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2. 25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial

Author

Bosson, Jean-Luc, Pichot, Olivier, Maufus, Mario, Guenneguez, Hervé, Ouvry, Pierre, Di Maio, Anna, Schmidt, Jeannot, Galanaud, Jean-Philippe, Bura-Rivière, Alessandra, Couturaud, Francis, Danguy Des Déserts, Marc, Grange, Claire, Mismetti, Patrick, Barrellier, Marie-Thérèse, Laneelle, Damien, Terriat, Béatrice, Stansal, Audrey, Martin, Myriam, Quashie, Constant, Bonaldi, Mickaël, Lanoye, Patrick, Ponchaux-Crépin, Francine, Berremili, Toufek, Sevestre-Pietri, Marie-Antoinette, Samy-Modeliar, Santhi, Addala, Azeddine, Toffin, Luc, Rouquet, Bruno, Michot-Casbas, Maïlys, Lacaze, Guillaume, Roy, Pierre-Marie, Durant, Cécile, Baldassini-Esquis, Anne-Laure, Cazanave, Alain, Rouvière, Damien, Skolka, Hélène, Salem, Tewfik, Monsallier, Jean-Michel, Roger, Benoit, Tra, Thien-Quang, Kalolwa, Mutendi, Diard, Antoine, Lambert, Marc, Taiar, Mebarka, Gaudout, Céline, Ancey, Sylvain, Jurus, Christine, Genty-Vermorel, Céline, Becker, François, Jabbour, Violaine, Blaise, Sophie, Comte, Alexa, Guenneguez, Herve, Richaud, Cécile, Rolland, Carole, Sevestre, Marie-Antoinette, and Verrière, François

Published
2022
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4. Long‐term risk of postthrombotic syndrome after symptomatic distal deep vein thrombosis: The CACTUS‐PTS study

Author

Galanaud, Jean‐Philippe, Righini, Marc, Le Collen, Lorris, Douillard, Aymeric, Robert‐Ebadi, Helia, Pontal, Daniel, Morrison, David, Barrellier, Marie‐Thérèse, Diard, Antoine, Guénnéguez, Hervé, Brisot, Dominique, Faïsse, Pascale, Accassat, Sandrine, Martin, Myriam, Delluc, Aurélien, Solymoss, Susan, Kassis, Jeannine, Carrier, Marc, Quéré, Isabelle, and Kahn, Susan R.

Published
2020
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7. 36-month clinical outcomes of patients with venous thromboembolism

Author

Alexander G.G. Turpie, Alfredo E. Farjat, Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Shinya Goto, Pantep Angchaisuksiri, Gloria Kayani, Renato D. Lopes, Chern-En Chiang, Harry Gibbs, Eric Tse, Peter Verhamme, Hugo ten Cate, Juan Muntaner, Sebastian Schellong, Henri Bounameaux, Paolo Prandoni, Uma Maheshwari, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool-Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera-Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann-Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau-Chung Wu, Cheng Hock Toh, Chevrier Elisa, Chien-Hsun Hsia, Chien-Lung Huang, Chi-Hang Kevin Kwok, Chih-Cheng Wu, Chi-Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret-Gris, Chung Yin Ha, Chun-Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, David - Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs-Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala-Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia-Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye-Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean-Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans-Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho-Young Yhim, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik-Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M. De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer-Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen-Yuan Kuo, Jhih-Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jørn Nielsen, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou-Gi Shyu, Kristel Vandenbosch, Kuan-Cheng Chang, Kuan-Ming Chiu, Kubina Jean-Manuel, Kwan Jing Wern, Kwo-Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool-Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El-Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon-Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan-Keim, Remedios Otero, Renate Murena-Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung-Hyun Nam, Sevestre-Pietri Marie-Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe-Nana Jean-Léopold, Somchai Wongkhantee, Soo-Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel-Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting-Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei-Hsiang Lin, Weihua Zhang, Wei-Kung Tseng, Wen-Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won Il Choi, Yang-Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung-Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, VU University medical center, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - B04 Clinical thrombosis and Haemostasis

Subjects
History, Anticoagulation, Registry, Polymers and Plastics, SDG 3 - Good Health and Well-being, Deep vein thrombosis, Pulmonary embolism, Hematology, Business and International Management, Industrial and Manufacturing Engineering, Venous thromboembolism
Abstract

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Published
2023

8. Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis

Author

Martin, Myriam, primary, Nilsson, Sara C., additional, Eikrem, David, additional, Fromell, Karin, additional, Scavenius, Carsten, additional, Vogt, Leonie M., additional, Bielecka, Ewa, additional, Potempa, Jan, additional, Enghild, Jan J., additional, Nilsson, Bo, additional, Ekdahl, Kristina N., additional, Kapetanovic, Meliha C., additional, and Blom, Anna M., additional

Published
2023
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9. Complement activation negatively affects the platelet response to thrombopoietin receptor agonists in patients with immune thrombocytopenia: a prospective cohort study.

