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Year of publication
- 2016 (125) (remove)
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- English (125)
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- HIV (2)
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- Institut für Ökologie, Evolution und Diversität (1)
Introduction: Neuronal death and subsequent denervation of target areas are hallmarks of many neurological disorders. Denervated neurons lose part of their dendritic tree, and are considered "atrophic", i.e. pathologically altered and damaged. The functional consequences of this phenomenon are poorly understood.
Results: Using computational modelling of 3D-reconstructed granule cells we show that denervation-induced dendritic atrophy also subserves homeostatic functions: By shortening their dendritic tree, granule cells compensate for the loss of inputs by a precise adjustment of excitability. As a consequence, surviving afferents are able to activate the cells, thereby allowing information to flow again through the denervated area. In addition, action potentials backpropagating from the soma to the synapses are enhanced specifically in reorganized portions of the dendritic arbor, resulting in their increased synaptic plasticity. These two observations generalize to any given dendritic tree undergoing structural changes.
Conclusions: Structural homeostatic plasticity, i.e. homeostatic dendritic remodeling, is operating in long-term denervated neurons to achieve functional homeostasis.
Lilienfeld-Toal, Marie von ; Berger, Annemarie ; Christopeit, Maximilian ; Hentrich, Marcus ; Heussel, Claus Peter ; Kalkreuth, Jana ; Klein, Michael ; Kochanek, Matthias ; Penack, Olaf ; Hauf, Elke ; Rieger, Christina ; Silling, Gerda ; Vehreschild, Maria J. G. T. ; Weber, Thomas ; Wolf, Hans-Heinrich ; Lehners, Nicola ; Schalk, Enrico ; Mayer, Karin
Background: Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly.
Methods: A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus.
Results: CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis.
Conclusions: CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome.
Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases
(2016)
Regula, Jörg Thomas ; Lundh von Leithner, Peter ; Foxton, Richard ; Barathi, Veluchamy A. ; Gemmy Cheung, Chui Ming ; Tun, Sai Bo Bo ; Wey, Yeo Sia ; Iwata, Daiju ; Dostalek, Miroslav ; Moelleken, Jörg ; Stubenrauch, Kay-Gunnar ; Nogoceke, Everson ; Widmer, Gabriella ; Strassburger, Pamela ; Koss, Michael Janusz ; Klein, Christian ; Shima, David T. ; Hartmann, Guido
Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A. Simultaneous VEGF-A and ANG-2 inhibition was found to reduce vessel lesion number, permeability, retinal edema, and neuron loss more effectively than either agent alone in a spontaneous choroidal neovascularization (CNV) model. We describe the generation of a bispecific domain-exchanged (crossed) monoclonal antibody (CrossMAb; RG7716) capable of binding, neutralizing, and depleting VEGF-A and ANG-2. RG7716 showed greater efficacy than anti-VEGF-A alone in a non-human primate laser-induced CNV model after intravitreal delivery. Modification of RG7716’s FcRn and FccR binding sites disabled the antibodies’ Fc-mediated effector functions. This resulted in increased systemic, but not ocular, clearance. These properties make RG7716 a potential nextgeneration therapy for neovascular indications of the eye.
Verbich, David ; Becker, Denise ; Vlachos, Andreas ; Mundel, Peter ; Deller, Thomas ; McKinney, R. Anne
Neurological diseases associated with neuronal death are also accompanied by axonal denervation of connected brain regions. In these areas, denervation leads to a decrease in afferent drive, which may in turn trigger active central nervous system (CNS) circuitry rearrangement. This rewiring process is important therapeutically, since it can partially recover functions and can be further enhanced using modern rehabilitation strategies. Nevertheless, the cellular mechanisms of brain rewiring are not fully understood. We recently reported a mechanism by which neurons remodel their local connectivity under conditions of network-perturbance: hippocampal pyramidal cells can extend spine head protrusions (SHPs), which reach out toward neighboring terminals and form new synapses. Since this form of activity-dependent rewiring is observed only on some spines, we investigated the required conditions. We speculated, that the actin-associated protein synaptopodin, which is involved in several synaptic plasticity mechanisms, could play a role in the formation and/or stabilization of SHPs. Using hippocampal slice cultures, we found that ~70 % of spines with protrusions in CA1 pyramidal neurons contained synaptopodin. Analysis of synaptopodin-deficient neurons revealed that synaptopodin is required for the stability but not the formation of SHPs. The effects of synaptopodin could be linked to its role in Ca(2+) homeostasis, since spines with protrusions often contained ryanodine receptors and synaptopodin. Furthermore, disrupting Ca(2+) signaling shortened protrusion lifetime. By transgenically reintroducing synaptopodin on a synaptopodin-deficient background, SHP stability could be rescued. Overall, we show that synaptopodin increases the stability of SHPs, and could potentially modulate the rewiring of microcircuitries by making synaptic reorganization more efficient.
