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1. Cost per Number Needed to Treat (NNT) for upadacitinib in the treatment of bio-exposed patients with moderately-severely active ulcerative rectocolitis

Author

Flavio Caprioli, Massimo Claudio Fantini, Francesca Marando, Dario Scaduto, and Roberto Ravasio

Subjects
Bio-exposed, Cost per NNT, Italian NHS, Ulcerative Rectocolitis, Upadacitinib, Medical technology, R855-855.5
Abstract

Background: Only limited information is available on cost efficacy of the advanced therapies for the treatment of ulcerative rectocolitis. We evaluated the efficacy and the treatment costs of these advanced therapies in the treatment of bio-exposed (primary failure to a biological agent) patients with moderately to severely active ulcerative rectocolitis. Methods: Data from a previous network meta-analysis (NMA) in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis was used. The analysis involved three therapies approved in Italy for the treatment of moderately to severely active ulcerative rectocolitis: upadacitinib (UPA), ustekinumab (UST) and vedolizumab (VDZ). According to the NMA results, the analysis was conducted considering two different timepoints: induction and maintenance. The pharmacoeconomic comparison between advanced therapies was carried out to estimate the respective cost for the NNT (Number Needed to Treat) compared to placebo using the clinical response (CRes) for the induction and clinical remission (CRem) and endoscopic improvement (EI) for the maintenance. Only the ex-factory price of each advanced therapy was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: Independently of the timepoint considered (induction or maintenance) and the clinical (CRem and CRes) or endoscopic endpoint (EI) evaluated, UPA had always the lower cost per NNT than UST and VDZ. For example, considering the induction and the CRes, the cost per NNT for upadacitinib (45 mg) was € 7,862.07 compared to € 30,459.38 for ustekinumab (6 mg/kg) and to € 67,868.00 for vedolizumab. Conclusion: Upadacitinib is a cost-effective therapeutic option compared to ustekinumab and vedolizumab in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis.

Published
2024
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2. Adherence to Mediterranean Diet and Diet Quality in Patients with Inflammatory Bowel Disease: A Single-Center, Observational, Case-Control Study

Author

Marta Cadoni, Agnese Favale, Rita Piras, Mauro Demurtas, Paola Soddu, Alessandra Usai, Ivan Ibba, Massimo Claudio Fantini, and Sara Onali

Subjects
Mediterranean diet, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, diet quality, Medi-Lite score, Nutrition. Foods and food supply, TX341-641
Abstract

The nutritional status in inflammatory bowel disease (IBD) is often impaired, and adherence to the Mediterranean diet (MedDiet) remains under-investigated. The aim of this study was to assess diet quality (DQ) and adherence to MedDiet in a cohort of Sardinian IBD patients. We conducted a case-control study in which 50 Crohn’s disease (CD) and 50 ulcerative colitis (UC) patients were matched with 100 healthy controls each. The Diet Quality Index (DQI-I) and Medi-Lite were used to assess DQ and adherence to MedDiet, respectively. Subgroup analysis by disease characteristics and use of advanced therapies were also carried out. DQI-I scored significantly lower in IBD, independently of disease localization and behavior (CD) and disease extent (UC): [DQI-I: CD 34.5 (IQR 33–37) vs. CTRL 40 (IQR 38.5–43) p < 0.0001; UC 34.5 (IQR 33–37) vs. CTRL 42 (IQR 40–44) p < 0.0001]. Medi-Lite scores were significantly lower in stricturing and ileo-colonic CD and in extensive UC: [Medi-Lite CD 7.5 (IQR 7–9)] vs. CTRL 9 (IQR 7–10) p = 0.0379]; [UC 8 (IQR7–10) vs. CTRL 9 (IQR 8–10.5) p = 0.0046]. IBD patients had a low DQ independently of disease type and phenotype. Patients with ileo-colonic stenosing CD or extensive UC had lower MedDiet adherence, suggesting that its benefits may be mitigated by low acceptance in specific subgroups.

Published
2024
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3. Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

Author

Marco Vincenzo Lenti, Maria Lia Scribano, Livia Biancone, Rachele Ciccocioppo, Daniela Pugliese, Luca Pastorelli, Gionata Fiorino, Edoardo Savarino, Flavio Andrea Caprioli, Sandro Ardizzone, Massimo Claudio Fantini, Gian Eugenio Tontini, Ambrogio Orlando, Gianluca Matteo Sampietro, Giacomo Carlo Sturniolo, Giovanni Monteleone, Maurizio Vecchi, Anna Kohn, Marco Daperno, Renata D’Incà, Gino Roberto Corazza, and Antonio Di Sabatino

Subjects
clinical complexity, Crohn’s disease, internal medicine, precision medicine, ulcerative colitis, Medicine (General), R5-920
Abstract

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

Published
2023
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4. Inhibitory Effect of Quercetin on Oxidative Endogen Enzymes: A Focus on Putative Binding Modes

Author

Stefania Olla, Chiara Siguri, Antonella Fais, Benedetta Era, Massimo Claudio Fantini, and Amalia Di Petrillo

Subjects
quercetin, xanthine oxidase, myeloperoxidase, nicotinamide adenine dinucleotide phosphate oxidase, lipoxygenase, monoamine oxidase, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by anti-oxidant defense systems. Cells can produce ROS during physiological processes, but excessive ROS can lead to non-specific and irreversible damage to biological molecules, such as DNA, lipids, and proteins. Mitochondria mainly produce endogenous ROS during both physiological and pathological conditions. Enzymes like nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO), and monoamine oxidase (MAO) contribute to this process. The body has enzymatic and non-enzymatic defense systems to neutralize ROS. The intake of bioactive phenols, like quercetin (Que), can protect against pro-oxidative damage by quenching ROS through a non-enzymatic system. In this study, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its anti-oxidant properties. Que can act as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups. Additionally, it can effectively inhibit the activity of several endogenous oxidative enzymes by binding them with high affinity and specificity. Que had the best molecular docking results with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Que’s binding to these enzymes was confirmed by subsequent molecular dynamics, revealing different stability phases depending on the enzyme bound. The 500 ns simulation showed a net evolution of binding for NOX and MPO. These findings suggest that Que has potential as a natural therapy for diseases related to oxidative stress.

