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17 results on '"D’Amato, D"'

1. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis

Author

Gordon, K. B, Blauvelt, A., Papp, K. A., Langley, R. G., Luger, T., Ohtsuki, M., Reich, K., Amato, D., Ball, S. G., Braun, D. K., Cameron, G. S., Erickson, J., Konrad, R. J., Muram, T. M., Nickoloff, B. J., Osuntokun, O. O., Secrest, R. J., Zhao, F., Mallbris, L., Leonardi, C. L., Uncover, 1 Study Group: Holly Hake Harris, Matheson, Robert T., Michael, Bukhalo, John H., Tu, Crowley, Jeffrey J., Grande, Kimberly K., Adnan, Nasir, Boni Elizabeth Elewski, James Alan Solomon, Liebhild, Stratmann, Claudia, Buettner, Thomas Peter Dirschka, Margrit Ruth Simon, Jens, Ulrich, Christine, Grigat, Mathias, Augustin, Andrei, Khariouzov, Gerhard, Sattler, Hans Michael Ockenfels, Fredrick Richard Behringer, Hector, Wiltz, Francisco, Flores, Kuettel, Kevin D., Ira Hughes Thorla, Jeffrey Keith Moore, Waterman, Gary L., George Joji Murakawa, Scott Alfred Fretzin, Frankel, Ellen H., Sunil Sharan Dhawan, Lucyna, Leszniewska, Maria, Poznanska, Anna Sobieszek Kundro, Chodorowska, Grazyna M., Katarzyna Turek Urasinska, Romuald, Maleszka, Andrzej, Kaszuba, Lidia, Rajzer, Elizbieta Barbara Szymanska, Lidia, Rudnicka, Neil James Korman, Jamie Debra Weisman, Truett, Artis P., Jeffry, Jacqmein, Steven Robert Cohen, Heller, Gary L., Jenkin, Peter J., Abe, Marcadis, George Sorin Tiplica, Anca Aghinitei Zbranca Toporas, Simona Laura Ianosi, Ion, Florea, Claus, Zachariae, Lars, Iversen, Annalisa, Patrizi, Romanelli, Marco, Christopher, Griffiths, John Berth Jones, John, Foerster, Savin, Ronald C., Nelson, Christopher G., Lyn Carol Chamberlain Guenther, Albrecht, Lorne E., Hong, Chih ho H., Arnon, Katz, Mani, Raman, Adam, David N., Aamir, Butt, Stephen Peter Shumack, Kurt Aaron Josef Gebauer, Lynda Jane Spelman, Shireen Kaur Sidhu, Michael George Freeman, Peter Anthony Foley, Lajos, Kemeny, Eva, Remenyik, Zsuzsanna, Karolyi, Marc, Bourcier, Wayne Douglas Carey, Victoria, Taraska, Derek, Haaland, Aditya Kumar Gupta, Catherine, Maari, Darryl Paul Toth, Michael, Sebastian, Sandra, Philipp, Roland, Kaufmann, Diamant, Thaci, Thomas Andreas Werfel, Leila, Parise, Ingo, Haase, Petra Staubach Renz, Shinichi, Imafuku, Juichiro, Nakayama, Tadashi, Terui, Hideki, Nakajima, Shigetoshi, Sano, Uncover, 2 Study Group, and Uncover, 3 Study Group

Subjects
Adult, Male, medicine.medical_specialty, Neutropenia, Tildrakizumab, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, Antibodies, law.invention, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Candidiasis, Female, Humans, Inflammatory Bowel Diseases, Intention to Treat Analysis, Middle Aged, Psoriasis, Medicine (all), Internal medicine, Monoclonal, Medicine, Humanized, Risankizumab, Intention-to-treat analysis, business.industry, General Medicine, Clinical trial, Ixekizumab, Guselkumab, 030220 oncology & carcinogenesis, Physical therapy, business
Abstract

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P

Published
2016

2. Brain microglia in psychiatric disorders

Author

Mondelli, Valeria, Vernon, Anthony C, Turkheimer, Federico, Dazzan, Paola, Pariante, Carmine M, Frost, JL, Schafer, DP, Banati, RB, Newcombe, J, Gunn, RN, al., et, Tang, Y, Le, W, Estes, ML, McAllister, AK, Ransohoff, RM, Davalos, D, Grutzendler, J, Yang, G, Peferoen, LA, Vogel, DY, Ummenthum, K, Norden, DM, Trojanowski, PJ, Villanueva, E, Navarro, E, Godbout, JP, Kreisel, T, Frank, MG, Licht, T, Wachholz, S, Eßlinger, M, Plümper, J, Manitz, MP, Juckel, G, Friebe, A, Trépanier, MO, Hopperton, KE, Mizrahi, R, Mechawar, N, Bazinet, RP, Torres-Platas, SG, Cruceanu, C, Chen, GG, Turecki, G, Steiner, J, Bielau, H, Brisch, R, Schnieder, TP, Trencevska, I, Rosoklija, G, Fillman, SG, Cloonan, N, Catts, VS, Rupprecht, R, Papadopoulos, V, Rammes, G, Qiu, ZK, Li, MS, He, JL, Hannestad, J, Gallezot, JD, Schafbauer, T, Israel, I, Ohsiek, A, Al-Momani, E, Mirzaei, N, Tang, SP, Ashworth, S, Gulyás, B, Makkai, B, Kása, P, Turkheimer, FE, Rizzo, G, Bloomfield, PS, Owen, DR, Yeo, AJ, DellaGioia, N, Setiawan, E, Wilson, AA, Su, L, Faluyi, YO, Hong, YT, Haarman, BC, Lek, RF Riemersma-Van der, Groot, JC de, Berckel, BN van, Bossong, MG, Boellaard, R, Doorduin, J, Vries, EF de, Willemsen, AT, Dierckx, RA, Klein, HC, Takano, A, Arakawa, R, Ito, H, Kenk, M, Selvanathan, T, Rao, N, Selvaraj, S, Veronese, M, Coughlin, JM, Wang, Y, Ambinder, EB, Doef, TF van der, Witte, LD de, Sutterland, AL, Hafizi, S, Tseng, HH, Holmes, SE, Hinz, R, Drake, RJ, Yaqub, M, Schuitemaker, A, Edison, P, Pavese, N, Lockhart, A, Davis, B, Matthews, JC, Quarantelli, M, Laule, C, Vavasour, IM, Kolind, SH, Pasternak, O, Sochen, N, Gur, Y, Intrator, N, Assaf, Y, Andreasen, NC, Ehrhardt, JC, Swayze, VW, Supprian, T, Hofmann, E, Warmuth-Metz, M, Franzek, E, Becker, T, Pfefferbaum, A, Sullivan, EV, Hedehus, M, Moseley, M, Lim, KO, Mandl, RC, Schnack, HG, Luigjes, J, Cahn, W, Bagary, MS, Symms, MR, Barker, GJ, Mutsatsa, SH, Joyce, EM, Ron, MA, Foong, J, Maier, M, Brocklehurst, S, Miller, DH, Kubicki, M, Park, H, Westin, CF, Bouix, S, Dahlben, B, Oestreich, LK, Shenton, ME, Amato, D, Beasley, CL, Hahn, MK, Vernon, AC, Natesan, S, Modo, M, Kapur, S, Mondelli, V, Reininghaus, U, Kempton, MJ, Valmaggia, L, Baumeister, D, Lightman, SL, Pariante, CM, Danese, A, Moffitt, TE, Ambler, A, Poulton, R, Caspi, A, Akhtar, R, Ciufolini, S, Meyer, U, So, PW, Lythgoe, DJ, Cotel, MC, Lenartowicz, EM, Anacker, C, Calcia, MA, Bonsall, DR, Barichello, T, Howes, OD, Burke, NN, Fan, CY, Trang, T, McMahon, SB, Russa, F La, Bennett, DL, Püntener, U, Booth, SG, Perry, VH, Teeling, JL, Hahn, YK, Podhaizer, EM, Farris, SP, Miles, MF, Hauser, KF, Knapp, PE, Notter, T, Gschwind, T, Varga, B, Markó, K, Hádinger, N, Cattaneo, A, Ferrari, C, Uher, R, Belvederi, Murri M, Sandiego, CM, Pittman, B, Weber, MD, Sheridan, JF, Raison, CL, Rutherford, RE, Woolwine, BJ, Möller, T, Boddeke, HW, O'Connor, JC, Lawson, MA, André, C, Hinwood, M, Morandini, J, Day, TA, Walker, FR, Bard, F, Bhattacharya, A, Pae, CU, Marks, DM, Han, C, Patkar, AA, Oya, K, Kishi, T, Iwata, N, Pathology, NCA - Neuroinflamation, Molecular cell biology and Immunology, Gastroenterology and hepatology, CCA - Disease profiling, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, NCA - Brain imaging technology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Otolaryngology / Head & Neck Surgery, EMGO - Quality of care, AII - Infectious diseases, CCA - Imaging, and Neurology

Subjects
0301 basic medicine, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Psychology, In patient, Psychiatry, Biological Psychiatry, Neuroinflammation, Inflammation, Microglia, business.industry, Macrophages, Mental Disorders, Brain, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Psychosocial stress, Treatment strategy, Autopsy, business, Neuroscience, 030217 neurology & neurosurgery, Stress, Psychological, Immune activation
Abstract

SummaryThe role of immune activation in psychiatric disorders has attracted considerable attention over the past two decades, contributing to the rise of a new era for psychiatry. Microglia, the macrophages of the brain, are progressively becoming the main focus of the research in this field. In this Review, we assess the literature on microglia activation across different psychiatric disorders, including post-mortem and in-vivo studies in humans and experimental studies in animals. Although microglia activation has been noted in all types of psychiatric disorder, no association was seen with specific diagnostic categories. Furthermore, the findings from these studies highlight that not all psychiatric patients have microglial activation. Therefore, the cause of the neuroinflammation in these cohorts and its implications are unclear. We discuss psychosocial stress as one of the main factors determining microglial activation in patients with psychiatric disorders, and explore the relevance of these findings for future treatment strategies.

Published
2016

3. Insulin resistance in offspring of hypertensive subjects

Author

Gordon F, M. E. Fonseca, Dolores Mino, Lifshitz A, Revilla C, Wacher N, Búrbano G, and Amato D

Subjects
Adult, Male, medicine.medical_specialty, Physiology, Offspring, medicine.medical_treatment, Blood Pressure, Insulin resistance, Internal medicine, Internal Medicine, medicine, Humans, Obesity, Family history, Pancreatic hormone, Aged, Family Health, business.industry, Insulin, Middle Aged, medicine.disease, Logistic Models, Endocrinology, Blood pressure, Socioeconomic Factors, Hypertension, Female, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract

OBJECTIVE To assess whether apparently healthy subjects with a family history of systemic hypertension have a higher risk of presenting the insulin resistance syndrome. SUBJECTS Three hundred and eighty-six subjects aged 20-65 years. SETTING A middle socio-economic class urban community from Mexico City. METHOD All subjects and, when necessary, their first-degree relatives, answered a questionnaire and underwent a physical examination with measurement of height, weight and blood pressure. Serum insulin, glucose, cholesterol and triglycerides were measured during fasting and 2 h after an oral load of 75 g glucose. RESULTS A family history of systemic hypertension was present for 167 (43%) of the subjects, of whom 123 (31%) were obese. Subjects with a family history of hypertension had higher systolic blood pressures than did those without such a history (120 +/- 15 versus 115 +/- 10 mmHg). In the logistic regression model, the body mass index and age showed statistically significant effects on the fasting glucose:insulin ratio and on serum insulin levels after an oral load of glucose. When men and women were analysed separately, only in men were higher systolic and mean blood pressures and lower glucose:insulin ratios observed. In the logistic regression analysis the body mass index was a significant predictor of the glucose:insulin ratio and serum insulin levels after an oral load of glucose, especially in men. CONCLUSION Apparently healthy male offspring of hypertensive parents have higher blood pressure levels and lower insulin sensitivities than do offspring of normotensive parents. Insulin resistance was related to obesity, but not to a family history of hypertension, as had previously been reported by other research groups.

