 PUFAs in IBD development and treatment, and highlight new therapeutic perspectives.

Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullos syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?

XII AIST 2018 Conference: “The thousand faces of cough: clinical and therapeutic updates”

This paper summarizes the presentations submitted for publication of the 12th AIST National Congress (Associazione Italiana Studio Tosse/Italian Association for Cough Study) entitled “The thousand facets of cough. A clinical and therapeutic update”, which occurred last February 2nd-3rd, 2018 in Bologna (Italy). It summarizes the contributions from leading experts of the sector, who, as in the previous editions, also this year have analyzed a problem too often underestimated which still has many dark sides as regards both the diagnosis and the therapy of cough. The Scientific Committee has chosen topics that had less space in previous editions and these are topical subjects representing a concrete opportunity for learning and comparison of opinions, as well as indispensable elements for the correct management of the symptoms.Hereby we report the abstracts of the works submitted for publication in this Meeting report.The main topics have covered Cough relationship with nerve vagus, ATP, air pollution, GERD, imaging, COPD, pediatric and therapy. Of particular interest it is the preliminary data on cough hydration ratio that shows a highly significant correlation between dehydration and cough.