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1. Cardiopoietic cell therapy for advanced ischemic heart failure : results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Author

Bartunek, Jozef, Terzic, Andre, Davison, Beth A, Filippatos, Gerasimos S, Radovanovic, Slavica, Beleslin, Branko, Merkely, Bela, Musialek, Piotr, Wojakowski, Wojciech, Andreka, Peter, Horvath, Ivan G, Katz, Amos, Dolatabadi, Dariouch, El Nakadi, Badih, Arandjelovic, Aleksandra, Edes, Istvan, Seferovic, Petar M, Obradovic, Slobodan, Vanderheyden, Marc, Jagic, Nikola, Petrov, Ivo, Atar, Shaul, Halabi, Majdi, Gelev, Valeri L, Shochat, Michael K, Kasprzak, Jaroslaw D, Sanz Ruiz, Ricardo, Heyndrickx, Guy R, Nyolczas, Noémi, Legrand, Victor, Guédès, Antoine, Heyse, Alex, Moccetti, Tiziano, Fernandez Aviles, Francisco, Jimenez Quevedo, Pilar, Bayes Genis, Antoni, Hernandez Garcia, Jose Maria, Ribichini, Flavio, Gruchala, Marcin, Waldman, Scott A, Teerlink, John R, Gersh, Bernard J, Povsic, Thomas J, Henry, Timothy D, Metra, Marco, Hajjar, Roger J, Tendera, Michal, Behfar, Atta, Alexandre, Bertrand, Seron, Aymeric, Stough, Wendy Gattis, Sherman, Warren, Cotter, Gad, Wijns, W. i. l. l. i. a. m. Collaborators Clinical investigators, Dens, sites Belgium: Ziekenhuis Oost Limburg: J., Dupont, M., Mullens, W., Janssens, M., Dolatabadi, Hoˆpital Civil de Charleroi: D., De Bruyne, Y., Lalmand, J., Dubois, P., El Nakadi, B., Aminian, A., De Vuyst, E., Gurnet, P., Gujic, M., Blankoff, I., Guedes, CHU Mont Godinne UCL: A., Gabriel, L., Seldrum, S., Doyen, C., Andre´, M., Heyse, AZ Glorieux: A., Van Durme, F., Verschuere, J., Legrand, Domaine Universitaire du Sart Tilman: V., Gach, O., D’Orio, V., Davin, L., Lancellotti, P., Baudoux, E., Ancion, A., Dulgheru, R., Vanderheyden, OLV Ziekenhuis Aalst – Cardiologie: M., Bartunek, J., Wijns, W., Verstreken, S., Penicka, . M., Gelev, P. Meeus Bulgaria: Tokuda Hospital Sofia: V., Zheleva Kichukova, I., Parapunova, R., Melamed, R., Sardovski, S., Radev, O., Yordanov, A., Radinov, A., Nenov, D., Amine, I., Petrov, City Hospital Clinic Cardiology Center: I., Kichukov, K., Nikitasov, L., Stankov, Z., Stoyanov, H., Tasheva Dimitrova, I., Angelova, M., Dimitrov, E., Minchev, M., Garvanski, I., Botev, C., Polomski, P., Alexandrovska University Hospital, Vassilev, Sofia: D., Karamfiloff, K., Tarnovska Kadreva, R., Vladimirova, L., Dimitrov, G., Hadzhiev, E., Tzvetkova, G., Andreka, . M. Atanasova Hungary: Gottsegen Gyo¨ rgy Orszagos Kardiologiai Inte´zet: P., Fontos, G., Fabian, J., Csepregi, A., Uzonyi, G., Gelei, A., Edes, Debreceni Egyetem Orvos e´s Ege´szse´gtudomanyi Centrum Altalanos Orvostudomanyi Kar Kardiologia Inte´zet: I., Balogh, L., Vajda, G., Darago, A., Gergely, S., Fulop, T., Jenei, C., Horvath, Pe´csi Tudomanyegyetem Klinikai Ko¨zpont Szıvgyogyaszati Klinika: I., Magyari, B., Nagy, A., Cziraki, A., Faludi, R., Kittka, B., Alizadeh, H., Merkely, Semmelweis Egyetem Varosmajori Szıv e´s Ergyogyaszati Klinika: B., Geller, L., Farkas, P., Szombath, G., Foldes, G., Skopal, J., Kovacs, A., Kosztin, A., Gara, E., Sydo, N., Nyolczas, MH Ege´szse´gu¨gyi Ko¨zpont Kardiologiai Osztaly: N., Kerecsen, G., Korda, A., Kiss, . M., Borsanyi, T., Polgar, B., Muk, B., Sharif, Z. Bari Ireland: HRB Clinical Research Facility: F., Atar, Y. M. Smyth Israel:Western Galilee Hospital: S., Shturman, A., Akria, L., Kilimnik, M., Brezins, M., Halabi, Ziv Medical Center: M., Dally, N., Goldberg, A., Aehab, K., Rosenfeld, I., Levinas, T., Saleem, D., Katz, Barzilai Medical Center: A., Plaev, T., Drogenikov, T., Nemetz, A., Barshay, Y., Jafari, J., Orlov, I., Nazareth Hospital EMMS: M. Omory, N. Kogan Nielsen, Shochat, Hillel Yaffe Medical Center: M., Shotan, A., Frimerman, A., Meisel, S., Asif, A., Sofer, O., Blondheim, D. S., Vazan, A., Metra, L. Arobov