G R Corazza

University of Pavia, Ticinum, Lombardy, Italy

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Publications (523)2394.36 Total impact

  • Antonio Di Sabatino, Marco Vincenzo Lenti, Gino Roberto Corazza
    Digestive and Liver Disease 03/2014; · 3.16 Impact Factor
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    ABSTRACT: Intestinal fibrosis with stricture formation is a complication of Crohn's disease (CD) that may mandate surgical resection. Accurate biomarkers that reflect the relative contribution of fibrosis to an individual stricture are an unmet need in managing patients with CD. The microRNA (miR)-29 family has been implicated in cardiac, hepatic and pulmonary fibrosis. We investigated the expression of miR-29a, miR-29b and miR-29c in mucosa overlying a stricture in CD patients (SCD) paired with mucosa from non-strictured areas (NSCD). There was significant down-regulation of the miR-29 family in mucosa overlying SCD compared to mucosa overlying NSCD. MiR-29b showed the largest fold-decrease and was selected for functional analysis. Over-expression of miR-29b in CD fibroblasts led to a down-regulation of collagen I and III transcripts and collagen III protein, but did not alter matrix metalloproteinase (MMP)-3, MMP-12 and tissue inhibitor of metalloproteinase (TIMP)-1 production. TGF-β1 up-regulated collagen I and III transcripts and collagen III protein as a consequence of the down-regulation of miR-29b and TGF-β1-induced collagen expression was reversed by exogenous overexpression of miR-29b. Furthermore, serum levels of miR-29 were lower in patients with stricturing disease compared to those without. These data implicate the miR-29 family in the pathogenesis of intestinal fibrosis in CD and provides impetus for the further evaluation of the miR-29 family as biomarkers.
    Clinical Science 03/2014; · 4.86 Impact Factor
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    ABSTRACT: Autoimmune enteropathy (AIE) is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes, and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset AIE cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping AIE in a compliant-to-diet young celiac girl. A 13-year-old celiac girl was admitted because of vomiting, weight loss, diarrhea, hypoproteinemia, and neurological disturbances such as head tremors, vertical nystagmus, and lower limb hyperesthesia. Before this, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. The diagnosis of AIE was established on histologic findings and on the presence of antienterocyte antibodies. She was initially treated with high-dose Methylprednisolone and Azathioprine. However, only Infliximab proved itself as a highly effective tool for achieving clinical remission and restoring small bowel villous architecture.
    Journal of clinical gastroenterology 03/2014; 48(3):264-6. · 2.21 Impact Factor
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    ABSTRACT: Several biomarkers have been proposed for the diagnosis of autoimmune atrophic gastritis (AAG), but at the present there is no appropriate testing strategy for the disease. The aim of this study was to develop and validate a laboratory score able to address the diagnosis of AAG in a general practice setting. We prospectively evaluated a number of serum biomarkers (vitamin B12, mean corpuscular volume, hemoglobin, gastrin, and chromogranin A levels) in a case-control population and built 2 biochemical scores, the first with all the parameters [Global Score (GS)], and the second as the best statistical combination of them [Simple Score (SS)]. In the second phase we validated the score that proved to be more efficient on a random population referred to our center (Gastroenterology Outpatient Clinic). Both models turned out to be reliable in detecting patients with suspected AAG, showing excellent accuracy [area under the receiver operating curve (AUC-ROC) 0.94; 95% confidence interval (CI), 0.91-0.97 for GS and AUC-ROC 0.93; 95% CI, 0.89-0.86 for SS]. The SS proved to be more convenient because of its accessibility and availability in a general setting and its low cost. The validation of the SS showed a sensitivity of 85.7% (95% CI, 57.2-98.2) and a specificity of 83.7% (95% CI, 74.2-90.89). Herein, we describe 2 nonexpensive and reliable score models, particularly the SS, that can be applied in daily medical practice for identifying patients potentially affected by AAG.
    Journal of clinical gastroenterology 02/2014; · 2.21 Impact Factor
  • Gino Roberto Corazza, Marco Vincenzo Lenti, Antonio Di Sabatino
    Internal and Emergency Medicine 01/2014; · 2.35 Impact Factor
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    ABSTRACT: The celiac disease is an ancient pathology, present since the introduction of the wheat in the diet, of which the first description of the compatible clinical symptoms and signs goes back to 250 A.D. Today it is known that the expression of this pathology is multifaceted, ranging from clinical features indicative of bowel disease and malabsorption, until symptoms once unexpected, because of their extra-digestive clinical features. With our work, we wanted to retrace the history of this disease, correlating it with the intake of gluten present in wheat after cooking , ever since mankind has increased the cultivation of cereals. Re-evaluating the clinical and instrumental methods for the diagnosis of Celiac Disease, and benefitting from the most modern techniques for the morphological, biochemical and genetic study of the patients, we sought to understand whether the incidence of the disease is actually increased or if has been considered less frequent for the lower valuation of the signs once deemed more atypical, but currently considered preliminary indicative of the pathology, for its association with other autoimmune diseases, and for the study of some genetic and familiar characteristics. Each of these factors has led the modern medicine to increase epidemiological studies and expand the research potential carriers of celiac disease with safer diagnostic tests.
