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Claudio fiocchi

Florian Rieder, Claudio Fiocchi, Gerhard Rogler
In the last 10 years, we have learned much about the pathogenesis, diagnosis, and management of intestinal fibrosis in patients with inflammatory bowel diseases (IBD). Just a decade ago, intestinal strictures were considered to be an inevitable consequence of long-term inflammation in patients who did not respond to anti-inflammatory therapies. IBD-associated fibrosis was seen as an irreversible process that frequently led to intestinal obstructions requiring surgical intervention. This paradigm has changed rapidly, due to the anti-fibrotic approaches that may become available...
October 5, 2016: Gastroenterology
Dalin Li, Jean-Paul Achkar, Talin Haritunians, Jonathan P Jacobs, Ken Y Hui, Mauro D'Amato, Stephan Brand, Graham Radford-Smith, Jonas Halfvarson, Jan-Hendrik Niess, Subra Kugathasan, Carsten Büning, L Philip Schumm, Lambertus Klei, Ashwin Ananthakrishnan, Guy Aumais, Leonard Baidoo, Marla Dubinsky, Claudio Fiocchi, Jürgen Glas, Raquel Milgrom, Deborah D Proctor, Miguel Regueiro, Lisa A Simms, Joanne M Stempak, Stephan R Targan, Leif Törkvist, Yashoda Sharma, Bernie Devlin, James Borneman, Hakon Hakonarson, Ramnik J Xavier, Mark Daly, Steven R Brant, John D Rioux, Mark S Silverberg, Judy H Cho, Jonathan Braun, Dermot P B McGovern, Richard H Duerr
BACKGROUND & AIMS: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA). METHODS: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed...
October 2016: Gastroenterology
Silvio Danese, Claudio Fiocchi, Julián Panés
No abstract text is available yet for this article.
August 2016: Gut
Silvio Danese, Claudio Fiocchi
The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid...
2016: Digestive Diseases
Heitor S P de Souza, Claudio Fiocchi
IBD is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities: Crohn's disease and ulcerative colitis. Although Crohn's disease and ulcerative colitis have historically been studied together because they share common features (such as symptoms, structural damage and therapy), it is now clear that they represent two distinct pathophysiological entities. Both Crohn's disease and ulcerative colitis are associated with multiple pathogenic factors including environmental changes, an array of susceptibility gene variants, a qualitatively and quantitatively abnormal gut microbiota and a broadly dysregulated immune response...
January 2016: Nature Reviews. Gastroenterology & Hepatology
Claudio Fiocchi
Personalized medicine is variably defined as a new system aimed at providing optimal medical care by using comprehensive pathophysiology-based information on all aspects and components of a disease process to prevent, diagnose and treat in ways that are custom-made for the individual patient. The need for personalized medicine derives from the realization that today's most challenging medical conditions are chronic complex diseases with multiple pathogenic components that interact with each other. Complexity and interaction together create unique molecular pathways that are only relevant to certain disease subtypes, but not to the entire population of patients with the same diagnosis...
September 14, 2015: Digestive Diseases
Elodie Mintet, Emilie Rannou, Valérie Buard, Gail West, Olivier Guipaud, Georges Tarlet, Jean-Christophe Sabourin, Marc Benderitter, Claudio Fiocchi, Fabien Milliat, Agnès François
The endothelial-to-mesenchymal transition (EndoMT) is a crucial cellular process during heart development necessary to the formation of cardiac valves. This embryonic process reappears in several pathological situations, such as vascular injury or organ fibrosis of various etiologies, as a mediator of extracellular matrix-producing cells. Because radiation induces both vascular damage and fibrosis, we investigated whether radiation exposure induces EndoMT in primary human intestinal microvascular endothelial cells (HIMECs) and whether EndoMT contributes to radiation-induced rectal damage in humans and in a preclinical model of radiation proctitis in mice...
September 2015: American Journal of Pathology
Frederick A Masoudi, Alan S Go, David J Magid, Andrea E Cassidy-Bushrow, Jerry H Gurwitz, Taylor I Liu, Kristi Reynolds, David H Smith, Liza M Reifler, Karen A Glenn, Frances Fiocchi, Robert Goldberg, Nigel Gupta, Pamela N Peterson, Claudio Schuger, Humberto Vidaillet, Stephen C Hammill, Robert T Greenlee
BACKGROUND: Patient sex and age may influence rates of death after receiving an implantable cardioverter-defibrillator for primary prevention. Differences in outcomes other than mortality and whether these differences vary by heart failure symptoms, etiology, and left ventricular ejection fraction are not well characterized. METHODS AND RESULTS: We studied 2954 patients with left ventricular ejection fraction ≤0.35 undergoing first-time implantable cardioverter-defibrillator for primary prevention within the Cardiovascular Research Network; 769 patients (26%) were women, and 2827 (62%) were aged >65 years...
June 2015: Journal of the American Heart Association
Melania Scarpa, Sean Kessler, Tammy Sadler, Gail West, Craig Homer, Christine McDonald, Carol de la Motte, Claudio Fiocchi, Eleni Stylianou
Intestinal epithelial cell (IEC) death is typical of inflammatory bowel disease (IBD). We investigated: i) whether IEC-released necrotic cell products (proinflammatory mediators) amplify mucosal inflammation, ii) the capacity of necrotic cell lysates from HT29 cells or human IECs to induce human intestinal fibroblasts' (HIF) production of IL-6 and IL-8, and iii) whether IL-1α, released by injured colonocytes, exacerbated experimental IBD. Necrotic cell lysates potently induced HIF IL-6 and IL-8 production independent of Toll-like receptors 2 and 4, receptor for advanced glycation end-products, high-mobility group box 1, uric acid, IL-33, or inflammasome activation...
June 2015: American Journal of Pathology
Claudio Fiocchi
Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease...
March 2015: Journal of Gastroenterology and Hepatology
Jun Hwan Yoo, Samantha Ho, Deanna Hoang-Yen Tran, Michelle Cheng, Kyriaki Bakirtzi, Yuzu Kukota, Ryan Ichikawa, Bowei Su, Diana Hoang-Ngoc Tran, Tressia C Hing, Irene Chang, David Q Shih, Richard E Issacson, Richard L Gallo, Claudio Fiocchi, Charalabos Pothoulakis, Hon Wai Koon
BACKGROUND AND AIMS: Cathelicidin (LL-37 in human and mCRAMP in mice) represents a family of endogenous antimicrobial peptides with anti-inflammatory effects. LL-37 also suppresses collagen synthesis, an important fibrotic response, in dermal fibroblasts. Here we determined whether exogenous cathelicidin administration modulates intestinal fibrosis in two animal models of intestinal inflammation and in human colonic fibroblasts. METHODS: C57BL/6J mice (n=6 per group) were administered intracolonically with a trinitrobenzene sulphonic acid (TNBS) enema to induce chronic (6-7 weeks) colitis with fibrosis...
January 2015: Cellular and Molecular Gastroenterology and Hepatology
Andrew T Schuster, Craig R Homer, Jacqueline R Kemp, Kourtney P Nickerson, Emily Deutschman, Yeojung Kim, Gail West, Tammy Sadler, Eleni Stylianou, Dawid Krokowski, Maria Hatzoglou, Carol de la Motte, Brian P Rubin, Claudio Fiocchi, Christine McDonald, Michelle S Longworth
BACKGROUND & AIMS: Defects in colonic epithelial barrier defenses are associated with ulcerative colitis (UC). The proteins that regulate bacterial clearance in the colonic epithelium have not been completely identified. The Drosophila chromosome-associated protein D3 (dCAP-D3) regulates responses to bacterial infection. We examined whether CAP-D3 promotes bacterial clearance in human colonic epithelium. METHODS: Clearance of Salmonella or adherent-invasive Escherichia coli LF82 was assessed by gentamycin protection assays in HT-29 and Caco-2 cells expressing small hairpin RNAs against CAP-D3...
June 2015: Gastroenterology
Claudio Fiocchi
The complexity of IBD is well recognized as are the putative four major components of its pathogenesis, i.e. environment, genetic makeup, gut microbiota and mucosal immune response. Each of these components is extremely complex on its own, and at present should be more appropriately defined by the terms 'exposome', 'genome', 'microbiome' and 'immunome', respectively, based on the 'ome' suffix that refers to a totality of some sort. None of these 'omes' is apparently capable of causing IBD by itself; it is instead the intricate and reciprocal interaction among them, through the so-called 'IBD interactome', that results in the emergence of IBD, or more appropriately the 'IBD integrome'...
2014: Digestive Diseases
Cynthia A Pise-Masison, Maria Fernanda de Castro-Amarante, Yoshimi Enose-Akahata, R Cody Buchmann, Claudio Fenizia, Robyn Washington Parks, Dustin Edwards, Martina Fiocchi, Luiz Carlos Alcantara, Izabela Bialuk, Jhanelle Graham, Jean-Claude Walser, Katherine McKinnon, Bernardo Galvão-Castro, Antoine Gessain, David Venzon, Steven Jacobson, Genoveffa Franchini
HTLV-1 orf-I is linked to immune evasion, viral replication and persistence. Examining the orf-I sequence of 160 HTLV-1-infected individuals; we found polymorphism of orf-I that alters the relative amounts of p12 and its cleavage product p8. Three groups were identified on the basis of p12 and p8 expression: predominantly p12, predominantly p8 and balanced expression of p12 and p8. We found a significant association between balanced expression of p12 and p8 with high viral DNA loads, a correlate of disease development...
November 2014: PLoS Pathogens
Kyriaki Bakirtzi, Gail West, Claudio Fiocchi, Ivy Ka Man Law, Dimitrios Iliopoulos, Charalabos Pothoulakis
The expression of neurotensin (NT) and its receptor (NTR1) is up-regulated in experimental colitis and inflammatory bowel disease; NT/NTR1 interactions regulate gut inflammation. During active inflammation, metabolic shifts toward hypoxia lead to the activation of hypoxia-inducible factor (HIF)-1, which enhances vascular endothelial growth factor (VEGF) expression, promoting angiogenesis. We hypothesized that NT/NTR1 signaling regulates intestinal manifestations of hypoxia and angiogenesis by promoting HIF-1 transcriptional activity and VEGFα expression in experimental colitis...
December 2014: American Journal of Pathology
Victor Uko, Eugene Vortia, Jean-Paul Achkar, Pinar Karakas, Claudio Fiocchi, Sarah Worley, Marsha H Kay
BACKGROUND: Increased abdominal visceral adipose tissue (VAT) is associated with systemic inflammation. The influence of VAT on pediatric inflammatory bowel disease (IBD) has not been studied. The objective of this study was to investigate the differences in VAT between pediatric patients with IBD and age-matched controls and identify associations between VAT and Crohn's disease (CD) outcomes. METHODS: Single-center retrospective cohort study of 114 pediatric patients with IBD (101 CD and 13 ulcerative colitis) who had abdominal computed tomography at diagnosis...
December 2014: Inflammatory Bowel Diseases
Silvia D'Alessio, Carmen Correale, Carlotta Tacconi, Alessandro Gandelli, Giovanni Pietrogrande, Stefania Vetrano, Marco Genua, Vincenzo Arena, Antonino Spinelli, Laurent Peyrin-Biroulet, Claudio Fiocchi, Silvio Danese
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown etiology that are associated with an aberrant mucosal immune response. Neoangiogenesis and vascular injury are observed in IBD along with increased lymphangiogenesis. While the pathogenic role of angiogenesis in IBD is well characterized, it is not clear how or if increased lymphangiogenesis promotes disease. Here, we determined that enhancing lymphangiogenesis and lymphatic function reduces experimental IBD...
September 2014: Journal of Clinical Investigation
Ilyssa O Gordon, Neha Agrawal, John R Goldblum, Claudio Fiocchi, Florian Rieder
Chronic intestinal inflammation and impaired tissue repair leading to intestinal fibrosis are a commonly observed complication in inflammatory bowel disease. This is particularly true for small bowel Crohn's disease. However, the development of fibrosis in ulcerative colitis has remained largely unexplored. This is surprising, given knowledge about its prevalence for decades, well described histopathologic features of fibrotic and stricturing ulcerative colitis, the relevance of the extracellular matrix for intestinal inflammation and fibrosis, and the clinical impact of fibrosis on stricture formation, motility, and the necessary discrimination from colonic malignancy...
November 2014: Inflammatory Bowel Diseases
Ivan J Fuss, Bharat Joshi, Zhiqiong Yang, Heba Degheidy, Stefan Fichtner-Feigl, Heitor de Souza, Florian Rieder, Franco Scaldaferri, Anja Schirbel, Melania Scarpa, Gail West, Chuli Yi, Lili Xu, Pamela Leland, Michael Yao, Peter Mannon, Raj K Puri, Claudio Fiocchi, Warren Strober
OBJECTIVE: Previous studies have shown that ulcerative colitis (UC) is associated with the presence of lamina propria non-invariant (Type II) NKT cells producing IL-13 and mediating epithelial cell cytotoxicity. Here we sought to define the antigen(s) stimulating the NKT cells and to quantitate these cells in the UC lamina propria. DESIGN: Detection of Type II NKT cells in UC lamina propria mononuclear cells (LPMC) with lyso-sulfatide loaded tetramer and quantum dot-based flow cytometry and staining...
November 2014: Gut
Florian Rieder, Ilche Nonevski, Jie Ma, Zhufeng Ouyang, Gail West, Cheryl Protheroe, Giovanni DePetris, Anja Schirbel, James Lapinski, John Goldblum, Tracey Bonfield, Rocio Lopez, Karen Harnett, James Lee, Ikuo Hirano, Gary Falk, Piero Biancani, Claudio Fiocchi
BACKGROUND & AIMS: Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. METHODS: Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls)...
May 2014: Gastroenterology
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