Grammatikos, Georgios ; Dietz, Julia ; Ferreirós Bouzas, Nerea ; Koch, Alexander ; Dultz, Georg ; Bon, Dimitra ; Karakasiliotis, Ioannis ; Lutz, Thomas ; Knecht, Gaby ; Gute, Peter ; Herrmann, Eva ; Zeuzem, Stefan ; Mavromara, Penelope ; Sarrazin, Christoph ; Pfeilschifter, Josef
Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations.
Pratschke, Johann ; Dragun, Duska ; Hauser, Ingeborg A. ; Horn, Sabine ; Mueller, Thomas F. ; Schemmer, Peter ; Thaiss, Friedrich
The wide range of immunosuppressive therapies and protocols permits tailored planning of the initial regimen according to the immunological risk status of individual patients. Pre-transplant risk assessment can include many factors, but there is no clear consensus on which parameters to take into account, and their relative importance. In general younger patients are known to be at higher risk for acute rejection, compounded by higher rates of non-adherence in adolescents. Donor age and recipient gender do not appear to exert a meaningful effect on risk of rejection per se, but black recipient ethnicity remains a well-established risk factor even under modern immunosuppression regimens. Little difference in risk is now observed between deceased- and living-donor recipients. Immunological risk assessment has developed substantially in recent years. Cross-match testing with cytotoxic analysis has long been supplemented by flow cytometry, but development of solid-phase single-bead antigen testing of solubilized human leukocyte antigens (HLA) to detect donor-specific antibodies (DSA) permits a far more nuanced stratification of immunological risk status, including the different classes and intensities of HLA antibodies Class I and/or II, including HLA-DSA. Immunologic risk evaluation is now often based on a combination of these tests, but other assessments are becoming more widely introduced, such as measurement of non-HLA antibodies against angiotensin type 1 (AT1) receptors or T-cell ELISPOT assay of alloantigen-specific donor. Targeted densensitization protocols can improve immunological risk, notably for DSA-positive patients with negative cytotoxicity and flow cross-match. HLA mismatch remains an important and undisputed risk factor for rejection. Delayed graft function also increases the risk of subsequent acute rejection, and the early regimen can be modified in such cases. Overall, there is a shift towards planning the immunosuppressive regimen based on pre-transplant immunology testing although certain conventional risk factors retain their importance.
Mohapatra, Namrata ; Tønnesen, Jan ; Vlachos, Andreas ; Kuner, Thomas ; Deller, Thomas ; Nägerl, U. Valentin ; Santamaria, Fidel ; Jedlička, Peter
Cl(-) plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl(-) is not well understood. The role of spines in Cl(-) diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl(-) changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl(-) dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl(-) diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl(-) extrusion altered Cl(-) diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl(-) diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl(-) diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed.
Adam, Jaroslav ; Adamová, Dagmar ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Alam, Sk Noor ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alexandre, Didier ; Alfaro Molina, Jose Ruben ; Alici, Andrea ; Alkin, Anton ; Millan Almaraz, Jesus Roberto ; Alme, Johan ; Alt, Torsten ; Altinpinar, Sedat ; Altsybeev, Igor ; Prado, Caio Alves Garcia ; Andrei, Cristian ; Andronic, Anton ; Anguelov, Venelin ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Aphecetche, Laurent Bernard ; Appelshaeuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arnold, Oliver Werner ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Audurier, Benjamin ; Augustinus, Andre ; Averbeck, Ralf Peter ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bagnasco, Stefano ; Bailhache, Raphaëlle ; Bala, Renu ; Balasubramanian, Supraja ; Baldisseri, Alberto ; Baral, Rama Chandra ; Barbano, Anastasia Maria ; Barbera, Roberto ; Barile, Francesco ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Ramillien Barret, Valerie ; Bartalini, Paolo ; Barth, Klaus ; Bartke, Jerzy ; Bartsch, Esther ; Basile, Maurizio ; Bastid, Nicole ; Basu, Sumit ; Bathen, Bastian ; Batigne, Guillaume ; Batista Camejo, Arianna ; Batyunya, Boris ; Bätzing, Paul Christoph ; Bearden, Ian Gardner ; Beck, Hans ; Bedda, Cristina ; Behera, Nirbhay Kumar ; Belikov, Iouri ; Bellini, Francesca ; Bello Martinez, Hector ; Bellwied, Rene ; Belmont Iii, Ronald John ; Belmont Moreno, Ernesto ; Belyaev, Vladimir ; Benacek, Pavel ; Bencédi, Gyula ; Beolè, Stefania ; Berceanu, Ionela ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Bertens, Redmer Alexander ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Bhat, Inayat Rasool ; Bhati, Ashok Kumar ; Bhattacharjee, Buddhadeb ; Bhom, Jihyun ; Bianchi, Livio ; Bianchi, Nicola ; Bianchin, Chiara ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Rathijit ; Biswas, Saikat ; Bjelogrlic, Sandro ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blume, Christoph ; Bock, Friederike ; Bogdanov, Alexey A. ; Bøggild, Hans ; Boldizsar, Laszlo ; Bombara, Marek ; Book, Julian ; Borel, Herve ; Borissov, Alexander ; Borri, Marcello ; Bossú, Francesco ; Botta, Elena ; Bourjau, Christian ; Braun-Munzinger, Peter ; Bregant, Marco ; Breitner, Timo ; Broker, Theo Alexander ; Browning, Tyler Allen ; Broz, Michal ; Brücken, Erik Jens ; Bruna, Elena ; Bruno, Giuseppe Eugenio ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bunčić, Predrag ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Bashir Butt, Jamila ; Buxton, Jesse Thomas ; Caffarri, Davide ; Cai, Xu ; Caines, Helen Louise ; Calero Diaz, Liliet ; Caliva, Alberto ; Calvo Villar, Ernesto ; Camerini, Paolo ; Carena, Francesco ; Carena, Wisla ; Carnesecchi, Francesca ; Castillo Castellanos, Javier Ernesto ; Castro, Andrew John ; Casula, Ester Anna Rita ; Ceballos Sanchez, Cesar ; Cerello, Piergiorgio ; Cerkala, Jakub ; Chang, Beomsu ; Chapeland, Sylvain ; Chartier, Marielle ; Charvet, Jean-Luc Fernand ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; Chauvin, Alex Henri Jean ; Chelnokov, Volodymyr ; Cherney, Michael Gerard ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Cho, Soyeon ; Chochula, Peter ; Choi, Kyungeon ; Chojnacki, Marek ; Choudhury, Subikash ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Chung, Suh-Urk ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Cleymans, Jean Willy Andre ; Colamaria, Fabio Filippo ; Colella, Domenico ; Collu, Alberto ; Colocci, Manuel ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Connors, Megan Elizabeth ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Corrales Morales, Yasser ; Cortes Maldonado, Ismael ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Crochet, Philippe ; Cruz Albino, Rigoberto ; Cuautle Flores, Eleazar ; Cunqueiro Mendez, Leticia ; Dahms, Torsten ; Dainese, Andrea ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Debasish ; Das, Indranil ; Das, Supriya ; Dash, Ajay Kumar ; Dash, Sadhana ; De, Sudipan ; De Caro, Annalisa ; De Cataldo, Giacinto ; Conti, Camila de ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Pasquale, Salvatore ; Deisting, Alexander ; Deloff, Andrzej ; Denes, Ervin Sandor ; Deplano, Caterina ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Di Nezza, Pasquale ; Diaz Corchero, Miguel Angel ; Dietel, Thomas ; Dillenseger, Pascal ; Divià, Roberto ; Djuvsland, Øystein ; Dobrin, Alexandru Florin ; Domenicis Gimenez, Diogenes ; Donigus, Benjamin ; Dordic, Olja ; Drozhzhova, Tatiana ; Dubey, Anand Kumar ; Dubla, Andrea ; Ducroux, Laurent ; Dupieux, Pascal ; Ehlers Iii, Raymond James ; Elia, Domenico ; Endress, Eric ; Engel, Heiko ; Epple, Eliane ; Erazmus, Barbara Ewa ; Erdemir, Irem ; Erhardt, Filip ; Espagnon, Bruno ; Estienne, Magali Danielle ; Esumi, ShinIchi ; Eum, Jongsik ; Evans, David ; Evdokimov, Sergey ; Eyyubova, Gyulnara ; Fabbietti, Laura ; Fabris, Daniela ; Faivre, Julien ; Fantoni, Alessandra ; Fasel, Markus ; Feldkamp, Linus ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Ferencei, Jozef ; Fernández Téllez, Arturo ; Gonzalez Ferreiro, Elena ; Ferretti, Alessandro ; Festanti, Andrea ; Feuillard, Victor Jose Gaston ; Figiel, Jan ; Figueredo, Marcel Araujo Silva ; Filchagin, Sergey ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fiore, Enrichetta Maria ; Fleck, Martin Gabriel ; Floris, Michele ; Foertsch, Siegfried Valentin ; Foka, Panagiota ; Fokin, Sergey ; Fragiacomo, Enrico ; Francescon, Andrea ; Frankenfeld, Ulrich ; Fronzé, Gabriele Gaetano ; Fuchs, Ulrich ; Furget, Christophe ; Furs, Artur ; Fusco Girard, Mario ; Gaardhoeje, Jens Joergen ; Gagliardi, Martino ; Gago Medina, Alberto Martín ; Gallio, Mauro ; Gangadharan, Dhevan Raja ; Ganoti, Paraskevi ; Gao, Chaosong ; Garabatos Cuadrado, Jose ; Garcia-Solis, Edmundo Javier ; Gargiulo, Corrado ; Gasik, Piotr ; Gauger, Erin Frances ; Germain, Marie ; Gheata, Andrei George ; Gheata, Mihaela ; Ghosh, Premomoy ; Ghosh, Sanjay Kumar ; Gianotti, Paola ; Giubellino, Paolo ; Giubilato, Piero ; Gładysz-Dziaduś, Ewa ; Glässel, Peter ; Gómez Coral, Diego Mauricio ; Gómez Ramírez, Andrés ; Gonzalez, Victor ; González Zamora, Pedro ; Gorbunov, Sergey ; Görlich, Lidia Maria ; Gotovac, Sven ; Grabski, Varlen ; Grachov, Oleg A. ; Graczykowski, Łukasz Kamil ; Graham, Katie Leanne ; Grelli, Alessandro ; Grigoras, Alina Gabriela ; Grigoraș, Costin ; Grigoryev, Vladislav ; Grigoryan, Ara ; Grigoryan, Smbat ; Grynyov, Borys ; Grion, Nevio ; Gronefeld, Julius Maximilian ; Große-Oetringhaus, Jan Fiete ; Grossiord, Jean-Yves ; Grosso, Raffaele ; Guber, Fedor ; Guernane, Rachid ; Guerzoni, Barbara ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Gupta, Anik ; Gupta, Ramni ; Haake, Rüdiger ; Haaland, Øystein Senneset ; Hadjidakis, Cynthia Marie ; Haiduc, Maria ; Hamagaki, Hideki ; Hamar, Gergö ; Hamon, Julien Charles ; Harris, John William ; Harton, Austin Vincent ; Hatzifotiadou, Despina ; Hayashi, Shinichi ; Heckel, Stefan Thomas ; Helstrup, Håvard ; Herghelegiu, Andrei Ionut ; Herrera Corral, Gerardo Antonio ; Hess, Benjamin Andreas ; Hetland, Kristin Fanebust ; Hillemanns, Hartmut ; Hippolyte, Boris ; Horak, David ; Hosokawa, Ritsuya ; Hristov, Peter ; Huang, Meidana ; Humanic, Thomas J. ; Hussain, Nur ; Hussain, Tahir ; Hutter, Dirk ; Hwang, Dae Sung ; Ilkaev, Radiy ; Inaba, Motoi ; Incani, Elisa ; Ippolitov, Mikhail ; Irfan, Muhammad ; Ivanov, Marian ; Ivanov, Vladimir ; Izucheev, Vladimir ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadhav, Manoj Bhanudas ; Jadlovska, Slavka ; Jadlovsky, Jan ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Jang, Haeng Jin ; Janik, Malgorzata Anna ; Pahula Hewage, Sandun ; Jena, Chitrasen ; Jena, Satyajit ; Jiménez Bustamante, Raúl Tonatiuh ; Jones, Peter Graham ; Jusko, Anton ; Kalinak, Peter ; Kalweit, Alexander Philipp ; Kamin, Jason Adrian ; Kang, Ju Hwan ; Kaplin, Vladimir ; Kar, Somnath ; Karasu Uysal, Ayben ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karayan, Lilit ; Karpechev, Evgeny ; Kebschull, Udo ; Keidel, Ralf ; Keijdener, Darius Laurens D. ; Keil, Markus ; Khan, Mohammed Mohisin ; Khan, Palash ; Khan, Shuaib Ahmad ; Khanzadeev, Alexei ; Kharlov, Yury ; Kileng, Bjarte ; Kim, Do Won ; Kim, Dong Jo ; Kim, Daehyeok ; Kim, Hyeonjoong ; Kim, Jinsook ; Kim, Minwoo ; Kim, Se Yong ; Kim, Taesoo ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Kiss, Gabor ; Klay, Jennifer Lynn ; Klein, Carsten ; Klein, Jochen ; Klein-Bösing, Christian ; Klewin, Sebastian ; Kluge, Alexander ; Knichel, Michael Linus ; Knospe, Anders Garritt ; Kobdaj, Chinorat ; Varga-Kofarago, Monika ; Kollegger, Thorsten ; Kolozhvari, Anatoly ; Kondratev, Valerii ; Kondratyeva, Natalia ; Kondratyuk, Evgeny ; Konevskikh, Artem ; Kopcik, Michal ; Kostarakis, Panagiotis ; Kour, Mandeep ; Kouzinopoulos, Charalampos ; Kovalenko, Oleksandr ; Kovalenko, Vladimir ; Kowalski, Marek ; Koyithatta Meethaleveedu, Greeshma ; Králik, Ivan ; Kravčáková, Adela ; Kretz, Matthias ; Krivda, Marian ; Krizek, Filip ; Kryshen, Evgeny ; Krzewicki, Mikolaj ; Kubera, Andrew Michael ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kumar, Ajay ; Kumar, Jitendra ; Lokesh, Kumar ; Kumar, Shyam ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kweon, Min Jung ; Kwon, Youngil ; La Pointe, Sarah Louise ; La Rocca, Paola ; Ladron de Guevara, Pedro ; Lagana Fernandes, Caio ; Lakomov, Igor ; Langoy, Rune ; Lara Martinez, Camilo Ernesto ; Lardeux, Antoine Xavier ; Lattuca, Alessandra ; Laudi, Elisa ; Lea, Ramona ; Leardini, Lucia ; Lee, Graham Richard ; Lee, Seongjoo ; Lehas, Fatiha ; Lemmon, Roy Crawford ; Lenti, Vito ; Leogrande, Emilia ; Leon Monzon, Ildefonso ; Leon Vargas, Hermes ; Leoncino, Marco ; Lévai, Peter ; Li, Shuang ; Li, Xiaomei ; Lien, Jørgen André ; Lietava, Roman ; Lindal, Svein ; Lindenstruth, Volker ; Lippmann, Christian ; Lisa, Michael A. ; Ljunggren, Hans Martin ; Lodato, Davide Francesco ; Lønne, Per-Ivar ; Loginov, Vitaly ; Loizides, Constantinos ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lowe, Andrew John ; Lüttig, Philipp ; Lunardon, Marcello ; Luparello, Grazia ; Lutz, Tyler Harrison ; Maevskaya, Alla ; Mager, Magnus ; Mahajan, Sanjay ; Mahmood, Sohail Musa ; Maire, Antonin ; Majka, Richard Daniel ; Malaev, Mikhail ; Maldonado Cervantes, Ivonne Alicia ; Malinina, Liudmila ; Mal’Kevich, Dmitry ; Malzacher, Peter ; Mamonov, Alexander ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Margutti, Jacopo ; Marin, Ana Maria ; Markert, Christina ; Marquard, Marco ; Martin, Nicole Alice ; Martin Blanco, Javier ; Martinengo, Paolo ; Martínez Hernández, Mario Iván ; García Martínez, Ginés ; Martinez Pedreira, Miguel ; Mas, Alexis Jean-Michel ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Mastroserio, Annalisa ; Matyja, Adam Tomasz ; Mayer, Christoph ; Mazer, Joel Anthony ; Mazzoni, Alessandra Maria ; Mcdonald, Daniel ; Meddi, Franco ; Melikyan, Yuri ; Menchaca-Rocha, Arturo Alejandro ; Meninno, Elisa ; Mercado Pérez, Jorge ; Meres, Michal ; Miake, Yasuo ; Mieskolainen, Matti Mikael ; Mikhaylov, Konstantin ; Milano, Leonardo ; Milošević, Jovan ; Minervini, Lazzaro Manlio ; Mischke, André ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Mitra, Jubin ; Mitu, Ciprian Mihai ; Mohammadi, Naghmeh ; Mohanty, Bedangadas ; Molnar, Levente ; Montaño Zetina, Luis Manuel ; Montes Prado, Esther ; Godoy, Denise Aparecida Moreira de ; Perez Moreno, Luis Alberto ; Moretto, Sandra ; Morreale, Astrid ; Morsch, Andreas ; Muccifora, Valeria ; Mudnic, Eugen ; Muhlheim, Daniel ; Muhuri, Sanjib ; Mukherjee, Maitreyee ; Mulligan, James Declan ; Gameiro Munhoz, Marcelo ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Naru, Muhammad Umair ; Luz, Pedro Hugo Ferreira Natal da ; Nattrass, Christine ; Rosado Navarro, Sebastian ; Nayak, Kishora ; Nayak, Ranjit ; Nayak, Tapan Kumar ; Nazarenko, Sergey ; Nedosekin, Alexander ; Nellen, Lukas ; Ng, Fabian ; Nicassio, Maria ; Niculescu, Mihai ; Niedziela, Jeremi ; Nielsen, Borge Svane ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Nomokonov, Petr V. ; Nooren, Gerardus ; Cabanillas Noris, Juan Carlos ; Norman, Jaime ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Oeschler, Helmut ; Oh, Saehanseul ; Oh, Sun Kun ; Ohlson, Alice ; Okatan, Ali ; Okubo, Tsubasa ; Oláh, László ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Onderwaater, Jacobus ; Oppedisano, Chiara ; Orava, Risto ; Ortiz Velasquez, Antonio ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Özdemir, Mahmut ; Pachmayer, Yvonne C. ; Pagano, Paola ; Paic, Guy ; Pal, Susanta Kumar ; Pan, Jinjin ; Pandey, Ashutosh Kumar ; Papikyan, Vardanush ; Pappalardo, Giuseppe Salvatore ; Pareek, Pooja ; Park, WooJin ; Parmar, Sonia ; Passfeld, Annika ; Paticchio, Vincenzo ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Pérez Lara, Carlos Eugenio ; Pérez Lezama, Edgar ; Peskov, Vladimir ; Pestov, Yury N. ; Petráček, Vojtech ; Petrov, Viacheslav ; Petrovici, Mihai A. ; Petta, Catia ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Ozelin de Lima Pimentel, Laís ; Pinazza, Ombretta ; Pinsky, Lawrence ; Piyarathna, Danthasinghe ; Płoskoń, Mateusz ; Planinic, Mirko ; Pluta, Jan Marian ; Pochybova, Sona ; Podesta Lerma, Pedro Luis Manuel ; Poghosyan, Martin G. ; Polishchuk, Boris ; Poljak, Nikola ; Poonsawat, Wanchaloem ; Pop, Amalia ; Porteboeuf, Sarah Julie ; Porter, R. Jefferson ; Pospisil, Jan ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Puddu, Giovanna ; Pujahari, Prabhat Ranjan ; Punin, Valery ; Putschke, Jörn H. ; Qvigstad, Henrik ; Rachevski, Alexandre ; Raha, Sibaji ; Rajput, Sonia ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rascanu, Bogdan Theodor ; Rathee, Deepika ; Read, Kenneth Francis ; Redlich, Krzysztof ; Reed, Rosi Jan ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Ren, Xiaowen ; Renfordt, Rainer Arno Ernst ; Reolon, Anna Rita ; Reshetin, Andrey ; Revol, Jean-Pierre ; Reygers, Klaus ; Riabov, Viktor ; Ricci, Renato Angelo ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Ristea, Cătălin-Lucian ; Rocco, Elena ; Rodrı́guez Cahuantzi, Mario ; Rodriguez Manso, Alis ; Røed, Ketil ; Rogochaya, Elena ; Rohr, David ; Röhrich, Dieter ; Romita, Rosa ; Ronchetti, Federico ; Ronflette, Lucile ; Rosnet, Philippe ; Rossi, Andrea ; Roukoutakis, Filimon ; Roy, Ankhi ; Roy, Christelle Sophie ; Roy, Pradip Kumar ; Rubio Montero, Antonio Juan ; Rui, Rinaldo ; Russo, Riccardo ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej ; Sadovskiy, Sergey ; Šafařík, Karel ; SahlmÜller, Baldo ; Sahoo, Pragati ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakai, Shingo ; Saleh, Mohammad Ahmad ; Salzwedel, Jai ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Šándor, Ladislav ; Sandoval, Andres ; Sano, Masato ; Sarkar, Debojit ; Sarma, Pranjal ; Scapparone, Eugenio ; Scarlassara, Fernando ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schuchmann, Simone ; Schukraft, Jürgen ; Schulc, Martin ; Schuster, Tim ; Schutz, Yves Roland ; Schwarz, Kilian Eberhard ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Scott, Rebecca Michelle ; Šefčík, Michal ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senosi, Kgotlaesele ; Senyukov, Serhiy ; Serradilla Rodriguez, Eulogio ; Sevcenco, Adrian ; Shabanov, Arseniy ; Shabetai, Alexandre ; Shadura, Oksana ; Shahoyan, Ruben ; Shangaraev, Artem ; Sharma, Ankita ; Sharma, Mona ; Sharma, Monika ; Sharma, Natasha ; Shigaki, Kenta ; Shtejer Diaz, Katherin ; Sibiryak, Yury ; Siddhanta, Sabyasachi ; Sielewicz, Krzysztof Marek ; Siemiarczuk, Teodor ; Silvermyr, David Olle Rickard ; Silvestre, Catherine Micaela ; Simatovic, Goran ; Simonetti, Giuseppe ; Singaraju, Rama Narayana ; Singh, Ranbir ; Singha, Subhash ; Singhal, Vikas ; Sinha, Bikash ; Sarkar - Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Slupecki, Maciej ; Smirnov, Nikolai ; Snellings, Raimond ; Snellman, Tomas Wilhelm ; Soegaard, Carsten ; Song, Jihye ; Song, Myunggeun ; Song, Zixuan ; Soramel, Francesca ; Sorensen, Soren Pontoppidan ; Souza, Rafael Derradi de ; Sozzi, Federica ; Spacek, Michal ; Spiriti, Eleuterio ; Sputowska, Iwona Anna ; Spyropoulou-Stassinaki, Martha ; Stachel, Johanna ; Stan, Ionel ; Stankus, Paul William ; Stefanek, Grzegorz ; Stenlund, Evert Anders ; Steyn, Gideon Francois ; Stiller, Johannes Hendrik ; Stocco, Diego ; Strmen, Peter ; Suaide, Alexandre Alarcon do Passo ; Sugitate, Toru ; Suire, Christophe Pierre ; Suleymanov, Mais Kazim Oglu ; Šuljić, Miljenko ; Sultanov, Rishat ; Šumbera, Michal ; Szabo, Alexander ; Toledo, Alejandro Szanto de ; Szarka, Imrich ; Szczepankiewicz, Adam ; Szymanski, Maciej Pawel ; Tabassam, Uzma ; Takahashi, Jun ; Tambave, Ganesh Jagannath ; Tanaka, Naoto ; Tangaro, Marco-Antonio ; Tarhini, Mohamad ; Tariq, Mohammad ; Tarzila, Madalina-Gabriela ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terasaki, Kohei ; Terrevoli, Cristina ; Teyssier, Boris ; Thäder, Jochen ; Thomas, Deepa ; Tieulent, Raphael Noel ; Timmins, Anthony Robert ; Toia, Alberica ; Trogolo, Stefano ; Trombetta, Giuseppe ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Tsuji, Tomoya ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Uras, Antonio ; Usai, Gianluca ; Utrobicic, Antonija ; Vajzer, Michal ; Vala, Martin ; Valencia Palomo, Lizardo ; Vallero, Sara ; Maarel, Jasper van der ; Hoorne, Jacobus Willem van ; Leeuwen, Marco van ; Vanat, Tomas ; Vyvre, Pierre vande ; Varga, Dezsö ; Vargas Treviño, Maria Aurora Diozcora ; Vargyas, Márton ; Varma, Raghava ; Vasileiou, Maria ; Vasiliev, Andrey ; Vauthier, Astrid ; Vechernin, Vladimir ; Veen, Annelies Marianne ; Veldhoen, Misha ; Velure, Arild ; Venaruzzo, Massimo ; Vercellin, Ermanno ; Vergara Limon, Sergio ; Vernet, Renaud ; Verweij, Marta ; Vicković, Linda ; Viesti, Giuseppe ; Viinikainen, Jussi Samuli ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Villatoro Tello, Abraham ; Vinogradov, Alexander ; Vinogradov, Leonid ; Vinogradov, Yury I. ; Virgili, Tiziano ; Vislavicius, Vytautas ; Viyogi, Yogendra P. ; Vodopyanov, Alexander ; Volkl, Martin Andreas ; Voloshin, Kirill ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Vranić, Danilo ; Vrlakova, Janka ; Vulpescu, Bogdan ; Wagner, Boris ; Wagner, Jan ; Wang, Hongkai ; Wang, Mengliang ; Watanabe, Daisuke ; Watanabe, Yosuke ; Weber, Michael ; Weber, Steffen Georg ; Weiser, Dennis ; Wessels, Johannes P. ; Westerhoff, Uwe ; Whitehead, Andile Mothegi ; Wiechula, Jens ; Wikne, Jon ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy John ; Williams, M. Crispin S. ; Windelband, Bernd ; Winn, Michael ; Yang, Hongyan ; Yang, Ping ; Yano, Satoshi ; Yasar, Cigdem ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-Kwon ; Yoon, Jin Hee ; Yurchenko, Volodymyr ; Yushmanov, Igor ; Zaborowska, Anna ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zaporozhets, Sergey ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zbroszczyk, Hanna Paulina ; Zgura, Sorin Ion ; Zhalov, Mikhail ; Zhang, Haitao ; Zhang, Xiaoming ; Zhang, Yonghong ; Chunhui, Zhang ; Zhang, Zuman ; Zhao, Chengxin ; Zhigareva, Natalia ; Zhou, Daicui ; Zhou, You ; Zhou, Zhuo ; Zhu, Hongsheng ; Zhu, Jianhui ; Zichichi, Antonino ; Zimmermann, Alice ; Zimmermann, Markus ; Zinovjev, Gennady M. ; Zyzak, Maksym
The production of K∗(892)0 and ϕ(1020) mesons has been measured in p–Pb collisions at √sNN = 5.02 TeV. K∗0 and ϕ are reconstructed via their decay into charged hadrons with the ALICE detector in the rapidity range - 0.5 < y < 0. The transverse momentum spectra, measured as a function of the multiplicity, have a pT range from 0 to 15 GeV/c for K∗0 and from 0.3 to 21 GeV/c for ϕ. Integrated yields, mean transverse momenta and particle ratios are reported and compared with results in pp collisions at √s = 7 TeV and Pb–Pb collisions at √sNN = 2.76 TeV. In Pb–Pb and p–Pb collisions, K∗0 and ϕ probe the hadronic phase of the system and contribute to the study of particle formation mechanisms by comparison with other identified hadrons. For this purpose, the mean transverse momenta and the differential proton-to-ϕ ratio are discussed as a function of the multiplicity of the event. The short-lived K∗0 is measured to investigate re-scattering effects, believed to be related to the size of the system and to the lifetime of the hadronic phase.
Welzel, Tania Mara ; Petersen, Jörg ; Herzer, Kerstin ; Ferenci, Peter ; Gschwantler, Michael ; Wedemeyer, Heiner ; Berg, Thomas ; Spengler, Ulrich ; Weiland, Ola ; Valk, Marc van der ; Rockstroh, Jürgen ; Peck-Radosavljevic, Markus ; Zhao, Yue ; Jimenez-Exposito, Maria Jesus ; Zeuzem, Stefan
Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.
Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).
Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.
Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.
Trial registration number NCT0209966.
Thiel, Uwe ; Wawer, Angela ; Teichert- von Lüttichau, Irene ; Bender, Hans-Ulrich ; Blaeschke, Franziska ; Grunewald, Thomas G. P. ; Steinborn, Marc ; Röper, Barbara ; Bönig, Halvard-Björn ; Klingebiel, Thomas ; Bader, Peter ; Koscielniak, Ewa ; Paulussen, Michael ; Dirksen, Uta ; Jürgens, Heribert ; Kolb, Hans-Jochem ; Burdach, Stefan
Purpose: Advanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.
Design: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992 consisted of induction chemotherapy, whole body imaging directed radiotherapy to the primary tumor and metastases, tandem high-dose chemotherapy and autologous rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy to the primary tumor only followed by consolidation chemotherapy.
Results: In MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992 (p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992. Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After exclusion of patients succumbing to treatment related complications (n=3), 7/10 patients survived without BM involvement, in contrast to 0/5 patients with BM involvement. This was confirmed in a multivariate analysis. There was no correlation between BM involvement and the number of metastases at diagnosis.
Conclusion: The MetaEICESS protocols yield long-term disease-free survival in patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was not associated with increased death of complications. Bone marrow involvement is a risk factor distinct from multiple bone metastases.