    Internal and Emergency Medicine 01/2014; · 2.35 Impact Factor
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    ABSTRACT: OBJECTIVES:Several immune-mediated gastrointestinal disorders, including celiac disease (CD), are associated with neuroendocrine cell hyperplasia. However, neuroendocrine cells have never been explored in refractory CD (RCD).METHODS:Serial duodenal sections from 17 patients with RCD (6 type 1 and 11 type 2), 16 uncomplicated CD patients before and after gluten-free diet, 14 patients with potential CD, 27 patients with non-CD villous atrophy, i.e., common variable immunodeficiency (n=12), Whipple's disease (n=10) and giardiasis (n=5), and 16 healthy subjects were processed for the immunohistochemical detection of chromogranin A (CgA), serotonin, and somatostatin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative reverse transcription-PCR. Serum CgA and 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) were assessed. Biopsies from treated CD patients were cultured with serotonin or peptic tryptic digest of gliadin (PT-gliadin), and interferon (IFN)-γ was detected by ELISA in culture supernatants.RESULTS:Epithelial cells positive for CgA and serotonin, but not somatostatin, were significantly increased in RCD. Raised mucosal transcripts of TpH-1, but not SERT, were found in RCD. On biopsies from treated CD patients, serotonin upregulated IFN-γ production at levels comparable to those induced by PT-gliadin. Serum CgA, but not urine 5-HIAA, was increased in RCD. No significant difference was found between RCD type 1 and type 2 in terms of neuroendocrine cells, mucosal TpH-1 transcripts, and serum CgA.CONCLUSIONS:Serotonin-producing neuroendocrine cells are increased in RCD mucosa. IFN-γ upregulation induced by serotonin suggests that this monoamine may have a role in sustaining the local inflammatory response in CD.Am J Gastroenterol advance online publication, 7 January 2014; doi:10.1038/ajg.2013.426.
    The American Journal of Gastroenterology 01/2014; · 7.55 Impact Factor
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    ABSTRACT: It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.
    PLoS ONE 01/2014; 9(1):e84163. · 3.73 Impact Factor
  • Journal of the American College of Cardiology 01/2014; 63(14):1457–1458. · 14.09 Impact Factor
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    ABSTRACT: Interleukin (IL)-13 has been implicated in the pathogenesis of ulcerative colitis (UC), and may have a role in animal models of gut fibrosis. We studied the involvement of IL-13 in inflammation and fibrosis in UC and Crohn's disease (CD). Intestinal biopsies and anti-CD3/CD28- or anti-CD2/CD28-stimulated lamina propria mononuclear cells (LPMCs) from UC and CD patients and control subjects were cultured, and IL-13, IL-4, IL-5, IL-17A and interferon (IFN)-γ production was measured. Mucosal IL-13-producing cells were characterised by flow cytometry. Gut explants from strictured CD, non-strictured CD and healthy donors were cultured ex vivo, and secreted IL-13, IL-1β and collagen were measured. IL-13 production by mucosal explants and activated LPMCs did not differ between CD, UC and control subjects, and was at least a log lower than IFN-γ and IL-17A. IL-13-producing cells, and in particular natural killer T cells, were uniformly low in all groups. IL-4 and IL-5 were undetectable in culture supernatants. Explants of CD strictures produced low amounts of IL-13, whereas IL-1β and collagen were elevated. We could not confirm that UC or strictured CD are associated with elevated IL-13 production. These data suggest that an anti-IL-13 antibody would not be an appropriate therapeutic strategy in inflammatory bowel disease. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 12/2013; · 4.97 Impact Factor
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    ABSTRACT: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.
    World Journal of Gastroenterology 12/2013; 19(45):8269-81. · 2.55 Impact Factor
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    ABSTRACT: Despite extensive use in clinical practice, difficulties regarding interpretation of hydrogen breath test are still very frequent, even on research grounds. After the administration of a non-absorbable sugar, such as lactulose, an increase of breath hydrogen and methane is evident; this phenomenon is considered an index of colonic fermentation. It is not clear, however, if the levels of these compounds correlate with the presence and severity of functional symptoms, nor if they accurately reflect gas production at colonic level. So far, apart from flatulence, we have no indications regarding the ability of hydrogen or methane to act as biomarkers of intraluminal events. On the other hand, it has been shown that in functional bowel disease a colonic dysbiosis exists, and that the modification of bacterial flora might result in a reduction of symptom severity. Consequently, it is not clear if hydrogen and methane colonic production could have a role in the pathophysiology of functional complaints, but it is possible that other fermentation products should be taken into consideration, such as acetate, propionate, and alcohol.
    European review for medical and pharmacological sciences 12/2013; 17(2 Suppl):36-38. · 1.09 Impact Factor
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    ABSTRACT: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality.
    Digestive and Liver Disease 11/2013; · 3.16 Impact Factor
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    ABSTRACT: Refractory celiac disease (RCD) is characterized by severe symptoms/signs of malabsorption and mucosal damage unresponsive to a gluten-free diet. The pathogenesis of RCD is not fully understood. Here we characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies were taken from patients with RCD, patients with active CD, and normal controls, and analyzed for inflammatory cytokines by real-time PCR and ELISA. IFN-γ and IL-21 transcripts were increased in active CD patients but not in RCD patients as compared to normal controls, while IL-17A RNA was up-regulated in both active CD and RCD. No significant increase in IL-15 transcripts was seen in both active CD and RCD, while IL-15 protein was increased in active CD. IL-6 and TNF-α were up-regulated only in RCD. As a proof, we present the case of a woman affected by RCD who responded to anti-TNF-α treatment with improvement of malabsorptive symptoms/signs but no healing of mucosal lesions. Data indicate that the profile of mucosal effector cytokines differs between RCD and active CD and suggest that TNF-α, IL-6 and IL-17A, but not Th1-type cytokines, could drive the detrimental response in this condition.