Published
1996

4. Cystic Peritoneal Mesothelioma: Report of a Case

Author

Claudio Letizia, Virgilio Nicolanti, Giorgio De Toma, Giuseppe Cavallaro, Amato D, and Plocco M

Subjects
Aged, 80 and over, Pathology, medicine.medical_specialty, business.industry, Mesothelioma, Cystic, General Medicine, Disease, medicine.disease, peritoneal neoplasm, Peritoneal Neoplasm, cystic peritoneal mesothelioma, Surgical oncology, Peritoneal mesothelioma, Humans, Medicine, Female, Surgery, business, Peritoneal Neoplasms, Aged, Rare disease
Abstract

Peritoneal mesothelioma is a rare disease, especially when it arises in a cystic form with tardive and often nonspecific symptoms. While diffuse neoplasms have an unfavorable prognosis, cystic forms are usually benign. An accurate diagnosis can only be made only with electron microscopy and immunohistochemical studies. A 92-year-old woman with an ultrastructurally ascertained cystic peritoneal mesothelioma was admitted to the hospital's emergency ward, and was considered to be unusual because of the size of the mass and the patient's age. A review of the literature is made, and the clinical and diagnostic aspects of this disease are also discussed.

Published
2000

5. Iliac-to-isolated hepatic artery bypass in the treatment of intestinal angina: two cases

Author

Giuseppe Cavallaro, Amato D, Luca di Marzo, Antonino Cavallaro, Andrea Mingoli, and Giorgio De Toma

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Ischemia, Revascularization, Iliac Artery, Angina, Hepatic Artery, Mesenteric Vascular Occlusion, medicine, Humans, Derivation, Iliac artery, business.industry, Middle Aged, medicine.disease, Surgery, Abdominal Pain, Intestines, Radiography, medicine.anatomical_structure, Blood supply, business, Splanchnic, Cardiology and Cardiovascular Medicine, Artery
Abstract

Two cases in which a severe form of intestinal angina was cured by revascularization of an isolated hepatic artery were studied. The collateral pathways to the hepatic artery may serve, in a retrograde fashion, to assure an acceptable blood supply to the splanchnic organs, even when the disease of the 3 main vessels is so extensive that the commonly used techniques of revascularization cannot be applied. (J Vasc Surg 1998;28:1115-9.)

Published
1998

7. Real-world experience with obeticholic acid in patients with primary biliary cholangitis

Author

Anna Morgando, Mauro Viganò, Ana Lleo, Maurizio Pompili, Elisabetta De Gasperi, Daphne D’Amato, Alessandro Mussetto, Nora Cazzagon, Pietro Invernizzi, Francesca Colapietro, Vincenzo Ronca, Sara Labanca, Ester Vanni, M.R. Cannavò, Francesco Losito, Ernesto Claar, G. Scifo, Giovanni Galati, Umberto Vespasiani-Gentilucci, Silvia Storato, Alessio Gerussi, Grazia Anna Niro, Antonio Izzi, Barbara Omazzi, Antonio De Vincentis, Valentina Feletti, Giuseppe Grassi, Valeria Pace Palitti, Clara Mancuso, Vincenza Calvaruso, Evelise Frazzetto, Roberto Boldizzoni, Marco Marzioni, Floriano Rosina, Andrea Palermo, Antonino Picciotto, Valentina Bellia, Gaetano Bertino, Italian Pbc Registry, Guido Poggi, Rodolfo Sacco, Domenico Alvaro, Luigi Muratori, Maria Vinci, Marie Graciella Pigozzi, Raffaele Cozzolongo, Natalia Terreni, Annarosa Floreani, Maurizio Russello, Marco Distefano, Rinaldo Pellicano, Maria D'Antò, Marco Carbone, Rosanna Venere, R. Fontana, Antonio Picardi, Silvia Casella, S. E. O'Donnell, Federica Malinverno, Stefano Fagiuoli, Laura Cristoferi, Luchino Chessa, Giacomo Mulinacci, Pietro Pozzoni, Antonino Castellaneta, Giulia Marconi, Adriano M. Pellicelli, Francesca Romana Ponziani, Leonardo Baiocchi, D'Amato, D, De Vincentis, A, Malinverno, F, Vigano, M, Alvaro, D, Pompili, M, Picciotto, A, Palitti, V, Russello, M, Storato, S, Pigozzi, M, Calvaruso, V, De Gasperi, E, Lleo, A, Castellaneta, A, Pellicelli, A, Cazzagon, N, Floreani, A, Muratori, L, Fagiuoli, S, Niro, G, Feletti, V, Cozzolongo, R, Terreni, N, Marzioni, M, Pellicano, R, Pozzoni, P, Baiocchi, L, Chessa, L, Rosina, F, Bertino, G, Vinci, M, Morgando, A, Vanni, E, Scifo, G, Sacco, R, D'Anto, M, Bellia, V, Boldizzoni, R, Casella, S, Omazzi, B, Poggi, G, Cristoferi, L, Gerussi, A, Ronca, V, Venere, R, Ponziani, F, Cannavo, M, Mussetto, A, Fontana, R, Losito, F, Frazzetto, E, Distefano, M, Colapietro, F, Labanca, S, Marconi, G, Grassi, G, Galati, G, O'Donnell, S, Mancuso, C, Mulinacci, G, Palermo, A, Claar, E, Izzi, A, Picardi, A, Invernizzi, P, Carbone, M, Vespasiani-Gentilucci, U, D'Amato D, De Vincentis A, Malinverno F, Viganò M, Alvaro D, Pompili M, Picciotto A, Palitti VP, Russello M, Storato S, Pigozzi MG, Calvaruso V, De Gasperi E, Lleo A, Castellaneta A, Pellicelli A, Cazzagon N, Floreani A, Muratori L, Fagiuoli S, Niro GA, Feletti V, Cozzolongo R, Terreni N, Marzioni M, Pellicano R, Pozzoni P, Baiocchi L, Chessa L, Rosina F, Bertino G, Vinci M, Morgando A, Vanni E, Scifo G, Sacco R, D'Antò M, Bellia V, Boldizzoni R, Casella S, Omazzi B, Poggi G, Cristoferi L, Gerussi A, Ronca V, Venere R, Ponziani F, Cannavò M, Mussetto A, Fontana R, Losito F, Frazzetto E, Distefano M, Colapietro F, Labanca S, Marconi G, Grassi G, Galati G, O'Donnell SE, Mancuso C, Mulinacci G, Palermo A, Claar E, Izzi A, Picardi A, Invernizzi P, Carbone M, Vespasiani-Gentilucci U, and Italian PBC Registry and the Club Epatologi Ospedalieri (CLEO)/Associazione Italiana Gastroenterologi ed Endoscopisti Digestivi Ospedalieri (AIGO) PBC Study Group.

Subjects
upper limit of normal, Cirrhosis, ALT, AMA, Autoimmunity, antinuclear antibodies, ULN, PBC, Gastroenterology, UDCA, Settore MED/12, ULN, upper limit of normal, obeticholic acid, aRR, adjusted risk ratio, CRFs, case record form, AST, aspartate transferase, Clinical endpoint, GGT, gamma-glutamyl transferase, QC, primary biliary cholangitis, Ursodeoxycholic acid, ANA, TCC, Cholestasi, TIPS, Treatment Completer Cohort, ANA, antinuclear antibodie, medicine.medical_specialty, RR, UDCA, ursodeoxycholic acid, TIPS, transjugular intrahepatic portosystemic shunt, OCA, Cirrhosi, ALP, alkaline phosphatase, autoimmune hepatitis, medicine.disease, digestive system diseases, Discontinuation, Keywords: AIH, autoimmune hepatiti, QC, quality control, chemistry, gamma-glutamyl transferase, randomised controlled trial, electronic data capture, antimitochondrial antibodies, aspartate transferase, Autoimmune hepatitis, chemistry.chemical_compound, AIH, CRFs, Immunology and Allergy, adjusted risk ratio, ANA, antinuclear antibodies, RR, risk ratio, Overall cohort, ALT, alanine transferase, AMA, antimitochondrial antibodie, Cholestasis, CRFs, case record forms, Obeticholic acid, Overlap PBC-AIH, ursodeoxycholic acid, OCA, obeticholic acid, Tolerability, alkaline phosphatase, RCT, Research Article, medicine.drug, case record forms, Context (language use), AMA, antimitochondrial antibodies, Internal medicine, EDC, electronic data capture, transjugular intrahepatic portosystemic shunt, Internal Medicine, medicine, RCT, randomised controlled trial, OC, lcsh:RC799-869, quality control, alanine transferase, AST, aRR, Hepatology, business.industry, AIH, autoimmune hepatitis, TCC, Treatment Completer Cohort, PBC, primary biliary cholangiti, GGT, risk ratio, OC, Overall cohort, ALP, lcsh:Diseases of the digestive system. Gastroenterology, PBC, primary biliary cholangitis, business, EDC
Abstract

Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.

Published
2021

8. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. 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Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

9. Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic

Author

Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari, Cardinale, F., Ciprandi, G., Barberi, S., Bernardini, R., Caffarelli, C., Calvani, M., Cavagni, G., Galli, E., Minasi, D., Del Giudice, M. M., Moschese, V., Novembre, E., Paravati, F., Peroni, D. G., Tosca, M. A., Traina, G., Tripodi, S., Marseglia, G. L., Amato, D., Anania, C., Anastasio, E., Antignani, R., Arasi, S., Baldassarre, M., Baldo, E., Barbalace, A., Barni, S., Betti, F., Bianchi, A., Bolzacchini, E., Bonini, M., Bottau, P., Bozzetto, S., Brighetti, M. A., Caimmi, D., Caimmi, S., Calzone, L., Cancrini, C., Caminiti, L., Capata, G., Capra, L., Capristo, C., Carboni, E., Carella, F., Castagnoli, R., Chiappini, E., Chiera, F., Chinellato, I., Chini, L., Cipriani, F., Civitelli, F., Comberiati, P., Contini, D., Corrente, S., Cravidi, C., Crisafulli, G., Cuomo, B., D'Auria, E., D'Elios, S., Decimo, F., Giustina, A. D., Piane, R. M. D., De Filippo, M., De Vittori, V., Diaferio, L., Di Mauro, M. E., Duse, M., Federici, S., Felice, G., Fenu, G., Ferrante, G., Foti, T., Franceschini, F., Ghiglioni, D., Giardino, G., Giovannini, M., Indirli, G. C., Indolfi, C., Landi, M., La Torre, F., Leone, L. M., Licari, A., Liotti, L., Lougaris, V., Maiello, N., Mantecca, P., Manti, S., Mariani, M. M., Martelli, A., Mastrorilli, C., Mastrorilli, V., Montin, D., Mori, F., Olcese, R., Ottaviano, G., Paglialunga, C., Pajno, G., Parisi, G., Pattini, S., Pecoraro, L., Pelosi, U., Pignata, C., Ricci, G., Ricci, S., Rizzi, S., Rizzo, C., Rosati, S., Rosso, P., Sangerardi, M., Santoro, A., Saretta, F., Sarti, L., Sartorio, M., Sgruletti, M., Soresina, A., Sfika, I., Sgrulletti, M., Tesse, N., Tranchino, V., Travaglini, A., Velia, M., Verduci, E., Vernich, M., Veronelli, E., Volpi, S., Votto, M., Zicari, A. M., Cardinale, Fabio, Ciprandi, Giorgio, Barberi, Salvatore, Bernardini, Roberto, Caffarelli, Carlo, Calvani, Mauro, Cavagni, Giovanni, Galli, Elena, Minasi, Domenico, Del Giudice, Michele Miraglia, Moschese, Viviana, Novembre, Elio, Paravati, Francesco, Peroni, Diego G, Tosca, Maria Angela, Traina, Giovanni, Tripodi, Salvatore, Marseglia, Gian Luigi, SIAIP task force Pignata, Claudio, Cardinale, F, Ciprandi, G, Barberi, S, Bernardini, R, Caffarelli, C, Calvani, M, Cavagni, G, Galli, E, Minasi, D, Del Giudice, M, Moschese, V, Novembre, E, Paravati, F, Peroni, D, Tosca, M, Traina, G, Tripodi, S, Marseglia, G, Amato, D, Anania, C, Anastasio, E, Antignani, R, Arasi, S, Baldassarre, M, Baldo, E, Barbalace, A, Barni, S, Betti, F, Bianchi, A, Bolzacchini, E, Bonini, M, Bottau, P, Bozzetto, S, Brighetti, M, Caimmi, D, Caimmi, S, Calzone, L, Cancrini, C, Caminiti, L, Capata, G, Capra, L, Capristo, C, Carboni, E, Carella, F, Castagnoli, R, Chiappini, E, Chiera, F, Chinellato, I, Chini, L, Cipriani, F, Civitelli, F, Comberiati, P, Contini, D, Corrente, S, Cravidi, C, Crisafulli, G, Cuomo, B, D'Auria, E, D'Elios, S, Decimo, F, Giustina, A, Piane, R, De Filippo, M, De Vittori, V, Diaferio, L, Di Mauro, M, Duse, M, Federici, S, Felice, G, Fenu, G, Ferrante, G, Foti, T, Franceschini, F, Ghiglioni, D, Giardino, G, Giovannini, M, Indirli, G, Indolfi, C, Landi, M, La Torre, F, Leone, L, Licari, A, Liotti, L, Lougaris, V, Maiello, N, Mantecca, P, Manti, S, Mariani, M, Martelli, A, Mastrorilli, C, Mastrorilli, V, Montin, D, Mori, F, Olcese, R, Ottaviano, G, Paglialunga, C, Pajno, G, Parisi, G, Pattini, S, Pecoraro, L, Pelosi, U, Pignata, C, Ricci, G, Ricci, S, Rizzi, S, Rizzo, C, Rosati, S, Rosso, P, Sangerardi, M, Santoro, A, Saretta, F, Sarti, L, Sartorio, M, Sgruletti, M, Soresina, A, Sfika, I, Sgrulletti, M, Tesse, N, Tranchino, V, Travaglini, A, Velia, M, Verduci, E, Vernich, M, Veronelli, E, Volpi, S, Votto, M, Zicari, A, and Fabio Cardinale, Giorgio Ciprandi, Salvatore Barberi, Roberto Bernardini, Carlo Caffarelli, Mauro Calvani, Giovanni Cavagni, Elena Galli, Domenico Minasi, Michele Miraglia Del Giudice, Viviana Moschese, Elio Novembre, Francesco Paravati, Diego G Peroni, Maria Angela Tosca, Giovanni Traina, Salvatore Tripodi, Gian Luigi Marseglia, Doriana Amato, Caterina Anania, Elisa Anastasio, Rachele Antignani, Stefania Arasi, Martire Baldassarre, Ermanno Baldo, Andrea Barbalace, Simona Barni, Federica Betti, Annamaria Bianchi, Ezio Bolzacchini, Maira Bonini, Paolo Bottau, Sara Bozzetto, Maria Antonia Brighetti, Davide Caimmi, Silvia Caimmi, Luigi Calzone, Caterina Cancrini, Lucia Caminiti, Giulia Capata, Lucetta Capra, Carlo Capristo, Elena Carboni, Francesco Carella, Riccardo Castagnoli, Elena Chiappini, Fernanda Chiera, Iolanda Chinellato, Loredana Chini, Francesca Cipriani, Flavio Civitelli, Pasquale Comberiati, Daniele Contini, Stefania Corrente, Claudio Cravidi, Giuseppe Crisafulli, Barbara Cuomo, Enza D'Auria, Sofia D'Elios, Fabio Decimo, Auro Della Giustina, Rosa Maria Delle Piane, Maria De Filippo, Valentina De Vittori, Lucia Diaferio, Maria Elisa Di Cicco, Dora Di Mauro, Marzia Duse, Silvia Federici, Giuseppe Felice, Maria Grazia Fenu, Giuliana Ferrante, Tiziana Foti, Fabrizio Franceschini, Daniele Ghiglioni, Giuliana Giardino, Mattia Giovannini, Giovanni Cosimo Indirli, Cristiana Indolfi, Massimo Landi, Francesco La Torre, Lucia Maddalena Leone, Amelia Licari, Lucia Liotti, Vassilios Lougaris, Nunzia Maiello, Paride Mantecca, Sara Manti, Marco Maria Mariani, Alberto Martelli, Carla Mastrorilli, Violetta Mastrorilli, Davide Montin, Francesca Mori, Roberta Olcese, Giorgio Ottaviano, Claudia Paglialunga, Giovanni Pajno, Giuseppe Parisi, Stefano Pattini, Luca Pecoraro, Umberto Pelosi, Claudio Pignata, Giampaolo Ricci, Silvia Ricci, Stefano Rizzi, Caterina Rizzo, Sara Rosati, Paolo Rosso, Maria Sangerardi, Angelica Santoro, Francesca Saretta, Lucrezia Sarti, Marco Sartorio, Majla Sgruletti, Annarosa Soresina, Ifigenia Sfika, Mayla Sgrulletti, Nuccia Tesse, Valentina Tranchino, Alessandro Travaglini, Malizia Velia, Elvira Verduci, Mario Vernich, Elisabetta Veronelli, Stefano Volpi, Martina Votto, Anna Maria Zicari

Subjects
Allergy, Review, 030207 dermatology & venereal diseases, Settore MED/38 - Pediatria Generale E Specialistica, 0302 clinical medicine, COVID-19, Child, Pandemic, Immunologic disease, Asthma, Adolescent, Viral, 030212 general & internal medicine, Disease management (health), Societies, Medical, pandemic, child, adolescent, allergy, asthma, immunologic disease, Incidence (epidemiology), lcsh:RJ1-570, Disease Management, General Medicine, Atopic dermatitis, Settore MED/38, Coronavirus Infections, Decision Making, Humans, Italy, Pneumonia, Viral, Pragmatic Clinical Trials as Topic, SARS-CoV-2, Allergy and Immunology, Betacoronavirus, Consensus, Pandemics, Latex allergy, Human, Telemedicine, Consensu, 03 medical and health sciences, Medical, medicine, Risk factor, Betacoronaviru, business.industry, Coronavirus Infection, lcsh:Pediatrics, Pneumonia, medicine.disease, Immunology, Societies, business, Rare disease
Abstract

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.

Published
2020

10. Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach

Author

Cristina Rigamonti, Rosanna Venere, Carla De Benedittis, Guido Carpino, Pietro Invernizzi, Italian Pbc Registry, Elisabetta Degasperi, Giacomo Mulinacci, Marco Carbone, Sarah Elisabeth O’Donnell, Diletta Overi, Sara Labanca, Vito Di Marco, A. Ciaccio, Vincenzo Cardinale, Mauro Viganò, Andrea Palermo, Annarosa Floreani, Daphne D’Amato, Nora Cazzagon, Vincenzo Ronca, Donatella Barisani, Laura Cristoferi, Federica Malinverno, Marco Marzioni, Domenico Alvaro, Clara Mancuso, Vincenza Calvaruso, Anna Fichera, Martina Lucà, Federica Cerini, Alessandra Nardi, Eugenio Gaudio, Antonino Picciotto, Nicola Zucchini, Monica Leutner, Alessio Gerussi, Laura Cristoferi, Vincenza Calvaruso, Diletta Overi 5 , Mauro Viganò 6 , Cristina Rigamonti 7 , Elisabetta Degasperi 8 , Vincenzo Cardinale 9 , Sara Labanca 10 , Nicola Zucchini 11 , Anna Fichera, Vito Di Marco, Monica Leutner 12 , Rosanna Venere 13 , Antonino Picciotto 10 , Martina Lucà 1 2 , Giacomo Mulinacci 1 2 , Andrea Palermo 1 2 , Alessio Gerussi 1 2 , Daphne D'Amato 1 2 , Sarah Elisabeth O'Donnell 1 2 , Federica Cerini 6 , Carla De Benedittis 7 , Federica Malinverno 1 2 , Vincenzo Ronca 1 2 , Clara Mancuso 1 2 , Nora Cazzagon 14 , Antonio Ciaccio 1 2 , Donatella Barisani 1 , Marco Marzioni 15 , Annarosa Floreani 16 17 , Domenico Alvaro 9 , Eugenio Gaudio 5 , Pietro Invernizzi 1 2 , Guido Carpino # 18 , Alessandra Nardi # 19 , Marco Carbone, Cristoferi, L, Calvaruso, V, Overi, D, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Fichera, A, Di Marco, V, Leutner, M, Venere, R, Picciotto, A, Lucà, M, Mulinacci, G, Palermo, A, Gerussi, A, D'Amato, D, O'Donnell, S, Cerini, F, De Benedittis, C, Malinverno, F, Ronca, V, Mancuso, C, Cazzagon, N, Ciaccio, A, Barisani, D, Marzioni, M, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, Nardi, A, and Carbone, M

Subjects
area under curve, 0301 basic medicine, medicine.medical_specialty, liver cirrhosis, Diagnostic accuracy, risk stratification, PBC, Gastroenterology, primary biliary cholangiti, elasticity imaging techniques, female, humans, biliary, male, middle aged, ROC curve, sensitivity and specificity, Therapy naive, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Hepatology, Receiver operating characteristic, medicine.diagnostic_test, Liver Cirrhosis, Biliary, business.industry, Original Articles, medicine.disease, transient elastography, Autoimmune, Cholestatic and Biliary Disease, 030104 developmental biology, Liver biopsy, Cohort, Original Article, 030211 gastroenterology & hepatology, diagnostic accuracy, Cut-off, Transient elastography, business, fibrosi
Abstract

Background & aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Non-invasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis at disease presentation in PBC. Approach & results We collected data from 167 consecutive treatment-naive PBC patients who underwent liver biopsy(LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves(AUROCs) for advanced fibrosis (Ludwig stage≥III). The effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. Derivation cohort consisted of 126 patients with valid LSM and LB, VCTE identified patients with advanced fibrosis with AUROC of 0.89. LSM cut-offs ≤6.5kPa and >11.0kPa enabled to exclude and confirm, respectively, advanced fibrosis (negative predictive value[NPV]=0.94, positive predictive value[PPV]=0.89, error rate=5.6%). These values were externally validated in an independent cohort of 91 PBC patients(NPV=0.93, PPV=0.89, error rate=8.6%). Multivariable analysis found the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions In a multicenter study of treatment-naive PBC patients, we identified two cut-offs (LSM≤6.5kPa and>11.0kPa) able to discriminate at diagnosis the presence or the absence, respectively, of advanced fibrosis in PBC patients, with external validation. In patients with LSM between these two cut-offs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Published
2021

11. Quality of life in patients with primary biliary cholangitis: A cross-geographical comparison

Author

Marco Carbone, Daphne D’Amato, L. Jopson, Luca Vecchio, Sesé Pilar, Massimo Miglioretti, Lorenzo Montali, Martina Lucà, S. E. O'Donnell, A Gerussi, Clara Mancuso, Pietro Invernizzi, Andrea Gragnano, Albert Parés, Dave Jones, Anna Reig, Alessandra Frigerio, Minami Yagi, George F. Mells, Vincenzo Ronca, Atsushi Tanaka, Laura Cristoferi, Montali, L, Gragnano, A, Miglioretti, M, Frigerio, A, Vecchio, L, Gerussi, A, Cristoferi, L, Ronca, V, D’Amato, D, O’Donnell, S, Mancuso, C, Lucà, M, Yagi, M, Reig, A, Jopson, L, Pilar, S, Jones, D, Pares, A, Mells, G, Tanaka, A, Carbone, M, and Invernizzi, P

Subjects
Factorial invariance, Research paper, Cholestasis, business.industry, Cognitive domain, Immunology, Mean age, Cognition, Autoimmunity, RC581-607, Quality of life, Liver, Cholestasi, Immunology and Allergy, Medicine, In patient, Sun exposure, Immunologic diseases. Allergy, business, Emotional dysfunction, Fatigue, Demography
Abstract

Background & aims Several symptoms impair the quality of life (QoL) of patients with primary biliary cholangitis (PBC). They are reported to vary significantly in different countries. Aim of our study was to explore whether there is a geographical clustering that accounts for symptoms in PBC. Methods Data was analysed from four cohorts of PBC patients from the UK, Spain, Japan and Italy using the PBC-27 scale. Results Overall, 569 patients from four cohorts were identified, including 515 females (90.5%) with a mean age of 61 years. The analysis provided evidence for strict factorial invariance of the scale, a robust indicator of its validity for cross-cultural research. The mean of the fatigue domain of British patients was significantly greater than that of the Japanese (p ​, Graphical abstract Image 1, Highlights • Primary Biliary Cholangitis (PBC) is a rare liver disease characterised by several symptoms that impair quality of life; • This study includes data from questionnaires provided to individuals with PBC in Italy, Japan, Spain and United Kingdom; • It shows a clear geographical pattern of distribution of PBC-related symptoms, with a significant difference based on latitude.

Published
2021

12. New Therapeutic Targets in Autoimmune Cholangiopathies

Author

Alessio Gerussi, Martina Lucà, Laura Cristoferi, Vincenzo Ronca, Clara Mancuso, Chiara Milani, Daphne D'Amato, Sarah Elizabeth O'Donnell, Marco Carbone, Pietro Invernizzi, Gerussi, A, Luca, M, Cristoferi, L, Ronca, V, Mancuso, C, Milani, C, D'Amato, D, O'Donnell, S, Carbone, M, and Invernizzi, P

Subjects
0301 basic medicine, Choleretic, FXR agonist, medicine.drug_class, Peroxisome proliferator-activated receptor, microbiome, Review, liver, digestive system, primary biliary cholangiti, PPAR agonist, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, medicine, Microbiome, Receptor, chemistry.chemical_classification, lcsh:R5-920, fibrate, gut-liver axis, Bile acid, FXR agonists, business.industry, primary biliary cholangitis, primary sclerosing cholangitis, General Medicine, medicine.disease, digestive system diseases, gut-liver axi, 030104 developmental biology, chemistry, Cancer research, Medicine, 030211 gastroenterology & hepatology, Farnesoid X receptor, fibrates, lcsh:Medicine (General), business
Abstract

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the “leaky gut” hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential . Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.

Published
2020

13. Additive beneficial effects of Fibrates combined with Obeticholic acid in the treatment of patients with Primary Biliary Cholangitis and inadequate response to second-line therapy: data from the Italian PBC Study Group

Author

G. Marconi, Clara Mancuso, Chiara Milani, Nora Cazzagon, A. Floreani, Laura Cristoferi, Alessio Gerussi, Marco Marzioni, S. E. O'Donnell, Federica Malinverno, Marco Carbone, Pietro Invernizzi, Daphne D’Amato, D'Amato, D, O'Donnell, S, Cazzagon, N, Marconi, G, Gerussi, A, Cristoferi, L, Malinverno, F, Mancuso, C, Milani, C, Marzioni, M, Floreani, A, Invernizzi, P, and Carbone, M

Subjects
medicine.medical_specialty, Second-line therapy, Hepatology, business.industry, Obeticholic Acid, Gastroenterology, Obeticholic acid, chemistry.chemical_compound, chemistry, Internal medicine, Medicine, Primary Biliary Cholangiti, Fibrate, New Therapy, business, Beneficial effects
Published
2020

14. Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians

Author

Valentina Tranchino, Giuliana Ferrante, Doriana Amato, Antonino Capizzi, Maria Furno, Carlo De Pieri, Valentina Agnese Ferraro, Stefania La Grutta, Maria Di Cicco, and Di Cicco ME, Ferrante G, Amato D, Capizzi A, De Pieri C, Ferraro VA, Furno M, Tranchino V, La Grutta S.

Subjects
Health, Toxicology and Mutagenesis, Child Welfare, Climate change, lcsh:Medicine, Review, 010501 environmental sciences, Health outcomes, 01 natural sciences, 03 medical and health sciences, Extreme weather, respiratory infections, 0302 clinical medicine, Settore MED/38 - Pediatria Generale E Specialistica, children, Air Pollution, Environmental health, Hypersensitivity, Humans, Medicine, Pediatricians, 030212 general & internal medicine, Child, Adverse effect, Respiratory health, 0105 earth and related environmental sciences, Asthma, allergic rhinitis, business.industry, Global warming, lcsh:R, Public Health, Environmental and Occupational Health, asthma, climate change, paediatricians, Allergens, medicine.disease, paediatrician, Call to action, business, allergic rhiniti
Abstract

Climate change (CC) is one of the main contributors to health emergencies worldwide. CC appears to be closely interrelated with air pollution, as some pollutants like carbon dioxide (CO2), nitrogen oxides (NOx) and black carbon are naturally occurring greenhouse gases. Air pollution may enhance the allergenicity of some plants and, also, has an adverse effect on respiratory health. Children are a uniquely vulnerable group that suffers disproportionately from CC burden. The increasing global warming related to CC has a big impact on plants’ lifecycles, with earlier and longer pollen seasons, as well as higher pollen production, putting children affected by asthma and allergic rhinitis at risk for exacerbations. Extreme weather events may play a role too, not only in the exacerbations of allergic respiratory diseases but, also, in favouring respiratory infections. Even though paediatricians are already seeing the impacts of CC on their patients, their knowledge about CC-related health outcomes with specific regards to children’s respiratory health is incomplete. This advocates for paediatricians’ increased awareness and a better understanding of the CC impact on children’s respiratory health. Having a special responsibility for children, paediatricians should actively be involved in policies aimed to protect the next generation from CC-related adverse health effects. Hence, there is an urgent need for them to take action and successfully educate families about CC issues. This paper aims at reviewing the evidence of CC-related environmental factors such as temperature, humidity, rainfall and extreme events on respiratory allergic diseases and respiratory infections in children and proposing specific actionable items for paediatricians to deal with CC-related health issues in their clinical practice.

Published
2020

15. Letter: histology is relevant for risk stratification in primary biliary cholangitis

Author

Daphne D’Amato, Gideon M. Hirschfield, Marco Carbone, George F. Mells, David Jones, Carbone, M, D'Amato, D, Hirschfield, G, Jones, D, and Mells, G

Subjects
Cholagogues and Choleretics, medicine.medical_specialty, Primary (chemistry), Hepatology, Liver Cirrhosis, Biliary, business.industry, Ursodeoxycholic Acid, Gastroenterology, Histology, Risk Assessment, Ursodeoxycholic acid, Internal medicine, Risk stratification, medicine, Humans, Pharmacology (medical), Cholagogues and Choleretic, Risk assessment, business, Human, medicine.drug
Published
2019

16. Multiple therapeutic targets in rare cholestatic liver diseases: Time to redefine treatment strategies

Author

A Gerussi, S. E. O'Donnell, Marco Carbone, Daphne D’Amato, Laura Cristoferi, Pietro Invernizzi, Gerussi, A, D'Amato, D, Cristoferi, L, O'Donnell, S, Carbone, M, and Invernizzi, P

Subjects
Cholagogues and Choleretics, FXR agonist, Gut–liver axi, Peroxisome Proliferator-Activated Receptors, Specialties of internal medicine, Receptors, Cytoplasmic and Nuclear, 0302 clinical medicine, Chalcones, MED/12 - GASTROENTEROLOGIA, Medicine, Fibrate, Pyrazolones, Sulfonamides, FXR agonists, Liver Cirrhosis, Biliary, Primary sclerosing cholangitis, Precision medicine, Ursodeoxycholic Acid, General Medicine, Fecal Microbiota Transplantation, Anti-Bacterial Agents, RC581-951, Primary biliary cholangiti, 030220 oncology & carcinogenesis, Treatment strategy, 030211 gastroenterology & hepatology, Steroids, Ustekinumab, medicine.medical_specialty, Pyridones, Cholangitis, Sclerosing, Tretinoin, Bile acid, Chenodeoxycholic Acid, Abatacept, 03 medical and health sciences, Humans, Immunologic Factors, Janus Kinase Inhibitors, Microbiome, Benzothiazoles, Intensive care medicine, Hepatology, business.industry, Primary biliary cholangitis, Isoxazoles, medicine.disease, Bile acids, Gastrointestinal Microbiome, Fibroblast Growth Factors, Purines, Azetidines, Pyrazoles, Bezafibrate, Propionates, business, Fibrates
Abstract

Primary biliary cholangitis and primary sclerosing cholangitis are rare diseases affecting the bile ducts and the liver. The limited knowledge of their pathogenesis leads to limited therapeutic options. Nevertheless, the landscape of novel therapies for these cholangiopathies is now rapidly changing, providing new treatment opportunities for patients and clinicians involved in their care. The aim of this review is to summarize the evidence of novel molecules under investigation for primary biliary cholangitis and primary sclerosing cholangitis and to discuss how they can potentially change current treatment paradigms.

Published
2019

17. Risk Management in Magnetic Resonance: Failure Mode, Effects, and Criticality Analysis

Author

Mario Sansone, Maria Triassi, Anna Russo, Antonella Petrillo, Roberta Fusco, Daniela Maria Amato, Vincenza Granata, Alessandro di Finizio, Nicola Raiano, Maria Zirpoli, Salvatore Filice, Tonino Pedicini, Eugenio Maria Covelli, Petrillo, A, Fusco, R, Granata, V, Filice, S, Raiano, N, Amato, D, Zirpoli, A, di Finizio, A, Sansone, Mario, Russo, A, Covelli, Em, Pedicini, T, and Triassi, Maria

Subjects
Male, Schedule, Article Subject, Process (engineering), Computer science, Control (management), lcsh:Medicine, Audit, General Biochemistry, Genetics and Molecular Biology, Humans, Operations management, Diagnostic Errors, Risk management, Risk Management, General Immunology and Microbiology, business.industry, lcsh:R, General Medicine, Magnetic Resonance Imaging, Failure mode, effects, and criticality analysis, Radiological weapon, Female, Management Audit, business, Failure mode and effects analysis, Research Article
Abstract

The aim of the study was to perform a risk management procedure in “Magnetic Resonance Examination” process in order to identify the critical phases and sources of radiological errors and to identify potential improvement projects including procedures, tests, and checks to reduce the error occurrence risk. In this study we used the proactive analysis “Failure Mode Effects Criticality Analysis,” a qualitative and quantitative risk management procedure; has calculated Priority Risk Index (PRI) for each activity of the process; have identified, on the PRI basis, the most critical activities and, for them, have defined improvement projects; and have recalculated the PRI after implementation of improvement projects for each activity. Time stop and audits are performed in order to control the new procedures. The results showed that the most critical tasks of “Magnetic Resonance Examination” process were the reception of the patient, the patient schedule drafting, the closing examination, and the organization of activities. Four improvement projects have been defined and executed. PRI evaluation after improvement projects implementation has shown that the risk decreased significantly following the implementation of procedures and controls defined in improvement projects, resulting in a reduction of the PRI between 43% and 100%.

Published
2013

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