Italy: A. O. Spedali Civili di Brescia: M., Bonadei, I., Inama, L., Chiari, E., Lombardi, C., Magatelli, M., Russo, D., Lazzarini, V., Carubelli, V., Vassanelli, AOUI Verona – Borgo Trento Hospital: C., Ribichini, Flavio Luciano, Bergamini, C., Krampera, Mauro, Cicoria, M. A., Zanolla, L., Dalla Mura, D., Gambaro, A., Rossi, A., Pesarini Poland: Jagiellonian University Department of Cardiac, G., Musialek, Vascular Diseases at John Paul II Hospital in Krakow: P., Mazurek, A., Drabik, L., Ka˛dzielski, A., Walter, Z., Dzieciuch Rojek, M., Rubis, P., Plazak, . W., Tekieli, L., Podolec, J., Orczyk, W., Sutor, U., Zmudka, K., Olszowska, M., Podolec, P., Gruchala, Uniwersyteckie Centrum Kliniczne: M., Ciecwierz, D., Mielczarek, M., Burakowski, S., Chmielecki, M., Zielinska, M., Frankiewicz, A., Wdowczyk, J., Stopczynska, I., Bellwon, J., Mosakowska, K., Nadolna, R., Wroblewska, J., Rozmyslowska, M., Rynkiewicz, M., Marciniak, I., Raczak, G., Tarnawska, M., Taszner, M., Kasprzak, Bieganski Hospital: J., Plewka, M., Fiutowska, D., Rechcinski, T., Lipiec, P., Sobczak, M., Weijner Mik, P., Wraga, M., Krecki, R., Markiewicz, M., Haval Qawoq, D., Wojakowski, Gornosla˛skie Centrum Medyczne Sla˛skie j. Akademii Medycznej: W., Ciosek, J., Dworowy, S., Gaszewska Zurek, E., Ochala, A., Cybulski, W., Jadczyk, T., Wanha, W., Parma, Z., Kozlowski, M., Dzierzak, M., Markiewicz Serbia: Clinical Hospital Center Zvezdara, M., Arandjelovic, Cardiology Clinic: A., Sekularac, N., Boljevic, D., Bogdanovic, A., Zivkovic, S., Cvetinovic, N., Loncar, G., Clinical Centre of Serbia, Beleslin, Cardiology Clinic: B., Nedeljkovic, M., Trifunovic, D., Giga, V., Banovic, M., Nedeljkovic, I., Stepanovic, J., Vukcevic, V., Djordjevic Dikic, A., Dobric, M., Obrenovic Kircanski, B., Seferovic, Cardiology Clinic: P., Orlic, D., Tesic, M., Petrovic, O., Milinkovic, I., Simeunovic, D., Jagic, Clinical Center of Kragujevac: N., Tasic, M., Nikolic, D., Miloradovic, V., Djurdjevic, P., Sreckovic, M., Zornic, N., Clinical Hospital Center Bezanijska Kosa, Radovanovic, Cardiology Department: S., Saric, J., Hinic, S., Djokovic, A., Ðordevic, S., Bisenic, V., Markovic, O., Stamenkovic, S., Malenkovic, V., Tresnjak, J., Misic, G., Cotra, D., Tomovic, L., Vuckovic, V., Clinic of Emergency Internal Medicine, Obradovic, Military Medical Academy: S., Jovic, Z., Vukotic, S., Markovic, D., Djenic, N., Ristic Andjelkov, A., Bayes Genis, D. Ljubinka Spain: Hospital Universitario Germans Trias I. Pujol: A., Rodriguez Leor, O., Labata, C., Vallejo, N., Ferrer, E., Batlle, M., Fernandez Aviles, Hospital General Universitario Gregorio Mara~non: F., Sanz Ruiz, R., Casado, A., Loughlin, G., Zatarain, E., Anguita, J., Ferna ndez Santos, M. E., Pascual, C., Bermejo, J., Hernandez Garcia, Hospital Clinico Universitario Virgen de la Victoria: J. M., Jimenez Navarro, M., Dominguez, A., Carrasco, F., Mu~noz, A., Garcia Pinilla, J. M., Ruiz, J., Queipo de Llano, M. P., Hernandez, A., Fernandez, A., Jimenez Quevedo, Hospital Clinico San Carlos: P., Guerra, R., Biagioni, C., Gonzalez, R. A., Gomez deDiego, J. J., Mansson Broberg, L. Perez de Isla Sweden: Karolinska University Hospital: A., Sylve´n, C., Leblanc, K., Winter, R., Blomberg, P., Gunyeli, E., Ruck, A., Silva, C., Fo¨rstedt Switzerland: CardioCentro Ticino, J., Moccetti, Switzerland: T., Rossi, M., Pasotti, E., Petrova, I., Crljenica, C., Monti, C., Murzilli, R., Su¨rder, D., Moccetti, M., Turchetto, L., Locicero, V., Chiumiento, L., Maspoli, S., Mombelli, M., Anesini, A., Biggiogero, M., Ponti, G., Camporini, C., Polledri, S., Hill, G. Dolci United Kingdom: Kings College Hospital: J., Plymen, C., Amin Youssef, G., Mcdonagh, T., Drasar, E., Mijovic, A., Jouhra, F., Mcloman, D., Dworakowski, R., Webb, I., Byrne, J., and Potter, V.

Subjects
0301 basic medicine, Male, Cardiopoiesis, Cardiovascular disease, Disease severity, Marker, Precision medicine, Regenerative medicine, Stem cell, Target population, Adult, Aged, Double-Blind Method, Female, Heart Failure, Humans, Mesenchymal Stem Cell Transplantation, Middle Aged, Myocardial Ischemia, Prospective Studies, Treatment Outcome, Young Adult, Cardiology and Cardiovascular Medicine, Cell- and Tissue-Based Therapy, mesenchymal stem-cells, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, outcomes, Fast-Track Clinical Research, Sudden cardiac death, 0302 clinical medicine, Ischemia, cardiovascular disease, Clinical endpoint, target population, CHART Program, Ejection fraction, bone-marrow, Heart Failure/Cardiomyopathy, 3. Good health, Cohort, Cardiology, Fast Track, disease severity, delivery, medicine.medical_specialty, precision medicine, Clinical Sciences, regenerative medicine, 03 medical and health sciences, cardiopoiesis, Internal medicine, medicine, Adverse effect, marker, disease, business.industry, medicine.disease, mortality, Confidence interval, Clinical trial, stem cell, Editor's Choice, 030104 developmental biology, predictors, Cardiovascular System & Hematology, Heart failure, business
Abstract

Altres ajuts: This work was supported by Celyad, SA (Mont-Saint-Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding). Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Published
2017

5. Abstracts

Author

Barthelemy, O., primary, Silvain, J., additional, Brieger, D., additional, Bellemain-Appaix, A., additional, Cayla, G., additional, Beygui, F., additional, Lancar, R., additional, Collet, J. P., additional, Mercadier, A., additional, Montalescot, G., additional, Cha, K. S., additional, Nam, Y. H., additional, Kim, J. H., additional, Park, S. Y., additional, Park, T. H., additional, Kim, M. H., additional, Kim, Y. D., additional, Lee, H. C., additional, Ahn, M. S., additional, Hong, T. J., additional, Blanco, R., additional, Blanco, F., additional, Szarfer, J., additional, Garcia Escudero, A., additional, Gigena, G., additional, Gagliardi, J., additional, Rodriguez, A., additional, Sarmiento, R., additional, Affatatto, S., additional, Riccitelli, M., additional, Petris, A., additional, Datcu, M. D., additional, Pop, C., additional, Radoi, M., additional, Arsenescu-Georgescu, C., additional, Petrescu, I., additional, Petrescu, L., additional, Serban, L., additional, Nechita, E., additional, Tatu-Chitoiu, G., additional, Dorobantu, M., additional, Benedek, I., additional, Craiu, E., additional, Sinescu, C., additional, Ionescu, D. D., additional, Ginghina, C., additional, Minescu, B., additional, Izzo, A., additional, Mantovani, P., additional, Tomasi, L., additional, Dall'oglio, L., additional, Bonatti, S., additional, Rosiello, R., additional, Romano, M., additional, Agostini, F., additional, Zanini, R., additional, Zhao, Z. Y., additional, Wu, Y. J., additional, Li, J. J., additional, Yany, Y. J., additional, Qian, H. Y., additional, Tang, Y. D., additional, Timoteo, A. T., additional, Toste, A., additional, Lousinha, A., additional, Ramos, R., additional, Oliveira, J. A., additional, Ferreira, M. L., additional, Ferreira, R. C., additional, Cabades, C., additional, Diez Gil, J. L., additional, Aguar, P., additional, Sanmiguel, D., additional, Lopez-March, A., additional, Marmol, R., additional, Guerra, L., additional, Girbes, V., additional, Ferrando, J., additional, Rincon De Arellano, A., additional, Patricio, L., additional, Blondal, M., additional, Ainla, T., additional, Marandi, T., additional, Eha, J., additional, Oliveira, M. M., additional, Silva, M. N., additional, Cunha, P. S., additional, Feliciano, J., additional, Silva, S., additional, Kanovsky, J., additional, Kala, P., additional, Parenica, J., additional, Poloczek, M., additional, Prymusova, K., additional, Kubkova, L., additional, Spinar, J., additional, Olinic, D., additional, Homorodean, C., additional, Ober, M., additional, Olinic, M., additional, Andrioaia, C., additional, Condac, A., additional, Masmoudi, M., additional, Berdaoui, B., additional, Labidi, S., additional, Tapia Ballesteros, C., additional, Hernandez Luis, C., additional, Sandin, M. G., additional, Vegas, J. M., additional, Andion, R., additional, Martinez, N., additional, Gonzalez, I. A., additional, Alvarado, M., additional, Amat, I. J., additional, San Roman, J. A., additional, Garcia Gonzalez, M. J., additional, Arroyo Ucar, E., additional, Hernandez Garcia, C., additional, Dorta Martin, M., additional, Marrero Rodriguez, F., additional, Dragu, R., additional, Kapeliovich, M., additional, Hammerman, H., additional, Silva, D., additional, Cortez-Dias, N., additional, Jorge, C., additional, Silva Marques, J., additional, Carilho Ferreira, P., additional, Robalo Martins, S., additional, Almeida Ribeiro, M., additional, Calisto, C., additional, Fiuza, M., additional, Lopes, M. G., additional, Milicevic, P., additional, Panic, M., additional, Stankovic, I., additional, Milicevic, D., additional, Kalezic, T., additional, Kafedzic, S., additional, Ilic, I., additional, Cerovic, M., additional, Putnikovic, B., additional, Neskovic, A., additional, Rott, D., additional, Leibowitz, D., additional, Monhart, Z., additional, Reissigova, J., additional, Grunfeldova, H., additional, Jansky, P., additional, Valente, B., additional, Villanueva Benito, I., additional, Solla, I., additional, Paredes, E., additional, Diaz Castro, O., additional, Calvo, F., additional, Baz, J. A., additional, Iniguez, A., additional, Aleksova, A., additional, Gerloni, R., additional, Belfiore, R., additional, Carriere, C., additional, Barbati, G., additional, Fabris, E., additional, Possa, F., additional, Nait, D., additional, Milo, M., additional, Sinagra, G., additional, Marques, N., additional, Mimoso, J., additional, Gomes, V., additional, Agra Bermejo, R. M., additional, Emad Abu Assi, E. A. A., additional, Sergio Raposeiras Roubin, S. R. R., additional, Pilar