    Clinical Science 10/2013; · 4.86 Impact Factor
  • European journal of clinical nutrition 10/2013; · 3.07 Impact Factor
  • Journal of the American College of Cardiology 08/2013; · 14.09 Impact Factor
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    ABSTRACT: Hepcidin, a peptide produced by hepatocytes, regulates body iron homeostasis. Inflammation increases serum hepcidin, and its determination can be useful in the differential diagnosis of anemias during inflammatory diseases. We measured serum hepcidin-25 and hepcidin-20 isoforms in 54 patients with inflammatory bowel diseases (IBD) and 54 reference subjects (36 healthy controls and 18 anemic patients without inflammation or renal failure). Disease activity, blood counts, iron status, and erythropoiesis-related parameters were obtained for all study subjects. In IBD hepcidin-25, the peptide bioactive isoform correlated positively with C-reactive protein and serum ferritin; an inverse correlation was observed with transferrin, the soluble transferrin receptor, and the soluble transferrin receptor to Log(ferritin) ratio. Similar correlations were found in reference subjects. Patients with anemia of inflammation had higher hepcidin-25 levels than those with iron deficiency anemia or a combination of iron deficiency anemia and inflammation (P = 0.0061). In patients with inflammation and serum ferritin concentration 100 to 200 ng/mL, hepcidin-25 was low, suggesting that these patients had iron deficiency. A serum hepcidin-25 concentration below 2.0 nM differentiated 85% of patients with iron deficiency anemia (with or without inflammation) from patients with anemia of inflammation. In IBD, hepcidin-20 correlated with both hepcidin-25 and C-reactive protein. In IBD, iron stores, inflammation, and iron requirement for erythropoiesis influence serum hepcidin-25. Hepcidin-25 determination can be useful in the differential diagnosis of IBD-associated anemias. Serum hepcidin-20 is linked to hepcidin-25, but inflammation has an independent regulatory role on its concentration, indicating that hepcidin-20 may have a biological function.
    Inflammatory Bowel Diseases 07/2013; · 5.12 Impact Factor
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    ABSTRACT: Interleukin (IL)-17A and IL-17E (also known as IL-25) have been implicated in fibrosis in various tissues. However, the role of these cytokines in the development of intestinal strictures in Crohn's disease (CD) has not been explored. We investigated the levels ofIL-17A and IL-17E and their receptors in CD strictured and non-strictured gut, and the effects of IL-17A and IL-17E on CD myofibroblasts.. IL-17A was significantly overexpressed in strictured compared with non-strictured CD tissues, whereas no significant difference was found in the expression of IL-17E or IL-17A and IL-17E receptors (IL-17RC and IL-17RB, respectively) in strictured and non-strictured CD areas. Strictured CD explants released significantly higher amounts of IL-17A than non-strictured explants, whereas no difference was found as for IL-17E, IL-6, or tumor necrosis factor-alpha production. IL-17A, but not IL-17E, significantly inhibited myofibroblast migration, and also significantly upregulated matrix metalloproteinase (MMP)-3, MMP-12, tissue inhibitor of metalloproteinase-1 and collagen production by myofibroblasts from strictured CD tissues. Our results suggest that IL-17A, but not IL-17E, is pro-fibrotic in CD. Further studies are needed to clarify whether the therapeutic blockade of IL-17A through the anti-IL-17A monoclonal antibody secukinumab is able to counteract the fibrogenic process in CD.
    Fibrogenesis & Tissue Repair 07/2013; 6(1):13.
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    ABSTRACT: Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by pre-formed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine (PCV) after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that PCV administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 06/2013; · 4.97 Impact Factor
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    ABSTRACT: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). The exact cause of IBD remains unknown. Available evidence suggests that an abnormal immune response against the microorganisms of the intestinal flora is responsible for the disease in genetically susceptible individuals. The adaptive immune response has classically been considered to play a major role in the pathogenesis of IBD. However, recent advances in immunology and genetics have clarified that the innate immune response is equally as important in inducing gut inflammation in these patients. In particular, an altered epithelial barrier function contributes to intestinal inflammation in patients with UC, while aberrant innate immune responses, such as antimicrobial peptides production, innate microbial sensing and autophagy are particularly associated to CD pathogenesis. On the other hand, besides T helper cell type (Th)1 and Th2 immune responses, other subsets of T cells, namely Th17 and regulatory T (Treg) cells, are likely to play a role in IBD. However, given the complexity and probably the redundancy of pathways leading to IBD lesions, and the fact that Th17 cells may also have protective functions, neutralization of IL-17A failed to induce any improvement in CD. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons in the knowledge about the immunologic mechanisms implicated in gut inflammation.
    Autoimmunity reviews 06/2013; · 6.37 Impact Factor