Author

Åkesson, Alexander, Bussel, James B., Martin, Myriam, Blom, Anna M., Klintman, Jenny, Ghanima, Waleed, Zetterberg, Eva, and Garabet, Lamya

Subjects
THROMBOPOIETIN receptor agonists, IDIOPATHIC thrombocytopenic purpura, COMPLEMENT activation, BLOOD platelets, PLATELET count
Abstract

Increased platelet destruction is central in the pathogenesis of immune thrombocytopenia. However, impaired platelet production is also relevant and its significance underlies the rationale for treatment with thrombopoietin receptor agonists (TPO-RAs). Previous studies have associated enhanced complement activation with increased disease severity. Additionally, treatment refractoriness has been demonstrated to resolve by the administration of complement-targeted therapeutics in a subset of patients. The association between complement activation and the platelet response to TPO-RA therapy has previously not been investigated. In this study, blood samples from patients with immune thrombocytopenia (n = 15) were prospectively collected before and two, six and 12 weeks after the initiation of TPORA therapy. Plasma levels of complement degradation product C4d and soluble terminal complement complexes were assessed. Patients with significantly elevated baseline levels of terminal complement complexes exhibited more often an inadequate platelet response (p = .04), were exclusively subjected to rescue therapy with intravenous immunoglobulin (p = .02), and did not respond with a significant platelet count increase during the study period. C4d showed a significant (p = .01) ability to distinguish samples with significant terminal complement activation, implying engagement of the classical complement pathway. In conclusion, elevated levels of complement biomarkers were associated with a worse TPO-RA treatment response. Larger studies are needed to confirm these results. Biomarkers of complement activation may prove valuable as a prognostic tool to predict which patients that potentially could benefit from complement-inhibiting therapy in the future. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Attachment, Relational Maintenance Behaviors and Relationship Quality in Romantic Long-Distance Relationships: A Dyadic Perspective

Author

Bouchard, Geneviève, Gaudet, Madeleine, Cloutier, Gabrielle, and Martin, Myriam

Subjects
couples, relational maintenance behaviors, long-distance relationships, dyadic data analysis, relationship quality, attachment
Abstract

This study tested an actor-partner interdependence mediation model (APIMeM) in which dyadic relational maintenance behaviors (RMBs) mediate the relationship between romantic attachment (i.e., anxious and avoidant) and multiple indicators of relationship quality among couples in long-distance relationships (LDRs). Data were collected from 137 couples (women’s mean age = 20.37 years; men’s mean age = 21.93) who were in a serious romantic LDR and who completed an attachment measure, a measure of dyadic RMBs, and four measures of relationship quality (i.e., relationship satisfaction, relational commitment, closeness with the partner, and connection with others). Path analyses revealed significant actor and partner effects. Moreover, a total mediation between women’s anxious attachment and both partners’ relationship quality, and a partial mediation between men’s and women’s avoidant attachment and their own relationship quality were uncovered. Overall, the results suggest that, for couples in LDRs, one partner’s behaviors, cognitions, or emotions influence each member of the dyad as well as the quality of the relationship.

Published
2023
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11. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial

Author

Righini, Marc, Galanaud, Jean-Philippe, Guenneguez, Hervé, Brisot, Dominique, Diard, Antoine, Faisse, Pascale, Barrellier, Marie-Thérèse, Hamel-Desnos, Claudine, Jurus, Christine, Pichot, Olivier, Martin, Myriam, Mazzolai, Lucia, Choquenet, Clarisse, Accassat, Sandrine, Robert-Ebadi, Helia, Carrier, Marc, Le Gal, Grégoire, Mermilllod, Bernadette, Laroche, Jean-Pierre, Bounameaux, Henri, Perrier, Arnaud, Kahn, Susan R, and Quere, Isabelle

Published
2016
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12. Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis

Author

Martin, Myriam, Nilsson, Sara C. C., Eikrem, David, Fromell, Karin, Scavenius, Carsten, Vogt, Leonie M. M., Bielecka, Ewa, Potempa, Jan, Enghild, Jan J. J., Nilsson, Bo, Ekdahl, Kristina N. N., Kapetanovic, Meliha C. C., Blom, Anna M. M., Martin, Myriam, Nilsson, Sara C. C., Eikrem, David, Fromell, Karin, Scavenius, Carsten, Vogt, Leonie M. M., Bielecka, Ewa, Potempa, Jan, Enghild, Jan J. J., Nilsson, Bo, Ekdahl, Kristina N. N., Kapetanovic, Meliha C. C., and Blom, Anna M. M.

