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Andrea Buda,1,* Sonia Facchin,1,* Elisa Dassie,2 Elisabetta Casarin,3 Mark A Jepson,4 Helmut Neumann,5 Giorgia Hatem,1 Stefano Realdon,6 Renata D’Incà,1 Giacomo Carlo Sturniolo,1 Margherita Morpurgo3 1Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, 2Department of Molecular Medicine, University of Padova, Padova, Italy; 3Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy; 4School of Biochemistry and Wolfson Bioimaging Facility, University of Bristol, Bristol, UK; 5Ludwig Demlig Endoscopic Center of Excellence, ESGE Endoscopy Training Center, University of Erlangen-Nuremberg, Erlangen, Germany; 6Veneto Institute of Oncology IOV-IRCCS, Padova, Italy *These authors contributed equally to this work Abstract: Inflammatory bowel diseases are chronic gastrointestinal pathologies causing great discomfort in both children and adults. The pathogenesis of inflammatory bowel diseases is not yet fully understood and their diagnosis and treatment are often challenging. Nanoparticle-based strategies have been tested in local drug delivery to the inflamed colon. Here, we have investigated the use of the novel avidin-nucleic acid nanoassembly (ANANAS) platform as a potential diagnostic carrier in an experimental model of inflammatory bowel diseases. Fluorescent-labeled ANANAS nanoparticles were administered to mice with chemically induced chronic inflammation of the large intestine. Localization of mucosal nanoparticles was assessed in vivo by dual-band confocal laser endomicroscopy. This technique enables characterization of the mucosal microvasculature and crypt architecture at subcellular resolution. Intravascular nanoparticle distribution was observed in the inflamed mucosa but not in healthy controls, demonstrating the utility of the combination of ANANAS and confocal laser endomicroscopy for highlighting intestinal inflammatory conditions. The specific localization of ANANAS in inflamed tissues supports the potential of this platform as a targeted carrier for bioactive moieties in the treatment of inflammatory bowel disease. Keywords: confocal laser endomicroscopy, inflammatory bowel disease, diagnostics, dextran sodium sulfate, avidin-nucleic acid nanoassembly, fluorescent nanoparticles, ulcerative colitis

Renata D'Incà, Roberta Caccaro Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Section, University of Padua, Padua, Italy Abstract: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting clinical behavior and dominated by intestinal inflammation. Being a chronic disorder that with time develops into a disabling disease, it is important to monitor the severity of inflammation to assess the efficacy of medication, rule out complications, and prevent progression. This is particularly true now that the goals of treatment are mucosal healing and deep remission. Endoscopy has always been the gold standard for assessing mucosal activity in CD, but its use is limited by its invasiveness and its inability to examine the small intestine, proximal to the terminal ileum. Enteroscopy and the less invasive small bowel capsule endoscopy enable the small bowel to be thoroughly explored and scores are emerging for classifying small bowel disease activity. Cross-sectional imaging techniques (ultrasound, magnetic resonance, computed tomography) are emerging as valid tools for monitoring CD patients, assessing inflammatory activity in the mucosa and the transmucosal extent of the disease, and for excluding extra-intestinal complications. Neither endoscopy nor imaging are suitable for assessing patients frequently, however. Noninvasive markers such as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin, are therefore useful to confirm the inflammatory burden of the disease and to identify patients requiring further investigations. Keywords: activity, biomarkers, Crohn, endoscopy, imaging, monitoring

Maurizio Vecchi,1 Piero Vernia,2 Gabriele Riegler,3 Renata D'Incà,4 Vito Annese,5 Siro Bagnoli51University of Milan, Department of Biomedical Sciences for Health, San Donato Milanese, Milan, 2Sapienza University of Rome, Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Rome, 3Second University of Naples, Gastroenterology and Endoscopy Unit, Naples, 4University of Padua, Department of Surgical and Gastroenterological Science, Gastroenterology Unit, Padua, 5University Hospital Careggi, Gastroenterology Unit, Florence, ItalyAbstract: Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.Keywords: ulcerative colitis, inflammatory bowel disease, guidelines, apheresis