Cabanas Grandio, P. C. G., additional, Carlos Pena Gil, C. P. G., additional, Jose Maria Garcia Acuna, J. M. G. A., additional, Jose Ramon Gonzalez Juanatey, J. R. G. J., additional, Daly, M. J., additional, Scott, P., additional, Owens, C. G., additional, Tomlin, A., additional, Smith, B., additional, Adgey, A. A. J., additional, Alvarez-Contreras, L. R., additional, Juarez, U., additional, Altamirano, A., additional, Arias, A., additional, Alvarez-San Gabriel, A., additional, Gonzalez-Pacheco, H., additional, Martinez-Sanchez, C., additional, Rahnavardi, M., additional, Keshtkar-Jahromi, M., additional, Vakili, H., additional, Gholamin, S., additional, Razavi, S. M., additional, Gilis-Januszewski, T., additional, Mellwig, K.- P., additional, Wiemer, M., additional, Gilis-Januszewski, J., additional, Peterschroeder, A., additional, Koerfer, J., additional, Horstkotte, D., additional, Vrsalovic, M., additional, Getaldic, B., additional, Vrkic, N., additional, Pintaric, H., additional, Khan, S., additional, Wasan, B., additional, Moretti, L., additional, Grossi, P., additional, Silenzi, S., additional, Testa, M., additional, Candelori, L., additional, Clementi, L. N., additional, Forlini, M., additional, Lando, L., additional, Pezzuoli, M. L., additional, Corradetti, P., additional, Leurent, G., additional, Pennec, P. Y., additional, Filippi, E., additional, Moquet, B., additional, Hacot, J. P., additional, Druelles, P., additional, Rialan, A., additional, Rouault, G., additional, Coudert, I., additional, Le Breton, H., additional, Gevaert, S., additional, Tromp, F., additional, Vandecasteele, E., additional, De Somer, F., additional, Van Belleghem, Y., additional, Bouchez, S., additional, Martens, F., additional, Herck, I., additional, De Pauw, M., additional, Ludka, O., additional, Sepsi, M., additional, Miklik, R., additional, Dusek, L., additional, Tomcikova, D., additional, Garcia-Acuna, J. M., additional, Aguiar-Souto, P., additional, Raposeiras Roubin, S., additional, Agra-Bermejo, R., additional, Jacquet, M., additional, Abu-Assi, E., additional, Gonzalez-Juanatey, J. R., additional, Ibatov, A., additional, Labrova, R., additional, Karlik, R., additional, Lokaj, P., additional, She, Q., additional, Deng, S. B., additional, Huang, S. H., additional, Gu, L. J., additional, Rong, J. I. A. N., additional, Wu, Z. K., additional, Li, Y., additional, Zhang, J., additional, Parascan, L., additional, Campanile, A., additional, Spinelli, L., additional, Santulli, G., additional, Ciccarelli, M., additional, De Gennaro, S., additional, Assante Di Panzillo, E., additional, Trimarco, B., additional, Iaccarino, G., additional, Bobescu, E., additional, Datcu, G., additional, Dobreanu, D., additional, Doka, B., additional, Charniot, J.- C., additional, Cosson, C., additional, Albertini, J. P., additional, Bittar, R., additional, Giral, P., additional, Cherfils, C., additional, Guillerm, E., additional, Bonnefont-Rousselot, D., additional, Rusali, A., additional, Cojocaru, L., additional, Parepa, I., additional, Koizumi, T., additional, Iida, S., additional, Sato, J., additional, Kikutani, T., additional, Muramatsu, T., additional, Nishimura, S., additional, Komiyama, N., additional, Lee, W. P., additional, Ong, B. B., additional, Haralambos, K., additional, Townsend, D., additional, Rees, J. A. E., additional, Williams, E. J., additional, Halcox, J. P., additional, Mcdowell, I., additional, Damjanovic, M., additional, Koracevic, G., additional, Djordjevic-Radojkovic, D., additional, Pavlovic, M., additional, Krstic, N., additional, Ciric-Zdravkovic, S., additional, Stojkovic, A., additional, Perisic, Z., additional, Apostolovic, S., additional, Faustino, A., additional, Seca, L., additional, Barra, S., additional, Caetano, F., additional, Providencia, R., additional, Silva, J., additional, Gomes, P., additional, Costa, G., additional, Costa, M., additional, Leitao-Marques, A., additional, Volkova, A. L., additional, Arutyunov, G. P., additional, Bylova, N. A., additional, Dayter, I. I., additional, Jao, Y. T. F. N., additional, Fang, C. C., additional, Chen, Y., additional, Yu, C. L., additional, Wang, S. P., additional, Valencia, J., additional, Perez-Berbel, P., additional, Ruiz-Nodar, J. M., additional, Pineda, J., additional, Bordes, P., additional, Quintanilla, M., additional, Mainar, V., additional, Sogorb, F., additional, Santos, N., additional, Serrao, M., additional, Cafe, H., additional, Silva, B., additional, Oliveira, R., additional, Caires, G., additional, Drumond, A., additional, Araujo, J., additional, Providencia, R. A., additional, Gomes, P. L., additional, Pais, J. R., additional, Mota, P., additional, Leitao-Marques, A. M., additional, Farhan, S., additional, Jarai, R., additional, Tentzeris, I., additional, Vogel, B., additional, Freynhofer, M. K., additional, Wojta, J., additional, Huber, K., additional, Poli, M., additional, Trambaiolo, P., additional, Corsi, F., additional, De Luca, M., additional, Mustilli, M., additional, Lukic, V., additional, Simonetti, M., additional, Ferraiuolo, G., additional, Lettino, M., additional, Casella, G., additional, Conte, M. R., additional, De Luca, L., additional, Geraci, G., additional, Ceravolo, R., additional, Pani, A., additional, Fradella, G., additional, Schratter, A., additional, Thiele, H., additional, Klemm, T., additional, Demmin, K., additional, Lehmann, D., additional, Mende, M., additional, Schuler, G., additional, Pittl, U., additional, Chernova, A., additional, Nikulina, S. U., additional, Naruke, T., additional, Inomata, T., additional, Yanagisawa, T., additional, Maekawa, E., additional, Mizutani, T., additional, Shinagawa, H., additional, Nishii, M., additional, Takeuchi, I., additional, Takehana, H., additional, Izumi, T., additional, Paulo, C., additional, Mascarenhas, J., additional, Patacho, M., additional, Pimenta, J., additional, Bettencourt, P., additional, Nardai, S., additional, Szabo, G. Y., additional, Berta, B., additional, Edes, I., additional, Merkely, B., additional, Delgado Silva, J., additional, Baptista, R., additional, Faria, R., additional, Trigo, J., additional, Gago, P., additional, Gheorghe, G., additional, Nanea, I. T., additional, Cristea, A., additional, Almarichi, S., additional, Martins, H., additional, Saraiva, F., additional, Jorge, E., additional, Mendes, P. L., additional, Monteiro, P., additional, Costa, S., additional, Franco, F., additional, Providencia, L. A., additional, Nanea, T., additional, Gheorghe, G. S., additional, Visan, S., additional, Paun, N., additional, Gaber, R., additional, Delewi, R., additional, Nijveldt, R., additional, De Bruin, H. A., additional, Hirsch, A., additional, Van Der Laan, A., additional, Bouma, B. J., additional, Tijssen, J. P. G., additional, Van Rossum, A. C., additional, Zijlstra, F., additional, Piek, J. J., additional, Rus, H., additional, Donea, M., additional, Ciurea, C., additional, Ifteni, G., additional, Casolo, G., additional, Chioccioli, M., additional, Magnacca, M., additional, Del Meglio, J., additional, Comella, A., additional, Baratto, M., additional, Lera, J., additional, Salvadori, L., additional, Tessa, C., additional, Vignali, C., additional, Keca, Z., additional, Momcilov Popin, T., additional, Panic, G., additional, White, R., additional, Mateen, F., additional, Weaver, A., additional, Agmon, Y., additional, Okisheva, E., additional, Tsaregorodtsev, D., additional, Sulimov, V., additional, Amat Santos, I. J., additional, Hernandez, C., additional, Tapia, C., additional, Campo, A., additional, Fredman, D., additional, Svensson, L., additional, Rosenqvist, M., additional, Tadel-Kocjancic, S., additional, Radsel, P., additional, Knafelj, R., additional, Gorjup, V., additional, Noc, M., additional, Zima, E., additional, Jenei, Z. S., additional, Kovacs, E., additional, Osztheimer, I., additional, Molnar, L., additional, Horvath, A., additional, Becker, D., additional, Geller, L., additional, Maggi, R., additional, Furukawa, T., additional, Viscardi, V., additional, Brignole, M., additional, Leal, S. R. N., additional, Dores, H., additional, Rosario, I., additional, Monge, J., additional, Carvalho, M. J., additional, Arroja, I., additional, Leitao, A., additional, Fonseca, C., additional, Aleixo, A., additional, Silva, A., additional, Keuleers, S., additional, Herijgers, P., additional, Herregods, M. C., additional, Budts, W., additional, Dubois, C., additional, Meuris, B., additional, Verhamme, P., additional, Flameng, W., additional, Van De Werf, F., additional, Adriaenssens, T., additional, Badran, H., additional, Elnoamany, M., additional, Lolah, T., additional, Olariu, C., additional, Macarie, C., additional, Mollik, M. A. H., additional, Hassan, A. I., additional, Paul, T. K., additional, Haque, M. 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Published
2010
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6. Mental Disease and Imputability: intervalla insaniae and Regime of Custody. From D. 1.18.14 (Macer De iudiciis publicis libri XIV) to the Contemporary Debate

Author

MINALE V, A. Kantancevic, M. Vukotic, S. Vandenbogaerde, V. M. Minale, and Minale, V

Subjects
Aemilius Macer - Imputability - Mental disease - Criminal process
Abstract

The Macer's passage preserved in D. 1.18.14 (together with Ulpian's D. 1.18.13.1 and Modestinus' D. 48.9.9.2) faces the matter of the imputability of a subject author of a crime, but unfit to plead because of mental disease. In our fragment the principle which denied the imputability in such a case, already existing in the Roman legal system, is restated in a rescript sent by Marcus Aurelius and the son Commodus to the functionary Scapula Tertullus concerning a certain Aelius Priscus, murderer of his mother. The emperors ask to investigate the possible presence of simulatio dementiae and mainly intervalla insaniae prescribing the measure of the detention, if necessary also in prison. The fact forces us to reflect about the high level of dogmatic speculation of the Severan jurists. In more criminological sense, instead, the main problem is represented by the social value given to a homicide inside the family and in particular toward a parent, a crime so atrocious to be perceived by the public opinion, now as much as in the past, “unnatural” or better even “against-natur”, on the basis of a kind of self-protection mechanism.

Published
2018

7. [Classification of physico-mechanical mechanisms in primary hypertension].

Author

Vukotic S and Kittnar O

Subjects
Hemodynamics, Hemorheology, Humans, Hypertension etiology, Hypertension physiopathology, Hypertension classification
Abstract

Arterial hypertension (AH) is a serious disease with high prevalence in the developed countries. In majority of the AH cases, their origin stays unknown (primary AH). There is a great number of variants in primary AH illustrating the complexity of the disease pathogenesis. We tried out to define a classification of primary AH based on the biomechanical mechanisms of elevated blood pressure, though we accept that the pathogenesis of AH includes also malfunction of one (or more) control mechanism for the initiation of compensation. We have brought some examples of unhomologated data in the literature dealing with flow conditions in the vascular system. This may explain the underestimation of the role of the rheological properties of the blood and the function of precapillary sphincters in the ethiopathogenesis of AH.

Published
1997

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