Abstract

Background Dysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation. Methods Citrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples. Results C1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples. Conclusion Citrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes

Published
2023
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14. 25 mm Hg versus 35 mm Hg elastic compression stockings to prevent post-thrombotic syndrome after deep vein thrombosis (CELEST): a randomised, double-blind, non-inferiority trial

Author

Galanaud, Jean-Philippe, primary, Genty-Vermorel, Céline, additional, Barrellier, Marie-Thérèse, additional, Becker, François, additional, Jabbour, Violaine, additional, Blaise, Sophie, additional, Bura-Rivière, Alessandra, additional, Comte, Alexa, additional, Grange, Claire, additional, Guenneguez, Herve, additional, Maufus, Mario, additional, Ouvry, Pierre, additional, Richaud, Cécile, additional, Rolland, Carole, additional, Schmidt, Jeannot, additional, Sevestre, Marie-Antoinette, additional, Verrière, François, additional, Bosson, Jean-Luc, additional, Pichot, Olivier, additional, Guenneguez, Hervé, additional, Di Maio, Anna, additional, Galanaud, Jean-Philippe, additional, Couturaud, Francis, additional, Danguy Des Déserts, Marc, additional, Mismetti, Patrick, additional, Laneelle, Damien, additional, Terriat, Béatrice, additional, Stansal, Audrey, additional, Martin, Myriam, additional, Quashie, Constant, additional, Bonaldi, Mickaël, additional, Lanoye, Patrick, additional, Ponchaux-Crépin, Francine, additional, Berremili, Toufek, additional, Sevestre-Pietri, Marie-Antoinette, additional, Samy-Modeliar, Santhi, additional, Addala, Azeddine, additional, Toffin, Luc, additional, Rouquet, Bruno, additional, Michot-Casbas, Maïlys, additional, Lacaze, Guillaume, additional, Roy, Pierre-Marie, additional, Durant, Cécile, additional, Baldassini-Esquis, Anne-Laure, additional, Cazanave, Alain, additional, Rouvière, Damien, additional, Skolka, Hélène, additional, Salem, Tewfik, additional, Monsallier, Jean-Michel, additional, Roger, Benoit, additional, Tra, Thien-Quang, additional, Kalolwa, Mutendi, additional, Diard, Antoine, additional, Lambert, Marc, additional, Taiar, Mebarka, additional, Gaudout, Céline, additional, Ancey, Sylvain, additional, and Jurus, Christine, additional

Published
2022
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16. Factor IX antibodies and tolerance in hemophilia B in the Nordic countries – The impact of F9 variants and complications

Author

Kihlberg, Kristina, primary, Baghaei, Fariba, additional, Bruzelius, Maria, additional, Funding, Eva, additional, Holme, Pål Andre, additional, Lassila, Riitta, additional, Martin, Myriam, additional, Nummi, Vuokko, additional, Ranta, Susanna, additional, Strandberg, Karin, additional, Andersson, Nadine Gretenkort, additional, Berntorp, Erik, additional, and Astermark, Jan, additional

Published
2022
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17. Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases

Author

Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, Ronnblom, Lars, Lundtoft, Christian, Pucholt, Pascal, Martin, Myriam, Bianchi, Matteo, Lundstrom, Emeli, Eloranta, Maija-Leena, Sandling, Johanna K., Sjöwall, Christopher, Jonsen, Andreas, Gunnarsson, Iva, Rantapaa-Dahlqvist, Solbritt, Bengtsson, Anders A., Leonard, Dag, Baecklund, Eva, Jonsson, Roland, Hammenfors, Daniel, Forsblad-dElia, Helena, Eriksson, Per, Mandl, Thomas, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglaend, Omdal, Roald, Kvarnstrom, Marika, Wahren-Herlenius, Marie, Notarnicola, Antonella, Andersson, Helena, Molberg, Oyvind, Diederichsen, Louise Pyndt, Almlof, Jonas, Syvanen, Ann-Christine, Kozyrev, Sergey V, Lindblad-Toh, Kerstin, Nilsson, Bo, Blom, Anna M., Lundberg, Ingrid E., Nordmark, Gunnel, Diaz-Gallo, Lina Marcela, Svenungsson, Elisabet, and Ronnblom, Lars

Abstract

Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjogrens syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account., Funding Agencies|Swedish Research Council for Medicine and Health; Swedish Rheumatism Association; Swedish Society of Medicine; Swedish Heart Lung Foundation; Stockholm County; Karolinska Institutet; Wallenberg Scholarship; King Gustav Vs 80-Year Foundation

Published
2022
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18. Factor IX antibodies and tolerance in hemophilia B in the Nordic countries – The impact of F9 variants and complications

Author

Kihlberg, Kristina, Baghaei, Fariba, Bruzelius, Maria, Funding, Eva, Holme, Pål Andre, Lassila, Riitta, Martin, Myriam, Nummi, Vuokko, Ranta, Susanna, Strandberg, Karin, Andersson, Nadine Gretenkort, Berntorp, Erik, Astermark, Jan, Kihlberg, Kristina, Baghaei, Fariba, Bruzelius, Maria, Funding, Eva, Holme, Pål Andre, Lassila, Riitta, Martin, Myriam, Nummi, Vuokko, Ranta, Susanna, Strandberg, Karin, Andersson, Nadine Gretenkort, Berntorp, Erik, and Astermark, Jan

Abstract

Introduction: The development of inhibitory antibodies (inhibitors) in persons with hemophilia B (PwHB) causes significant morbidity. Data on the impact of the F9 variant and immune tolerance induction (ITI) outcome are limited. The aim of this study was to investigate the presence of neutralizing and non-neutralizing antibodies (NNA) in severe hemophilia B (HB) and to evaluate ITI outcome and complications in relation to the pathogenic F9 variant. Materials and methods: Persons with severe HB in the Nordic countries were enrolled and information on F9 variants, inhibitors, ITI and complications were collected. Analyses of anti-FIX antibodies with a fluorescence-immunoassay (xFLI) and an ELISA method were conducted. Results: Seventy-nine PwHB were enrolled. Null variants were seen in 33 (42 %) PwHB and 12 (15 %) had a current or former inhibitor. Eleven (92 %) of the inhibitor patients had experienced allergic manifestations and three (25 %) nephrotic syndrome. Of 10 PwHB with at least one ITI attempt, eight (80 %) were considered tolerant at enrolment. Immunosuppression was included in seven of eight successful or partially successful attempts. Five PwHB had at least one ITI failure before a successful or partially successful ITI. No NNA could be identified. Conclusion: A high proportion of severe F9 gene defects among persons with severe HB in the Nordic countries may explain the observed relatively high prevalence of inhibitors. ITI success was independent of the F9 variant and attained despite allergic manifestations and previous ITI failures. Inclusion of immunosuppression tentatively enhances the chances of ITI success. No NNA were observed.

Published
2022

19. Methods for anti‐factor VIII antibody levels in haemophilia A patients – validation of a multiplex immunoassay and comparability with assays measuring non‐neutralising and neutralising antibodies (inhibitors).

Author

Martin, Myriam, Augustsson, Cecilia, Lind, Vivian, Al‐Sabti, Riam, Lam, My Chi, Andersson, Nadine G., and Strandberg, Karin

Subjects
*BLOOD coagulation factor VIII antibodies, *IMMUNOASSAY, *HEMOPHILIA, *IMMUNOGLOBULINS, *ENZYME-linked immunosorbent assay
Abstract

Introduction: The development of neutralising (inhibitors) and non‐neutralising antibodies (NNAs) is a complication to factor replacement therapy in haemophilia. The diagnostic methods available lack standardisation, have high inter‐laboratory variation, and false‐negative as well as false‐positive results may affect treatment. Both functional inhibitors and NNAs may be detected with higher reproducibility, sensitivity and specificity using the immunological Luminex xMAP‐based fluorescence‐immunoassay (xFLI). Aim: Validation of our xFLI and comparability with enzyme‐linked immunosorbent assay (ELISA) and chromogenic Nijmegen‐Bethesda assay (CBA) for anti‐FVIII antibodies in haemophilia A (HA) patients. Methods: The xFLI method was developed with full‐length and B‐domain deleted factor coupled to magnetic beads, optimised and validated for performance characteristics. Comparability with ELISA and CBA was evaluated in HA patient samples (n = 112), serial samples in six inhibitor patients and reference interval and decision‐limits in healthy donors (n = 44). Results: The intra‐ and inter‐assay precision (CV%) for the xFLI method was below 6% and detection limit (LLOQ).084 ng/mL (NovoEight). All ELISA‐positive samples were positive with either Advate or NovoEight. Additionally, 10.7%–14.3% were xFLI‐positive and ELISA‐negative. All but one CBA‐positive sample was above 3SD with xFLI; one was between 2 and 3SD. 29.1% were xFLI‐positive and CBA negative. The overall concordance between xFLI and ELISA was 82.1% and xFLI and CBA 77.9%. Conclusion: The anti‐FVIII antibody xFLI method is adaptable to clinical practice and more sensitive and reproducible than ELISA and CBA. Actual NNA titers are determined to both full‐length and B‐domain deleted FVIII. The xFLI is thus valuable for confirmation of all anti‐FVIII antibodies. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Biomarkers of complement and platelet activation are not correlated with the one or twenty-four hours corrected count increments in prophylactically platelet transfused hematological patients: a prospective cohort study

Author

Åkesson, Alexander, primary, Ljungkvist, Marcus, additional, Martin, Myriam, additional, Blom, Anna M., additional, Klintman, Jenny, additional, Schött, Ulf, additional, Zetterberg, Eva, additional, and Kander, Thomas, additional

Published
2021
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23. Clinical characterization and identification of rare genetic variants in atypical hemolytic uremic syndrome:A Swedish retrospective observational study

Author

Åkesson, Alexander, Martin, Myriam, Blom, Anna M., Rossing, Maria, Gabrielaite, Migle, Zetterberg, Eva, Klintman, Jenny, Åkesson, Alexander, Martin, Myriam, Blom, Anna M., Rossing, Maria, Gabrielaite, Migle, Zetterberg, Eva, and Klintman, Jenny

Abstract

Complement-mediated atypical hemolytic uremic syndrome (aHUS) is an ultra-rare renal disease primarily caused by genetic alterations in complement proteins. The genetic work-up required for confirmation of diagnosis is complicated and not always logistically accessible. The aim of the present study was to apply a diagnostic scheme compliant with the American College of Medical Genetics and Genomics guidelines to investigate the prevalence of complement-mediated aHUS among subjects formerly included in a retrospective cohort of clinically suspected aHUS. Clinical outcomes and genetic correlations to complement analyses were assessed. Subjects were investigated with medical record reviewing, inquiries, and laboratory analyses composed of whole genome sequencing; enzyme-linked immunosorbent assays for factor I, factor H, and factor H-specific antibodies; nephelometry for complement components three of four; flow cytometry for CD46 surface expression and immunoblotting for the presence of factor H-related protein 1. In total, 45% (n = 60/134) of the subjects were deceased at the time of study. Twenty of the eligible subjects consented to study participation. Based on genetic sequencing and clinical characteristics, six were categorized as definite/highly suspected complement-mediated aHUS, 10 as non-complement-mediated aHUS and four as having an HUS-like phenotype. In the complement-mediated aHUS group, two subjects had not received an aHUS diagnosis during the routine clinical management. Disease-contributing/likely disease-contributing genetic variants were identified in five subjects, including a novel missense variant in the complement factor H gene (c.3450A>G, p.I1150M). This study illustrates the risk for misdiagnosis in the management of patients with complement-mediated aHUS and the importance of a comprehensive assessment of both phenotype and genotype to reach a diagnosis.

Published
2021

24. Severe Congenital Thrombocytopenia Characterized by Decreased Platelet Sialylation and Moderate Complement Activation Caused by Novel Compound Heterozygous Variants in GNE

Author

Smolag, Karolina I., Fager Ferrari, Marcus, Zetterberg, Eva, Leinoe, Eva, Ek, Torben, Blom, Anna M., Rossing, Maria, Martin, Myriam, Smolag, Karolina I., Fager Ferrari, Marcus, Zetterberg, Eva, Leinoe, Eva, Ek, Torben, Blom, Anna M., Rossing, Maria, and Martin, Myriam

Abstract

Background: Hereditary thrombocytopenias constitute a genetically heterogeneous cause of increased bleeding. We report a case of a 17-year-old boy suffering from severe macrothrombocytopenia throughout his life. Whole genome sequencing revealed the presence of two compound heterozygous variants in GNE encoding the enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, crucial for sialic acid biosynthesis. Sialic acid is required for normal platelet life span, and biallelic variants in GNE have previously been associated with isolated macrothrombocytopenia. Furthermore, sialic acid constitutes a key ligand for complement factor H (FH), an important inhibitor of the complement system, protecting host cells from indiscriminate attack. Methods: Sialic acid expression and FH binding to platelets and leukocytes was evaluated by flow cytometry. The binding of FH to erythrocytes was assessed indirectly by measuring the rate of complement mediated hemolysis. Complement activation was determined by measuring levels of C3bBbP (alternative pathway), C4d (classical/lectin pathway) and soluble terminal complement complex assays. Results: The proband exhibited markedly decreased expression of sialic acid on platelets and leukocytes. Consequently, the binding of FH was strongly reduced and moderate activation of the alternative and classical/lectin complement pathways was observed, together with an increased rate of erythrocyte lysis. Conclusion: We report two previously undescribed variants in GNE causing severe congenital macrothrombocytopenia in a compound heterozygous state, as a consequence of decreased platelet sialylation. The decreased sialylation of platelets, leukocytes and erythrocytes affects the binding of FH, leading to moderate complement activation and increased hemolysis.

Published
2021

28. Plasma C4d Correlates With C4d Deposition in Kidneys and With Treatment Response in Lupus Nephritis Patients

Author

Martin, Myriam, Trattner, Rebecca, Nilsson, Sara C., Björk, Albin, Zickert, Agneta, Blom, Anna M., and Gunnarsson, Iva

Subjects
lupus nephritis, Adult, Immunosuppression Therapy, Male, kidney deposition, Immunology, treatment response, Complement C4, Antigen-Antibody Complex, Middle Aged, Kidney, C4d, Young Adult, systemic lupus erythematosus, Disease Progression, Humans, Immunology and Allergy, complement, Female, Biomarkers, Original Research, Aged
Abstract

Objective To examine whether C4d plasma levels correlate with treatment response and C4d kidney deposition in systemic lupus erythematosus (SLE) with lupus nephritis (LN). Methods C4d plasma levels were analyzed by a unique assay specifically detecting C4d arising from complement activation and C4 plasma levels were quantified with competitive ELISA. SLE patients with LN (71) and active SLE patients without LN (22) plus 145 controls were included. For 52 LN patients samples were available both at baseline and after immunosuppressive treatment. C4d kidney deposition was detected using immunohistochemistry in two matching kidney biopsies of 12 LN patients. Results In comparison to population-based controls, plasma C4d levels were significantly increased in SLE patients (0.33 mg/L versus 0.94 mg/ml, p < 0.0001) with significantly higher levels in LN patients (1.02 mg/L) than in non-renal SLE patients (0.57 mg/L, p = 0.004). The C4d/C4 ratio was also significantly higher in LN (11.2) than in non-renal SLE patients (2.5, p = 0.0002). According to ROC curve analysis, C4d was found to be an accurate marker to discriminate LN from non-renal SLE patients (p = 0.004). The C4d/C4 ratio displayed even higher specificity, sensitivity and overall accuracy as marker for LN than C4d and C4 alone. At baseline, C4d levels correlated significantly with urine-albumin to creatinine ratio (rs = 0.43, p = 0.011) and with renal activity index (rs = 0.37, p = 0.002). Immunohistochemical staining showed glomerular deposits of C4d in kidney biopsies, which strikingly correlated with plasma C4d levels (rs = 0.7, p = 0.0002). Plasma C4d declined significantly after treatment in patients that experienced favorable clinical and histopathological response (p < 0.0001), while levels remained mainly unchanged in non-responders. Conclusion Plasma C4d discriminates LN from active non-renal SLE, correlates with C4d kidney deposits and appears valuable in monitoring responsiveness to various treatments. The C4d/C4 ratio might be superior to C4d alone.

Published
2020
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32. Biomarkers of Complement and Platelet Activation are not correlated with the One or Twenty-Four Hours Corrected Count Increments in Prophylactically Platelet Transfused Hematological Patients: a Prospective Cohort Study.

Author

Åkesson, Alexander, Ljungkvist, Marcus, Martin, Myriam, Blom, Anna M., Klintman, Jenny, Schött, Ulf, Zetterberg, Eva, and Kander, Thomas

Subjects
BLOOD platelet activation, COMPLEMENT activation, BLOOD platelet transfusion, BLOOD platelets, LONGITUDINAL method
Abstract

Platelet transfusion refractoriness is a serious clinical concern that complicates the management of thrombocytopenic patients. Previous studies have suggested a potential role for both complement and platelet activation based on in vitro analyses of platelet concentrates. In this study, the post-transfusion platelet response, as indicated by the corrected count increment at 1 and 24 h after prophylactic platelet transfusions, respectively, was correlated with the 1 h post-transfusion Δconcentration (1 h post-transfusion – pretransfusion) of complement and platelet activation biomarkers. The study was registered as a clinical trial at ClinicalTrials.gov (identifier: NCT02601131) and patients were recruited during inpatient care in the hematological department. Soluble terminal complement complexes, soluble P-selectin and soluble CD40 ligand were analyzed. Confirmed alloimmunized patients were excluded. Included subjects were either given platelet transfusions (n = 43) and categorized into four clinical study groups or included in a non-transfused control group (n = 10). In total, 54 transfusions were included. No transfusion-mediated complement activation was observed. The transfusions were associated with a significant increase in the concentration of soluble P-selectin (p <.001), primarily corresponding to the passive infusion of soluble P-selectin-containing plasma residuals. The Δconcentration of soluble P-selectin was, however, not significantly correlated with the corrected count increments. Thus, significant correlations between biomarkers of complement and platelet activation and the post-transfusion platelet response could not be demonstrated in this study. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients

Author

Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Alexander G.G. Turpie, Shinya Goto, Pantep Angchaisuksiri, Joern Dalsgaard Nielsen, Gloria Kayani, Audrey Zaghdoun, Alfredo E. Farjat, Sebastian Schellong, Henri Bounameaux, Lorenzo G. Mantovani, Paolo Prandoni, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool‐Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera‐Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim, Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann‐Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau‐Chung Wu, Cheng Hock Toh, Chern‐En Chiang, Chevrier Elisa, Chien‐Hsun Hsia, Chien‐Lung Huang, Chi‐Hang Kevin Kwok, Chih‐Cheng Wu, Chi‐Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret‐Gris, Chung Yin Ha, Chun‐Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs‐Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala‐Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia‐Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye‐Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean‐Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans‐Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Harry Gibbs, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho‐Young Yhim, Hugo ten Cate, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik‐Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer‐Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen‐Yuan Kuo, Jhih‐Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou‐Gi Shyu, Kristel Vandenbosch, Kuan‐Cheng Chang, Kuan‐Ming Chiu, Kubina Jean‐Manuel, Kwan Jing Wern, Kwo‐Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool‐Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El‐Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon‐Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Peter Verhamme, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan‐Keim, Remedios Otero, Renate Murena‐Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung‐Hyun Nam, Sevestre‐Pietri Marie‐Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe‐Nana Jean‐Léopold, Somchai Wongkhantee, Soo‐Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel‐Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting‐Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei‐Hsiang Lin, Weihua Zhang, Wei‐Kung Tseng, Wen‐Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won II Choi, Yang‐Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung‐Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Haas, S, Ageno, W, Weitz, J, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Dalsgaard Nielsen, J, Kayani, G, Zaghdoun, A, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, and Kakkar, A

Subjects
Male, pulmonary embolism, Time Factors, Deep vein, direct oral anticoagulant, Practice Patterns, 030204 cardiovascular system & hematology, heparin, Direct oral anticoagulants, 0302 clinical medicine, Pregnancy, Deep vein thrombosis, 80 and over, Registries, Practice Patterns, Physicians', ddc:616, Aged, 80 and over, Venous Thrombosis, Anticoagulant, Hematology, Heparin, Middle Aged, Thrombosis, Pulmonary embolism, medicine.anatomical_structure, Treatment Outcome, Practice Guidelines as Topic, Female, Guideline Adherence, medicine.drug, medicine.medical_specialty, medicine.drug_class, venous thromboembolism, direct oral anticoagulants, deep vein thrombosis, Aged, Anticoagulants, Blood Coagulation, Drug Utilization, Healthcare Disparities, Humans, Pulmonary Embolism, Venous Thromboembolism, 03 medical and health sciences, Thromboembolism, Internal medicine, medicine, In patient, cardiovascular diseases, Rivaroxaban, Physicians', business.industry, deep vein thrombosi, deep vein thrombosis, direct oral anticoagulants, heparin, pulmonary embolism, venous thromboembolism, equipment and supplies, Venous, medicine.disease, business, Venous thromboembolism
Abstract

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Published
2019

38. La victimización sexual de menores en el Código penal español y en la política criminal internacional.

Author

Cabrera Martín, Myriam and Cabrera Martín, Myriam

Subjects
Child sexual abuse--Spain, Criminal law--Spain
Abstract

La obra aborda el tratamiento que recibe el fenómeno de la victimización sexual de menores, no solo desde la dogmática jurídico-penal, sino también desde la política criminal que se propugna por parte de los organismos internacionales. Para ello se estructura en torno a dos Partes. En la Parte I se procede a realizar un análisis de los delitos que, en el Código Penal español, se refieren de una manera específica a la victimización sexual de menores, así como de las controversias que plantea su interpretación y aplicación, valorando si la legislación española da respuesta a la realidad de la victimización sexual de menores y en qué medida lo hace de una forma coherente, racional y respetuosa con los principios informadores del Derecho Penal. Asimismo, se analiza si la regulación contenida en el Código Penal responde adecuadamente a las exigencias de la Directiva 2011/93/UE, relativa a la lucha contra los abusos sexuales y la explotación sexual de los menores y la pornografía infantil, teniendo en cuenta que esta Directiva constituye el instrumento jurídico que de manera más inmediata y precisa vincula al legislador nacional, y que es también el más ambicioso en relación con las medidas relativas al Derecho Penal sustantivo. En la Parte II, previa exposición de los instrumentos jurídicos que poseen mayor relevancia en la lucha contra la victimización sexual de menores en el plano internacional, y previo establecimiento de un marco terminológico sobre la materia, se realiza una exposición y sistematización de las directrices internacionales relativas a la lucha contra la victimización sexual de menores, centrando la atención en aquellas medidas que poseen carácter penal y, dentro de estas, en las referentes a la tipificación de conductas y al establecimiento de penas.

Published
2019

40. Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages.

Author

Smolag, Karolina I., Mueni, Christine M., Leandersson, Karin, Jirström, Karin, Hagerling, Catharina, Mörgelin, Matthias, Barlow, Paul N., Martin, Myriam, and Blom, Anna M.