Publication Stats

6k Citations
2,394.36 Total Impact Points

Institutions

  • 1999–2014
    • University of Pavia
      • • Department of Molecular Medicine
      • • Department of Public Health, Neuroscience, Experimental and Forensic Medicine
      • • Department of Internal Medicine and Therapeutics
      Ticinum, Lombardy, Italy
    • University of Catania
      Catania, Sicily, Italy
  • 2013
    • University of Oxford
      • Division of Experimenal Medicine
      Oxford, ENG, United Kingdom
    • University of Verona
      Verona, Veneto, Italy
  • 2011–2013
    • Università degli Studi di Teramo
      Teramo, Abruzzo, Italy
  • 2010–2012
    • University of Rome Tor Vergata
      • Dipartimento di Medicina dei Sistemi
      Roma, Latium, Italy
    • University College London
      • Centre for Gastroenterology and Nutrition
      London, ENG, United Kingdom
  • 2001–2012
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Radiologia - Istituto di Radiologia
      Ticinum, Lombardy, Italy
  • 2008
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1983–2008
    • University of Bologna
      • • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      • • School of Medicine
      Bolonia, Emilia-Romagna, Italy
  • 2007
    • Queen Mary, University of London
      • The Blizard Institute of Cell and Molecular Science
      London, ENG, United Kingdom
  • 1990–2007
    • Università degli Studi dell'Aquila
      • • Department of Experimental Medicine
      • • SS in Internal Medicine
      • • Department of Life, Health and Environmental Sciences
      • • Department of Internal Medicine and Public Health
      Aquila, Abruzzo, Italy
  • 1997–2006
    • Catholic University of the Sacred Heart
      • Institute of Internal and Geriatric Medicine
      Milano, Lombardy, Italy
  • 2000–2003
    • Università degli studi di Palermo
      • Dipartimento di Discipline Chirurgiche, Oncologiche e Stomatologiche (Di.Chir.On.S.)
      Palermo, Sicily, Italy
  • 2002
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1998
    • Clínica Palermo
      Santa Rosalía de Guagua, Huila, Colombia
  • 1996
    • University of Milan
      Milano, Lombardy, Italy
  • 1992–1993
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy