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108. Oral Abstract session: Diagnosis and clinical impact of imaging in valvular heart disease: Thursday 4 December 2014, 14:00-15:30 * Location: Agora

Author

Amin, A E H, Ammar, WAA, Farrag, A A F, Elaroussy, W A E, Enache, R, Popescu, BA, Muraru, D, Piazza, R, Calin, A, Beladan, CC, Rosca, M, Nicolosi, GL, Ginghina, C, Hamadanchi, A, Goebel, B, Schmidt-Winter, C, Otto, S, Jung, C, Figulla, HR, Poerner, TC, Bandera, F, Generati, G, Pellegrino, M, Labate, V, Alfonzetti, E, Guazzi, M, Cho, EJ, Park, S-J, Lim, HJ, Yoon, HR, Chang, S-A, Lee, S-C, Park, SW, Henri, C, Dulgheru, R, Magne, J, Caballero, L, Laaraibi, S, Kou, S, Voilliot, D, Davin, L, Pierard, L, Lancellotti, P, Ancona, R, Comenale Pinto, S, Caso, P, Monteforte, I, Coppola, MG, Sellitto, V, Izzo, M, Macrino, M, Calabro, R, Lee, S, Lee, SP, Kim, HJ, Park, JB, Hong, MK, Kim, JH, Kim, HK, Kim, YJ, and Sohn, DW

Abstract

Purpose: Patients with rheumatic mitral stenosis (MS) are at increased risk of thromboembolic consequences. Owing to the higher risk of these complications, anticoagulant therapy is mandatory in MS associated with atrial fibrillation (AF). However, time to begin prophylactic anticoagulant therapy in normal sinus rhythm (NSR) is not yet clear. Left atrial (LA) enlargement has been proposed as potential surrogate for thrombus formation and subsequent embolization. We examined various LA echocardiographic parameters to detect possible predictors of embolization in MS and NSR. Methods: Our study included 79 patients with rheumatic MS in NSR. Case group (n=36) included patients with history of prior embolic events; while control group (n=43) included patients without history of embolization. All the studied population underwent history taking, clinical examination and ECG to rule out AF and confirm manifestations of embolization in the case group. Patients with CVS underwent bilateral carotid duplex to rule out Carotid artery stenosis. Other causes of embolization were excluded. Routine transthoracic echocardiogram (TTE) was done and LA volumes (LAV) were measured using both area-length (A-L) and prolate-ellipsoid methods. LAV maximum (end systolic; Vmax), LAV minimum (end diastolic;Vmin) and LAV at onset of atrial systole (end of P wave on surface ECG;Vp) were measured by the two methods. The LA phasic indices were calculated given the aforementioned LAVs as follows: Passive emptying volume (PEV)= Vmax-Vp, Passive emptying fraction (PEF) = PEV/Vmax, Active emptying volume (AEV)= Vp-Vmin, Active emptying fraction (AEF) = AEV/Vp and Total emptying volumes (TEV) = PEV + AEV. Comparison between case and control groups was done using two-tailed unpaired student t test for continuous variables and the Pearson's chi-square test for categorical variables. Correlations between normally distributed variables were done using Pearson correlation coefficient. p value < 0.05 was considered significant for all tests. Results: Female gender predominated the studied group (83.7%). The mean age of our population was 32.6 ± 6.7.Both groups were age and gender matched. All patients were neither diabetic nor hypertensive. Both groups had comparable degree of mitral stenosis. There was no statistical difference in LAV between both groups. However, PEF using Prolate-ellipsoid method was significantly lower in the case group (p=0.017). Conclusion: LA phasic indices may be better indicator of LA dysfunction than conventional LAV. LA PEF may be a predictor of thrombus formation and subsequent embolization in rheumatic MS and NSR.

Published
2014
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111. New Insights from Metabolomics in Pediatric Renal Diseases

Author

Simona Riccio, Maria Sole Valentino, Antonio Paride Passaro, Marica Izzo, Stefano Guarino, Emanuele Miraglia del Giudice, Pierluigi Marzuillo, Anna Di Sessa, Riccio, S., Valentino, M. S., Passaro, A. P., Izzo, M., Guarino, S., Giudice, E. M., Marzuillo, P., and Di Sessa, A.

Subjects
Pediatrics, Perinatology and Child Health, Disease, Metabolomic, Review, Renal, Pediatrics, metabolomics, Children, RJ1-570
Abstract

Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.

Published
2022

112. Riuso come pratica civile necessaria

Author

Molinari L, L. Molinari, G. Durbiano, R. Capozzi, O. Carpenzano, C. Piscopo, C. Andriani, C. Gambardella, B. Messina, L. Sciascia, E. Pitzalis, F. Toppetti, C. Moccia, F. Izzo, M. Russo, F. Costanzo, R. Picozzi, F. Costanzo, F. Defilippis, F. Visconti, and Molinari, L

Subjects
riuso, progetto, Italia
Published
2021

113. Predictors of Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Receiving EGFR Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis

Author

Luca Scafuri, Brigitta Mucci, Roberto Bianco, Fernanda Picozzi, Simone Carrano, Carlo Buonerba, Martina Pagliuca, Ferdinando Costabile, Pasquale Dolce, Sabino De Placido, Giuseppe Di Lorenzo, Michela Izzo, Davide Bosso, Luigi Formisano, Simona Iaccarino, Vittorio Riccio, Dario Ribera, Buonerba, C., Iaccarino, S., Dolce, P., Pagliuca, M., Izzo, M., Scafuri, L., Costabile, F., Riccio, V., Ribera, D., Mucci, Brigitta, Carrano, S., Picozzi, F., Bosso, D., Formisano, L., Bianco, R., De Placido, S., and Di Lorenzo, G.

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Epidermal growth factor receptor tyrosine kinase inhibitor, Population, Review, epidermal growth factor receptor tyrosine kinase inhibitors, lcsh:RC254-282, law.invention, 03 medical and health sciences, Exon, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Medicine, sex, Epidermal growth factor receptor, Lung cancer, education, non-small cell lung cancer, education.field_of_study, biology, business.industry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, respiratory tract diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, Meta-analysis, biology.protein, Non small cell, business, Tyrosine kinase
Abstract

Some commonly available patient or disease characteristics may be associated with progression-free survival (PFS) and overall survival (OS) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKIs (epidermal growth factor receptor - tyrosine kinase inhibitors). We performed a systematic review and meta-analysis of randomized control trials (RCTs) to explore differences in outcomes associated with EGFR-TKIs among subgroups of EGFR-mutant NSCLC patients. Pooled HRs for progression or death (PFS-HRs) and pooled HRs for death (OS-HRs) were compared among sub-groups defined according to baseline clinical and demographic variables as well as type of EGFR mutation. In the entire assessable population of 4465 EGFR-mutant NSCLC patients, significant interactions with PFS were found for gender (males vs. females; pooled ratio of the PFS-HRs = 1.2; 95% CI 1.12–1.56), smoking history (smokers vs. non-smokers; pooled ratio of the PFS-HRs = 1.26; 95% CI 1.05–1.51), and type of EGFR mutation (patients with exon 21 L858R mutation vs. exon 19 deletion; pooled ratio of the PFS-HRs = 1.39; 95% CI 1.18–1.63). Male patients, smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients, non-smokers and patients with EGFR exon 19 deletion.

Published
2019

114. Correction to: Laparoscopic right hemicolectomy: the SICE (Società Italiana di Chirurgia Endoscopica e Nuove Tecnologie) network prospectivetrial on 1225 cases comparing intra corporeal versus extra corporeal ileo‑colic side‑to‑side anastomosis (Surgical Endoscopy, (2019), 10.1007/s00464-019-07255-2)

Author

M. Sorrentino, A. Alo, G. L. Canu, F. Monari, A. G. Marrosu, E. Soligo, Wanda Petz, A. Gattolin, R. Vicentini, S. Razzi, M. Zago, S. Neri, A. Pisani Ceretti, D. Apa, F. Gatti, A. Donini, F. Medas, D. Cassetti, S. Rubino, R. Lombardi, G. D. DePalma, Alberto Arezzo, G. Soliani, P. Checcacci, G. Concone, Emanuele Botteri, F. Scognamillo, Ferdinando Agresta, Pierluigi Marini, S. Gelati, Luigi Boni, A. Coratti, Andrea Picchetto, G. Guerriero, M. Calgaro, Francesca Pecchini, A. Contine, Andrea Valeri, N. DeManzini, M. Clementi, A. Balani, F. Fidanza, R. Galleano, Carlo Bergamini, A. Brescia, G. Arcuri, Elio Jovine, E. Rosso, A. Oldani, E. Artioli, Nereo Vettoretto, Giuseppe Navarra, G. Sarro, E. Restini, Chiara Morotti, S. Giannessi, F. DeAngelis, M. Degiuli, G. Talamo, G. Alemanno, L. Cafagna, P. Cumbo, V. Violi, S. Targa, Irnerio Angelo Muttillo, A. Martino, M. DeLuca, Elisa Cassinotti, Alessandro Puzziello, S. Sala, Riccardo Rosati, E. Erdas, R. Petri, A. Deserra, A. Gioffre, G. Viola, E. Stratta, Mario Guerrieri, E. Minciotti, Mauro Podda, Giuseppe Spinoglio, F. Borghi, Micaela Piccoli, C. DeNisco, P. Carcoforo, D. Delogu, Giuseppe Resta, P. Corleone, D. Pennisi, Gianfranco Silecchia, E. Opocher, A. Taddei, A. Budassi, Paolo Delrio, A. Meloni, Marco E. Allaix, A. Ambrosi, H. Impellizzeri, N. Portolani, L. Guerriero, G. Ercolani, A. Guariniello, M. Antoniutti, M. Cesari, A. P. Luzzi, M. Izzo, M. Longoni, R. Mazza, C. Benvenuto, S. Gobbi, P. G. Calo, C. Feo, Antonino Agrusa, L. Covotta, L. Presenti, V. Adamo, Gian Luca Baiocchi, E. Osenda, R. Ottonello, Giancarlo D'Ambrosio, F. Roviello, V. Grammatico, G. Moretto, L. Zampino, Valerio Caracino, Giovanni Ferrari, D. Rega, V. Robustelli, Diego Cuccurullo, F. Vasta, Ugo Elmore, R. Campagnacci, Gianfranco Cocorullo, O. Ghazouani, G. Ricci, S. Berti, F. Colombo, Alberto Sartori, S. Scabini, S. Mazzoccato, B. Pirrera, A. Altamura, N. Tartaglia, E. Romairone, G. Baldazzi, Marco Catarci, G. Garulli, Lorenzo Casali, S. Testa, R. Brachet Contul, M. Basti, U. Rivolta, D. Pertile, M. Pavanello, M. Pisano, Marco Milone, A. Verzelli, P. Ubiali, L. Solaini, M. Coppola, G Anania, Massimo Carlini, F. Corcione, P. DePaolis, P. Ciano, M. Santarelli, V. Panebianco, Nicola Perrotta, R. Sechi, M. Rigamonti, G. Lezoche, L. Fabris, C. Lirusso, D. Foschi, G. Canova, P. Soliani, Roberta Gelmini, Stefano Olmi, A. Lucchi, Giorgia Valpiani, L. Pellegrino, Anania, G., Agresta, F., Artioli, E., Rubino, S., Resta, G., Vettoretto, N., Petz, W. L., Bergamini, C., Arezzo, A., Valpiani, G., Morotti, C., Silecchia, G., Adamo, V., Agrusa, A., Alemanno, G., Allaix, M. E., Alo, A., Altamura, A., Ambrosi, A., Antoniutti, M., Apa, D., Arcuri, G., Baiocchi, G. L., Balani, A., Baldazzi, G., Basti, M., Benvenuto, C., Berti, S., Boni, L., Borghi, F., Botteri, E., Brachet Contul, R., Brescia, A., Budassi, A., Cafagna, L., Calgaro, M., Calo, P. G., Campagnacci, R., Canova, G., Canu, G. L., Caracino, V., Carcoforo, P., Carlini, M., Casali, L., Cassetti, D., Cassinotti, E., Catarci, M., Cesari, M., Checcacci, P., Ciano, P., Clementi, M., Cocorullo, G., Colombo, F., Concone, G., Contine, A., Coppola, M., Coratti, A., Corcione, F., Corleone, P., Covotta, L., Cuccurullo, D., Cumbo, P., D'Ambrosio, G., Deangelis, F., Deluca, M., Demanzini, N., Denisco, C., Depalma, G. D., Depaolis, P., Degiuli, M., Delogu, D., Delrio, P., Deserra, A., Donini, A., Elmore, U., Ercolani, G., Erdas, E., Fabris, L., Ferrari, G., Feo, C., Fidanza, F., Foschi, D., Galleano, R., Garulli, G., Gatti, F., Gattolin, A., Gelati, S., Gelmini, R., Ghazouani, O., Gioffre, A., Gobbi, S., Grammatico, V., Guariniello, A., Giannessi, S., Guerrieri, M., Guerriero, L., Guerriero, G., Impellizzeri, H., Izzo, M., Jovine, E., Lezoche, G., Lirusso, C., Lombardi, R., Longoni, M., Lucchi, A., Luzzi, A. P., Marini, P., Marrosu, A. G., Martino, A., Mazza, R., Mazzoccato, S., Medas, F., Meloni, A., Milone, M., Minciotti, E., Monari, F., Moretto, G., Muttillo, I. A., Navarra, G., Neri, S., Oldani, A., Olmi, S., Opocher, E., Osenda, E., Ottonello, R., Panebianco, V., Pavanello, M., Pecchini, F., Pellegrino, L., Pennisi, D., Perrotta, N., Pertile, D., Petri, R., Picchetto, A., Piccoli, M., Pirrera, B., Pisani Ceretti, A., Pisano, M., Podda, M., Portolani, N., Presenti, L., Puzziello, A., Razzi, S., Rega, D., Restini, E., Ricci, G., Rigamonti, M., Rivolta, U., Robustelli, V., Romairone, E., Rosati, R., Rosso, E., Roviello, F., Sala, S., Santarelli, M., Sarro, G., Sartori, A., Scabini, S., Scognamillo, F., Sechi, R., Solaini, L., Soliani, G., Soliani, P., Soligo, E., Sorrentino, M., Spinoglio, G., Stratta, E., Taddei, A., Talamo, G., Targa, S., Tartaglia, N., Testa, S., Ubiali, P., Valeri, A., Vasta, F., Verzelli, A., Vicentini, R., Viola, G., Violi, V., Zago, M., and Zampino, L.

Subjects
medicine.medical_specialty, colon cancer right hemcolectomy, business.industry, medicine, Surgery, business, Side to side anastomosis, Surgical endoscopy, Laparoscopic right hemicolectomy, NO, LS7_4
Abstract

Due to an error in production the members of SICE CoDIG (Colon Dx Italian Group) listed in the Acknowledgments were not tagged correctly as authors in the XML of this article. This listing is presented again here:.

Published
2019

115. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author

Kausik K Ray, Helen M Colhoun, Michael Szarek, Marie Baccara-Dinet, Deepak L Bhatt, Vera A Bittner, Andrzej J Budaj, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Virginie Loizeau, Renato D Lopes, Angèle Moryusef, Jan Murin, Robert Pordy, Arsen D Ristic, Matthew T Roe, José Tuñón, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, Philippe Gabriel Steg, Gregory G. Schwartz, Ph. Gabriel Steg, Deepak L. Bhatt, Vera A. Bittner, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Guillaume Lecorps, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S. Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Zlatko Fras, Anthony J. Dalby, H. Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mehmed Kulić, Azra Durak-Nalbantic, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro G de B Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin-Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Juhani K Helsinki, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, 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III, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Islam, O, Subherwal, S, Ranadive, N, Vakili, B, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Zahr, F, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, M, Schmalfuss, C, Picone, M, Pederson, R, Herzog, W, Friedman, K, Lindsey, J, Nowins, R, Timothy, E, Leonard, P, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, Alonso, A, May, W, Christopher, D, Galski, T, Chu, A, Mody, F, Ramin, E, Hodes, Z, Rossi, J, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, Vetrovec, G, King, M, Carey, C, Gerber, J, Younis, L, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Kuvin, J, Silver, K, Foster, M, Tonnessen, G, Espinoza, A, Amlani, M, Wali, A, Malozzi, C, Jong, G, Massey, C, Wattanakit, K, O'Donnell, P, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Blonder, R, Akyea-Djamson, A, Labroo, A, Marais, H, Claxton, E, Weiss, R, Kathryn, R, Berk, M, Joshi, P, Khera, A, Khaira, A, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Erenrich, N, Farrar, M, Pollock, S, French, W, Diamantis, S, Guy, D, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Albert, S, Spriggs, D, Strain, J, Mittal, S, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, F, Nahhas, A, Pope, T, Nager, P, Vohra, R, Sharma, M, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Stapleton, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, P, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Dohad, S, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Henry, J, Schifferdecker, B, Gilbert, J, Chalavarya, G, Eaton, C, Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi

Subjects
Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, STATIN THERAPY, blood-glucose, Endocrinology, Diabetes and Metabolism, GUIDELINES, PCSK9, 0302 clinical medicine, Endocrinology, GENETIC-VARIANTS, Cardiovascular Disease, Diabetes Complication, Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances, Clinical endpoint, Medicine, guidelines, 030212 general & internal medicine, Prediabetes, Myocardial infarction, myocardial-infarction, genetic-variants, statin therapy, risk, pcsk9, association, liraglutide, evolocumab, RISK, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, BLOOD-GLUCOSE, ASSOCIATION, Middle Aged, Cardiovascular Diseases, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, Acute coronary syndrome, PCSK9 inhibitor, acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, 030209 endocrinology & metabolism, Antibodies, Monoclonal, Humanized, Diabetes Complications, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Aged, Alirocumab, diabetes, PCSK9, hyperlipidemia, Science & Technology, ODYSSEY OUTCOMES Committees and Investigators, business.industry, Unstable angina, EVOLOCUMAB, medicine.disease, MYOCARDIAL-INFARCTION, LIRAGLUTIDE, Human medicine, business
Abstract

Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.

Published
2019

116. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author

Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M Sizova, Marina Ballyuzek, Nikolay Tarasov, Elena Demchenko, Olga Barbarash, Valentin Moiseev, Valentin Markov, Vadim Kuznetsov, Inna Viktorova, Igor Sergienko, Lyudmila Ermoshkina, Niyaz Khasanov, Tatiana Khlevchuk, Andrey Baglikov, Sergey Shalaev, Elena Zonova, Elena Reznik, Larisa Haisheva, Tatyana Morugova, Nikita Lomakin, Alexander Vishnevsky, Yuri Shvarts, Olga Magnitskaya, Marina Mikhailusova, Elena Pavlysh, Igor Libov, Anna Zateyschikova, Victor Kostenko, Anton Edin, Yaroslava Khovaeva, Konstantin Zakharov, Raisa Stryuk, Vladimir Khirmanov, Sergey Kanorskiy, Sergey Yakushin, Anna Barabashkina, Hongwei Li, Qiang Zhao, Jian Zhang, Jianhua Ma, Yong He, Ming Luo, Aidong Zhang, Ningru Zhang, Yingru Chai, Genshan Ma, Hao Wang, Zhigang Liu, Lanjie He, Zhifang Song, Xiaolin Dong, Liang Tao, Zhanquan Li, Xi Su, Xiangqing Kong, Heping Niu, Junbo Ge, Zhurong Luo, Wenjun Huang, Daoquan Peng, Zuyi Yuan, Maria Milanova, Doncho Tenev, Antoni Gogov, Dimitar Karageorgiev, Todor Kolchev, Nikolay Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna Kulyk, Olena Levchenko, Oleksandr Prokhorov, Dmytro Reshotko, Mykhaylo Sorokivskyy, Nataliia Velichko, Valentyn Maslovskyi, Zinaida Teliatnikova, Sergiy Dotsenko, Olena Krakhmalova, Igor Kraiz, Viktoria Zharinova, Larysa Bula, Igor Kaydashev, Valeriy Molodtsov, Lesya Rasputina, Viktoriya Pidlisna, Olena Lysunets, Anatoliy Kravchenko, Liubomyr Glushko, Tetyana Khomazyuk, Yevgeniya Svyshchenko, Oleksandr Parkhomenko, Boris Mankovsky, Orest Abrahamovych, Andriy Yagensky, Mykola Stanislavchuk, Larisa Vasilyeva, Liubov Sokolova, Oleg Sychov, Vira Tseluyko, Igor Kyrychenko, Mykola Rishko, Sergiy Furkalo, Richard Gallo, Olivier Bertrand, Shamir Mehta, Christian Constance, Bruce Sussex, Remo Zadra, Simon Kouz, Raja Chehayeb, Amritanshu Pandey, Danielle Dion, Gordon Bailey, Laurie Hill, Krishnan Ramanathan, Micha Dorsch, Alykhan Nanji, Mohan Babapulle, Martine Montigny, Gilbert Gosselin, Payam Dehghani, Dennis Rupka, Michel Le May, Francis Pichette, Francois St-Maurice, Patrick Teefy, Samer Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, Dusan Kucera, Ondrej Jerabek, Michaela Honkova, Vratislav Dedek, Ivan Rihacek, Pavel Kos, Josef Slaby, Martina Machkova, Eva Zidkova, Lubomir Elbl, Hana Grunfeldova, Jiri Carda, Vladimir Mrozek, Jiri Maly, Richard Milkovic, Jan Malecha, Hana Skalicka, Ivo Oral, Eva Krcova, Libor Lisa, Jan Belohlavek, Roman Miklik, Ondrej Cermak, Jana Bednarova, Zdenek Peroutka, Jindrich Spinar, Andreas Wilke, Karl-Friedrich Appel, Jens Taggeselle, Andreas Förster, Nicole Toursarkissian, Ekkehard Schmidt, Jochen Bott, Ayham Al-Zoebi, Dirk Hennig, Sabine Fischer, Norbert Schön, Joachim Sauter, Gregor Simonis, Ruth Nischik, Werner Rieker, Isabelle Schenkenberger, Thomas Behnke, Gerhard Klausmann, Michael Jeserich, Dietmar Trenk, Ingo Weigmann, Hannes Reuter, Reinhard Rummel, Candy von Münchhausen, Charlotte von Engelhardt, Eishun Horibe, Taro Shibasaki, Tomohiko Sato, Tsunekazu Kakuta, Ichiro Michishita, Michinao Tan, Ryoji Ishiki, Takahiko Aoyama, Shinichi Higashiue, Yawara Niijima, Akira Idogaki, Toru Hasegawa, Arihiro Kiyosue, Yoshiaki Tomobuchi, Katsunori Kawamitsu, Satsuki Kawasaki, Yoshiki Hata, Kazuki Fukui, Kozaburo Seki, Takashi Takenaka, Mitsuru Abe, Noriaki Utsu, Atsuyuki Oono, Kazuhisa Mitsuo, Atsushi Sueyoshi, Atsushi Hirohata, Mitsuru Tsujimoto, Osamu Ueda, Shinichi Takase, Masahiro Suzuki, Satoru Sakuragi, Fumi Yamamoto, Noritaka Fujimoto, Shigeo Kakinoki, Tatsushi Sugiura, Hiroshi Sugino, Toshihiro Nakamura, Toshiaki Kadokami, Hiroki Uehara, Masahiro Ono, Koichi Yokoya, Akihiro Koike, Sei Komatsu, Masahiro Sonoda, Hideki Ueno, Tomofumi Doi, Yuichiro Takagi, Kazuteru Fujimoto, Yutaka Eki, Munenori Okubo, Kenichiro Sasaki, Martijn van Eck, Eelko Ronner, Salem The, Ruud van de Wal, Pieter Nierop, Cornelis de Nooijer, Henri Werner, Iris Westendorp, Coen van der Zwaan, Hendrikus Crijns, Jan H Cornel, Sipke Strikwerda, Robert Bos, Edwin de Melker, Adrianus Kuijper, Hans Louwerenburg, Jacobus Plomp, Jan-Melle Dantzig, Francisco Prins, Henricus van Kesteren, Frank Willems, Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, Saleem Dawood, Ismail Mitha, Trevenesan Padayachee, Farzana Hoosen, Anthony Dalby, null Prabhavathi, Prakash Gowdaiah, Vimal Mehta, Milan Chag, Milind Gadkari, Kannaiyan Ramamurthee, Asit Das, Jitendra S Sawhney, Suvro Banerjee, Prachee Sathe, Srilakshmi Adhyapak, Tuan Nguyen, Vinh Pham, Huan Do, Anh Nguyen, Hien Nguyen, Binh Truong, Shahnaz Jamil-Copley, Chim Lang, Alastair Pell, Azfar Zaman, Robert Storey, Neil Swanson, Simon Smith, David Sharman, Denise Braganza, Peter Hammond, Andrew Moriarty, Stephen Bain, Maurice Pye, Andrew Sharp, Mark Blagden, Harpal Randeva, Timothy Myhill, Girish Viswanathan, Philip Keeling, Piers Clifford, Manish Saxena, Kristopher Lyons, John McMurray, Feeroz Jaafar, Clare Murphy, Simon Cartwright, Kamal Abouglila, Lubomir Antalik, Peter Krajci, Miroslav Urban, Frantisek Fazekas, Daniel Pella, Daniel Koleny, Tatiana Vykoukalova, Vladimir Macek, Daniela Vinanska, Livia Jamriskova, Slavomir Such, Peter Fulop, Stefan Farsky, Viliam Bugan, Jaroslava Strbova, Karol Micko, Juraj Palka Jr, Vladimir Sivak, Dalby Kristensen, Jens Refsgaard, Lene Holmvang, Ulrik Dixen, Henrik Nielsen, Kenneth Egstrup, Lisette O Jensen, Roman Sykulski, Ole Rasmussen, Alin Andries, Anders Luckow, Gitte Nielsen, Torben Sørensen, Chaiyasith Wongvipaporn, Noppadol Chamnarnphol, Suphot Srimahachota, Nakarin Sansanayudh, Srun Kuanprasert, Damras Tresukosol, Bancha Sookananchai, Mehmet Kanadasi, Turkay Ozcan, Murathan Kucuk, Zeki Ongen, Ertugrul Okuyan, Alev Arat, Sadik Acikel, Ahmet Yalcin, Umit Guray, Ceyhun Ceyhan, Necla Ozer, Sakir Arslan, Oskar Angerås, Nina Johnston, Ann-Charlotte Weiderman, Stellan Bandh, Ole Hansen, Hans Larnefeldt, Dawid Kusiak, Carl-Johan Lindholm, Anders Hedman, David Erlinge, Dan Curiac, Pia Lundman, Roberto Zucconi-Mazzini, Layth Aladellie, Jens Jensen, Jan Verwerft, Mathias Vrolix, Dirk Faes, Harry Striekwold, Peter Sinnaeve, Patrick Timmermans, Antoine Guedes, Marc Delforge, Jan Nimmegeers, Francis Stammen, Ian Buysschaert, Etienne Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, Timo Strandberg, Marc Klutstein, Gabriel Greenberg, Yoseph Rozenman, Ehud Chorin, Ariel Roguin, Basil Lewis, Amir Bashkin, Edgar Tan, Jose P Prado, Arthur Ferrolino, Noe Babilonia, Benny Barbas, Generoso Matiga, Raul M Coching, Heinz Drexel, Helmut Brath, Christoph Schnack, Ursula Hanusch, Evelyn Fließer-Görzer, Bernhard Paulweber, Christoph Ebenbichler, Rudolf Prager, Kurt Huber, Michael Wolzt, Johann Auer, Rudolf Berger, Gerit-Holger Schernthaner, Gabriela Stanciulescu, Mihai Creteanu, Marilena Spiridon, Viorica Dobreanu, Dragos Vinereanu, Laura C Iosipescu, Octavian Istratoaie, Ioan Coman, Constantin Militaru, Mircea Cinteza, Peter R Sinnaeve, José C Nicolau, José F Kerr Saraiva, Ramón Corbalán, Petr Widimský, Steen D Kristensen, Juha Hartikainen, Harald Darius, Hung F Tse, Robert G Kiss, Prem Pais, Eli Lev, Leonardo de Luca, Gabriel A Ramos López, Frederic Kontny, Noe A Babilonia, Dmitry A Zateyshchikov, Mikhail Ruda, Omer Elamin, František Kovář, Anthony J Dalby, Héctor Bueno, Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, Lee, M, Pouzar, J, Revtyak, G, Gonzalez, J, Nakhle, S, Murillo, A, Young, D, Makam, S, Syed, M, Woolf, K, Grena, P, Alfata, S, Mahal, S, Hoffman, D, Kizhakekuttu, T, Deering, J, Bhavsar, J, Mikesell, S, Wilson, W, Wilson, V, El, S, Spinale, F, Kannarkat, V, Rao, S, Hanson, L, Bertsch, J, Gonzalez-Ortiz, E, Severino, N, Willis, J, Schock, J, Bakhtari, L, Gazmuri, R, Ansari, S, Hall, J, Mehta, A, Shealy, N, Zarich, S, Singh, D, Vora, K, Andrawis, N, Molter, D, Maron, D, Cardona, J, D'Agostino, R, Arshad, T, Samaan, R, Jones, D, Presser, D, Heath, J, Green, S, Bittar, G, Henry, S, Korn, D, Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, Drelich, G, Konieczny, M, Starczewski, P, Pawlowicz, L, Jesionowski, P, Jurowiecki, J, Gniot, J, Czyzycki, M, Stania, K, Kucharczyk-Bauman, I, Busz-Papiez, B, Karczmarczyk, A, Sudnik, W, Koszek, A, Kolodziej, P, Skwarna, B, Jaramillo, N, Jankowski, M, Czochra, W, Kinasz, L, Miklaszewicz, B, Stasinska, T, Pluta, W, Basiak, M, Rusicka, T, Niedbal-Yahfouf, I, Popenda, G, Korzeniak, R, Mirek, A, Mariankowski, R, Wojnowski, L, Korol, M, Baszak, J, Podolec, P, Piesiewicz, W, Zurakowski, A, Luengas, C, Skura, M, Pilecki, P, Majchrzak, P, Krzyzagorska, E, Drozd, M, Kaczmarek, B, Sliwinska, T, Zelazowska, K, Sztembis, R, Landa, K, Matyszczak-Toniak, L, Strojek, K, Piepiorka, M, Malinowski, R, Gorska, M, Stolarczyk-Sowa, E, Romanowski, L, Zinka, E, Reszka, Z, Skierkowska, J, Uzunow, A, Laskowska-Derlaga, E, Puntus, E, Kosmacheva, E, Koziolova, N, Pavlov, P, Supryadkina, T, Didenko, Y, Kopylov, P, Kazakov, A, Aksentiev, S, Vishneva, E, Repin, A, Smolenskaya, O, Mantserova, O, Khrustalev, O, Privalova, E, Konstantinov, V, Boldueva, S, Ezhov, A, Chernyavsky, A, Kamalov, G, Galyavich, A, Zubeeva, G, Nechaeva, G, Shustov, S, Dzhaiani, N, Treshkur, T, Osokina, N, Panov, A, Shutemova, E, Makukhin, V, Kropotina, T, Tsyba, L, Karpov, Y, Sizova, J, Ballyuzek, M, Tarasov, N, Demchenko, E, Barbarash, O, Moiseev, V, Markov, V, Kuznetsov, V, Viktorova, I, Sergienko, I, Ermoshkina, L, Khasanov, N, Khlevchuk, T, Baglikov, A, Shalaev, S, Zonova, E, Reznik, E, Haisheva, L, Morugova, T, Lomakin, N, Vishnevsky, A, Shvarts, Y, Magnitskaya, O, Mikhailusova, M, Pavlysh, E, Libov, I, Zateyschikova, A, Kostenko, V, Edin, A, Khovaeva, Y, Zakharov, K, Stryuk, R, Khirmanov, V, Kanorskiy, S, Yakushin, S, Barabashkina, A, Li, H, Zhao, Q, Zhang, J, Ma, J, He, Y, Luo, M, Zhang, A, Zhang, N, Chai, Y, Ma, G, Wang, H, Liu, Z, He, L, Song, Z, Dong, X, Tao, L, Li, Z, Su, X, Kong, X, Niu, H, Ge, J, Luo, Z, Huang, W, Peng, D, Yuan, Z, Milanova, M, Tenev, D, Gogov, A, Karageorgiev, D, Kolchev, T, Rusev, N, Georgieva, N, Kondov, R, Rusinov, V, Petrov, I, Stanchev, G, Konteva, M, Dincheva, A, Yaneva, Z, Vatova, R, Ilieva, K, Runev, N, Kolomanov, B, Iliev, N, Tisheva, S, Chompalova, B, Tokmakova, M, Raev, D, Byanov, K, Markov, D, Mihov, L, Mihov, A, Milcheva, N, Minchev, M, Mollov, M, Borisov, B, Tihchev, T, Karakolev, V, Dimov, B, Georgiev, S, Smilov, L, Koo, B, Ahn, T, Hong, S, Yoon, J, Oh, S, Jeong, M, Kim, D, Chang, K, Kim, W, Hahn, J, Cha, K, Lee, J, Choi, S, Nam, C, Chae, I, Park, Y, Tahk, S, Shin, W, Chae, J, Kim, B, Bae, J, Park, W, Rha, S, Choi, Y, Hwang, J, Park, H, Baracioli, L, Guimaraes, F, Vasconcellos, E, Saraiva, J, Pereira, A, Santos, Q, Rossi, P, Maia, L, Madeira, M, Pereira, M, Botelho, R, Reis, G, Eliaschewitz, F, Borges, J, Nascimento, C, Fortes, J, de Souza, W, Pimentel, P, Hissa, M, Franchetti, M, Precoma, D, Ortiz, C, Hernandes, M, Saporito, W, dos Santos, F, Kormann, A, Neuenschwander, F, Dutra, O, Rassi, N, Tanajura, L, Souza, J, Junior, D, Leaes, P, Forte, A, Bonansea, T, Marin, J, Machado, B, Cerqueira, M, Silva, F, Michalaros, Y, Manenti, E, Cercato, C, Figueiredo, E, Liu, M, Wang, Y, Lee, T, Fang, C, Wu, Y, Ueng, K, Sheu, H, Lai, W, Hsieh, I, Chen, Z, Chiang, C, Shyu, K, Hsia, C, Mar, G, Chan, S, Wu, C, Tseng, W, Yeh, H, Wang, J, Hou, C, Sorokina, I, Dolzhenko, M, Horoshko, O, Karpenko, O, Rudenko, L, Vakaliuk, I, Kulyk, A, Levchenko, O, Prokhorov, O, Reshotko, D, Sorokivskyy, M, Velichko, N, Maslovskyi, V, Teliatnikova, Z, Dotsenko, S, Krakhmalova, O, Kraiz, I, Zharinova, V, Bula, L, Kaydashev, I, Molodtsov, V, Rasputina, L, Pidlisna, V, Lysunets, O, Kravchenko, A, Glushko, L, Khomazyuk, T, Svyshchenko, Y, Parkhomenko, O, Mankovsky, B, Abrahamovych, O, Yagensky, A, Stanislavchuk, M, Vasilyeva, L, Sokolova, L, Sychov, O, Tseluyko, V, Kyrychenko, I, Rishko, M, Furkalo, S, Gallo, R, Bertrand, O, Constance, C, Sussex, B, Zadra, R, Kouz, S, Chehayeb, R, Pandey, A, Dion, D, Bailey, G, Hill, L, Ramanathan, K, Dorsch, M, Nanji, A, Babapulle, M, Montigny, M, Gosselin, G, Dehghani, P, Rupka, D, Le May, M, Pichette, F, St-Maurice, F, Teefy, P, Mansour, S, Kassam, S, Cheung, S, Siega, A, O'Keefe, D, Sabbah, E, Bell, A, Chouinard, G, Wong, B, Miller, M, Gaudet, D, Lachance, P, Bata, I, Petrella, R, Gossard, D, Dumas, R, Ing, D, Boyrazian, H, Bessoudo, R, Huynh, T, Hart, R, Belle-Isle, J, Shukla, D, Kelly, A, Mazza, G, Cha, J, Henein, S, Frechette, A, Vizel, S, Liutkus, J, O'Mahony, M, Halperin, F, Kooy, J, Graham, J, Bailey, A, Wojcik, R, Wilderman, I, Turi, T, Motyovszki, A, Merkely, B, Kiss, R, Kiraly, C, Andrassy, P, Sarszegi, Z, Fulop, T, Zilahi, Z, Edes, I, Papp, A, Muller, G, Czigany, A, Zolyomi, S, Koranyi, L, Takacs, J, Juhasz, F, Benczur, B, Kancz, S, Foldi, A, Nagy, A, Bakai, J, Greschik, I, Puski, L, Nagy, L, Kirschner, R, Kuchar, R, Hajek, P, Busak, L, Michalik, D, Matyasek, I, Marusincova, I, Kucera, D, Jerabek, O, Honkova, M, Dedek, V, Rihacek, I, Kos, P, Slaby, J, Machkova, M, Zidkova, E, Elbl, L, Grunfeldova, H, Carda, J, Mrozek, V, Maly, J, Milkovic, R, Malecha, J, Skalicka, H, Oral, I, Krcova, E, Lisa, L, Belohlavek, J, Miklik, R, Cermak, O, Bednarova, J, Peroutka, Z, Spinar, J, Wilke, A, Appel, K, Taggeselle, J, Forster, A, Toursarkissian, N, Schmidt, E, Bott, J, Al-Zoebi, A, Hennig, D, Schon, N, Sauter, J, Simonis, G, Nischik, R, Rieker, W, Schenkenberger, I, Behnke, T, Klausmann, G, Jeserich, M, Trenk, D, Weigmann, I, Reuter, H, Rummel, R, von Munchhausen, C, von Engelhardt, C, Horibe, E, Shibasaki, T, Sato, T, Kakuta, T, Michishita, I, Tan, M, Ishiki, R, Aoyama, T, Higashiue, S, Niijima, Y, Idogaki, A, Hasegawa, T, Kiyosue, A, Tomobuchi, Y, Kawamitsu, K, Kawasaki, S, Hata, Y, Fukui, K, Seki, K, Takenaka, T, Abe, M, Utsu, N, Oono, A, Mitsuo, K, Sueyoshi, A, Hirohata, A, Tsujimoto, M, Ueda, O, Takase, S, Suzuki, M, Sakuragi, S, Yamamoto, F, Fujimoto, N, Kakinoki, S, Sugiura, T, Sugino, H, Nakamura, T, Kadokami, T, Uehara, H, Ono, M, Yokoya, K, Koike, A, Komatsu, S, Sonoda, M, Ueno, H, Doi, T, Takagi, Y, Fujimoto, K, Eki, Y, Okubo, M, Sasaki, K, van Eck, M, Ronner, E, The, S, van de Wal, R, Nierop, P, de Nooijer, C, Werner, H, Westendorp, I, van der Zwaan, C, Crijns, H, Cornel, J, Strikwerda, S, Bos, R, de Melker, E, Kuijper, A, Louwerenburg, H, Plomp, J, Dantzig, J, Prins, F, van Kesteren, H, Willems, F, Amoroso, G, Carnero, G, Duronto, E, Besada, D, Chacon, C, Zangroniz, P, Solis, S, Liberman, A, Sernia, V, Alvarisqueta, A, Maffei, L, Vilamajo, O, Garcia, C, Sicer, M, Muntaner, J, Bordonava, A, Albisu, J, Zanini, A, Rista, L, Hominal, M, Estrada, J, Prado, A, Gosparini, D, Schiavi, B, Castillo, A, Martinez, G, Lopez, V, Rosas, E, Lopez, G, Cantu, E, de los Rios Ibarra, M, Padilla, F, Carrasco, J, Carrillo, L, Garcia, J, Askar, A, Salinas, C, Gamba, M, Sanchez, C, Cantu, A, Sanchez, R, Madrigal, J, Urbano, R, Romo, A, Gonzalez Juanatey, J, Racugno, P, Fillat, A, de la Torre Hernandez, J, Pelaez, J, Cortada, J, Pavia, P, Navarro, M, Asenjo, R, Diaz, F, Peligero, E, Manterola, F, Ortiz, A, Mediavilla Garcia, J, Ortuno, F, Vera, T, Gonzalez, A, Vinas, J, Fernandez Portales, F, Mayordomo, P, Ojeda, F, Dominguez, A, Gonzalez, R, Guerrero, D, Ruiz Nodar, J, Marimon, X, Margaez, J, Aguilera, R, Diaz Fernandez, J, Zamorano Gomez, J, Gonzalez, V, del Blanco, B, Perez, I, Moreno, M, Ereno, A, Garcia Lledo, J, Prieto, J, Villablanca, A, Raffo, C, Pincetti, C, Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London

Subjects
Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Published
2019

117. Thyroid neoplasms: surgical and cyto-histopathological connections on a six year cases study

Author

T, Fontana, M, Izzo, P, Venturelli, V L, Lentini, N, Falco, L, Gulotta, A M, Florena, G, Cocorullo, Fontana, T, Izzo, M, Venturelli, P, Lentini, V L, Falco, N, Gulotta, L, Florena, A, and Cocorullo, G

Subjects
Adenoma, Adult, Male, Databases, Factual, Incidence, Biopsy, Fine-Needle, Middle Aged, Thyroid Diseases, Carcinoma, Papillary, Age Distribution, Adenocarcinoma, Follicular, Thyroidectomy, thyroid - Bethesda, Adenoma, Oxyphilic, Humans, Female, Thyroid Neoplasms, Thyroid Nodule, Sex Distribution, Aged, Retrospective Studies
Abstract

This study aims to evaluate the percentage of cyto-histologic correlation in patients with a thyroid disease documented through clinical-instrumental, cytological (FNAB), histological and surgical examinations. The purpose of this study is also to determine the percentage of disease incidence and evaluating any surgical indication in relation to biological behavior (benign, malignant or indeterminate lesions, occult carcinomas), sex, and age.Almost all of thyroid neoplasms is manifested through thyroid nodule. Therefore, clinical evidence of the thyroid nodule analysis is primarily related to the need to exclude malignant pathology or carcinoma of the thyroid, present in 4-6.5% of cases.The trial was conducted analyzing the data including cytological and histology thyroid reports recorded from 1 March 2010 to 1 March 2016, for a total of 5,956 reports. To determine the cyto-histological correlations, have been considered eligible all patients of both sexes, that have performed at least one cytologic exam followed by an histologic exam. Thus, the total number of the cases studied is 554 cases.Cyto-histologic compliance was 93% with a diagnostic accuracy of 4% higher than the literature examined.The results thus obtained show, furthermore, that there is a non-negligible percentage of thyroid disease with malignant biological behavior and involvement of male individuals. Therefore, the execution of the FNAB is of utmost importance for the purpose of a correct surgical indication.

Published
2018

119. The influence of prednisone on the efficacy of cabazitaxel in men with metastatic castration-resistant prostate cancer

Author

Brigitta Mucci, Livio Puglia, Sabino De Placido, Guru Sonpavde, Francesca Foschini, Carlo Buonerba, Simona Iaccarino, Ileana Di Costanzo, Giuseppe Di Lorenzo, Francesca Vitrone, Vincenzo Tortora, Vittorio Riccio, Luca Scafuri, Margherita Muratore, Dario Ribera, Davide Bosso, Mirta Mosca, Martina Pagliuca, Nicola Cesarano, Michela Izzo, Rocco Morra, Buonerba, C., Sonpavde, G., Vitrone, F., Bosso, D., Puglia, L., Izzo, M., Iaccarino, S., Scafuri, L., Muratore, M., Foschini, F., Mucci, B., Tortora, V., Pagliuca, M., Ribera, D., Riccio, V., Morra, R., Mosca, M., Cesarano, N., Di Costanzo, I., De Placido, S., and Di Lorenzo, G.

Subjects
Oncology, medicine.medical_specialty, PSA decline, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, Taxane, Cabazitaxel, business.industry, medicine.disease, Docetaxel, 030220 oncology & carcinogenesis, Concomitant, Cohort, Prednisolone, business, Research Paper, medicine.drug
Abstract

Background: Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients. Patients and methods: Medical records of deceased patients with documented mCRPC treated with cabazitaxel following prior docetaxel between January, 2011 and January, 2017 were reviewed at the single participating center. Patients who were receiving daily doses of systemic corticosteroids other than low dose daily prednisone or prednisolone (30% PSA decline at 12 weeks. Prednisone use was not significantly prognostic for overall survival or PSA decline ≥30% rates on regression analyses. Importantly, a >30% PSA decline at 12, but not at 3, 6, 9 weeks, was prognostic for improved survival at multivariate analysis Conclusions: The data presented here support the hypothesis that omitting daily corticosteroids in cabazitaxel-treated patients has no negative impact on either survival or safety profile. In the large prospective trial CABACARE, cabazitaxel-treated patients will be randomized to receive or not receive daily prednisone. The CABACARE (EudraCT n. 2016-003646-81) study is currently ongoing at University Federico II of Naples and at other multiple participating centers in Italy.

Published
2017

120. Patrimonio architettonico e infrastrutture culturali

Author

CASTAGNARO, ALESSANDRO, A.Castagnaro, F. IZZO, M. CERRETA, and Castagnaro, Alessandro

Abstract

Nel delineare e riqualificare elementi della Città Storica di Napoli in qualità di hub in una rete di valori culturali e sociali, un contributo fondamentale deriva dall’attività di ricerca e di sperimentazione legate alle istituzioni culturali, delle loro relazioni con le singole società ed enti e con un contesto esterno, intorno al quale gravita la loro fruizione. Una delle contraddizioni che caratterizzano la nostra realtà partenopea risiede in una forma di non bilanciamento fra eccellenze della cultura - con ricerche sviluppate dalle Università ed enti di ricerca, o dalle attività culturali poste in essere da associazioni - e la capacità di manifestarsi all’esterno dei luoghi in cui essa viene prodotta. Infatti, ad un elevato livello della ricerca scientifica e della cultura locale, che fa della città uno dei principali centri di prestigio del paese, corrisponde una realtà che spesso rimane chiusa in sé stessa, riuscendo con difficoltà a raggiungere l’attenzione del pubblico e della cittadinanza che, talvolta, rimane incurante o concentrata su altri obiettivi e piani. Una delle cause di questo limite potrebbe essere rintracciata nella chiusura che, talvolta, le istituzioni mostrano, oltre che verso l’esterno, anche tra loro, non potendo interfacciarsi e confrontarsi sulla base di una rete di relazioni che, nell’epoca della comunicazione, risulta essere un imperativo sempre più categorico. Tale fenomeno si avverte sia alla scala di istituzioni culturali afferenti ad ambiti disciplinari diversi, sia alla scala di realtà che si occupano di ambiti disciplinari affini e/o correlati.

Published
2016

121. PSA declines and survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

Author

Giacomo Cartenì, Sabino De Placido, Guru Sonpavde, Franco Morelli, Sabrina Rossetti, Gregory R. Pond, Giuseppe Di Lorenzo, Gaetano Facchini, Bruno Daniele, Vittorino Montanaro, Giuseppe Lucarelli, Matteo Ferro, Michela Izzo, Sarah Scagliarini, Teresa Bellelli, Carlo Buonerba, Francesca Vitrone, Livio Puglia, Davide Bosso, Martina Pagliuca, Bosso, D., Pagliuca, M., Sonpavde, G., Pond, G., Lucarelli, G., Rossetti, S., Facchini, G., Scagliarini, S., Carteni, G., Daniele, B., Morelli, F., Ferro, M., Puglia, L., Izzo, M., Montanaro, V., Bellelli, T., Vitrone, F., De Placido, S., Buonerba, C., and Di Lorenzo, G.

Subjects
Male, Oncology, medicine.medical_specialty, castration-resistant setting, Antineoplastic Agents, Hormonal, Prognosi, Severity of Illness Index, PSA, 03 medical and health sciences, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Retrospective Studie, Internal medicine, Phenylthiohydantoin, Severity of illness, Biomarkers, Tumor, medicine, Enzalutamide, 030212 general & internal medicine, Multivariate Analysi, Survival analysis, Aged, enzalutamide, Proportional hazards model, business.industry, Medical record, Retrospective cohort study, General Medicine, Prostate-Specific Antigen, prostate cancer, medicine.disease, Survival Analysis, Prostatic Neoplasms, Castration-Resistant, Prostate-specific antigen, chemistry, 030220 oncology & carcinogenesis, Proportional Hazards Model, business, Human
Abstract

Rationale PSA responses have been associated with a survival benefit in patients treated with enzalutamide in retrospective analyses. Patient concerns However the prognostic value of PSA declines in highly pretreated patients receiving enzalutamide remains to be defined. Diagnoses and interventations Medical records of patients with documented mCRPC treated with enzalutamide between September 2011 and August 2016 were reviewed at multiple participating centers and assessed for overall survival (OS), PSA variations, and other variables of interest. Univariable and multivariable analyses were conducted. Outcomes A total of 129 patients received enzalutamide. PSA response rates (>50% PSA declines) were 58/119 (48.7%), 58/115 (50.4%), 54/110 (49.1%), and 47/91 (51.7%) at weeks 4, 8, 12, and 16, respectively. Having a PSA response was a statistically significant prognostic factor of improved OS at 8 and 12 weeks in univariable analysis, whereas it was significant at 12 weeks in the multivariable analysis. Patients treated with enzalutamide had a median OS of 7.8 months. Lessons Our study supports the prognostic value of PSA declines in heavily treated patients receiving enzalutamide.

Published
2017

122. Carboplatin plus etoposide in heavily pretreated castration-resistant prostate cancer patients

Author

Tania Policastro, Piera Federico, Giuseppina Della Vittoria Scarpati, Francesco Perri, Ciro Imbimbo, Ottavio De Cobelli, Sabino De Placido, Carlo Buonerba, Michele Aieta, Davide Bosso, Nicola Longo, Michela Izzo, Matteo Ferro, Giuseppe Di Lorenzo, Livio Puglia, Buonerba, C, Federico, P, Bosso, D, Puglia, L, Policastro, T, Izzo, M, Perri, F, Vittoria Scarpati, Gd, Ferro, M, Cobelli, Od, DE PLACIDO, Sabino, Aieta, M, Imbimbo, Ciro, Longo, Nicola, and Di Lorenzo, G.

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Carboplatin, chemistry.chemical_compound, Prostate cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Enzalutamide, Humans, Neoplasm Metastasis, Etoposide, Aged, business.industry, General Medicine, Prostate-Specific Antigen, medicine.disease, Combined Modality Therapy, Prostatic Neoplasms, Castration-Resistant, Treatment Outcome, chemistry, Docetaxel, Cabazitaxel, Neoplasm Grading, business, Progressive disease, medicine.drug
Abstract

ABSTRACT: Aims: Carboplatin plus etoposide has modest efficacy in docetaxel-pretreated castration-resistant prostate cancer patients. We hypothesized that carboplatin–etoposide could still exert some therapeutic activity after docetaxel, cabazitaxel and either abiraterone or enzalutamide. Patients & methods: We enrolled 15 patients in the first step of a Phase II trial. The target sample size is 46 patients. The primary end point of the study was progression-free survival after 12 weeks. Results: The median progression-free survival was 11 weeks (range: 8–18), while median overall survival was 18 weeks (range: 12–26). Of seven patients with measurable disease, two had a partial response, two showed stable disease and the remaining three had progressive disease as the best radiological response. Five patients were considered progression-free after 12 weeks, prompting continuation of the trial. Conclusion: Our preliminary findings support the hypothesis that carboplatin plus etoposide may yield some clinical benefit in a population of patients who failed all currently approved therapeutic options for prostate cancer.

Published
2014

123. Immunofluorescence analysis of diazepam-induced mitotic apparatus anomalies and chromosome loss in Chinese hamster cells

Author

Caterina Tanzarella, Antonio Antoccia, Francesca Degrassi, Massimo Izzo, Izzo, M, Antoccia, Antonio, Degrassi, F, and Tanzarella, C.

Subjects
Health, Toxicology and Mutagenesis, Dynein, Aneuploidy, Spindle Apparatus, Toxicology, Immunofluorescence, Chromosomes, Chinese hamster, Cell Line, chemistry.chemical_compound, Cricetulus, Tubulin, Cricetinae, Genetics, medicine, Animals, Kinetochores, Mitosis, Cytochalasin B, Cells, Cultured, Genetics (clinical), Centrosome, Chromosome Aberrations, Diazepam, medicine.diagnostic_test, biology, Kinetochore, Dyneins, Phosphoproteins, biology.organism_classification, medicine.disease, Molecular biology, Cell biology, Staining, Microscopy, Fluorescence, chemistry, Anaphase, Biomarkers
Abstract

To study the mechanisms leading to diazepam (DZ)-induced chromosome loss, we evaluated the effect of the drug on the distribution of cytoplasmic and mitotic apparatus proteins using specific antibodies. The use of antibodies directed against dynein and kinetochores (CREST staining) suggested that chromosomes arranged in monopolar spindles were interacting with short fibers originating from the monopole. Interestingly, nearly 50% of DZ-induced monopolar mitoses showed a punctate staining of centrosomes when evaluated with an anti-gamma-tubulin antibody. The extent of phosphorylation of mitotic proteins was not affected by drug treatment, as shown by staining the cells with an antibody against mitotic phosphorylated proteins (MPM-2). After recovery of DZ, nearly 20% of anaphases were abnormal and mainly consisted of multipolar anaphases and lagging chromosomes; this was consistent with a high frequency of kinetochore-containing micronuclei as evaluated by CREST antibody staining in cells that had divided only once after drug removal, i.e. binucleate cells obtained by cytochalasin-B treatment. Our data confirmed that DZ is a powerful inducer of chromosome loss in cultured rodent cells. Moreover, our results indicate that DZ interfered with the correct assembly of centrosomes.

Published
1998

124. Non-AIDS-related Kaposi's sarcoma: A single-institution experience

Author

Giovannella Palmieri, Mario Delfino, Michela Izzo, Tania Policastro, Elide Matano, Piera Federico, Sabino De Placido, Davide Bosso, Giuseppe Di Lorenzo, Luca Vaccaro, Francesco Perri, Gianfranco Cimmino, Gaia De Fata, Pasquale Rescigno, Carlo Buonerba, Antonella Virtuoso, Rossella Di Trolio, Rescigno, P, Di Trolio, R, Buonerba, C, De Fata, G, Federico, P, Bosso, D, Virtuoso, A, Izzo, M, Policastro, T, Vaccaro, L, Cimmino, G, Perri, F, Matano, E, Delfino, Mario, DE PLACIDO, Sabino, Palmieri, G, and Di Lorenzo, G.

Subjects
medicine.medical_specialty, Chemotherapy, Multivariate analysis, Taxane, Brief Article, medicine.drug_class, business.industry, medicine.medical_treatment, Hazard ratio, virus diseases, medicine.disease, Gastroenterology, Surgery, Vinca alkaloid, Vinblastine, Oncology, Refractory, Internal medicine, medicine, business, Kaposi's sarcoma, medicine.drug
Abstract

To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS).Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value0.05 was considered statistically significant, and all tests were two-sided.Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133).Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.

Published
2013

125. The detection and evaluation of aneugenic chemicals

Author

James M Parry, E.M Parry, R Boumer, A Doherty, S Ellard, J O'Donovan, B Hoebee, J.M de Stoppelaar, G.R Mohn, A Önfelt, A Renglin, N Schultz, C Soderpalm-Bemdes, K.G Jensen, M Kirsch-Volders, A Elhajouji, P Van Hummelen, F Degrassi, A Antoccia, D Cimini, M Izzo, C Tanzarella, I.-D Adler, U Kliesch, G Schriever-Schwemmer, P Gasser, R Crebelli, A Carere, C Andreoli, R Benigni, P Leopardi, F Marcon, Z Zinjo, A.T Natarajan, J.J.W.A Boei, A Kappas, G Voutsinas, F.E Zarani, A Patrinelli, F Pachierotti, C Tiveron, P Hess, Parry, Jm, Parry, Em, Bourner, R, Doherty, A, Ellard, S, O'Donovan, J, Hoebee, B, de Stoppelaar, Jm, Mohn, Gr, Onfelt, A, Renglin, A, Schultz, N, Söderpalm Berndes, C, Jensen, Kg, Kirsch Volders, M, Elhajouji, A, Van Hummelen, P, Degrassi, F, Antoccia, Antonio, Cimini, D, Izzo, M, Tanzarella, C, Adler, Id, Kliesch, U, and Hess, P.

Subjects
Male, Health, Toxicology and Mutagenesis, Mitosis, Aneuploidy, Biology, Mice, Tubulin, Cricetinae, Centromere, Genetics, medicine, Animals, Humans, media_common.cataloged_instance, European union, Molecular Biology, media_common, Chromosome, medicine.disease, Rats, Cell Transformation, Neoplastic, DNA Topoisomerases, Type II, Biochemistry, Micronucleus test, Chromatid, Chromosome Deletion, Chromosome breakage, Mutagens
Abstract

Although aneuploidy makes a significant contribution to both somatic and inherited disease the mechanisms by which environmental chemicals may induce numerical chromosome aberrations are only poorly defined. The European Union Project was aimed to further our understanding of those chemical interactions with the components of the mitotic and meiotic cell division cycle which may lead to aneuploidy and to characterise the parameters such as cellular metabolism which may influence the activity of aneugenic chemicals. C-mitosis can be induced by the highly lipophilic polychlorinated biphenyl and the completion of mitosis and cleavage can be modified by agents which deplete cellular levels of reduced glutathione. Modifications of the fidelity of chromosome segregation were produced by inhibiting the functioning of topoisomerase II during chromatid separation. In contrast, the modification of centromere integrity resulted in chromosome breakage as opposed to disturbance of segregation. Modifiers of tubulin assembly and centriolar functioning in somatic cells such as acrylamide, vinblastine and diazepam reproduced their activity in rodent bone marrow and male germ cells. The analysis of chromosome malsegregation in Aspergillus nidulans by a structurally related series of halogenated hydrocarbons was used to develop a QSAR model which had high predictive value for the results of fungal tests for previously untested related chemicals. Metabolic studies of potential aneugens in genetically engineered human lymphoblastoid cells demonstrated the detoxification of the aneugenic activity of chloral hydrate and the activation of 2,3-dichlorobutane, 1,1,2-trichloroethane and trichloroethylene by Phase I biotransforming enzymes. Cell transformation studies in Syrian hamster dermal cultures using a panel of 22 reference and or potential aneugens indicated that 15 of the 22 produced positive results following single exposures. Five of the aneugens which were negative following single exposures produced positive results where cultures were continuously exposed for up to 6 weeks to low concentrations following a single non-transforming exposure to the mutagen dimethyl sulphate. The transformation studies indicate that a significant proportion of chemical aneugens are potential complete carcinogens and/or co-carcinogens. To optimise the enumeration of chromosomes following exposure to potential chemical aneugens whole chromosome paints and centromere specific probes suitable for use in fluorescence in situ hybridisation (FISH) were developed for the rat, mouse and Chinese hamster and selected human probes evaluated for their suitability for routine use. Molecular chromosome probes were used to develop protocols for enumerating chromosomes in metaphase cells and centromeres and micronuclei in interphase cells. The analysis of segregation of specific centromeres in binucleate cells following cytochalasin B treatment was shown to be a potentially valuable system for characterising non-disjunction following chemical exposure. Whole chromosome paints and centromere specific probes were used to demonstrate the presence of dose-response thresholds following treatment with a reference panel of spindle inhibiting chemicals. These data indicate that the FISH technology is suitable for evaluating the relative hazards of low-dose exposures to aneugenic chemicals.

Published
1996

126. Bi ordered phases on Cu(100): periodic arrays of dislocations influence the electronic properties

Author

Maria Grazia Izzo, Fabio Bussolotti, Maria Grazia Betti, Pierluigi Gargiani, Simona Achilli, M. I. Trioni, Gargiani, P, Izzo, M, Bussolotti, F, Betti, M, Achilli, S, and Trioni, M

Subjects
fermi level, binding energy, long-range order, bismuth, photoelectron spectra, phase separation, semimetallic thin films, band structure, ab initio calculations, periodic structures, dislocation arrays, Superstructure, Materials science, Condensed matter physics, Binding energy, Fermi level, Ab initio, General Physics and Astronomy, chemistry.chemical_element, Surface electronic propertie, Bismuth, symbols.namesake, chemistry, overlayers on metal, Phase (matter), symbols, Work function, Physical and Theoretical Chemistry, Electronic band structure, photoemission
Abstract

A single layer of bismuth deposited on the Cu(100) surface forms long range ordered structural phases at various Bi density. A highly ordered c(2 x 2) reconstruction is accomplished at 0.5 ML, further Bi deposition induces a c(9square root of 2 x square root of 2)R45 degrees structure and a subsequent p(10 x 10) phase related to the formation of regular dislocations arrays. The transition from a c(2 x 2) superstructure to the c(9square root of 2 x square root of 2)R45 degrees phase is accompanied by a sudden decrease in the work function. Photoemission measurements reveal that the Bi induced states close to the Fermi level, associated to the c(2 x 2) phase, are strongly quenched when the arrays of dislocations are formed, while at higher binding energies, they undergo an energy shift probably due to a confinement effect. The low-energy single particle excitations and the electron dispersion of the Bi induced states of the c(2 x 2) phase are compared to the electronic states deduced by theoretical band structure obtained by ab initio calculation performed within the embedding method applied to a realistic semi-infinite system.

Published
2010

127. I percorsi di Andrea Vaccaro (1604 - 1670)

Author

LATTUADA, Riccardo, Izzo, M., and Lattuada, Riccardo

Subjects
pittura, Napoli, Vaccaro, Andrea
Abstract

First modern essay devoted to one of the most important painters in Naples in the XVIIth Century

Published
2009

129. Bimodal functionality of highly conductive nanostructured silver film towards improved performance of photosystem I-based graphene photocathode.

Author

Szalkowski M, Kiliszek M, Harputlu E, Izzo M, Gokhan Unlu C, Mackowski S, Ocakoglu K, Kargul J, and Kowalska D

Abstract

We present the novel design of photosystem I (PSI)-based biosolar cell, whereby conductive transparent electrode materials, such as ITO or FTO, are replaced with glass covered with silver island film. This nanostructured metallic layer combines high electric conductance with enhancing the absorption efficiency of the PSI biocatalyst via the plasmonic effect. We demonstrate strong enhancement of the photocurrent generated in the biohybrid electrode composed of oriented layers of PSI reaction centers due to plasmonic interactions of the PSI fluorophores and redox centres with the conductive silver island film., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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130. Antimicrobial prescribing guidelines for dairy cattle.

Author

House JK, Izzo MM, Page SW, Browning GF, and Norris JM

Subjects
Cattle, Animals, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Dairying, Drug Resistance, Bacterial, Anti-Infective Agents, Cattle Diseases drug therapy, Cattle Diseases prevention & control
Published
2024
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131. Early life events associated with first lactation reproductive performance in southwest Victorian pasture-based dairy herds.

Author

Chuck GM, Mansell PD, Stevenson MA, and Izzo MM

Subjects
Humans, Pregnancy, Cattle, Animals, Female, Prospective Studies, Weight Gain, Victoria, Reproduction, Lactation
Abstract

This was a prospective cohort study to determine how events from birth until first calving affect reproductive performance in the first lactation in pasture-based dairy herds in Victoria, Australia. Events during the preweaning (0 to 84 days), weaning to first breeding (85 to 473 days) and first breeding to first calving periods (474 to 804 days) were recorded and their association with reproductive performance during the first lactation was quantified. Reproductive performance outcomes included the number of days from first mating start date to first service (MSD-S1) and the number of days from first mating start date to first conception (MSD-CON). Predictors for reproductive performance included: passive transfer status as a calf; season of birth; age and breed of the dam; breed; the presence or absence of dystocia at the time of the heifer's birth; active feeding of colostrum versus being left on the dam for colostrum intake; presence of twinning; the presence or absence of preweaning diarrhoea; preweaning, prepubertal and postpubertal average daily gain; the presence or absence of periparturient disease at first calving; age at first calving; body condition score at first calving; sex of the first-born calf; the presence or absence of a stillborn calf at the first calving and requirement of assistance at first calving. Two Cox proportional hazards regression models were developed: the first for early life event variables associated with MSD-S1 and the second for early life events associated with MSD-CON. Heifers born in autumn and winter had 2.89 (95% CI 1.50 to 5.59, P = 0.002) times and 1.97 (95% CI 1.12 to 3.44, P = 0.018) times the daily hazard of being inseminated compared with heifers born in spring, respectively. For the MSD-S1 analyses heifers that gave birth to a live calf had 1.64 (95% CI 1.14 to 2.36, P = 0.008) times the daily hazard of being inseminated compared with heifers that had a stillborn calf. Increases in weight gain during the first breeding to first calving period by 0.1 kg/day increments increased the daily hazard of first insemination by a factor of 1.10 (95% CI 1.00 to 1.22, P = 0.043). Heifers that experienced periparturient disease had a significantly lower hazard of conception per day compared with heifers that did not experience periparturient disease at the first calving (HR 0.67, 95% CI 0.50 to 0.91, P = 0.009). Increases in weight gain during the first breeding to first calving period by 0.1 kg/day increased the daily hazard of conception by a factor of 1.10 (95% CI 1.01 to 1.21, P = 0.038). We conclude that of all the growth periods assessed in this study, events that occurred during the first breeding to first calving period (474 to 804 days) had the greatest association with reproductive performance in the first lactation. There should be a focus on increasing growth rates during this period and reducing the risk of stillbirth and periparturient disease to improve reproductive performance in the subsequent mating period after calving., (© 2023 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Published
2024
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132. Risk factors for postoperative cervical haematoma in patients undergoing thyroidectomy: a retrospective, multicenter, international analysis (REDHOT study).

Author

Canu GL, Medas F, Cappellacci F, Rossi L, Gjeloshi B, Sessa L, Pennestrì F, Djafarrian R, Mavromati M, Kotsovolis G, Pliakos I, Di Filippo G, Lazzari G, Vaccaro C, Izzo M, Boi F, Brazzarola P, Feroci F, Demarchi MS, Papavramidis T, Materazzi G, Raffaelli M, and Calò PG

Abstract

Background: Postoperative cervical haematoma represents an infrequent but potentially life-threatening complication of thyroidectomy. Since this complication is uncommon, the assessment of risk factors associated with its development is challenging. The main aim of this study was to identify the risk factors for its occurrence., Methods: Patients undergoing thyroidectomy in seven high-volume thyroid surgery centers in Europe, between January 2020 and December 2022, were retrospectively analysed. Based on the onset of cervical haematoma, two groups were identified: Cervical Haematoma (CH) Group and No Cervical Haematoma (NoCH) Group. Univariate analysis was performed to compare these two groups. Moreover, employing multivariate analysis, all potential independent risk factors for the development of this complication were assessed., Results: Eight thousand eight hundred and thirty-nine patients were enrolled: 8,561 were included in NoCH Group and 278 in CH Group. Surgical revision of haemostasis was performed in 70 (25.18%) patients. The overall incidence of postoperative cervical haematoma was 3.15% (0.79% for cervical haematomas requiring surgical revision of haemostasis, and 2.35% for those managed conservatively). The timing of onset of cervical haematomas requiring surgical revision of haemostasis was within six hours after the end of the operation in 52 (74.28%) patients. Readmission was necessary in 3 (1.08%) cases. At multivariate analysis, male sex ( P  < 0.001), older age ( P  < 0.001), higher BMI ( P  = 0.021), unilateral lateral neck dissection ( P  < 0.001), drain placement ( P  = 0.007), and shorter operative times ( P  < 0.001) were found to be independent risk factors for cervical haematoma., Conclusions: Based on our findings, we believe that patients with the identified risk factors should be closely monitored in the postoperative period, particularly during the first six hours after the operation, and excluded from outpatient surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Canu, Medas, Cappellacci, Rossi, Gjeloshi, Sessa, Pennestrì, Djafarrian, Mavromati, Kotsovolis, Pliakos, Di Filippo, Lazzari, Vaccaro, Izzo, Boi, Brazzarola, Feroci, Demarchi, Papavramidis, Materazzi, Raffaelli, Calò and REDHOT Study Collaborative Group.)

Published
2023
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133. Oncological Outcomes of Patients with High-Volume mCRPC: Results from a Longitudinal Real-Life Multicenter Cohort.

Author

Ferriero M, Prata F, Anceschi U, Astore S, Bove AM, Brassetti A, Calabrò F, Chiellino S, De Nunzio C, Facchini G, Franzese E, Izzo M, Mastroianni R, Misuraca L, Naspro R, Papalia R, Pappalardo A, Tema G, Tuderti G, Turchi B, Tubaro A, and Simone G

Abstract

Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. We retrospectively collected data on mCRPC patients treated at six centers. The dataset was queried for high-volume disease (defined as more than 6 bone lesions or bulky nodes ≥ 5 cm). We compared the main clinical features of chemo-naïve versus chemo-treated patients. The Mann-Whitney U test and Chi-squared test were used to compare continuous and categorial variables, respectively. The Kaplan-Meier method was used to compare differences in terms of progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS) in an upfront ARTA or chemo-treated setting. Survival probabilities were computed at 12, 24, 48, and 60 months. Out of 216 patients, 88 cases with high-volume disease were selected. Sixty-nine patients (78.4%) received upfront ARTA, while 19 patients received chemotherapy as the first-line treatment option. Forty-eight patients received Abiraterone (AA), 21 patients received Enzalutamide (EZ) as the first-line treatment. The ARTA population was older ( p = 0.007) and less likely to receive further lines of treatment ( p = 0.001) than the chemo-treated cohort. The five-year PFS, CSS and OS were 60%, 73.3%, and 72.9%, respectively. Overall, 28 patients (31.8%) shifted after their first-line therapy to a second-line therapy: EZ was prescribed in 17 cases, AA in seven cases and radiometabolic therapy in four patients. Sixteen cases (18.2%) developed significant progression and were treated with chemotherapy. At Kaplan-Meyer analysis PFS, CSS and OS were comparable for upfront ARTA vs chemo-treated patients (log rank p = 0.10, p = 0.64 and p = 0.36, respectively). We reported comparable survival probabilities in a real-life series of high-volume mCRPC patients who either received upfront ARTA or chemotherapy. Patients primarily treated with chemotherapy were younger and more likely to receive further treatment lines than the upfront ARTA cohort. Our data support the use of novel antiandrogens as first line treatment regardless tumor burden, delaying the beginning of a more toxic chemotherapy in case of significant disease progression.

Published
2023
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134. Vertebral osteomyelitis due to Lactobacillus paracasei in a diabetic patient. A case report and literature review.

Author

Carrega G, Ricciardi B, Bartolacci V, Brenci S, Izzo M, Morelli P, Tigano S, and Riccio G

Abstract

Staphylococci are the most frequent cause of vertebral osteomyelitis, but infections due to unusual pathogens are also reported. We describe a rare case of spondylodiscitis due to Lactobacillus paracasei . A 74-year-old diabetic male was evaluated for fever and back pain. Blood cultures and vertebral biopsy were positive for Lactobacillus paracasei . He often took laxatives and probiotics for chronic constipation. After target treatment the patient improved but he died for a heart attack two months after the end of the treatment. Although Lactobacillus paracasei is usually not pathogenic, sepsis is described in immunocompromised patients while vertebral osteomyelitis is rare., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest regarding the publication of this paper.

Published
2023
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135. Design of an Herbal Preparation Composed by a Combination of Ruscus aculeatus L. and Vitis vinifera L. Extracts, Magnolol and Diosmetin to Address Chronic Venous Diseases through an Anti-Inflammatory Effect and AP-1 Modulation.

Author

Nocera R, Eletto D, Santoro V, Parisi V, Bellone ML, Izzo M, Tosco A, Dal Piaz F, Donadio G, and De Tommasi N

Abstract

Chronic venous disease (CVD) is an often underestimated inflammatory pathological condition that can have a serious impact on quality of life. Many therapies have been proposed to deal with CVD, but unfortunately the symptoms recur with increasing frequency and intensity as soon as treatments are stopped. Previous studies have shown that the common inflammatory transcription factor AP-1 (activator protein-1) and nuclear factor kappa-activated B-cell light chain enhancer (NF-kB) play key roles in the initiation and progression of this vascular dysfunction. The aim of this research was to develop a herbal product that acts simultaneously on different aspects of CVD-related inflammation. Based on the evidence that several natural components of plant origin are used to treat venous insufficiency and that magnolol has been suggested as a putative modulator of AP-1, two herbal preparations based on Ruscus aculeatus root extracts, and Vitis vinifera seed extracts, as well as diosmetin and magnolol, were established. A preliminary MTT-based evaluation of the possible cytotoxic effects of these preparations led to the selection of one of them, named DMRV-2, for further investigation. First, the anti-inflammatory efficacy of DMRV-2 was demonstrated by monitoring its ability to reduce cytokine secretion from endothelial cells subjected to LPS-induced inflammation. Furthermore, using a real-time PCR-based protocol, the effect of DMRV-2 on AP-1 expression and activity was also evaluated; the results obtained demonstrated that the incubation of the endothelial cells with this preparation almost completely nullified the effects exerted by the treatment with LPS on AP-1. Similar results were also obtained for NF-kB, whose activation was evaluated by monitoring its distribution between the cytosol and the nucleus of endothelial cells after the different treatments.

Published
2023
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136. Increased Levels of Circulating Iron-Albumin Complexes in Peripheral Arterial Disease Patients.

Author

Schiano E, Cappello E, Cecere D, Pompeo F, Novellino E, Stornaiuolo M, and Izzo M

Abstract

Under physiological conditions, extracellular iron circulates in the blood bound to transferrin. As a consequence of several pathologies, the circulating level of a Non-Transferrin Bound pool of Iron (NTBI) increases. The NTBI pool is biologically heterogeneous and represented by iron chelated either by small metabolites (citrate, amino acids, or cofactors) or by serum proteins. By promoting reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation, NTBI causes oxidative stress and alteration of membrane lipids, seriously compromising the healthy state of organs and tissues. While NTBI involvement in several pathologies has been clarified, its contribution to vascular diseases remains to be investigated. Here we measure and analyze the pool of NTBI in the serum of a small group of peripheral arterial disease (PAD) patients. We show that: (i) the NTBI pool shifts from low molecular complexes to high-molecular ones in PAD patients compared to healthy controls; (ii) most of this NTBI is bound to the serum protein Albumin; (iii) this NTBI-Albumin complex can be isolated and quantitated following a simple immunoisolation procedure amenable to automation and suitable for clinical screening purposes.

Published
2023
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137. Management of systemic prostate cancer: current algorithm from castration sensitive to castration resistant setting.

Author

D'Aniello C, Cavaliere C, Foglia C, Facchini S, Uricchio F, Balsamo R, Franzese E, De Falco S, Izzo M, Laterza M, Liguori C, Coppola P, Diessa Y, Fasano M, Di Lauro G, Lai S, Cocetta V, Pisconti S, Montesarchio V, and Facchini G

Subjects
Male, Humans, Immunotherapy, Algorithms, Knowledge, Castration, Prostatic Neoplasms drug therapy, Prostatic Neoplasms surgery
Abstract

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Published
2022
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138. Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.

Author

Izzo M, Battistini J, Provenzano C, Martelli F, Cardinali B, and Falcone G

Subjects
Gene Editing, Humans, Myotonin-Protein Kinase genetics, Myotonin-Protein Kinase metabolism, Trinucleotide Repeat Expansion genetics, Myotonic Dystrophy drug therapy, Myotonic Dystrophy genetics
Abstract

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy affecting many different body tissues, predominantly skeletal and cardiac muscles and the central nervous system. The expansion of CTG repeats in the DM1 protein-kinase ( DMPK ) gene is the genetic cause of the disease. The pathogenetic mechanisms are mainly mediated by the production of a toxic expanded CUG transcript from the DMPK gene. With the availability of new knowledge, disease models, and technical tools, much progress has been made in the discovery of altered pathways and in the potential of therapeutic intervention, making the path to the clinic a closer reality. In this review, we describe and discuss the molecular therapeutic strategies for DM1, which are designed to directly target the CTG genomic tract, the expanded CUG transcript or downstream signaling molecules.

Published
2022
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139. Interactions among 17 respiratory pathogens: a cross-sectional study using clinical and community surveillance data.

Author

Burstein R, Althouse BM, Adler A, Akullian A, Brandstetter E, Cho S, Emanuels A, Fay K, Gamboa L, Han P, Huden K, Ilcisin M, Izzo M, Jackson ML, Kim AE, Kimball L, Lacombe K, Lee J, Logue JK, Rogers J, Chung E, Sibley TR, Van Raay K, Wenger E, Wolf CR, Boeckh M, Chu H, Duchin J, Rieder M, Shendure J, Starita LM, Viboud C, Bedford T, Englund JA, and Famulare M

Abstract

Background: Co-circulating respiratory pathogens can interfere with or promote each other, leading to important effects on disease epidemiology. Estimating the magnitude of pathogen-pathogen interactions from clinical specimens is challenging because sampling from symptomatic individuals can create biased estimates., Methods: We conducted an observational, cross-sectional study using samples collected by the Seattle Flu Study between 11 November 2018 and 20 August 2021. Samples that tested positive via RT-qPCR for at least one of 17 potential respiratory pathogens were included in this study. Semi-quantitative cycle threshold (Ct) values were used to measure pathogen load. Differences in pathogen load between monoinfected and coinfected samples were assessed using linear regression adjusting for age, season, and recruitment channel., Results: 21,686 samples were positive for at least one potential pathogen. Most prevalent were rhinovirus (33·5%), Streptococcus pneumoniae ( SPn , 29·0%), SARS-CoV-2 (13.8%) and influenza A/H1N1 (9·6%). 140 potential pathogen pairs were included for analysis, and 56 (40%) pairs yielded significant Ct differences (p < 0.01) between monoinfected and co-infected samples. We observed no virus-virus pairs showing evidence of significant facilitating interactions, and found significant viral load decrease among 37 of 108 (34%) assessed pairs. Samples positive with SPn and a virus were consistently associated with increased SPn load., Conclusions: Viral load data can be used to overcome sampling bias in studies of pathogen-pathogen interactions. When applied to respiratory pathogens, we found evidence of viral- SPn facilitation and several examples of viral-viral interference. Multipathogen surveillance is a cost-efficient data collection approach, with added clinical and epidemiological informational value over single-pathogen testing, but requires careful analysis to mitigate selection bias.

Published
2022
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140. New Insights from Metabolomics in Pediatric Renal Diseases.

Author

Riccio S, Valentino MS, Passaro AP, Izzo M, Guarino S, Miraglia Del Giudice E, Marzuillo P, and Di Sessa A

Abstract

Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of 'new' biomarkers to the 'old' group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.

Published
2022
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141. Participatory Design and Process Testing to Optimize Utility, Usability, and Acceptability of a Mobile Game for Promoting Evidence-Driven Public Health Decision-Making in Resource-Constrained Settings.

Author

Sinnatwah JD Jr, Kenneh H, Coker AA, Harmon-Gray WM, Zankah J, Day L, Hubbell E, Murphy MJ, Izzo M, Kong D, Sylwester P, Long Q, Bertozzi E, and Skrip LA

Abstract

Innovative game-based training methods that leverage the ubiquity of cellphones and familiarity with phone-based interfaces have the potential to transform the training of public health practitioners in low-income countries such as Liberia. This article describes the design, development, and testing of a prototype of the Figure It Out mobile game. The prototype game uses a disease outbreak scenario to promote evidence-based decision-making in determining the causative agent and prescribing intervention measures to minimize epidemiological and logistical burdens in resource-limited settings. An initial prototype of the game developed by the US team was playtested and evaluated by focus groups with 20 University of Liberia Masters of Public Health (UL MPH) students. Results demonstrate that the learning objectives-improving search skills for identifying scientific evidence and considering evidence before decision-making during a public health emergency-were considered relevant and important in a setting that has repeatedly and recently experienced severe threats to public health. However, some of the game mechanics that were thought to enhance engagement such as trial-and-error and choose-your-own-path gameplay, were perceived by the target audience as distracting or too time-consuming, particularly in the context of a realistic emergency scenario. Gameplay metrics that mimicked real-world situations around lives lost, money spent, and time constraints during public health outbreaks were identified as relatable and necessary considerations. Our findings reflect cultural differences between the game development team and end users that have emphasized the need for end users to have an integral part of the design team; this formative evaluation has critically informed next steps in the iterative development process. Our multidisciplinary, cross-cultural and cross-national design team will be guided by Liberia-based public health students and faculty, as well as community members who represent our end user population in terms of experience and needs. These stakeholders will make key decisions regarding game objectives and mechanics, to be vetted and implemented by game design experts, epidemiologists, and software developers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sinnatwah, Kenneh, Coker, Harmon-Gray, Zankah, Day, Hubbell, Murphy, Izzo, Kong, Sylwester, Long, Bertozzi and Skrip.)

Published
2022
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142. Time-controlled and muscle-specific CRISPR/Cas9-mediated deletion of CTG-repeat expansion in the DMPK gene.

Author

Cardinali B, Provenzano C, Izzo M, Voellenkle C, Battistini J, Strimpakos G, Golini E, Mandillo S, Scavizzi F, Raspa M, Perfetti A, Baci D, Lazarevic D, Garcia-Manteiga JM, Gourdon G, Martelli F, and Falcone G

Abstract

CRISPR/Cas9-mediated therapeutic gene editing is a promising technology for durable treatment of incurable monogenic diseases such as myotonic dystrophies. Gene-editing approaches have been recently applied to in vitro and in vivo models of myotonic dystrophy type 1 (DM1) to delete the pathogenic CTG-repeat expansion located in the 3' untranslated region of the DMPK gene. In DM1-patient-derived cells removal of the expanded repeats induced beneficial effects on major hallmarks of the disease with reduction in DMPK transcript-containing ribonuclear foci and reversal of aberrant splicing patterns. Here, we set out to excise the triplet expansion in a time-restricted and cell-specific fashion to minimize the potential occurrence of unintended events in off-target genomic loci and select for the target cell type. To this aim, we employed either a ubiquitous promoter-driven or a muscle-specific promoter-driven Cas9 nuclease and tetracycline repressor-based guide RNAs. A dual-vector approach was used to deliver the CRISPR/Cas9 components into DM1 patient-derived cells and in skeletal muscle of a DM1 mouse model. In this way, we obtained efficient and inducible gene editing both in proliferating cells and differentiated post-mitotic myocytes in vitro as well as in skeletal muscle tissue in vivo ., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Published
2021
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143. ISA API: An open platform for interoperable life science experimental metadata.

Author

Johnson D, Batista D, Cochrane K, Davey RP, Etuk A, Gonzalez-Beltran A, Haug K, Izzo M, Larralde M, Lawson TN, Minotto A, Moreno P, Nainala VC, O'Donovan C, Pireddu L, Roger P, Shaw F, Steinbeck C, Weber RJM, Sansone SA, and Rocca-Serra P

Subjects
Databases, Factual, Software, Biological Science Disciplines, Metadata
Abstract

Background: The Investigation/Study/Assay (ISA) Metadata Framework is an established and widely used set of open source community specifications and software tools for enabling discovery, exchange, and publication of metadata from experiments in the life sciences. The original ISA software suite provided a set of user-facing Java tools for creating and manipulating the information structured in ISA-Tab-a now widely used tabular format. To make the ISA framework more accessible to machines and enable programmatic manipulation of experiment metadata, the JSON serialization ISA-JSON was developed., Results: In this work, we present the ISA API, a Python library for the creation, editing, parsing, and validating of ISA-Tab and ISA-JSON formats by using a common data model engineered as Python object classes. We describe the ISA API feature set, early adopters, and its growing user community., Conclusions: The ISA API provides users with rich programmatic metadata-handling functionality to support automation, a common interface, and an interoperable medium between the 2 ISA formats, as well as with other life science data formats required for depositing data in public databases., (© The Author(s) 2021. Published by Oxford University Press GigaScience.)

Published
2021
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144. Development of a Novel Nanoarchitecture of the Robust Photosystem I from a Volcanic Microalga Cyanidioschyzon merolae on Single Layer Graphene for Improved Photocurrent Generation.

Author

Izzo M, Jacquet M, Fujiwara T, Harputlu E, Mazur R, Wróbel P, Góral T, Unlu CG, Ocakoglu K, Miyagishima S, and Kargul J

Subjects
Light, Oxidation-Reduction drug effects, Rhodophyta chemistry, Signal Transduction drug effects, Graphite chemistry, Microalgae chemistry, Nanostructures chemistry, Photosystem I Protein Complex chemistry
Abstract

Here, we report the development of a novel photoactive biomolecular nanoarchitecture based on the genetically engineered extremophilic photosystem I (PSI) biophotocatalyst interfaced with a single layer graphene via pyrene-nitrilotriacetic acid self-assembled monolayer (SAM). For the oriented and stable immobilization of the PSI biophotocatalyst, an His 6 -tag was genetically engineered at the N -terminus of the stromal PsaD subunit of PSI, allowing for the preferential binding of this photoactive complex with its reducing side towards the graphene monolayer. This approach yielded a novel robust and ordered nanoarchitecture designed to generate an efficient direct electron transfer pathway between graphene, the metal redox center in the organic SAM and the photo-oxidized PSI biocatalyst. The nanosystem yielded an overall current output of 16.5 µA·cm -2 for the nickel- and 17.3 µA·cm -2 for the cobalt-based nanoassemblies, and was stable for at least 1 h of continuous standard illumination. The novel green nanosystem described in this work carries the high potential for future applications due to its robustness, highly ordered and simple architecture characterized by the high biophotocatalyst loading as well as simplicity of manufacturing.

Published
2021
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145. Enhancement of direct electron transfer in graphene bioelectrodes containing novel cytochrome c 553 variants with optimized heme orientation.

Author

Izzo M, Osella S, Jacquet M, Kiliszek M, Harputlu E, Starkowska A, Łasica A, Unlu CG, Uśpieński T, Niewiadomski P, Bartosik D, Trzaskowski B, Ocakoglu K, and Kargul J

Subjects
Amino Acid Sequence, Electrodes, Electron Transport, Cytochrome c Group chemistry, Cytochrome c Group genetics, Graphite chemistry, Heme, Mutation
Abstract

The highly efficient bioelectrodes based on single layer graphene (SLG) functionalized with pyrene self-assembled monolayer and novel cytochromec 553 (cytc 553 )peptide linker variants were rationally designed to optimize the direct electron transfer (DET) between SLG and the heme group of cyt. Through a combination of photoelectrochemical and quantum mechanical (QM/MM) approaches we show that the specific amino acid sequence of a short peptide genetically inserted between the cytc 553 holoprotein and thesurface anchoring C-terminal His 6 -tag plays a crucial role in ensuring the optimal orientation and distance of the heme group with respect to the SLG surface. Consequently, efficient DET occurring between graphene and cyt c 553 leads to a 20-fold enhancement of the cathodic photocurrent output compared to the previously reported devices of a similar type. The QM/MM modeling implies that a perpendicular or parallel orientation of the heme group with respect to the SLG surface is detrimental to DET, whereas the tilted orientation favors the cathodic photocurrent generation. Our work confirms the possibility of fine-tuning the electronic communication within complex bio-organic nanoarchitectures and interfaces due to optimization of the tilt angle of the heme group, its distance from the SLG surface and optimal HOMO/LUMO levels of the interacting redox centers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
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146. Development of a universal conductive platform for anchoring photo- and electroactive proteins using organometallic terpyridine molecular wires.

Author

Jacquet M, Izzo M, Osella S, Kozdra S, Michałowski PP, Gołowicz D, Kazimierczuk K, Gorzkowski MT, Lewera A, Teodorczyk M, Trzaskowski B, Jurczakowski R, Gryko DT, and Kargul J

Subjects
Electrochemistry, Electrodes, Electron Transport, Oxidation-Reduction, Biosensing Techniques
Abstract

The construction of an efficient conductive interface between electrodes and electroactive proteins is a major challenge in the biosensor and bioelectrochemistry fields to achieve the desired nanodevice performance. Concomitantly, metallo-organic terpyridine wires have been extensively studied for their great ability to mediate electron transfer over a long-range distance. In this study, we report a novel stepwise bottom-up approach for assembling bioelectrodes based on a genetically modified model electroactive protein, cytochrome c553 (cyt c553) and an organometallic terpyridine (TPY) molecular wire self-assembled monolayer (SAM). Efficient anchoring of the TPY derivative (TPY-PO(OH)2) onto the ITO surface was achieved by optimising solvent composition. Uniform surface coverage with the electroactive protein was achieved by binding the cyt c553 molecules via the C-terminal His6-tag to the modified TPY macromolecules containing Earth abundant metallic redox centres. Photoelectrochemical characterisation demonstrates the crucial importance of the metal redox centre for the determination of the desired electron transfer properties between cyt and the ITO electrode. Even without the cyt protein, the ITO-TPY nanosystem reported here generates photocurrents whose densities are 2-fold higher that those reported earlier for ITO electrodes functionalised with the photoactive proteins such as photosystem I in the presence of an external mediator, and 30-fold higher than that of the pristine ITO. The universal chemical platform for anchoring and nanostructuring of (photo)electroactive proteins reported in this study provides a major advancement for the construction of efficient (bio)molecular systems requiring a high degree of precise supramolecular organisation as well as efficient charge transfer between (photo)redox-active molecular components and various types of electrode materials.

Published
2021
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147. Molecular mechanism of direct electron transfer in the robust cytochrome-functionalised graphene nanosystem.

Author

Jacquet M, Kiliszek M, Osella S, Izzo M, Sar J, Harputlu E, Unlu CG, Trzaskowski B, Ocakoglu K, and Kargul J

Abstract

Construction of green nanodevices characterised by excellent long-term performance remains high priority in biotechnology and medicine. Tight electronic coupling of proteins to electrodes is essential for efficient direct electron transfer (DET) across the bio-organic interface. Rational modulation of this coupling depends on in-depth understanding of the intricate properties of interfacial DET. Here, we dissect the molecular mechanism of DET in a hybrid nanodevice in which a model electroactive protein, cytochrome c 553 (cyt c 553 whose kinetics and directionality depends on the metal incorporated into the bio-organic interface: Co enhances the cathodic current from SLG to haem, whereas Ni exerts the opposite effect. QM/MM simulations yield the mechanistic model of interfacial DET based on either tunnelling or hopping of electrons between graphene, pyr-NTA-M via the conductive self-assembled monolayer (SAM) formed by pyrene-nitrilotriacetic acid (pyr-NTA) molecules chelated to transition metal redox centers. We demonstrate that efficient DET occurs between graphene and cyt c 553 whose kinetics and directionality depends on the metal incorporated into the bio-organic interface: Co enhances the cathodic current from SLG to haem, whereas Ni exerts the opposite effect. QM/MM simulations yield the mechanistic model of interfacial DET based on either tunnelling or hopping of electrons between graphene, pyr-NTA-M 2+ SAM and cyt c 553 depending on the metal in SAM. Considerably different electronic configurations were identified for the interfacial metal redox centers: a closed-shell system for Ni and a radical system for the Co with altered occupancy of HOMO/LUMO levels. The feasibility of fine-tuning the electronic properties of the bio-molecular SAM upon incorporation of various metal centers paves the way for the rational design of the optimal molecular interface between abiotic and biotic components of the viable green hybrid devices, e.g. solar cells, optoelectronic nanosystems and solar-to-fuel assemblies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Published
2021
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148. Vitamin D: Not Just Bone Metabolism but a Key Player in Cardiovascular Diseases.

Author

Izzo M, Carrizzo A, Izzo C, Cappello E, Cecere D, Ciccarelli M, Iannece P, Damato A, Vecchione C, and Pompeo F

Abstract

Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.

Published
2021
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149. Spontaneous movements in the newborns: a tool of quantitative video analysis of preterm babies.

Author

Tacchino C, Impagliazzo M, Maggi E, Bertamino M, Blanchi I, Campone F, Durand P, Fato M, Giannoni P, Iandolo R, Izzo M, Morasso P, Moretti P, Ramenghi L, Shima K, Shimatani K, Tsuji T, Uccella S, Zanardi N, and Casadio M

Subjects
Child, Humans, Infant, Infant, Newborn, Infant, Premature, Movement
Abstract

Background and Objectives: The number of preterm babies is steadily growing world-wide and these neonates are at risk of neuro-motor-cognitive deficits. The observation of spontaneous movements in the first three months of age is known to predict such risk. However, the analysis by specifically trained physiotherapists is not suited for the clinical routine, motivating the development of simple computerized video analysis systems, integrated with a well-structured Biobank to make available for preterm babies a growing service with diagnostic, prognostic and epidemiological purposes., Methods: MIMAS (Markerless Infant Movement Analysis System) is a simple, low-cost system of video analysis of spontaneous movements of newborns in their natural environment, based on a single standard RGB camera, without markers attached to the body. The original videos are transformed into binarized sequences highlighting the silhouette of the baby, in order to minimize the illumination effects and increase the robustness of the analysis; such sequences are then coded by a large set of parameters (39) related to the spatial and spectral changes of the silhouette. The parameter vectors of each baby were stored in the Biobank together with related clinical information., Results: The preliminary test of the system was carried out at the Gaslini Pediatric Hospital in Genoa, where 46 preterm (PT) and 21 full-term (FT) babies (as controls) were recorded at birth (T0) and 8-12 weeks thereafter (T1). A simple statistical analysis of the data showed that the coded parameters are sensitive to the degree of maturation of the newborns (comparing T0 with T1, for both PT and FT babies), and to the conditions at birth (PT vs. FT at T0), whereas this difference tends to vanish at T1. Moreover, the coding method seems also able to detect the few 'abnormal' preterm babies in the PT populations that were analyzed as specific case studies., Conclusions: Preliminary results motivate the adoption of this tool in clinical practice allowing for a systematic accumulation of cases in the Biobank, thus for improving the accuracy of data analysis performed by MIMAS and ultimately allowing the adoption of data mining techniques., Competing Interests: Declaration of Competing Interest Authors have no competing interests to declare., (Copyright © 2020. Published by Elsevier B.V.)

Published
2021
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150. Study on the Therapeutic Efficacy of a Polyphitho Therapeutic Compound in Primary and Secondary Lymphedema.

Author

Michelini S, Gasbarro V, Izzo M, and Albergati FG

Subjects
Chronic Disease, Humans, Pain, Upper Extremity, Lymphedema, Quality of Life
Abstract

The role of the interstitial matrix in regulating exchanges and interactions at the level of the microvascular units, between the corpuscular component and the vascular and nerve structures, has long been known. Equally known are the objective and subjective clinical manifestations that these pathologies trigger in the patient, both in primary and secondary forms: embarrassment, asthenia, alterations of exteroceptive and proprioceptive sensitivity, pain, reduced capacity, and functional autonomy, affecting both the lower and the upper limbs. The authors studied 136 patients with I and II clinical stage lymphedema according to the International Society of Lymphology stadiation. Patients were treated with Lymdiaral, 20 drops three times a day for 90 consecutive days. The following parameters were examined in basal conditions and after treatment: ultrasound measurement of suprafascial thickness, short form healthy survey version 12 (SF12), body mass index, and limb circumferences in specific points of reference. The results demonstrate the effectiveness of the therapeutic principle both in the reduction of limb circumferences and in the improvement of the parameters related to the quality of life expressed by the SF12 items. There were no substantial differences in the results between primary and secondary forms.

Published
2021
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