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1. Flow control of three-dimensional cylinders transitioning to turbulence via multi-agent reinforcement learning

Author

Suárez, P., Álcantara-Ávila, F., Rabault, J., Miró, A., Font, B., Lehmkuhl, O., and Vinuesa, R.

Subjects
Physics - Fluid Dynamics
Abstract

Designing active-flow-control (AFC) strategies for three-dimensional (3D) bluff bodies is a challenging task with critical industrial implications. In this study we explore the potential of discovering novel control strategies for drag reduction using deep reinforcement learning. We introduce a high-dimensional AFC setup on a 3D cylinder, considering Reynolds numbers ($Re_D$) from $100$ to $400$, which is a range including the transition to 3D wake instabilities. The setup involves multiple zero-net-mass-flux jets positioned on the top and bottom surfaces, aligned into two slots. The method relies on coupling the computational-fluid-dynamics solver with a multi-agent reinforcement-learning (MARL) framework based on the proximal-policy-optimization algorithm. MARL offers several advantages: it exploits local invariance, adaptable control across geometries, facilitates transfer learning and cross-application of agents, and results in a significant training speedup. For instance, our results demonstrate $21\%$ drag reduction for $Re_D=300$, outperforming classical periodic control, which yields up to $6\%$ reduction. To the authors' knowledge, the present MARL-based framework represents the first time where training is conducted in 3D cylinders. This breakthrough paves the way for conducting AFC on progressively more complex turbulent-flow configurations., Comment: Under review in Nature Engineering Communications

Published
2024

2. Active flow control for drag reduction through multi-agent reinforcement learning on a turbulent cylinder at $Re_D=3900$

Author

Suárez, P., Álcantara-Ávila, F., Miró, A., Rabault, J., Font, B., Lehmkuhl, O., and Vinuesa, R.

Subjects
Physics - Fluid Dynamics
Abstract

This study presents novel active-flow-control (AFC) strategies aimed at achieving drag reduction for a three-dimensional cylinder immersed in a flow at a Reynolds number based on freestream velocity and cylinder diameter of (Re_D=3900). The cylinder in this subcritical flow regime has been extensively studied in the literature and is considered a classic case of turbulent flow arising from a bluff body. The strategies presented are explored through the use of deep reinforcement learning. The cylinder is equipped with 10 independent zero-net-mass-flux jet pairs, distributed on the top and bottom surfaces, which define the AFC setup. The method is based on the coupling between a computational-fluid-dynamics solver and a multi-agent reinforcement-learning (MARL) framework using the proximal-policy-optimization algorithm. Thanks to the acceleration in training facilitated by exploiting the local invariants with MARL, a drag reduction of (8\%) was achieved, with a mass cost efficiency two orders of magnitude lower than those of the existing classical controls in the literature. This development represents a significant advancement in active flow control, particularly in turbulent regimes critical to industrial applications., Comment: Under review in "Special Issue": Progress in Engineering Turbulence Modelling, Simulation and Measurements

Published
2024

8. Abstracts of posters

Author

Suffisseau L., Taugourdeau M. C., Goldstein F. W., Mainardi J. L., Larrouturou Ph., Romero, M., Cervino, A. R., Albertone, G., Di Pasquale, R., Venturini, F., Congedo, R., Benettolo, F., Pistolesi, C., Olivato, R., Casasin T., Agusti C., Gurrera M. T., Fabregas X., Rizo A., Badia J. M., Santa-Olalla M., Marini, P., Rampazzo, R., Scroccaro, G., Dell'Aera, M., Luzzi, R., Ciccarone, G., Martinet, N., Beney, J., Marty, S., Reymond, J. -Ph., Cairns, Chris, Morgutti M., Posco M., Moltempi M., Lonqhini P., Rossignoli A., Rihet, P., Carles, G., Braguer, D., Azulay, J. P., Pouget, J., Pelletier, J., Crevat, A., Past.o, L., Barroso, E., Pujol, R., Ferrer, I., Ibars, M., Llop, J. M., Frankfort, Ellen, van Dongen, Robert T. M., Hekster, Yechiel A., Kart, T., Rasmussen, M., Horn, A., Wested, L., Gagyi, O., Markó, E., Regazzi M. B., Martinelli L., Goggi C., Bellotti E., Molinaro M., Rinaldi M., Gavazzi A., Buggia I., Daneri A., Guarnone E., Bascapē V., Viganô M., Lazzaro, A., Palozzo, A., Banfi R., Borselli G., Fabbiani P., Marinai C., Delorme, J., Tubiana, N., Buck, M., Chinot, O., De Wever, C., Robays, H., Montoro J. B., Flores G., Juárez J. C., Juste C., Jardí R., Altisent C., Tusell J. M., Arpinelli, F., De Carli, G., Olivieri, A., Recchia, G., Rossignoli A., Longhini P., La Guidara C., Russo B., Moltempi M., Tamés, M. J., Cajaraville, G., Ponz, L., Echaniz, E., Garcia, B., van Mil, J. W. Foppe, Leufkens, Hubert G., v. Haelst, Ingrid M. M., Parel, Piet C. M., Scholten, Wim K., Sessink, F. G. M., Raschatt, R., Traversa, G., Donini, G., Arpino, C., Da Cas, R., Pasquin, P., Bernadotte af Wisborg G., Claesson C., Lundberg O., Thorslund M., Ferraro L., Marrazzo E., Ostino G., Tognoni G., Heerdink, Eibert R., Koppedraaijer, Corrie, Bakker, Albert, Bidoli E., Battistin M., Troncon M. G., Franceschi S., Serraino D., Marino, M., Matera, M. G., Berrino, L., Contaldi, C., Piucci, B., Rossi, F., Rolle C., Marrazzo E. 0., Murgia, V., Bussi, R., Schievano, P., Pedrini, A., Baraghini, M., Benini, A., Cataldo, M. M., Galletti, P., Magnani, M., Manzoli, M., Novi, M. V., Pezzi, O., Font M., Salmaso A. B., Mezzalira L., Braybrook, Saran, Walker, Roger, van Mil, J. W. F., Tromp, F. T. J., de Jong-v.d. Berg, L. T. W., Bakker, A., Paes, A. H. P., Soe-Agnie, C., Llopis, P., Tortajada, J. J., Font, I., Climente, M., Real, J. V., Almenar, D., Molins, C., Jiménez, N. V., Bellés Medall MD, Casterá Melchor DE, Marco Sena MA, Cantarinz Marti I., Abad Gimeno FJ, Török, J., Thurzó, L., Juárez J. C., Oliveras M., Hidalgo E., Cabañas M. J., Barroso C., Moraga F. A., Sánchez de Toledo J., Kollöffel, W. J., Driessen, F. G. W. H. M., Goldhoorn, P. B., Moral, M. A., Roglan, A., Mangues, M. A., Bonal, J., Clopés, A., Badell, I., Fraga, G., Deinum, J. T., van Lingen, R. A., Quak, J. M. E., Kuizenga, A. J., van Dam, J. G., Villani P., Maserati R., Viale P., Alberici F., Iacona I., Wasieczko, A., Szymura-Oleksiak, J., Wyska, E., Magulova, L., Sirotiakova, J., Letkovicova, M., Branger, E., Besse, D., Blin, O., Bille, F., Serratrice, G., Desnuelle, C., Grassin, J., Reben, I., Meunier, Ph., Antier, D., Berthet, M., Søndergaard B., Herborg H., Frøkjær B., Hepler C., Steckner, H., Bergold, A., Drings, P., Märkel, A., Manegold, C., Venning, Mary, Pazzagli, Luciana, Semmola, Maria Vittoria, Mannoni, Alessandro, Tersen I., Huchet J., Sevilla, E., Ferrari, J. M., Herreros de Tejada, A., Congedo, R., Font, M., Fraccaro, A., Osti, M., Pappagallo, G., Spolaor, A., Terrazzani, G., Vezzani, M., Edouard B., Laine G., Geeraerts D., Robays H., Carrera-Hueso, F. J., Font, B., Marquina, C., Idoate, A., Giráldez, J., Fernández, E., Lacasa, C., Guzzo, D., Martini, N., Boya, P. Giner, González, M. M. Negredo, Agulló, J. Muñoz, Mansilla, L. Lorente, Nahata, Milap C., Troncon, M. G., Cattaruzzi, C., Bilbao G., Galende I., Atañé C., Bermudez de Castro A., Delgado O., Escribano B., Frías J., Gabriel R., Gómez J. A., Gracia D., Gutiérrez E., Hellín T., Izquierdo J. L., Moreno A., Requena T., Sainz-Terreros M., Tejedor J. C., Torralba A., Vigil D., Scuffi, C., Trallori, G., Messori, A., Bardazzi, G., Bonanomi, A., Silvano, R., D'Albasio, G., Bardelli, F., Verona, Firenzee, Bardelli, F., Corrado, A., Ferriols R., Aleixander M. J., Garcia J., Faus M., Ibañez E., Alós M., Rinaldi, M., Pharmacy & Therapeutic Committee (Ps&TC), Collaborative Group, SIFO-Veneto Working Group on Clinical Trials, Working Group on the Elaboration of an Approval Conditions Document to certify the Clinical Trials Ethics Committees in the Autonomous Community of Madrid, and Area SIFO di Metanalisi

Published
1994
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13. Abstracts of papers and posters safe handling of medicines

Author

Meyer, H. -J., Tromp, Th(Dick) F. J., van der Kleijn, E., Fields, Suzanne M., Moors, J. P. P., Enlund, H., Luscombe, D. K., Remond, J -Ph, Martv, S., Dhillon, S., Taylor, D., Kostrzewski, A., Bluml, B. M., Enlow, M. L., Metzler, S. E., de Vries, Philip A., Duty, C. J., Lee, H. Y., Ábrahám, Tibor, Cardoni, A. A., Sýkora, J., Szücsová, S., Reymond, J. -Ph, Marty, S, Engová, D., Sheridan, J., Vlček, J., Webb, D. G., Bates, I. P., Tabachnik A., Cass Y., Jacobs J., Vexler A., Gorodetsky, R., Whittlesea, C. M. C., Walker, R., Khan, F., Houghton, J., Phillips, I., Szymura-Oleksiak, J., Wasieczko, A., Wyska, E., Ayani, I., Errecalde, M. F., Rodriauez-Sasiain, J. M., Aouirre, C., Bellés Medall M. D., Casabó Alos V. G., Hervás Botella M. A., Cabrera Pérez A., Jiménez Torres N. V., Casterá Melchor D. E., Abad Gimeno F. J., Clark, J. E., Gomez, E. C., Cruz, A. C., Wilbur, R. L., Alfonso, I., Grout, C. H., Goldstein, R., Rivers, P., Stutz, K., Mühlcbach, S., Udeani, George, Zervopoulous, Irene, Patel, Krishna, Mullane, Michael, Radziwill, R., Dudek, J., Herbst, U., Bency, J., Muff, P., Marty, S., Rcymond, J. -Ph, Aumente M. D., Panadero M. D., Latre J. M., Torres M., Villegas M. J., Alvarez J., van Dijk, E. A., Logman, E. M., Ploeger, B., van der Schors, T. G., Steensma, D. J., Langlois-Karaga, A., Davignon, A., Bues-Charbit, M., Somme, V., Albanese, J., Durbec, O., Martin, C., Morati, N., Balansard, G., Pereira, M. E. Araújo, Nogueira, A., Silva, J. C., Mega, I., Costa, A. Gomes, Morais, J. A., Prata, M. M., Cajaraville, G., Tamés, M. J., García, B., Batel Marqucs F. J., Capela H. S., Pomingues P., Feio J. A., Siha C., Wolter, K., Fritschka, E., Schneesann, H., Stuurman, A., Gudjonsdottir, A., Angelo, H. R., Rasmuassen, M., Rasmussen, S. N., Carrera, J., Idoate, A., Modrego, A., Tejedor, I., Giráldez, J., Mangues, M. A., Farré, R., Demestre, X., Ginovart, G., Orozco, J., Julio, G., Moral, M. A., Busin, C., Bardin, C., Seroux, C., Sauvageon-Martre, H., Sraer, J. -D., Chast, F., Real, J. V., Climente, M., Font, I., Pérez, C., Ordovás, J. P., Hermenegildo, M., Catalán, J. L., Juan, J., Jiménez, N. V., Amiot, F., Clavel, S., Sarrut, B., Doreau, C., Hips, F. Zs, Soós, Gy, Petô-Nagy, G., Vincze, Z., Robays H., Freidank, A., Fischer, A., Cordovilla, H., Font, B., Ortega, A., Salek, M. S., Thomas, S., Baver, A. J., Vandenbroucke J., Ekedahl, A., Tuovinen K., Wallenius K., Enlund H., Boeke, A. W., Veenstra, E. J., van de Poll, M. A. P. C., Nonkes, K., Carlen, I., Tanner, M., Reinke, C., Escher, J., Fischer, J., Marly, S., Ooi, G. K., Cottle, A., Savage, A., Temesvári, E., Montero, M. C., Pastor, M., Valdivia, M. L., Buenestado, C., Lluch, A., Atienza, M., Santos, B., Echeverria Roca M., Fernandez Gallastegui S., Alonso Rizaldos C., Arce Trueba M. D., Booth, C. D., Aldaz, A., Lacasa, C., Cordovilla, M., Alzina, V., Sheridan, J. L., Webb, D. G., Usselmann, B., Carstens, G., Falcao, A. C., Femández de Gatta, M. M., Cobo, F. Nieto, Gorzátez, A. C. Alonso, Lanao, J. M., Dominguez -Gil, A., Burr, A., Ferreira, M. P., Rodrigues, M. O., Pereira, M. E., Marques, M. F., Vicente, M. C., Carrondo, A. P., Pires, M. A., Granja, M. A., Tuneu L., Serna J., Saló E., Cerutti P., Cardona P., Bonal J., Cosh, D. G., Abbott, F., Alderman, C. P., Mav, F. W., Peters, P. G., Scott, S. D., Jenkins, D., Cairns, C., Barber, N. D., Cammie, S. M., Burr, A. J., Brännström, I., Boya, P. Giner, Aliaga, C. Parreño, González, M. M. Negredo, Mansilla, L. Lorente, Pidrman, V., Fendrich, Z., Alberola, C., Castillo, B., Girón, C., Morell, A., López-Calull C., Carcia-Capdevila L., Sanz M., Cardona D., Castro I., Farré R., Saura R., Pérez J. M., Johnsen, Eva, Krogsgård, Ole, Pinheiro, R. L., Morais, I. A., Batel Marques F. J., Domingues P., Feio J. A., Silva C., Astdrager, C. L. L., Schnlekamp, T., de Gier, J. J., Rutten, C. W. H., Rivera, M. C., Vilanova, M., Mattei, I., Roglan, A., Serna, J., and Bonal, J.

Published
1993
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21. Barcelona conference on epigenetics and cancer 2016-beyond cancer genomes

Author

Dumbovic, G, Biayna, J, Font, B, Buschbeck, M, and Forcales, SV

Subjects
epigenetics, nuclear organization, stem cells, RNA biology, novel therapies, tumor heterogeneity, Cancer
Abstract

The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Beyond Cancer Genomes" took place October 13th and 14th 2016 in Barcelona. The 2016 BCEC was the fourth edition of a series of annual conferences coordinated by Marcus Buschbeck and subsequently organized by leading research centers in Barcelona together with B.DEBATE, a joint initiative of BIOCAT and "La Caixa" Foundation. Salvador Aznar-Benitah, Eduard Batlle, and Raul Mendez from the Institute for Research in Biomedicine in Barcelona selected the 2016 BCEC panel of speakers. As the title indicates, this year's conference expanded the epigenetic focus to include additional cancer-relevant topics, such as tumor heterogeneity and RNA regulation. Methods to develop therapeutic approaches on the basis of novel insights have been discussed in great detail. The conference has attracted 217 participants from 11 countries.

Published
2017

24. Impact of early valve surgery on outcome of staphylococcus aureus prosthetic valve infective endocarditis: Analysis in the international collaboration of endocarditis-prospective cohort study.

Author

Vincelj J., Sexton D.J., Corey G.R., Chu V.H., Wang A., Erpelding M.-L., Durante-Mangoni E., Fernandez-Hidalgo N., Giannitsioti E., Hannan M.M., Lejko-Zupanc T., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Holland T., Lalani T., Mudrick D., Samad Z., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Chirouze C., Alla F., Fowler V.G., Miro J.M., Munoz P., Murdoch D.R., Tattevin P., Tribouilloy C., Hoen B., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Freiberger T., Pol J., Zaloudikova B., Zainab A., El Kholy A., Mishaal M., Rizk H., Aissa N., Alauzet C., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Bernard Y., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Athanasia S., Deliolanis I., Giamarellou H., Tsaganos T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Casillo R., Cuccurullo S., Dialetto G., Irene M., Ragone E., Tripodi M.F., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Moreno A., Ninot S., Vincelj J., Sexton D.J., Corey G.R., Chu V.H., Wang A., Erpelding M.-L., Durante-Mangoni E., Fernandez-Hidalgo N., Giannitsioti E., Hannan M.M., Lejko-Zupanc T., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Holland T., Lalani T., Mudrick D., Samad Z., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Chirouze C., Alla F., Fowler V.G., Miro J.M., Munoz P., Murdoch D.R., Tattevin P., Tribouilloy C., Hoen B., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Freiberger T., Pol J., Zaloudikova B., Zainab A., El Kholy A., Mishaal M., Rizk H., Aissa N., Alauzet C., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Bernard Y., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Athanasia S., Deliolanis I., Giamarellou H., Tsaganos T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Casillo R., Cuccurullo S., Dialetto G., Irene M., Ragone E., Tripodi M.F., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Moreno A., and Ninot S.

Abstract

Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.Copyright © The Author 2014.

Published
2015

25. Candida infective endocarditis: An observational cohort study with a focus on therapy.

Author

Campagnac C., Llopis J., Marco F., Mestres C.A., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Leoni M.E.G., Robles J.A.G., Ramallo V.G., Cruz A.F., Kestler M., Marin M., Selles M.M., Abella H.R., Roda J.R., Lopez R.A., Pinilla B., Pinto A., Valerio M., Vazquez P., Verde E., Almirante B., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Wang A., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Karchmer A.W., Sexton D.J., Durack D.T., Eykyn S., Moreillon P., Sexton. D.J., Arnold C.J., Johnson M., Bayer A.S., Bradley S., Giannitsioti E., Miro J.M., Tornos P., Tattevin P., Strahilevitz J., Spelman D., Athan E., Nacinovich F., Lamas C., Barsic B., Fernandez-Hidalgo N., Munoz P., Chu V.H., Clara L., Sanchez M., Casabe J., Cortes C., Oses P.F., Ronderos R., Sucari A., Thierer J., Altclas J., Kogan S., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Weksler C., Ferraiuoli G., Golebiovski W., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Helen G., Sofia A., Ioannis D., Thomas T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hannan M.M., Hurley J.P., Cahan A., Gilon D., Israel S., Korem M., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Kanafani Z., Kanj S.S., Sharif-Yakan A., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., Heras M., Campagnac C., Llopis J., Marco F., Mestres C.A., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Leoni M.E.G., Robles J.A.G., Ramallo V.G., Cruz A.F., Kestler M., Marin M., Selles M.M., Abella H.R., Roda J.R., Lopez R.A., Pinilla B., Pinto A., Valerio M., Vazquez P., Verde E., Almirante B., De Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Wang A., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Karchmer A.W., Sexton D.J., Durack D.T., Eykyn S., Moreillon P., Sexton. D.J., Arnold C.J., Johnson M., Bayer A.S., Bradley S., Giannitsioti E., Miro J.M., Tornos P., Tattevin P., Strahilevitz J., Spelman D., Athan E., Nacinovich F., Lamas C., Barsic B., Fernandez-Hidalgo N., Munoz P., Chu V.H., Clara L., Sanchez M., Casabe J., Cortes C., Oses P.F., Ronderos R., Sucari A., Thierer J., Altclas J., Kogan S., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., De Oliveira Ramos A., Weksler C., Ferraiuoli G., Golebiovski W., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Helen G., Sofia A., Ioannis D., Thomas T., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Sharma G., Francis J., Nair L., Thomas V., Venugopal K., Hannan M.M., Hurley J.P., Cahan A., Gilon D., Israel S., Korem M., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Kanafani Z., Kanj S.S., Sharif-Yakan A., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Falces C., Garcia-De-La-Maria C., Fita G., Gatell J.M., and Heras M.

Abstract

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.Copyright © 2015, American Society for Microbiology.

Published
2015

28. One-year outcome following biological or mechanical valve replacement for infective endocarditis.

Author

Pangercic A., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D.J., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Dipersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Delahaye F., Chu V.H., Altclas J., Barsic B., Delahaye A., Freiberger T., Gordon D.L., Hannan M.M., Hoen B., Kanj S.S., Lejko-Zupanc T., Mestres C.A., Pachirat O., Pappas P., Lamas C., Selton-Suty C., Tan R., Tattevin P., Wang A., Clara L., Sanchez M., Casabe J., Cortes C., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., Tranchesi R.A.M., Paiva M.G., Fortes C.Q., Ramos A.O., Ferraiuoli G., Golebiovski W., Weksler C., Santos M., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Sharma G., Rudez I., Vincelj J., Pol J., Zaloudikova B., Ashour Z., El Kholy A., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Goehringer F., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Thomas T., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Papanikolaou K., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Anouti K., Chahoud J., Kanafani Z., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-la-maria C., Fita G., Gatell J.M., Heras M., Llopis J., Marco F., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Pangercic A., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Olaison L., Snygg-Martin U., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D.J., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Dipersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Levine D., Riddle J., Rybak M., Cabell C.H., Baloch K., Dixon C.C., Harding T., Jones-Richmond M., Park L.P., Sanderford B., Stafford J., Anstrom K., Bayer A.S., Karchmer A.W., Durack D.T., Eykyn S., Moreillon P., Delahaye F., Chu V.H., Altclas J., Barsic B., Delahaye A., Freiberger T., Gordon D.L., Hannan M.M., Hoen B., Kanj S.S., Lejko-Zupanc T., Mestres C.A., Pachirat O., Pappas P., Lamas C., Selton-Suty C., Tan R., Tattevin P., Wang A., Clara L., Sanchez M., Casabe J., Cortes C., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., Tranchesi R.A.M., Paiva M.G., Fortes C.Q., Ramos A.O., Ferraiuoli G., Golebiovski W., Weksler C., Santos M., Karlowsky J.A., Keynan Y., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Fernandez R., Franco L., Gonzalez J., Jaramillo A.N., Bukovski S., Krajinovic V., Sharma G., Rudez I., Vincelj J., Pol J., Zaloudikova B., Ashour Z., El Kholy A., Mishaal M., Osama D., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Goehringer F., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Vandenesch F., Donal E., Donnio P.Y., Flecher E., Michelet C., Revest M., Chevalier F., Jeu A., Remadi J.P., Rusinaru D., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Neuerburg C., Mazaheri B., Thomas T., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Papanikolaou K., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Durante-Mangoni E., Mattucci I., Pinto D., Agrusta F., Senese A., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Anouti K., Chahoud J., Kanafani Z., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Murdoch D.R., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Liew Y.-Y., Tan R.-S., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Garcia-De-la-maria C., Fita G., Gatell J.M., Heras M., Llopis J., Marco F., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J.M., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., and Marin M.

Abstract

Methods and results Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p <.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Conclusions Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction. Background Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Published
2014

29. Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with beta2-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues

Author

Morimoto, H., Wada, J., Font, B., Mott, Jd, Hulmes, Dj, Ookoshi, T., Naiki, H., Yasuhara, A., Nakatsuka, A., Fukuoka, K., Takatori, Y., Ichikawa, H., Akagi, S., Nakao, K., Makino, H., and Deleage, Gilbert

Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

Dialysis related amyloidosis (DRA) is a progressive and serious complication in patients under long-term hemodialysis and mainly leads to osteo-articular diseases. Although beta(2)-microglobulin (beta2-m) is the major structural component of beta2-m amyloid fibrils, the initiation of amyloid formation is not clearly understood. Here, we have identified procollagen C-proteinase enhancer-1 (PCPE-1) as a new interacting protein with beta2-m by screening a human synovium cDNA library. The interaction of beta2-m with full-length PCPE-1 was confirmed by immunoprecipitation, solid-phase binding and pull-down assays. By yeast two-hybrid analysis and pull-down assay, beta2-m appeared to interact with PCPE-1 via the NTR (netrin-like) domain and not via the CUB (C1r/C1s, Uegf and BMP-1) domain region. In synovial tissues derived from hemodialysis patients with DRA, beta2-m co-localized and formed a complex with PCPE-1. beta2-m did not alter the basal activity of bone morphogenetic protein-1/procollagen C-proteinase (BMP-1/PCP) nor BMP-1/PCP activity enhanced by PCPE-1. PCPE-1 did not stimulate beta2-m amyloid fibril formation from monomeric beta2-m in vitro under acidic and neutral conditions as revealed by thioflavin T fluorescence spectroscopy and electron microscopy. Since PCPE-1 is abundantly expressed in connective tissues rich in type I collagen, it may be involved in the initial accumulation of beta2-m in selected tissues such as tendon, synovium and bone. Furthermore, since such preferential deposition of beta2-m may be linked to subsequent beta2-m amyloid fibril formation, the disruption of the interaction between beta2-m and PCPE-1 may prevent beta2-m amyloid fibril formation and therefore PCPE-1 could be a new target for the treatment of DRA.Dialysis related amyloidosis (DRA) is a progressive and serious complication in patients under long-term hemodialysis and mainly leads to osteo-articular diseases. Although beta(2)-microglobulin (beta2-m) is the major structural component of beta2-m amyloid fibrils, the initiation of amyloid formation is not clearly understood. Here, we have identified procollagen C-proteinase enhancer-1 (PCPE-1) as a new interacting protein with beta2-m by screening a human synovium cDNA library. The interaction of beta2-m with full-length PCPE-1 was confirmed by immunoprecipitation, solid-phase binding and pull-down assays. By yeast two-hybrid analysis and pull-down assay, beta2-m appeared to interact with PCPE-1 via the NTR (netrin-like) domain and not via the CUB (C1r/C1s, Uegf and BMP-1) domain region. In synovial tissues derived from hemodialysis patients with DRA, beta2-m co-localized and formed a complex with PCPE-1. beta2-m did not alter the basal activity of bone morphogenetic protein-1/procollagen C-proteinase (BMP-1/PCP) nor BMP-1/PCP activity enhanced by PCPE-1. PCPE-1 did not stimulate beta2-m amyloid fibril formation from monomeric beta2-m in vitro under acidic and neutral conditions as revealed by thioflavin T fluorescence spectroscopy and electron microscopy. Since PCPE-1 is abundantly expressed in connective tissues rich in type I collagen, it may be involved in the initial accumulation of beta2-m in selected tissues such as tendon, synovium and bone. Furthermore, since such preferential deposition of beta2-m may be linked to subsequent beta2-m amyloid fibril formation, the disruption of the interaction between beta2-m and PCPE-1 may prevent beta2-m amyloid fibril formation and therefore PCPE-1 could be a new target for the treatment of DRA.

Published
2008

30. Insights into how CUB domains can exert specific functions while sharing a common fold: conserved and specific features of the CUB1 domain contribute to the molecular basis of procollagen C-proteinase enhancer-1 activity

Author

Blanc, G., Font, B., Eichenberger, D., Moreau, C., Ricard-Blum, S., Hulmes, Dj, Moali, C., and Deleage, Gilbert

Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

Procollagen C-proteinase enhancers (PCPE-1 and -2) are extracellular glycoproteins that can stimulate the C-terminal processing of fibrillar procollagens by tolloid proteinases such as bone morphogenetic protein-1. They consist of two CUB domains (CUB1 and -2) that alone account for PCPE-enhancing activity and one C-terminal NTR domain. CUB domains are found in several extracellular and plasma membrane-associated proteins, many of which are proteases. We have modeled the structure of the CUB1 domain of PCPE-1 based on known three-dimensional structures of CUB-containing proteins. Sequence alignment shows conserved amino acids, notably two acidic residues (Asp-68 and Asp-109) involved in a putative surface-located calcium binding site, as well as a conserved tyrosine residue (Tyr-67). In addition, three residues (Glu-26, Thr-89, and Phe-90) are found only in PCPE CUB1 domains, in putative surface-exposed loops. Among the conserved residues, it was found that mutations of Asp-68 and Asp-109 to alanine almost completely abolished PCPE-1 stimulating activity, whereas mutation of Tyr-67 led to a smaller reduction of activity. Among residues specific to PCPEs, mutation of Glu-26 and Thr-89 had little effect, whereas mutation of Phe-90 dramatically decreased the activity. Changes in activity were paralleled by changes in binding of different PCPE-1 mutants to a mini-procollagen III substrate, as shown by surface plasmon resonance. We conclude that PCPE-stimulating activity requires a calcium binding motif in the CUB1 domain that is highly conserved among CUB-containing proteins but also that PCPEs contain specific sites that could become targets for the development of novel anti-fibrotic therapies.Procollagen C-proteinase enhancers (PCPE-1 and -2) are extracellular glycoproteins that can stimulate the C-terminal processing of fibrillar procollagens by tolloid proteinases such as bone morphogenetic protein-1. They consist of two CUB domains (CUB1 and -2) that alone account for PCPE-enhancing activity and one C-terminal NTR domain. CUB domains are found in several extracellular and plasma membrane-associated proteins, many of which are proteases. We have modeled the structure of the CUB1 domain of PCPE-1 based on known three-dimensional structures of CUB-containing proteins. Sequence alignment shows conserved amino acids, notably two acidic residues (Asp-68 and Asp-109) involved in a putative surface-located calcium binding site, as well as a conserved tyrosine residue (Tyr-67). In addition, three residues (Glu-26, Thr-89, and Phe-90) are found only in PCPE CUB1 domains, in putative surface-exposed loops. Among the conserved residues, it was found that mutations of Asp-68 and Asp-109 to alanine almost completely abolished PCPE-1 stimulating activity, whereas mutation of Tyr-67 led to a smaller reduction of activity. Among residues specific to PCPEs, mutation of Glu-26 and Thr-89 had little effect, whereas mutation of Phe-90 dramatically decreased the activity. Changes in activity were paralleled by changes in binding of different PCPE-1 mutants to a mini-procollagen III substrate, as shown by surface plasmon resonance. We conclude that PCPE-stimulating activity requires a calcium binding motif in the CUB1 domain that is highly conserved among CUB-containing proteins but also that PCPEs contain specific sites that could become targets for the development of novel anti-fibrotic therapies.

Published
2007

31. Substrate-specific modulation of a multisubstrate proteinase. C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1

Author

Moali, C., Font, B., Ruggiero, Florence, Eichenberger, D., Rousselle, P., François, V., Oldberg, A., Bruckner-Tuderman, Leena, Hulmes, David J. S., Deleage, Gilbert, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], and Albert-Ludwigs-Universität Freiburg

Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, macromolecular substances, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract

International audience; Members of the bone morphogenetic protein-1/tolloid (BMP-1/Tld) family of metalloproteinases, also known as procollagen C-proteinases (PCPs), control multiple biological events (including matrix assembly, cross-linking, cell adhesion/migration and pattern formation) through enzymatic processing of several extracellular substrates. PCP activities on fibrillar procollagens can be stimulated by another family of extracellular proteins, PCP enhancers (PCPE-1, PCPE-2), which lack intrinsic enzymatic activity. While PCPs have multiple substrates, the extent to which PCPEs is involved in the processing of proteins other than fibrillar procollagens is unknown. In the experiments reported here, PCPE-1 was found to have no effect on the in vitro BMP-1 processing of procollagen VII, the procollagen V N-propeptide, the laminin 5 gamma2 chain, osteoglycin, prolysyl oxidase, or chordin. In contrast, PCPE-1 enhanced C-terminal processing of human fibrillar procollagen III but only when this substrate was in its native, disulfide-bonded conformation. Surprisingly, processing of procollagen III continued to be enhanced when essentially all the triple-helical region was removed. These and previous results (Ricard-Blum, S., Bernocco, S., Font, B., Moali, C., Eichenberger, D., Farjanel, J., Burchardt, E. R., van der Rest, M., Kessler, E., and Hulmes, D. J. S. (2002) J. Biol. Chem. 277, 33864-33869; Bernocco, S., Steiglitz, B. M., Svergun, D. I., Petoukhov, M. V., Ruggiero, F., Ricard-Blum, S., Ebel, C., Geourjon, C., Deleage, G., Font, B., Eichenberger, D., Greenspan, D. S., and Hulmes, D. J. S. (2003) J. Biol. Chem. 278, 7199-7205) indicate that the mechanism of PCPE-1 action involves recognition sites in both the C-propeptide domain and in the C-telopeptide region of the procollagen molecule. PCPEs therefore define a new class of extracellular adaptor proteins that stimulate proteinase activity in a substrate-specific manner, thereby providing a new target for the selective regulation of PCP activity on fibrillar procollagen substrates.Members of the bone morphogenetic protein-1/tolloid (BMP-1/Tld) family of metalloproteinases, also known as procollagen C-proteinases (PCPs), control multiple biological events (including matrix assembly, cross-linking, cell adhesion/migration and pattern formation) through enzymatic processing of several extracellular substrates. PCP activities on fibrillar procollagens can be stimulated by another family of extracellular proteins, PCP enhancers (PCPE-1, PCPE-2), which lack intrinsic enzymatic activity. While PCPs have multiple substrates, the extent to which PCPEs is involved in the processing of proteins other than fibrillar procollagens is unknown. In the experiments reported here, PCPE-1 was found to have no effect on the in vitro BMP-1 processing of procollagen VII, the procollagen V N-propeptide, the laminin 5 gamma2 chain, osteoglycin, prolysyl oxidase, or chordin. In contrast, PCPE-1 enhanced C-terminal processing of human fibrillar procollagen III but only when this substrate was in its native, disulfide-bonded conformation. Surprisingly, processing of procollagen III continued to be enhanced when essentially all the triple-helical region was removed. These and previous results (Ricard-Blum, S., Bernocco, S., Font, B., Moali, C., Eichenberger, D., Farjanel, J., Burchardt, E. R., van der Rest, M., Kessler, E., and Hulmes, D. J. S. (2002) J. Biol. Chem. 277, 33864-33869; Bernocco, S., Steiglitz, B. M., Svergun, D. I., Petoukhov, M. V., Ruggiero, F., Ricard-Blum, S., Ebel, C., Geourjon, C., Deleage, G., Font, B., Eichenberger, D., Greenspan, D. S., and Hulmes, D. J. S. (2003) J. Biol. Chem. 278, 7199-7205) indicate that the mechanism of PCPE-1 action involves recognition sites in both the C-propeptide domain and in the C-telopeptide region of the procollagen molecule. PCPEs therefore define a new class of extracellular adaptor proteins that stimulate proteinase activity in a substrate-specific manner, thereby providing a new target for the selective regulation of PCP activity on fibrillar procollagen substrates.

Published
2005

32. Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

Author

Zaloudikova B., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Barsic B., Dickerman S., Krajinovic V., Pappas P., Altclas J., Carosi G., Casabe J.H., Chu V.H., Delahaye F., Edathodu J., Fortes C.Q., Olaison L., Pangercic A., Patel M., Rudez I., Tamin S.S., Vincelj J., Bayer A.S., Wang A., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Cereceda M., Fica A., Mella R.M., Bukovski S., Freiberger T., Pol J., Sharma G., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber G.C., Neuerburg C., Mazaheri B., Naber C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas D.M.V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., Rosa F.D., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Murdoch D.R., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., Falces C., Zaloudikova B., Garcia-De-La-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Bouza E., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Munoz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., De Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Corey G.R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., Di Persio J., Salstrom S.-J., Baddley J., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Cabell C.H., Morris A.M., Rubinstein E., Jones S.B., Garcia P., Barsic B., Dickerman S., Krajinovic V., Pappas P., Altclas J., Carosi G., Casabe J.H., Chu V.H., Delahaye F., Edathodu J., Fortes C.Q., Olaison L., Pangercic A., Patel M., Rudez I., Tamin S.S., Vincelj J., Bayer A.S., Wang A., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Jones P., Konecny P., Lawrence R., Rees D., Ryan S., Feneley M.P., Harkness J., Post J., Reinbott P., Gattringer R., Wiesbauer F., Andrade A.R., De Brito A.C.P., Guimaraes A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., De Medeiros Tranchesi R.A., Paiva M.G., De Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Cereceda M., Fica A., Mella R.M., Bukovski S., Freiberger T., Pol J., Sharma G., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Raoult D., Thuny F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Revest M., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Hoen B., Leroy J., Plesiat P., Naber G.C., Neuerburg C., Mazaheri B., Naber C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas D.M.V., Venugopal K., Hannan M., Hurley J., Cahan A., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., Rosa F.D., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Martinez E.R., Nieto G.I.S., Van Der Meer J.T.M., Chambers S., Murdoch D.R., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Kirill O., Vadim K., Vinogradova T., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castaneda X., Cervera C., Del Rio A., and Falces C.

Abstract

Background. The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Methods. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Results. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval[CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). Conclusions. There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.Copyright © The Author 2012.

Published
2013

33. HACEK Infective Endocarditis: Characteristics and Outcomes from a Large, Multi-National Cohort.

Author

Revest M., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castan~eda X., Cervera C., Rio A., Falces C., Garcia-de-la-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Mun~oz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Baloch K., Corey G.R., Dixon C.C., Fowler Jr. V.G., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Chu V.H., Karchmer A.W., Murdoch D.R., Sexton D.J., Wang A., Bayer A.S., Cabell C.H., Chu V., Durack D.T., Eykyn S., Hoen B., Moreillon P., Olaison L., Raoult D., Rubinstein E., Chambers S.T., Murdoch D., Bouza E., Hannan M.M., Kanafani Z.A., Lang S., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Silvia Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Ryan S., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimara~es A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., de Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., de Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Sharma G., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Mazaheri B., Neuerburg C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., Chipigina N., Revest M., Kirill O., Vadim K., Vinogradova T., Edathodu J., Halim M., Lum L.-N., Tan R.-S., Lejko-Zupanc T., Logar M., Mueller-Premru M., Commerford P., Commerford A., Deetlefs E., Hansa C., Ntsekhe M., Almela M., Armero Y., Azqueta M., Castan~eda X., Cervera C., Rio A., Falces C., Garcia-de-la-Maria C., Fita G., Gatell J.M., Marco F., Mestres C.A., Miro J.M., Moreno A., Ninot S., Pare C., Pericas J., Ramirez J., Rovira I., Sitges M., Anguera I., Font B., Guma J.R., Bermejo J., Fernandez M.A.G., Gonzalez-Ramallo V., Marin M., Mun~oz P., Pedromingo M., Roda J., Rodriguez-Creixems M., Solis J., Almirante B., Fernandez-Hidalgo N., Tornos P., de Alarcon A., Parra R., Alestig E., Johansson M., Snygg-Martin U., Pachirat O., Pachirat P., Pussadhamma B., Senthong V., Casey A., Elliott T., Lambert P., Watkin R., Eyton C., Klein J.L., Bradley S., Kauffman C., Bedimo R., Crowley A.L., Douglas P., Drew L., Fowler V.G., Holland T., Lalani T., Mudrick D., Samad Z., Sexton D., Stryjewski M., Woods C.W., Lerakis S., Cantey R., Steed L., Wray D., Dickerman S.A., Bonilla H., DiPersio J., Salstrom S.-J., Baddley J., Patel M., Peterson G., Stancoven A., Afonso L., Kulman T., Levine D., Rybak M., Baloch K., Corey G.R., Dixon C.C., Fowler Jr. V.G., Harding T., Jones-Richmond M., Pappas P., Park L.P., Redick T., Stafford J., Anstrom K., Chu V.H., Karchmer A.W., Murdoch D.R., Sexton D.J., Wang A., Bayer A.S., Cabell C.H., Chu V., Durack D.T., Eykyn S., Hoen B., Moreillon P., Olaison L., Raoult D., Rubinstein E., Chambers S.T., Murdoch D., Bouza E., Hannan M.M., Kanafani Z.A., Lang S., Clara L., Sanchez M., Nacinovich F., Oses P.F., Ronderos R., Sucari A., Thierer J., Casabe J., Cortes C., Altclas J., Silvia Kogan S., Spelman D., Athan E., Harris O., Kennedy K., Tan R., Gordon D., Papanicolas L., Eisen D., Grigg L., Street A., Korman T., Kotsanas D., Dever R., Konecny P., Lawrence R., Rees D., Feneley M.P., Harkness J., Jones P., Post J., Reinbott P., Ryan S., Gattringer R., Wiesbauer F., Andrade A.R., de Brito A.C.P., Guimara~es A.C., Grinberg M., Mansur A.J., Siciliano R.F., Strabelli T.M.V., Vieira M.L.C., de Medeiros Tranchesi R.A., Paiva M.G., Fortes C.Q., de Oliveira Ramos A., Ferraiuoli G., Golebiovski W., Lamas C., Santos M., Weksler C., Karlowsky J.A., Keynan Y., Morris A.M., Jones S.B., Garcia P., Cereceda M., Fica A., Mella R.M., Barsic B., Bukovski S., Krajinovic V., Pangercic A., Rudez I., Vincelj J., Freiberger T., Pol J., Zaloudikova B., Ashour Z., Kholy A.E., Mishaal M., Rizk H., Aissa N., Alauzet C., Alla F., Campagnac C., Doco-Lecompte T., Selton-Suty C., Casalta J.-P., Fournier P.-E., Habib G., Thuny F., Delahaye F., Delahaye A., Vandenesch F., Donal E., Donnio P.Y., Michelet C., Sharma G., Tattevin P., Violette J., Chevalier F., Jeu A., Rusinaru D.M.D., Sorel C., Tribouilloy C., Bernard Y., Chirouze C., Leroy J., Plesiat P., Naber C., Mazaheri B., Neuerburg C., Athanasia S., Giannitsioti E., Mylona E., Paniara O., Papanicolaou K., Pyros J., Skoutelis A., Francis J., Nair L., Thomas V., Venugopal K., Hannan M., Hurley J., Gilon D., Israel S., Korem M., Strahilevitz J., Tripodi M.F., Casillo R., Cuccurullo S., Dialetto G., Durante-Mangoni E., Irene M., Ragone E., Utili R., Cecchi E., De Rosa F., Forno D., Imazio M., Trinchero R., Tebini A., Grossi P., Lattanzio M., Toniolo A., Goglio A., Raglio A., Ravasio V., Rizzi M., Suter F., Carosi G., Magri S., Signorini L., Baban T., Kanafani Z., Kanj S.S., Sfeir J., Yasmine M., Abidin I., Tamin S.S., Martinez E.R., Nieto G.I.S., van der Meer J.T.M., Chambers S., Holland D., Morris A., Raymond N., Read K., Dragulescu S., Ionac A., Mornos C., Butkevich O.M., and Chipigina N.

Abstract

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences. © 2013 Chambers et al.

Published
2013

34. HACEK Infective Endocarditis: Characteristics and Outcomes from a Large, Multi-National Cohort

Author

Abbate, A, Chambers, ST, Murdoch, D, Morris, A, Holland, D, Pappas, P, Almela, M, Fernandez-Hidalgo, N, Almirante, B, Bouza, E, Forno, D, del Rio, A, Hannan, MM, Harkness, J, Kanafani, ZA, Lalani, T, Lang, S, Raymond, N, Read, K, Vinogradova, T, Woods, CW, Wray, D, Corey, GR, Chu, VH, Clara, L, Sanchez, M, Nacinovich, F, Fernandez Oses, P, Ronderos, R, Sucari, A, Thierer, J, Casabe, J, Cortes, C, Altclas, J, Kogan, S, Spelman, D, Athan, E, Harris, O, Kennedy, K, Tan, R, Gordon, D, Papanicolas, L, Eisen, D, Grigg, L, Street, A, Korman, T, Kotsanas, D, Dever, R, Jones, P, Konecny, P, Lawrence, R, Rees, D, Ryan, S, Feneley, MP, Post, J, Reinbott, P, Gattringer, R, Wiesbauer, F, Andrade, AR, Passos de Brito, AC, Guimaraes, AC, Grinberg, M, Mansur, AJ, Siciliano, RF, Varejao Strabelli, TM, Campos Vieira, ML, de Medeiros Tranchesi, RA, Paiva, MG, Fortes, CQ, Ramos, ADO, Ferraiuoli, G, Golebiovski, W, Lamas, C, Santos, M, Weksler, C, Karlowsky, JA, Keynan, Y, Morris, AM, Rubinstein, E, Jones, SB, Garcia, P, Cereceda, M, Fica, A, Mella, RM, Barsic, B, Bukovski, S, Krajinovic, V, Pangercic, A, Rudez, I, Vincelj, J, Freiberger, T, Pol, J, Zaloudikova, B, Ashour, Z, El Kholy, A, Mishaal, M, Rizk, H, Aissa, N, Alauzet, C, Alla, F, Campagnac, C, Doco-Lecompte, T, Selton-Suty, C, Casalta, J-P, Fournier, P-E, Habib, G, Raoult, D, Thuny, F, Delahaye, F, Delahaye, A, Vandenesch, F, Donal, E, Donnio, PY, Michelet, C, Revest, M, Tattevin, P, Violette, J, Chevalier, F, Jeu, A, Dan, Rusinaru, Sorel, C, Tribouilloy, C, Bernard, Y, Chirouze, C, Hoen, B, Leroy, J, Plesiat, P, Naber, C, Neuerburg, C, Mazaheri, B, Athanasia, S, Giannitsioti, E, Mylona, E, Paniara, O, Papanicolaou, K, Pyros, J, Skoutelis, A, Sharma, G, Francis, J, Nair, L, Thomas, V, Venugopal, K, Hannan, M, Hurley, J, Gilon, D, Israel, S, Korem, M, Strahilevitz, J, Tripodi, MF, Casillo, R, Cuccurullo, S, Dialetto, G, Durante-Mangoni, E, Irene, M, Ragone, E, Utili, R, Cecchi, E, De Rosa, F, Imazio, M, Trinchero, R, Tebini, A, Grossi, P, Lattanzio, M, Toniolo, A, Goglio, A, Raglio, A, Ravasio, V, Rizzi, M, Suter, F, Carosi, G, Magri, S, Signorini, L, Baban, T, Kanafani, Z, Kanj, SS, Sfeir, J, Yasmine, M, Abidin, I, Tamin, SS, Martinez, ER, Nieto, GIS, van der Meer, JTM, Chambers, S, Murdoch, DR, Dragulescu, S, Ionac, A, Mornos, C, Butkevich, OM, Chipigina, N, Kirill, O, Vadim, K, Edathodu, J, Halim, M, Lum, L-N, Tan, R-S, Lejko-Zupanc, T, Logar, M, Mueller-Premru, M, Commerford, P, Commerford, A, Deetlefs, E, Hansa, C, Ntsekhe, M, Armero, Y, Azqueta, M, Castaneda, X, Cervera, C, Falces, C, Garcia-de-la-Maria, C, Fita, G, Gatell, JM, Marco, F, Mestres, CA, Miro, JM, Moreno, A, Ninot, S, Pare, C, Pericas, J, Ramirez, J, Rovira, I, Sitges, M, Anguera, I, Font, B, Guma, JR, Bermejo, J, Garcia Fernandez, MA, Gonzalez-Ramallo, V, Marin, M, Munoz, P, Pedromingo, M, Roda, J, Rodriguez-Creixems, M, Solis, J, Tornos, P, de Alarcon, A, Parra, R, Alestig, E, Johansson, M, Olaison, L, Snygg-Martin, U, Pachirat, O, Pachirat, P, Pussadhamma, B, Senthong, V, Casey, A, Elliott, T, Lambert, P, Watkin, R, Eyton, C, Klein, JL, Bradley, S, Kauffman, C, Bedimo, R, Crowley, AL, Douglas, P, Drew, L, Fowler, VG, Holland, T, Mudrick, D, Samad, Z, Sexton, D, Stryjewski, M, Wang, A, Lerakis, S, Cantey, R, Steed, L, Dickerman, SA, Bonilla, H, DiPersio, J, Salstrom, S-J, Baddley, J, Patel, M, Peterson, G, Stancoven, A, Afonso, L, Kulman, T, Levine, D, Rybak, M, Cabell, CH, Baloch, K, Dixon, CC, Harding, T, Jones-Richmond, M, Park, LP, Redick, T, Stafford, J, Anstrom, K, Bayer, AS, Karchmer, AW, Sexton, DJ, Chu, V, Durack, DT, Phil, D, Eykyn, S, Moreillon, P, Abbate, A, Chambers, ST, Murdoch, D, Morris, A, Holland, D, Pappas, P, Almela, M, Fernandez-Hidalgo, N, Almirante, B, Bouza, E, Forno, D, del Rio, A, Hannan, MM, Harkness, J, Kanafani, ZA, Lalani, T, Lang, S, Raymond, N, Read, K, Vinogradova, T, Woods, CW, Wray, D, Corey, GR, Chu, VH, Clara, L, Sanchez, M, Nacinovich, F, Fernandez Oses, P, Ronderos, R, Sucari, A, Thierer, J, Casabe, J, Cortes, C, Altclas, J, Kogan, S, Spelman, D, Athan, E, Harris, O, Kennedy, K, Tan, R, Gordon, D, Papanicolas, L, Eisen, D, Grigg, L, Street, A, Korman, T, Kotsanas, D, Dever, R, Jones, P, Konecny, P, Lawrence, R, Rees, D, Ryan, S, Feneley, MP, Post, J, Reinbott, P, Gattringer, R, Wiesbauer, F, Andrade, AR, Passos de Brito, AC, Guimaraes, AC, Grinberg, M, Mansur, AJ, Siciliano, RF, Varejao Strabelli, TM, Campos Vieira, ML, de Medeiros Tranchesi, RA, Paiva, MG, Fortes, CQ, Ramos, ADO, Ferraiuoli, G, Golebiovski, W, Lamas, C, Santos, M, Weksler, C, Karlowsky, JA, Keynan, Y, Morris, AM, Rubinstein, E, Jones, SB, Garcia, P, Cereceda, M, Fica, A, Mella, RM, Barsic, B, Bukovski, S, Krajinovic, V, Pangercic, A, Rudez, I, Vincelj, J, Freiberger, T, Pol, J, Zaloudikova, B, Ashour, Z, El Kholy, A, Mishaal, M, Rizk, H, Aissa, N, Alauzet, C, Alla, F, Campagnac, C, Doco-Lecompte, T, Selton-Suty, C, Casalta, J-P, Fournier, P-E, Habib, G, Raoult, D, Thuny, F, Delahaye, F, Delahaye, A, Vandenesch, F, Donal, E, Donnio, PY, Michelet, C, Revest, M, Tattevin, P, Violette, J, Chevalier, F, Jeu, A, Dan, Rusinaru, Sorel, C, Tribouilloy, C, Bernard, Y, Chirouze, C, Hoen, B, Leroy, J, Plesiat, P, Naber, C, Neuerburg, C, Mazaheri, B, Athanasia, S, Giannitsioti, E, Mylona, E, Paniara, O, Papanicolaou, K, Pyros, J, Skoutelis, A, Sharma, G, Francis, J, Nair, L, Thomas, V, Venugopal, K, Hannan, M, Hurley, J, Gilon, D, Israel, S, Korem, M, Strahilevitz, J, Tripodi, MF, Casillo, R, Cuccurullo, S, Dialetto, G, Durante-Mangoni, E, Irene, M, Ragone, E, Utili, R, Cecchi, E, De Rosa, F, Imazio, M, Trinchero, R, Tebini, A, Grossi, P, Lattanzio, M, Toniolo, A, Goglio, A, Raglio, A, Ravasio, V, Rizzi, M, Suter, F, Carosi, G, Magri, S, Signorini, L, Baban, T, Kanafani, Z, Kanj, SS, Sfeir, J, Yasmine, M, Abidin, I, Tamin, SS, Martinez, ER, Nieto, GIS, van der Meer, JTM, Chambers, S, Murdoch, DR, Dragulescu, S, Ionac, A, Mornos, C, Butkevich, OM, Chipigina, N, Kirill, O, Vadim, K, Edathodu, J, Halim, M, Lum, L-N, Tan, R-S, Lejko-Zupanc, T, Logar, M, Mueller-Premru, M, Commerford, P, Commerford, A, Deetlefs, E, Hansa, C, Ntsekhe, M, Armero, Y, Azqueta, M, Castaneda, X, Cervera, C, Falces, C, Garcia-de-la-Maria, C, Fita, G, Gatell, JM, Marco, F, Mestres, CA, Miro, JM, Moreno, A, Ninot, S, Pare, C, Pericas, J, Ramirez, J, Rovira, I, Sitges, M, Anguera, I, Font, B, Guma, JR, Bermejo, J, Garcia Fernandez, MA, Gonzalez-Ramallo, V, Marin, M, Munoz, P, Pedromingo, M, Roda, J, Rodriguez-Creixems, M, Solis, J, Tornos, P, de Alarcon, A, Parra, R, Alestig, E, Johansson, M, Olaison, L, Snygg-Martin, U, Pachirat, O, Pachirat, P, Pussadhamma, B, Senthong, V, Casey, A, Elliott, T, Lambert, P, Watkin, R, Eyton, C, Klein, JL, Bradley, S, Kauffman, C, Bedimo, R, Crowley, AL, Douglas, P, Drew, L, Fowler, VG, Holland, T, Mudrick, D, Samad, Z, Sexton, D, Stryjewski, M, Wang, A, Lerakis, S, Cantey, R, Steed, L, Dickerman, SA, Bonilla, H, DiPersio, J, Salstrom, S-J, Baddley, J, Patel, M, Peterson, G, Stancoven, A, Afonso, L, Kulman, T, Levine, D, Rybak, M, Cabell, CH, Baloch, K, Dixon, CC, Harding, T, Jones-Richmond, M, Park, LP, Redick, T, Stafford, J, Anstrom, K, Bayer, AS, Karchmer, AW, Sexton, DJ, Chu, V, Durack, DT, Phil, D, Eykyn, S, and Moreillon, P

Abstract

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Published
2013

35. Folding and activity of recombinant human procollagen C-proteinase enhancer

Author

Moschcovich, L., Bernocco, S., Font, B., Rivkin, H., Eichenberger, D., Chejanovsky, N., Hulmes, Dj, Kessler, E., and Deleage, Gilbert

Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

Recombinant human procollagen C-proteinase enhancer (rPCPE) was expressed using a baculovirus system and purified to homogeneity using a three-step procedure including heparin affinity chromatography. Heparin binding was dependent on the C-terminal netrin-like domain. The recombinant protein was found to be active, increasing the activity of procollagen C-proteinase/bone morphogenetic protein-1 on type I procollagen in a manner comparable to the native protein. Enhancing activity was dependent on intact disulfide bonding within the protein. By circular dichroism, the observed secondary structure of rPCPE was consistent with the known three-dimensional structures of proteins containing homologous domains.Recombinant human procollagen C-proteinase enhancer (rPCPE) was expressed using a baculovirus system and purified to homogeneity using a three-step procedure including heparin affinity chromatography. Heparin binding was dependent on the C-terminal netrin-like domain. The recombinant protein was found to be active, increasing the activity of procollagen C-proteinase/bone morphogenetic protein-1 on type I procollagen in a manner comparable to the native protein. Enhancing activity was dependent on intact disulfide bonding within the protein. By circular dichroism, the observed secondary structure of rPCPE was consistent with the known three-dimensional structures of proteins containing homologous domains.

Published
2001

36. Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1

Author

Borel, A., Eichenberger, D., Farjanel, J., Kessler, E., Gleyzal, C., Hulmes, Dj, Sommer, P., Font, B., and Deleage, Gilbert

Subjects
integumentary system, cardiovascular system, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, macromolecular substances, eye diseases
Abstract

Recently several cDNAs have been described encoding lysyl oxidase-like proteins. Their deduced amino acid sequences are characterized by a strong similarity in the C-terminal region, corresponding to the lysyl oxidase family catalytic domain, and by marked differences in the N-terminal regions. Different biological functions have been described for lysyl oxidases in addition to their traditionally assumed cross-linking role. To answer the question of whether these different functions are carried out by different lysyl oxidases, purified and active forms of these enzymes are required. At present only the classical form of lysyl oxidase has been purified and characterized. The purpose of this study was to isolate and characterize the lysyl oxidase-like protein. In view of the strong sequence homology with the C-terminal domain of other lysyl oxidases, we chose to purify the protein from bovine aorta using antibodies specific to the N-terminal domain of the proenzyme. We have isolated a 56-kDa protein identified by amino acid sequencing as the bovine lysyl oxidase-like precursor, which is cleaved at the Arg-Arg-Arg sequence at positions 89-91 by a furin-like activity, as revealed after deblocking of the N-terminal residue. The immunopurified protein was largely inactive, but further processing in vitro by bone morphogenetic protein-1 led to an enzyme that was active on elastin and collagen substrates.Recently several cDNAs have been described encoding lysyl oxidase-like proteins. Their deduced amino acid sequences are characterized by a strong similarity in the C-terminal region, corresponding to the lysyl oxidase family catalytic domain, and by marked differences in the N-terminal regions. Different biological functions have been described for lysyl oxidases in addition to their traditionally assumed cross-linking role. To answer the question of whether these different functions are carried out by different lysyl oxidases, purified and active forms of these enzymes are required. At present only the classical form of lysyl oxidase has been purified and characterized. The purpose of this study was to isolate and characterize the lysyl oxidase-like protein. In view of the strong sequence homology with the C-terminal domain of other lysyl oxidases, we chose to purify the protein from bovine aorta using antibodies specific to the N-terminal domain of the proenzyme. We have isolated a 56-kDa protein identified by amino acid sequencing as the bovine lysyl oxidase-like precursor, which is cleaved at the Arg-Arg-Arg sequence at positions 89-91 by a furin-like activity, as revealed after deblocking of the N-terminal residue. The immunopurified protein was largely inactive, but further processing in vitro by bone morphogenetic protein-1 led to an enzyme that was active on elastin and collagen substrates.

Published
2001

37. Non-HACEK gram-negative bacillus endocarditis.

Author

Delahaye F., Patel M., Dismukes W., Pan A., Caros G., Tribouilloy A.B.M.C., Ramallo V., Raoult D., Thuny F., Habib G., Casalta J.-P., Fournier P.-E., Chipigina N., Kirill O., Vinogradova T., Kulichenko V.P., Butkevich O.M., Lion C., Selton-Suty C., Alla F., Coyard H., Doco-Lecompte T., Durante-Mangoni E., Ragone E., Dialetto G., Tripodi M.F., Utili R., Casillo R., Kumar A.S., Sharma G., Street A., Eisen D.P., McBryde E.S., Grigg L., Abrutyn E., Michelet C., Donnio P.Y., Fortes C.Q., Edathodu J., Al-Hegelan M., Font B., Anguera I., Guma J.R., Cereceda M., Oyonarte M.J., Mella R.M., Garcia P., Jones S.B., Paiva M.G., Tranchesi R.A.D.M., Woon L.L., Lum L.-N., Tan R.-S., Rees D., Kornecny P., Lawrence R., Dever R., Post J., Jones P., Ryan S., Harkness J., Feneley M., Rubinstein E., Strahilewitz J., Ionac A., Mornos C., Dragulescu S., Forno D., Cecchi E., De Rosa F., Imazio M., Trinchero R., Wiesbauer F., Gattringer R., Deans G., Andrasevic A.T., Barsic B., Klinar I., Vincelj J., Bukovski S., Krajinovic V., Stafford J., Baloch K., Redick T., Harding T., Bayer A.S., Durack D.T., Moreillon P., Eykyn S., Morpeth S., Murdoch D., Cabell C.H., Karchmer A.W., Pappas P., Levine D., Nacinovich F., Tattevin P., Fernandez-Hidalgo N., Dickerman S., Bouza E., Del Rio A., Lejko-Zupanc T., De Oliveira Ramos A., Iarussi D., Klein J., Chirouze C., Bedimo R., Corey G.R., Fowler Jr. V.G., Gordon D., Devi U., Spelman D., Van Der Meer J.T.M., Kauffman C., Bradley S., Armstrong W., Giannitsioti E., Giamarellou H., Lerakis S., Moreno A., Mestres C.A., Pare C., Garcia De La Maria C., De Lazzario E., Marco F., Gatell J.M., Miro J.M., Almela M., Azqueta M., Jimenez-Exposito M.J., De Benito N., Perez N., Almirante B., Rodriguez De Vera P., Tornos P., Falco V., Claramonte X., Armero Y., Sidani N., Kanj-Sharara S., Kanafani Z., Raglio A., Goglio A., Gnecchi F., Suter F., Valsecchi G., Rizzi M., Ravasio V., Hoen B., Leroy J., Plesiat P., Bernard Y., Casey A., Lambert P., Watkin R., Elliott T., Goissen T., Delahaye A., Vandenesch F., Vizzotti C., Nacinovich F.M., Trivi M., Lombardero M., Cortes C., Casabe J.H., Altclas J., Kogan S., Clara L., Sanchez M., Commerford A., Hansa C., Deetlefs E., Ntsekhe M., Commerford P., Wray D., Steed L.L., Church P., Cantey R., Morris A., Chambers S., Read K., Raymond N., Holland D., Lang S., Kotsanas D., Korman T.M., Peterson G., Purcell J., Southern Jr. P.M., Shah M., Reddy A., Dhar G., Hanlon-Feeney A., Hannan M., Kelly S., Wang A., Woods C.W., Sexton D.J., Benjamin Jr. D., McDonald J.R., Federspiel J., Engemann J.J., Reller L.B., Drew L., Caram L.B., Stryjewski M., Lalani T., Chu V., Mazaheri B., Neuerburg C., Naber C., Athan E., Henry M., Harris O., Alestig E., Olaison L., Wikstrom L., Snygg-Martin U., Francis J., Venugopal K., Nair L., Thomas V., Chaiworramukkun J., Pachirat O., Chetchotisakd P., Suwanich T., Kamarulzaman A., Tamin S.S., Mueller Premru M., Logar M., Orezzi C., Moreno M., Rodriguez-Creixems M., Marin M., Fernandez M., Munoz P., Fernandez R., Delahaye F., Patel M., Dismukes W., Pan A., Caros G., Tribouilloy A.B.M.C., Ramallo V., Raoult D., Thuny F., Habib G., Casalta J.-P., Fournier P.-E., Chipigina N., Kirill O., Vinogradova T., Kulichenko V.P., Butkevich O.M., Lion C., Selton-Suty C., Alla F., Coyard H., Doco-Lecompte T., Durante-Mangoni E., Ragone E., Dialetto G., Tripodi M.F., Utili R., Casillo R., Kumar A.S., Sharma G., Street A., Eisen D.P., McBryde E.S., Grigg L., Abrutyn E., Michelet C., Donnio P.Y., Fortes C.Q., Edathodu J., Al-Hegelan M., Font B., Anguera I., Guma J.R., Cereceda M., Oyonarte M.J., Mella R.M., Garcia P., Jones S.B., Paiva M.G., Tranchesi R.A.D.M., Woon L.L., Lum L.-N., Tan R.-S., Rees D., Kornecny P., Lawrence R., Dever R., Post J., Jones P., Ryan S., Harkness J., Feneley M., Rubinstein E., Strahilewitz J., Ionac A., Mornos C., Dragulescu S., Forno D., Cecchi E., De Rosa F., Imazio M., Trinchero R., Wiesbauer F., Gattringer R., Deans G., Andrasevic A.T., Barsic B., Klinar I., Vincelj J., Bukovski S., Krajinovic V., Stafford J., Baloch K., Redick T., Harding T., Bayer A.S., Durack D.T., Moreillon P., Eykyn S., Morpeth S., Murdoch D., Cabell C.H., Karchmer A.W., Pappas P., Levine D., Nacinovich F., Tattevin P., Fernandez-Hidalgo N., Dickerman S., Bouza E., Del Rio A., Lejko-Zupanc T., De Oliveira Ramos A., Iarussi D., Klein J., Chirouze C., Bedimo R., Corey G.R., Fowler Jr. V.G., Gordon D., Devi U., Spelman D., Van Der Meer J.T.M., Kauffman C., Bradley S., Armstrong W., Giannitsioti E., Giamarellou H., Lerakis S., Moreno A., Mestres C.A., Pare C., Garcia De La Maria C., De Lazzario E., Marco F., Gatell J.M., Miro J.M., Almela M., Azqueta M., Jimenez-Exposito M.J., De Benito N., Perez N., Almirante B., Rodriguez De Vera P., Tornos P., Falco V., Claramonte X., Armero Y., Sidani N., Kanj-Sharara S., Kanafani Z., Raglio A., Goglio A., Gnecchi F., Suter F., Valsecchi G., Rizzi M., Ravasio V., Hoen B., Leroy J., Plesiat P., Bernard Y., Casey A., Lambert P., Watkin R., Elliott T., Goissen T., Delahaye A., Vandenesch F., Vizzotti C., Nacinovich F.M., Trivi M., Lombardero M., Cortes C., Casabe J.H., Altclas J., Kogan S., Clara L., Sanchez M., Commerford A., Hansa C., Deetlefs E., Ntsekhe M., Commerford P., Wray D., Steed L.L., Church P., Cantey R., Morris A., Chambers S., Read K., Raymond N., Holland D., Lang S., Kotsanas D., Korman T.M., Peterson G., Purcell J., Southern Jr. P.M., Shah M., Reddy A., Dhar G., Hanlon-Feeney A., Hannan M., Kelly S., Wang A., Woods C.W., Sexton D.J., Benjamin Jr. D., McDonald J.R., Federspiel J., Engemann J.J., Reller L.B., Drew L., Caram L.B., Stryjewski M., Lalani T., Chu V., Mazaheri B., Neuerburg C., Naber C., Athan E., Henry M., Harris O., Alestig E., Olaison L., Wikstrom L., Snygg-Martin U., Francis J., Venugopal K., Nair L., Thomas V., Chaiworramukkun J., Pachirat O., Chetchotisakd P., Suwanich T., Kamarulzaman A., Tamin S.S., Mueller Premru M., Logar M., Orezzi C., Moreno M., Rodriguez-Creixems M., Marin M., Fernandez M., Munoz P., and Fernandez R.

Abstract

Background: Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is rare, is poorly characterized, and is commonly considered to be primarily a disease of injection drug users. Objective(s): To describe the clinical characteristics and outcomes of patients with non-HACEK gram-negative bacillus endocarditis in a large, international, contemporary cohort of patients. Design(s): Observations from the International Collaboration on Infective Endocarditis Prospective Cohort Study (ICE-PCS) database. Setting(s): 61 hospitals in 28 countries. Patient(s): Hospitalized patients with definite endocarditis. Measurements: Characteristics of non-HACEK gram-negative bacillus endocarditis cases were described and compared with those due to other pathogens. Result(s): Among the 2761 case-patients with definite endocarditis enrolled in ICE-PCS, 49 (1.8%) had endocarditis (20 native valve, 29 prosthetic valve or device) due to non-HACEK, gram-negative bacilli. Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]) were the most common pathogens. Most patients (57%) with non-HACEK gram-negative bacillus endocarditis had health care-associated infection, whereas injection drug use was rare (4%). Implanted endovascular devices were frequently associated with non-HACEK gram-negative bacillus endocarditis compared with other causes of endocarditis (29% vs. 11%; P < 0.001). The in-hospital mortality rate of patients with endocarditis due to non-HACEK gram-negative bacilli was high (24%) despite high rates of cardiac surgery (51%). Limitation(s): Because of the small number of patients with non-HACEK gram-negative bacillus endocarditis in each treatment group and the lack of long-term follow-up, strong treatment recommendations are difficult to make. Conclusion(s): In this large, prospective, multinational

Published
2008

38. Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region

Author

Font, B., Eichenberger, D., Goldschmidt, D., Boutillon, Mm, Hulmes, Dj, and Deleage, Gilbert

Subjects
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

Published
1998

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