Subjects
COMPLEMENT factor H, CANCER cells, ECULIZUMAB, BREAST cancer, MONOCYTES, MACROPHAGES
Abstract

Macrophages are a major immune cell type in the tumor microenvironment, where they display a tumor-supporting phenotype. Factor H (FH) is a complement inhibitor that also plays a role in several cellular functions. To date, the phenotype of monocytes stimulated with FH has been unexplored. We discovered that FH is a survival factor for CD14+ primary human monocytes, promoting their differentiation into macrophages in serum-free medium. This activity was localized to the C-terminal domains of FH and it was inhibited in plasma, indicating that the phenomenon may be most relevant in tissues. FH-induced macrophages display characteristics of immunosuppressive cells including expression of CD163 and CD206, release of the anti-inflammatory cytokine IL-10 and changes in metabolism. Furthermore, FH-induced macrophages express low levels of HLA-DR but high levels of co-inhibitory molecule programmed death-ligand 1 (PD-L1), and accordingly, a reduced capacity for T-cell activation. Finally, we show that FH is expressed by human breast cancer cells and that this correlates with the presence of immunosuppressive macrophages, breast cancer recurrence and severity of the disease. We propose that the expression of FH by tumor cells and the promotion of an immunosuppressive cancer microenvironment by this protein should be taken into account when considering the effectiveness of immunotherapies against breast cancer. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Usages de la terre crue dans les habitats de la fin du Hallstatt en Moselle : l’exemple des habitats d’Illange (Moselle)

Author

Mathiot, Dimitri, Martin, Myriam, Centre départemental d’archéologie de Moselle, Département de la Moselle, Archéologie et histoire ancienne : Méditerranée - Europe (ARCHIMEDE), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Ministère de l'Education Nationale, AFEAF, SRA-DRAC Bretagne, Musée de Bretagne, CreAAH (UMR 6566), Inrap, Herma (EA 3811), Université de Poitiers, and Coquet, Nicolas

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

44. Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes.

Author

Martin, Myriam, Leffler, Jonatan, Smolag, Karolina, Mytych, Jennifer, Björk, Albin, Chaves, L D, Alexander, J J, Quigg, R J, Blom, Anna, Martin, Myriam, Leffler, Jonatan, Smolag, Karolina, Mytych, Jennifer, Björk, Albin, Chaves, L D, Alexander, J J, Quigg, R J, and Blom, Anna

Abstract

Factor H (FH) binds apoptotic cells to limit the inflammatory potential of complement. Here we report that FH is actively internalized by apoptotic cells to enhance cathepsin L-mediated cleavage of endogenously expressed C3, which results in increased surface opsonization with iC3b. In addition, internalized FH forms complexes with nucleosomes, facilitates their phagocytosis by monocytes and induces an anti-inflammatory biased cytokine profile. A similar cytokine response was noted for apoptotic cells coated with FH, confirming that FH diminishes the immunogenic and inflammatory potential of autoantigens. These findings were supported by in vivo observations from CFH(-/-) MRL-lpr mice, which exhibited higher levels of circulating nucleosomes and necrotic cells than their CFH(+/+) littermates. This unconventional function of FH broadens the established view of apoptotic cell clearance and appears particularly important considering the strong associations with genetic FH alterations and diseases such as systemic lupus erythematosus and age-related macular degeneration.Cell Death and Differentiation advance online publication, 15 January 2016; doi:10.1038/cdd.2015.164.

Published
2016

45. Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome

Author

Leffler, Jonatan, primary, Prohászka, Zoltán, additional, Mikes, Bálint, additional, Sinkovits, György, additional, Ciacma, Katarzyna, additional, Farkas, Péter, additional, Réti, Marienn, additional, Kelen, Kata, additional, Reusz, György S., additional, Szabó, Attila J., additional, Martin, Myriam, additional, and Blom, Anna M., additional

Published
2016
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47. C4d as new biomarker in systemic lupus erythematosus

Author

Martin, Myriam, primary, Smoląg, Karolina I., additional, Björk, Albin, additional, Gullstrand, Birgitta, additional, Okroj, Marcin, additional, Leffler, Jonatan, additional, Jönsen, Andreas, additional, Nilsson, Jan-Å ke, additional, Bengtsson, Anders A., additional, and Blom, Anna M., additional

Published
2016
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49. A subset of patients with systemic lupus erythematosus fails to degrade DNA from multiple clinically relevant sources.

Author

Leffler, Jonatan, Ciacma, Katarzyna, Gullstrand, Birgitta, Bengtsson, Anders, Martin, Myriam, Blom, Anna, Leffler, Jonatan, Ciacma, Katarzyna, Gullstrand, Birgitta, Bengtsson, Anders, Martin, Myriam, and Blom, Anna

Abstract

Patients with systemic lupus erythematosus (SLE) have a decreased ability to clear cell remnants and multiple deficiencies in the ability to degrade cellular chromatin have been linked to the disease. Since the discovery of neutrophil extracellular traps (NETs), a renewed interest has been sparked in this field of research with multiple studies reporting a decreased ability of patients with SLE to degrade NETs. In this study we extend these findings by investigating the ability of patients with SLE to degrade chromatin from multiple clinically relevant sources.

Published
2015

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