Published
2023
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5. Crohn’s disease and ulcerative colitis patient-reported outcomes signs and symptoms for the remote management of inflammatory bowel disease during the COVID-19 pandemic

Author

Sergio Pinto, Erica Loddo, Salvatore Paba, Agnese Favale, Fabio Chicco, Sara Onali, Paolo Usai, and Massimo Claudio Fantini

Subjects
Patient-reported outcome, Inflammatory bowel disease, COVID-19, Telemedicine, Public aspects of medicine, RA1-1270
Abstract

Abstract Background and aims The COVID-19 pandemic has led to a deep reorganization of hospital services including inflammatory bowel disease (IBD) units. In this situation, conversion of in-person routine follow-up visits into phone consultations might be necessary. Here we explored the feasibility of using the validated Crohn’s Disease (CD) or Ulcerative Colitis (UC) Patient-Reported Outcomes Signs and Symptoms (CD- and UC-PRO/SS) to collect data about abdominal symptoms (abdominal/S) and bowel signs and symptoms (bowel/SS) remotely. Methods CD- and UC-PRO/SS were collected during phone consultations and compared among patients with active and inactive disease. The effectiveness of therapeutic intervention in patients with active disease was assessed by PRO/SS variation. Results Twenty-one CD and 56 UC patients were evaluated by phone. Six (28.6%) CD and 15 (26.8%) UC patients were considered to have active disease. In CD the bowel/SS but not the abdominal/S module was significantly higher in active patients (mean bowel/SS 2.50 [SE ± 0.44] active vs 0.76 [SE ± 0.18] remission, p = 0.008, AUC 0.87; mean abdominal/S 1.11 [SE ± 0.38] active vs 0.24 [SE ± 0.13] remission, p = 0.066). UC-PRO/SS measures were significantly higher in active patients as compared to patients in remission (median bowel/SS 1.63 [SE ± 0.24] active vs 0.33 [SE ± 0.04] remission; p

Published
2021
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6. Comparison of two strategies for the management of postoperative recurrence in Crohn’s disease patients with one clinical risk factor: A multicentre IG‐IBD study

Author

Gabriele Dragoni, Fabiana Castiglione, Cristina Bezzio, Daniela Pugliese, Rocco Spagnuolo, Anna Viola, Francesco Cocomazzi, Annalisa Aratari, Edoardo Vincenzo Savarino, Paola Balestrieri, Sara Onali, Chiara Viganò, Davide Giuseppe Ribaldone, Tommaso Innocenti, Anna Testa, Simone Saibeni, Giuseppe Privitera, Monica Milla, Alessandro Armuzzi, Massimo Claudio Fantini, and Gionata Fiorino

Subjects
Crohn's disease, Oncology, inflammatory bowel disease, postoperative Crohn's disease, Gastroenterology, Rutgeerts Score, endoscopic recurrence, ileo-colonic resection, immunoprophylaxis, postoperative recurrence
Published
2023

7. Clinical and epidemiological features of ulcerative colitis patients in Sardinia, Italy: Results from a multicenter study

Author

Salvatore Magrì, Mauro Demurtas, Maria Francesca Onidi, Marcello Picchio, Walter Elisei, Manuela Marzo, Federica Miculan, Roberto Manca, Maria Pina Dore, Bianca Maria Quarta Colosso, Antonio Cicu, Luigi Cugia, Monica Carta, Laura Binaghi, Paolo Usai, Mariantonia Lai, Fabio Chicco, Massimo Claudio Fantini, Alessandro Armuzzi, and Giammarco Mocci

Subjects
General Medicine
Abstract

There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden.To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy.We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit.Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy.Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

Published
2022

9. Data from 2-Methoxy-5-Amino-N-Hydroxybenzamide Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis by Regulating Death Receptor 5 and Survivin Expression

Author

Giovanni Monteleone, Francesco Pallone, Massimo Claudio Fantini, Ivan Monteleone, Angela Rotondi, Angelamaria Rizzo, Eleonora Franzè, Roberta Caruso, and Carmine Stolfi

Abstract

TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is a crucial event in the control of tumor growth. However, many cancer cells, including colon cancer cells, are resistant to TRAIL-driven cell death. We have recently shown that 2-methoxy-5-amino-N-hydroxybenzamide (herein termed 2-14), a novel derivative of mesalamine, induces endoplasmic reticulum stress in colon cancer cells. Because endoplasmic reticulum stress-induced signals regulate the expression of molecules involved in TRAIL-driven apoptosis, we examined whether 2-14 makes colon cancer cells sensitive to TRAIL. Colon cancer cells were cultured with 2-14 and/or TRAIL. Death receptor (DR) 4/DR5 were analyzed by real-time PCR and flow cytometry. TRAIL pathway–associated proteins and extracellular signal–regulated kinase (ERK) were assessed by Western blotting. The in vivo capability of 2-14 to sensitize colon cancer cells to TRAIL-induced apoptosis was evaluated in a syngenic colon cancer model in which CT26-derived grafts were induced in mice. 2-14 promoted ERK-dependent induction of DR5, thereby enhancing TRAIL-mediated caspase-8 activation and apoptosis. Analysis of TRAIL-related pro- and antiapoptotic factors and functional studies revealed that survivin is involved in the protection of colon cancer cells against TRAIL-driven apoptosis. Notably, 2-14 enhanced ubiquitination and proteasome-mediated degradation of survivin. These data were confirmed in a murine model of TRAIL-resistant colon cancer in which 2-14 upregulated DR5, reduced survivin expression, and synergized with TRAIL in inhibiting tumor growth. Similarly, intraperitoneal administration of 2-14 to mice upregulated DR5 and downregulated survivin in a model of colitis-associated colon cancer. These findings indicate that 2-14 acts as a sensitizer for TRAIL-induced apoptosis and suggest that 2-14 can be useful in the therapy for TRAIL-resistant colon cancer. Mol Cancer Ther; 10(10); 1969–81. ©2011 AACR.

Published
2023

10. COVID-19 triggers attacks in HAE patients without worsening disease outcome

Author

María Margarita Olivares, Ricardo Dario Zwiener, Lina Maria Leiva Panqueva, Francisco Alberto Contreras Verduzco, Eli Mansour, Jairo Antonio Rodriguez, Solange Oliveira Rodrigues Valle, Sandra Nieto-Martínez, Jane da Silva, Daniel O. Vazquez, Oscar Calderon Llosa, Fernanda Casares Marcelino, Manuel Ratti Sisa, Ileana María Madrigal Beas, Rafael Zaragoza Urdaz, Eliana Toledo, Natalia Lorena Fili, Olga M. Barrera, Juan Carlos Fernandez de Cordova Aguirre, Sergio Castro Mora, Mauricio Sarrazola, Rodolfo Jaller Raad, Edison Morales Cardenas, Dario Oscar Josviack, Claudio Fantini, Monica Marocco, Elma I. Nievas, Faradiba Sarquis Serpa, Herberto J. Chong-Neto, Maria Luiza Oliva Alonso, Sergio Dortas Junior, Raisa Gusso Ulaf, Nelson Rosário, Rodolfo Ramón Leyva Barrero, and Anete Sevciovic Grumach

Subjects
Hereditary Angioedema, Hereditary Angioedema with normal C1-INH, C1 inhibitor, Treatment Outcome, SARS-CoV-2, Angioedemas, Hereditary, COVID-19, Humans, Immunology and Allergy, Clinical Communications, Risk factor, Complement C1 Inhibitor Protein, Androgen
Published
2022

11. Use of biologics for the management of Crohn's disease: IG-IBD clinical guidelines based on the GRADE methodology

Author

Fabio Salvatore Macaluso, Claudio Papi, Ambrogio Orlando, Stefano Festa, Daniela Pugliese, Stefanos Bonovas, Claudia Pansieri, Daniele Piovani, Gionata Fiorino, Massimo Claudio Fantini, Flavio Caprioli, Marco Daperno, Alessandro Armuzzi, Lorenzo Bertani, Cristina Bezzio, Giorgia Bodini, Fabrizio Bossa, Andrea Buda, Emma Calabrese, Federica Furfaro, Salvatore Leone, Filippo Mocciaro, Sara Onali, Luca Pastorelli, Enrica Previtali, Mariabeatrice Principi, Sara Renna, Davide Giuseppe Ribaldone, Antonio Rispo, Fernando Rizzello, Simone Saibeni, Gianluca Matteo Sampietro, Edoardo Savarino, Anna Testa, Angela Variola, Angelo Viscido, Sandro Ardizzone, Livia Biancone, Maria Cappello, Fabiana Castiglione, Rachele Ciccocioppo, Michele Comberlato, Francesco Costa, Renata D'Incà, Silvio Danese, Antonio Di Sabatino, Walter Fries, Paolo Gionchetti, Giovanni Latella, Francesco Manguso, Mauro Mastronardi, Gianmichele Meucci, Monica Milla, Maria Lia Scribano, and Maurizio Vecchi

Subjects
Clinical guidelines, Crohn's disease, GRADE, IG-IBD, Hepatology, Gastroenterology, Biologics
Published
2023

12. Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease: Data from ESCAPE-IBD, an IG-IBD study

Author

Fabio Salvatore Macaluso, Mariabeatrice Principi, Federica Facciotti, Antonella Contaldo, Alessia Todeschini, Simone Saibeni, Cristina Bezzio, Fabiana Castiglione, Olga Maria Nardone, Rocco Spagnuolo, Massimo Claudio Fantini, Gaia Riguccio, Flavio Caprioli, Chiara Viganò, Carla Felice, Gionata Fiorino, Carmen Correale, Giorgia Bodini, Monica Milla, Giulia Scardino, Marta Vernero, Federico Desideri, Mariella Mannino, Giuseppe Rizzo, Ambrogio Orlando, Arnaldo Amato, Marta Ascolani, Giulio Calabrese, Angelo Casà, Michele Comberlato, Francesco Simone Conforti, Manuela De Bona, Maria Giulia Demarzo, Patrizia Doldo, Gabriele Dragoni, Federica Furfaro, Giacomo Mulinacci, Oriana Olmo, Nicole Piazza O'Sed, Salvatore Paba, Simona Radice, Sara Renna, Davide Giuseppe Ribaldone, Giulia Rizzuto, Macaluso, F, Principi, M, Facciotti, F, Contaldo, A, Todeschini, A, Saibeni, S, Bezzio, C, Castiglione, F, Nardone, O, Spagnuolo, R, Fantini, M, Riguccio, G, Caprioli, F, Vigano, C, Felice, C, Fiorino, G, Correale, C, Bodini, G, Milla, M, Scardino, G, Vernero, M, Desideri, F, Mannino, M, Rizzo, G, Orlando, A, Amato, A, Ascolani, M, Calabrese, G, Casa, A, Comberlato, M, Conforti, F, De Bona, M, Demarzo, M, Doldo, P, Dragoni, G, Furfaro, F, Mulinacci, G, Olmo, O, O'Sed, N, Paba, S, Radice, S, Renna, S, Ribaldone, D, Rizzuto, G, Macaluso, F. S., Principi, M., Facciotti, F., Contaldo, A., Todeschini, A., Saibeni, S., Bezzio, C., Castiglione, F., Nardone, O. M., Spagnuolo, R., Fantini, M. C., Riguccio, G., Caprioli, F., Vigano, C., Felice, C., Fiorino, G., Correale, C., Bodini, G., Milla, M., Scardino, G., Vernero, M., Desideri, F., Mannino, M., Rizzo, G., Orlando, A., Amato, A., Ascolani, M., Calabrese, G., Casa, A., Comberlato, M., Conforti, F. S., De Bona, M., Demarzo, M. G., Doldo, P., Dragoni, G., Furfaro, F., Mulinacci, G., Olmo, O., O'Sed, N. P., Paba, S., Radice, S., Renna, S., Ribaldone, D. G., and Rizzuto, G.

Subjects
Vaccines, Hepatology, Biologic, SARS-CoV-2, Gastroenterology, Biologics, Vaccine
Abstract

Background: Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims: To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) Methods: Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Results: 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%; p

Published
2023

13. Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf

Author

Massimo Claudio Fantini, Agnese Favale, Sara Onali, and Federica Facciotti

Subjects
colorectal cancer, colitis-associated colorectal cancer, regulatory T cells, inflammation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Regulatory T cells represent a class of specialized T lymphocytes that suppress unwanted immune responses and size the activation of the immune system whereby limiting collateral damages in tissues involved by inflammation. In cancer, the accumulation of Tregs is generally associated with poor prognosis. Many lines of evidence indicate that Tregs accumulation in the tumor microenvironment (TME) suppresses the immune response against tumor-associated antigens (TAA), thus promoting tumor progression in non-small cell lung carcinoma (NSLC), breast carcinoma and melanoma. In colorectal cancer (CRC) the effect of Tregs accumulation is debated. Some reports describe the association of high number of Tregs in CRC stroma with a better prognosis while others failed to find any association. These discordant results stem from the heterogeneity of the immune environment generated in CRC in which anticancer immune response may coexists with tumor promoting inflammation. Moreover, different subsets of Tregs have been identified that may exert different effects on cancer progression depending on tumor stage and their location within the tumor mass. Finally, Tregs phenotypic plasticity may be induced by cytokines released in the TME by dysplastic and other tumor-infiltrating cells thus affecting their functional role in the tumor. Here, we reviewed the recent literature about the role of Tregs in CRC and in colitis-associated colorectal cancer (CAC), where inflammation is the main driver of tumor initiation and progression. We tried to explain when and how Tregs can be considered to be the “good” or the “bad” in the colon carcinogenesis process on the basis of the available data concluding that the final effect of Tregs on sporadic CRC and CAC depends on their localization within the tumor, the subtype of Tregs involved and their phenotypic plasticity.

Published
2020
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14. Reciprocal Regulation Between Smad7 and Sirt1 in the Gut

Author

Silvia Sedda, Eleonora Franzè, Gerolamo Bevivino, Martina Di Giovangiulio, Angelamaria Rizzo, Alfredo Colantoni, Angela Ortenzi, Enrico Grasso, Mario Giannelli, Giuseppe S. Sica, Massimo Claudio Fantini, and Giovanni Monteleone

Subjects
mucosal inflammation, colitis, transforming growth factor-β, Sirt1, inflammatory bowel diseases, Immunologic diseases. Allergy, RC581-607
Abstract

In inflammatory bowel disease (IBD) mucosa, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine transforming growth factor-β1, due to post-transcriptional mechanisms that enhance Smad7 acetylation status thus preventing ubiquitination-mediated proteosomal degradation of the protein. IBD-related inflammation is also marked by defective expression of Sirt1, a class III NAD+-dependent deacetylase, which promotes ubiquitination-mediated proteosomal degradation of various intracellular proteins and triggers anti-inflammatory signals. The aim of our study was to determine whether, in IBD, there is a reciprocal regulation between Smad7 and Sirt1. Smad7 and Sirt1 were examined in mucosal samples of IBD patients and normal controls by Western blotting and immunohistochemistry, and Sirt1 activity was assessed by a fluorimetric assay. To determine whether Smad7 is regulated by Sirt1, normal or IBD lamina propria mononuclear cells (LPMC) were cultured with either Sirt1 inhibitor (Ex527) or activator (Cay10591), respectively. To determine whether Smad7 controls Sirt1 expression, ex vivo organ cultures of IBD mucosal explants were treated with Smad7 sense or antisense oligonucleotide. Moreover, Sirt1 expression was evaluated in LPMC isolated from Smad7-transgenic mice given dextran sulfate sodium (DSS). Upregulation of Smad7 was seen in both the epithelial and lamina propria compartments of IBD patients and this associated with reduced expression and activity of Sirt1. Activation of Sirt1 in IBD LPMC with Cay10591 reduced acetylation and enhanced ubiquitination-driven proteasomal-mediated degradation of Smad7, while inhibition of Sirt1 activation in normal LPMC with Ex527 increased Smad7 expression. Knockdown of Smad7 in IBD mucosal explants enhanced Sirt1 expression, thus suggesting a negative effect of Smad7 on Sirt1 induction. Consistently, mucosal T cells of Smad7-transgenic mice contained reduced levels of Sirt1, a defect that was amplified by induction of DSS colitis. The data suggest the existence of a reciprocal regulatory mechanism between Smad7 and Sirt1, which could contribute to amplify inflammatory signals in the gut.

Published
2018
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15. Diagnostic delay in adult coeliac disease: An Italian multicentre study

Author

Marco Vincenzo Lenti, Nicola Aronico, Paola Ilaria Bianchi, Carmela Cinzia D'Agate, Matteo Neri, Umberto Volta, Maria Gloria Mumolo, Marco Astegiano, Antonino Salvatore Calabrò, Fabiana Zingone, Giovanni Latella, Antonio Di Sario, Antonio Carroccio, Carolina Ciacci, Francesco Luzza, Carmela Bagnato, Massimo Claudio Fantini, Luca Elli, Giovanni Cammarota, Antonio Gasbarrini, Piero Portincasa, Mario Andrea Latorre, Clarissa Petrucci, Claudia Quatraccioni, Chiara Iannelli, Nicoletta Vecchione, Carlo Maria Rossi, Giacomo Broglio, Gianluca Ianiro, Ilaria Marsilio, Stefano Bibbò, Beatrice Marinoni, Donatella Tomaselli, Ludovico Abenavoli, Riccardo Pilia, Giovanni Santacroce, Erica Lynch, Antonella Carrieri, Pasquale Mansueto, Margherita Gabba, Giacomo Alunno, Chiara Rossi, Francesca Onnis, Konstantinos Efthymakis, Nicola Cesaro, Marta Vernero, Federica Baiano Svizzero, Francesco Paolo Semeraro, Marco Silano, Alessandro Vanoli, Catherine Klersy, Gino Roberto Corazza, and Antonio Di Sabatino

Subjects
Diagnosis, Enteropathy, Gluten, Malabsorption, Villi, Hepatology, Settore MED/12 - GASTROENTEROLOGIA, Gastroenterology
Abstract

There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD).To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD.CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted.Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay.We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented.

Published
2022

16. Use of biologics and small molecule drugs for the management of moderate to severe ulcerative colitis: IG-IBD clinical guidelines based on the GRADE methodology

Author

Fabio Salvatore Macaluso, Ambrogio Orlando, Claudio Papi, Stefano Festa, Daniela Pugliese, Stefanos Bonovas, Claudia Pansieri, Daniele Piovani, Gionata Fiorino, Massimo Claudio Fantini, Flavio Caprioli, Marco Daperno, Alessandro Armuzzi, Lorenzo Bertani, Cristina Bezzio, Giorgia Bodini, Fabrizio Bossa, Andrea Buda, Emma Calabrese, Federica Furfaro, Salvatore Leone, Filippo Mocciaro, Sara Onali, Luca Pastorelli, Enrica Previtali, Mariabeatrice Principi, Sara Renna, Davide Giuseppe Ribaldone, Antonio Rispo, Fernando Rizzello, Simone Saibeni, Gianluca Matteo Sampietro, Edoardo Savarino, Anna Testa, Angela Variola, Angelo Viscido, Sandro Ardizzone, Livia Biancone, Maria Cappello, Fabiana Castiglione, Rachele Ciccocioppo, Michele Comberlato, Francesco Costa, Renata D'Incà, Silvio Danese, Antonio Di Sabatino, Walter Fries, Paolo Gionchetti, Giovanni Latella, Francesco Manguso, Mauro Mastronardi, Gianmichele Meucci, Monica Milla, Maria Lia Scribano, Maurizio Vecchi, Macaluso F.S., Orlando A., Papi C., Festa S., Pugliese D., Bonovas S., Pansieri C., Piovani D., Fiorino G., Fantini M.C., Caprioli F., Daperno M., Armuzzi A., Bertani L., Bezzio C., Bodini G., Bossa F., Buda A., Calabrese E., Furfaro F., Leone S., Mocciaro F., Onali S., Pastorelli L., Previtali E., Principi M., Renna S., Ribaldone D.G., Rispo A., Rizzello F., Saibeni S., Sampietro G.M., Savarino E., Testa A., Variola A., Viscido A., Ardizzone S., Biancone L., Cappello M., Castiglione F., Ciccocioppo R., Comberlato M., Costa F., D'Inca R., Danese S., Di Sabatino A., Fries W., Gionchetti P., Latella G., Manguso F., Mastronardi M., Meucci G., Milla M., Scribano M.L., and Vecchi M.

Subjects
Clinical guidelines, Biological Products, IG-IBD, Hepatology, Biologic, Gastroenterology, Biologics, GRADE, Small molecule drugs, Adalimumab, Humans, Infliximab, Colitis, Ulcerative, Inflammatory Bowel Diseases, Ulcerative, Colitis, Settore MED/12, Clinical guideline
Abstract

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

Published
2022

17. Advanced imaging and Crohn’s disease: An overview of clinical application and the added value of artificial intelligence

Author

Giovanni, Grassi, Maria Elena, Laino, Massimo Claudio, Fantini, Giovanni Maria, Argiolas, Maria Valeria, Cherchi, Refky, Nicola, Clara, Gerosa, Giulia, Cerrone, Lorenzo, Mannelli, Antonella, Balestrieri, Jasjit S, Suri, Alessandro, Carriero, and Luca, Saba

Subjects
Diffusion Magnetic Resonance Imaging, Crohn Disease, Artificial Intelligence, Humans, Contrast Media, Radiology, Nuclear Medicine and imaging, General Medicine, Tomography, X-Ray Computed, Magnetic Resonance Imaging
Abstract

The purpose of this narrative review is to describe the clinical applications of advanced computed tomography (CT) and magnetic resonance (MRI) techniques in patients affected by Crohn's disease (CD), giving insights about the added value of artificial intelligence (AI) in this field.We performed a literature search comparing standardized and advanced imaging techniques for CD diagnosis. Cross-sectional imaging is essential for the identification of lesions, the assessment of active or relapsing disease and the evaluation of complications.The studies reviewed show that new advanced imaging techniques and new MRI sequences could be integrated into standard protocols, to achieve a reliable quantification of CD activity, improve the lesions' characterization and the evaluation of therapy response. These promising tools are: dual-energy CT (DECT) post-processing techniques, diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI), Magnetization Transfer MRI (MT-MRI) and CINE-MRI. Furthermore, AI solutions show a potential when applied to radiological techniques in these patients. Machine learning (ML) algorithms and radiomic features prove to be useful in improving the diagnostic accuracy of clinicians and in attempting a personalized medicine approach, stratifying patients by predicting their prognosis.Advanced imaging is crucial in the diagnosis, lesions' characterisation and in the estimation of the abdominal involvement in CD. New AI developments are promising tools that could support doctors in the management of CD affected patients.

Published
2022

18. Corrigendum to: Immunological Variables Associated With Clinical and Endoscopic Response to Vedolizumab in Patients With Inflammatory Bowel Diseases

Author

Coletta, Marina, primary, Paroni, Moira, additional, Alvisi, Maria Francesca, additional, De Luca, Matilde, additional, Rulli, Eliana, additional, Mazza, Stefano, additional, Facciotti, Federica, additional, Lattanzi, Georgia, additional, Strati, Francesco, additional, Abrignani, Sergio, additional, Claudio Fantini, Massimo, additional, Vecchi, Maurizio, additional, Geginat, Jens, additional, and Caprioli, Flavio, additional

Published
2021
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19. Patients With Hereditary Angioedema Do Not Develop More Severe COVID-19 but SARS-CoV-2 Infection May Trigger Attacks: 66 Cases

Author

Claudio Fantini, Natalia Fili, Edison Morales Cardenas, Lina Maria Leiva Panqueva, Juan Carlos Fernandez de Cordova Aguirre, Jairo A. Rodríguez, Jane da Silva, Oscar Calderon Llosa, Dario Oscar Josviak, Sergio Castro Mora, Herberto José Chong Neto, Raisa G. Ulaf, Olga M Barrero, Maria Margarita Olivares, Eli Mansour, Francisco Alberto Contreras Verduzco, Faradiba Sarquis Serpa, Solange Oliveira Rodrigues Valle, Mauricio Sarrazola, Rafael Zaragoza-Urdaz, Sérgio Duarte Dortas Junior, Maria Luiza Oliva Alonso, Rodolfo Jaller Raad, Eliana C. Toledo, Sandra Nieto, Fernanda Casares Marcelino, Monica B. Marocco, Ileana María Madrigal Beas, Rodolfo Ramón Leyva Barrero, Ricardo Dario Zwiener, Anete Sevciovic Grumach, Nelson Rosario, Manuel Ratti-Sisa, Elma I Nievas, and Daniel O. Vázquez

Subjects
Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hereditary angioedema, Immunology, medicine, medicine.disease, business
Abstract

PurposeHereditary angioedema (HAE) is a rare genetic disease with hyperactivated contact and kallikrein-kinin systems leading to bradykinin (BK) release and edema. SARS-CoV-2 infection results in inflammatory exacerbation. C1 inhibitor (C1-INH) deficiency could aggravate clinical outcomes, with HAE patients at a greater risk of adverse outcomes of COVID-19, however, data are still limited. Our aim was to characterize the course and severity of COVID-19 in patients with HAE.MethodsLatin American HAE reference centers evaluated SARS-CoV-2 infection in this population. Patients with confirmed diagnosis of HAE with (HAE-C1-INH) or without C1-INH deficiency (HAE-nC1-INH) were included. HAE symptomatology and the course of COVID-19 were characterized with the application of a questionnaire. Results66 patients from 10 countries (HAE-C1-INH 80,3%; HAE-nC1-INH 19.6%) were reported with SARS-CoV-2 infection. Comorbidities were absent in 69.7% of the patients and obesity present in 12.1%. Attacks occurred in 45.5% of patients with HAE during SARS-CoV-2 infection. Long term prophylaxis was reported in 52% (34/66) of HAE patients. Complete cure was observed in 61 patients (92.4%), pulmonary sequelae in 4 and death in one HAE-C1-INH patient. The cause of death was septic shock secondary to bacterial pulmonary coinfection. Disease progression was not impacted by sex, therapy or type of HAE (p = 0.803). Conclusion Attacks occurred in almost half of HAE patients suggesting that SARS-CoV-2 infection is a trigger. HAE did not represent a risk factor for a worse outcome of COVID-19, even in use of androgens.

Published
2021

20. Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

Author

Gionata Fiorino, Flavio Caprioli, Marco Daperno, Filippo Mocciaro, Mariabeatrice Principi, Angelo Viscido, Massimo Claudio Fantini, Ambrogio Orlando, Claudio Papi, Vito Annese, Silvio Danese, Maurizio Vecchi, Fernando Rizzello, Alessandro Armuzzi, Salvatore Leone, Enrica Previtali, Marina Aloi, Patrizia Alvisi, Elisabetta Antonelli, Sandro Ardizzone, Marco Astegiano, Monia Baldoni, Marina Beltrami, Livia Biancone, Giorgia Bodini, Andrea Buda, Fabrizio Bossa, Fiammetta Bracci, Emma Calabrese, Maria Cappello, Fabiana Castiglione, Carolina Ciacci, Michele Cicala, Rachele Ciccocioppo, Michele Comberlato, Claudio Camillo Cortelezzi, Rocco Cosintino, Francesco Costa, Giuseppe Costantino, Salvatore Cucchiara, Antonio Cuomo, Renata D’Incà, Maria Carla Di Paolo, Antonio Di Sabatino, Antonio Di Sario, Giuseppe Frieri, Walter Fries, Antonio Gasbarrini, Andrea Geccherle, Paolo Gionchetti, Maria Giovanna Graziani, Laurino Grossi, Luisa Guidi, Gianni Imperiali, Giovanni Latella, Paolo Lionetti, Gaetano Inserra, Giovanni Maconi, Francesco Manguso, Marco Marino, Mauro Mastronardi, Silvia Mazzuoli, Gianmichele Meucci, Marco Mendolaro, Monica Milla, Giammarco Mocci, Giovanni Monteleone, Francesco Neri Bortoluzzi, Cristiano Pagnini, Luca Pastorelli, Roberta Pica, Simona Piergallini, Antonello Privitera, Sara Renna, Davide Giuseppe Ribaldone, Chiara Ricci, Antonio Rispo, Rodolfo Rocca, Claudio Romano, Marco Romano, Giovanni Russo, Renato Sablich, Simone Saibeni, Edoardo Savarino, Maria Lia Scribano, Rocco Spagnuolo, Elisa Stasi, Maria Maddalena Terpin, Anna Testa, Daniela Valpiani, Angela Variola, Piero Vernia, Giovanna Vitale, Giorgio Zoli, Fiorino, G, Caprioli, F, Daperno, M, Mocciaro, F, Principi, M, Viscido, A, Fantini, Mc, Orlando, A, Papi, C, Annese, V, Danese, S, Vecchi, M, Rizzello, F, Armuzzi, A, Leone, S, Previtali, E, Aloi, M, Alvisi, P, Antonelli, E, Ardizzone, S, Astegiano, M, Baldoni, M, Beltrami, M, Biancone, L, Bodini, G, Buda, A, Bossa, F, Bracci, F, Calabrese, E, Cappello, M, Castiglione, F, Ciacci, C, Cicala, M, Ciccocioppo, R, Comberlato, M, Cortelezzi, Cc, Cosintino, R, Costa, F, Costantino, G, Cucchiara, S, Cuomo, A, D'Inca, R, Di Paolo, Mc, Di Sabatino, A, Di Sario, A, Frieri, G, Fries, W, Gasbarrini, A, Geccherle, A, Gionchetti, P, Graziani, Mg, Grossi, L, Guidi, L, Imperiali, G, Latella, G, Lionetti, P, Inserra, G, Maconi, G, Manguso, F, Marino, M, Mastronardi, M, Mazzuoli, S, Meucci, G, Mendolaro, M, Milla, M, Mocci, G, Monteleone, G, Bortoluzzi, Fn, Pagnini, C, Pastorelli, L, Pica, R, Piergallini, S, Privitera, A, Renna, S, Ribaldone, Dg, Ricci, C, Rispo, A, Rocca, R, Romano, C, Romano, M, Russo, G, Sablich, R, Saibeni, S, Savarino, E, Scribano, Ml, Spagnuolo, R, Stasi, E, Terpin, Mm, Testa, A, Valpiani, D, Variola, A, Vernia, P, Vitale, G, Zoli, G, and Gionata Fiorino, Flavio Caprioli, Marco Daperno, Filippo Mocciaro, Mariabeatrice Principi, Angelo Viscido, Massimo Claudio Fantini, Ambrogio Orlando, Claudio Papi, Vito Annese, Silvio Danesea, Maurizio Vecchi, Fernando Rizzello, Alessandro Armuzzi

Subjects
medicine.medical_specialty, Anti-TNF Biosimilars Crohn’s disease Inflammatory bowel disease Tumor necrosis factor alpha Ulcerative colitis, Inflammatory bowel disease, Antibodies, 03 medical and health sciences, Anti-TNFα, 0302 clinical medicine, Medical, Monoclonal, Adalimumab, medicine, Humans, Intensive care medicine, Biosimilar Pharmaceuticals, Societies, Medical, Randomized Controlled Trials as Topic, Biosimilars, Crohn's disease, Hepatology, business.industry, Tumor necrosis factor alpha, Tumor Necrosis Factor-alpha, Gastroenterology, Antibodies, Monoclonal, Biosimilar, anti-TNFα, biosimilars, crohn's disease, inflammatory bowel disease, tumor necrosis factor alpha, ulcerative colitis, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, Infliximab, Italy, 030220 oncology & carcinogenesis, Position paper, 030211 gastroenterology & hepatology, business, Societies, Patient education, medicine.drug
Abstract

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.

Published
2019

21. Definition, aims, and implementation of GA [sup] 2 LEN/HAEi Angioedema Centers of Reference and Excellence

Author

Kemal Özyurt, Teresa Caballero, Aharon Kessel, Andrew J. MacGinnitie, Solange Oliveira Rodrigues Valle, Anthony J. Castaldo, Markus Magerl, Regis A. Campos, Adam Reich, Heike Röckmann-Helmbach, R. Y. Meshkova, Mario Sánchez-Borges, Richard G. Gower, Anna Zalewska-Janowska, Daria Fomina, Célia Costa, Allen P. Kaplan, Marc A. Riedl, Naoko Inomata, Avner Reshef, Alejandro Malbrán, Aurélie Du-Thanh, N. Prior, Hilary Longhurst, Margarida Gonçalo, Kiran Godse, Rosana Câmara Agondi, Andreas Kleinheinz, Inmaculada Martinez-Saguer, Mona Al-Ahmad, Thilo Jakob, Luis Felipe Ensina, José Ignacio Larco Sousa, Anna Tagka, Chikako Nishigori, Nicola Wagner, Hye Ryun Kang, Michael Makris, Nicholas Brodszki, Ricardo Dario Zwiener, Jan Nicolay, Alicja Kasperska-Zając, Iris V Medina, Ignacio J. Ansotegui, Marcin Stobiecki, Alejandro Berardi, Danny M. Cohn, Claudio A S Parisi, Angèle Soria, Torsten Zuberbier, Dario O. Josviack, E Serra-Baldrich, Jonathan A. Bernstein, Anette Bygum, Isao Ohsawa, Henriette Farkas, Iman Nasr, Thomas Buttgereit, Jonathan Peter, Carsten Bindslev-Jensen, Paulo Ricardo Criado, Wolfgang Pfützner, Natalia Fili, Silvia Mariel Ferrucci, Petra Staubach, Peter Schmid-Grendelmeier, M. Gotua, Marcus Maurer, Jose Fabiani, Gordon Sussman, A. Marsland, Konrad Bork, Andrea Zanichelli, Simon Francis Thomsen, Isabelle Boccon-Gibod, Mauro Cancian, German D. Ramon, Zuotao Zhao, Nikolaos G. Papadopoulos, Martijn B. A. van Doorn, Andrea Bauer, Kanokvalai Kulthanan, Claudio Fantini, Henrik Balle Boysen, Lilian Varga, Dorota Krasowska, Ana Giménez-Arnau, Werner Aberer, Ivan Cherrez-Ojeda, Roberta F. Criado, Constance H. Katelaris, Martin Metz, Riccardo Asero, Mitja Košnik, Stephen Betschel, M Sendhil Kumaran, Sigurd Broesby-Olsen, Moshe Ben-Shoshan, Rand Arnaout, Regina Treudler, Laurence Bouillet, Natalia Ilina, Maryam Ali Al-Nesf, Emek Kocatürk, Emel Aygören-Pürsün, William R. Lumry, Guillermo Guidos-Fogelbach, Yuxiang Zhi, Mark Gompels, Andac Salman, Christina Weber-Chrysochoou, Michihiro Hide, Young Min Ye, Aslı Gelincik, William B Smith, Timothy J. Craig, Bruce Ritchie, Daniel O. Vázquez, Mojca Bizjak, Atsushi Fukunaga, Ragıp Ertaş, Urs C. Steiner, Faradiba Sarquis Serpa, Farrukh R. Sheikh, Michael Rudenko, Paula J. Busse, Luisa Karla de Paula Arruda, Liangchun Wang, Todor A. Popov, Anete Sevciovic Grumach, Joachim Dissemond, Dorottya Csuka, Ignasi Figueras-Nart, Aleena Banerji, Tıp Fakültesi, Kemal Özyurt / 0000-0002-6913-8310, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Dermatology, Göncü, Özgür Emek Kocatürk (ORCID 0000-0003-2801-0959 & YÖK ID 217219), Maurer, Marcus, Werner, Aberer, Agondi, Rosana, Al-Ahmad, Mona, Al-Nesf, Maryam Ali, Ansotegui, Ignacio, Arnaout, Rand, Arruda, Luisa Karla, Asero, Riccardo, Aygoeren-Puersue, Emel, Banerji, Aleena, Bauer, Andrea, Ben-Shoshan, Moshe, Berardi, Alejandro, Bernstein, Jonathan A, Betschel, Stephen, Bindslev-Jensen, Carsten, Bizjak, Mojca, Boccon-Gibod, Isabelle, Bork, Konrad, Bouillet, Laurence, Boysen, Henrik Balle, Brodszki, Nicholas, Broesby-Olsen, Sigurd, Busse, Paula, Buttgereit, Thomas, Bygum, Anette, Caballero, Teresa, Campos, Regis A., Cancian, Mauro, Cherrez-Ojeda, Ivan, Cohn, Danny M., Costa, Celia, Craig, Timothy, Criado, Paulo Ricardo, Criado, Roberta F., Csuka, Dorottya, Dissemond, Joachim, Du-Thanh, Aurelie, Ensina, Luis Felipe, Ertaş, Ragıp, Fabiani, Jose E., Fantini, Claudio, Farkas, Henriette, Ferrucci, Silvia Mariel, Figueras-Nart, Ignasi, Fili, Natalia L., Fomina, Daria, Fukunaga, Atsushi, Gelincik, Aslı, Gimenez-Arnau, Ana, Godse, Kiran, Gompels, Mark, Goncalo, Margarida, Gotua, Maia, Gower, Richard, Grumach, Anete S, Guidos-Fogelbach, Guillermo, Hide, Michihiro, Ilina, Natalia, Inomata, Naoko, Jakob, Thilo, Josviack, Dario O., Kang, Hye-Ryun, Kaplan, Allen, Kasperska-Zajac, Alicja, Katelaris, Constance, Kessel, Aharon, Kleinheinz, Andreas, Kosnik, Mitja, Krasowska, Dorota, Kulthanan, Kanokvalai, Kumaran, M. Sendhil, Larco Sousa, Jose Ignacio, Longhurst, Hilary J., Lumry, William, MacGinnitie, Andrew, Magerl, Markus, Makris, Michael P., Malbran, Alejandro, Marsland, Alexander, Martinez-Saguer, Inmaculada, Medina, Iris V., Meshkova, Raisa, Metz, Martin, Nasr, Iman, Nicolay, Jan, Nishigori, Chikako V., Nishigori, Chikako, Ohsawa, Isao, Özyurt, Kemal, Papadopoulos, Nikolaos G., Parisi, Claudio A. S., Peter, Jonathan Grant, Pfuetzner, Wolfgang, Popov, Todor, Prior, Nieves, Ramon, German D., Reich, Adam, Reshef, Avner, Riedl, Marc A., Ritchie, Bruce, Rockmann-Helmbach, Heike, Rudenko, Michael, Salman, Andaç, Sanchez-Borges, Mario, Schmid-Grendelmeier, Peter, Serpa, Faradiba S., Serra-Baldrich, Esther, Sheikh, Farrukh R., Smith, William, Soria, Angele, Staubach, Petra, Steiner, Urs C., Stobiecki, Marcin, Sussman, Gordon, Tagka, Anna, Thomsen, Simon Francis, Treudler, Regina, Valle, Solange, van Doorn, Martijn, Varga, Lilian, Vazquez, Daniel O., Wagner, Nicola, Wang, Liangchun, Weber-Chrysochoou, Christina, Ye, Young-Min, Zalewska-Janowska, Anna, Zanichelli, Andrea, Zhao, Zuotao, Zhi, Yuxiang, Zuberbier, Torsten, Zwiener, Ricardo D., Castaldo, Anthony, and School of Medicine

Subjects
medicine.medical_specialty, Edema angioneuròtic, Urticaria, media_common.quotation_subject, Immunology, education, GA2LEN, Angioedema, Center, Excellence, Management, urticaria, centres of reference and excelence, immune system diseases, center, medicine, Immunology and Allergy, Center (algebra and category theory), Angioneurotic edema, skin and connective tissue diseases, media_common, udc:616.1, business.industry, angioedema, humanities, referenčni centri odličnosti, Medicine, Allergy, Family medicine, excellence, medicine.symptom, business, Global Allergy and Asthma European Network, Urticària, management
Abstract

This document summarizes the aims of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence (ACAREs) and elaborates the requirements that ACAREs must fulfill to become certified. It also provides (see Appendix S1) background information on GA2LEN and HAEi, including HAEi member organizations and regional patient advocates, on why we need an Angioedema Center of Reference and Excellence (ACARE) program and network, and on the accreditation and certification process, governance and funding, and on the interaction with other GA2LEN networks of centers of reference and excellence. The protocols, aims, requirements, and provisions related to becoming a certified CARE are based on (a) the experience of the GA2LEN UCARE network and (b) input from angioedema patients, general practitioners, and angioedema specialists.

Published
2020

22. Definition, aims, and implementation of GA

Author

Marcus, Maurer, Werner, Aberer, Rosana, Agondi, Mona, Al-Ahmad, Maryam Ali, Al-Nesf, Ignacio, Ansotegui, Rand, Arnaout, Luisa Karla, Arruda, Riccardo, Asero, Emel, Aygören-Pürsün, Aleena, Banerji, Andrea, Bauer, Moshe, Ben-Shoshan, Alejandro, Berardi, Jonathan A, Bernstein, Stephen, Betschel, Carsten, Bindslev-Jensen, Mojca, Bizjak, Isabelle, Boccon-Gibod, Konrad, Bork, Laurence, Bouillet, Henrik Balle, Boysen, Nicholas, Brodszki, Sigurd, Broesby-Olsen, Paula, Busse, Thomas, Buttgereit, Anette, Bygum, Teresa, Caballero, Régis A, Campos, Mauro, Cancian, Ivan, Cherrez-Ojeda, Danny M, Cohn, Célia, Costa, Timothy, Craig, Paulo Ricardo, Criado, Roberta F, Criado, Dorottya, Csuka, Joachim, Dissemond, Aurélie, Du-Thanh, Luis Felipe, Ensina, Ragıp, Ertaş, José E, Fabiani, Claudio, Fantini, Henriette, Farkas, Silvia Mariel, Ferrucci, Ignasi, Figueras-Nart, Natalia L, Fili, Daria, Fomina, Atsushi, Fukunaga, Asli, Gelincik, Ana, Giménez-Arnau, Kiran, Godse, Mark, Gompels, Margarida, Gonçalo, Maia, Gotua, Richard, Gower, Anete S, Grumach, Guillermo, Guidos-Fogelbach, Michihiro, Hide, Natalia, Ilina, Naoko, Inomata, Thilo, Jakob, Dario O, Josviack, Hye-Ryun, Kang, Allen, Kaplan, Alicja, Kasperska-Zając, Constance, Katelaris, Aharon, Kessel, Andreas, Kleinheinz, Emek, Kocatürk, Mitja, Košnik, Dorota, Krasowska, Kanokvalai, Kulthanan, M Sendhil, Kumaran, José Ignacio, Larco Sousa, Hilary J, Longhurst, William, Lumry, Andrew, MacGinnitie, Markus, Magerl, Michael P, Makris, Alejandro, Malbrán, Alexander, Marsland, Inmaculada, Martinez-Saguer, Iris V, Medina, Raisa, Meshkova, Martin, Metz, Iman, Nasr, Jan, Nicolay, Chikako, Nishigori, Isao, Ohsawa, Kemal, Özyurt, Nikolaos G, Papadopoulos, Claudio A S, Parisi, Jonathan Grant, Peter, Wolfgang, Pfützner, Todor, Popov, Nieves, Prior, German D, Ramon, Adam, Reich, Avner, Reshef, Marc A, Riedl, Bruce, Ritchie, Heike, Röckmann-Helmbach, Michael, Rudenko, Andaç, Salman, Mario, Sanchez-Borges, Peter, Schmid-Grendelmeier, Faradiba S, Serpa, Esther, Serra-Baldrich, Farrukh R, Sheikh, William, Smith, Angèle, Soria, Petra, Staubach, Urs C, Steiner, Marcin, Stobiecki, Gordon, Sussman, Anna, Tagka, Simon Francis, Thomsen, Regina, Treudler, Solange, Valle, Martijn, van Doorn, Lilian, Varga, Daniel O, Vázquez, Nicola, Wagner, Liangchun, Wang, Christina, Weber-Chrysochoou, Young-Min, Ye, Anna, Zalewska-Janowska, Andrea, Zanichelli, Zuotao, Zhao, Yuxiang, Zhi, Torsten, Zuberbier, Ricardo D, Zwiener, and Anthony, Castaldo

Subjects
Urticaria, Humans, Angioedema
Published
2020

23. Intestinal inflammation and colorectal cancer: a double-edged sword?

Author

Angelamaria, Rizzo, Francesco, Pallone, Giovanni, Monteleone, and Massimo Claudio, Fantini

Subjects
Inflammation, Interleukin-6, Tumor Necrosis Factor-alpha, Review, Inflammatory Bowel Diseases, digestive system diseases, Interleukin-10, Intestines, Cell Transformation, Neoplastic, Transforming Growth Factor beta, Immune System, Animals, Humans, Chemokines, Colorectal Neoplasms
Abstract

Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer (CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn’s disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. In recent years, the role of immune cells and their products have been shown to be pivotal in initiation and progression of colitis-associated CRC. On the other hand, activation of the immune system has been shown to cause dysplastic cell elimination and cancer suppression in other settings. Clinical and experimental data herein reviewed, while confirming chronic inflammation as a risk factor for colon carcinogenesis, do not completely rule out the possibility that under certain conditions the chronic activation of the mucosal immune system might protect from colonic dysplasia.

Published
2010

26. Mesalazine negatively regulates CDC25A protein expression and promotes accumulation of colon cancer cells in S phase.

Author

Carmine Stolfi, Daniele Fina, Roberta Caruso, Flavio Caprioli, Massimo Claudio Fantini, Angelamaria Rizzo, Massimiliano Sarra, Francesco Pallone, and Giovanni Monteleone

Subjects
ANTI-inflammatory agents, GENETIC regulation, GENE expression, BIOACCUMULATION, CANCER cell growth, COLON cancer risk factors, INFLAMMATORY bowel diseases, PHOSPHORYLATION, PATIENTS, PREVENTION
Abstract

Regular consumption of mesalazine has been associated with a reduced risk of colorectal cancer (CRC) in patients with inflammatory bowel disease. The molecular mechanisms underlying the antineoplastic effect of 5-aminosalicylic acid remain, however, poorly characterized. In this study, we examined whether mesalazine affects cell cycle progression and analyzed specific checkpoint pathways in experimental models of CRC. Mesalazine inhibited the growth of HCT-116 and HT-29 cells, two CRC cell lines that express either a wild-type or mutated p53. Cell cycle analysis revealed that mesalazine induced cells to accumulate in S phase. This effect was associated with a sustained phosphorylation of the cyclin-dependent kinase (CDK)2 at threonine 14 and tyrosine 15 residues, an event that inactivates the CDK2–cyclin complex and blocks S–G2 phase cell cycle transition. Consistently, mesalazine reduced the protein content of CDC25A, a phosphatase that regulates CDK2 phosphorylation status. Analysis of upstream kinases that negatively control CDC25A expression showed that mesalazine enhanced the activation of CHK1 and CHK2. However, silencing of CHK1 and CHK2 did not prevent the mesalazine-induced CDC25A protein downregulation. In contrast, CDC25A protein ubiquitination and degradation and accumulation of cells in S phase following mesalazine exposure were reverted by proteasome inhibitors. Notably, mesalazine also inhibited CDC25A in human CRC explants. Finally, we showed that mesalazine downregulated CDC25A in CT26, a murine CRC cell line, and prevented the formation of CT26-derived tumors in mice. Data show that mesalazine negatively regulates CDC25A protein expression, thus delaying CRC cell progression. [ABSTRACT FROM AUTHOR]

Published
2008
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