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Koch, Elias Andreas Thomas ; Petzold, Anne ; Wessely, Anja ; Dippel, Edgar ; Gesierich, Anja Heike ; Gutzmer, Ralf ; Hassel, Jessica C. ; Haferkamp, Sebastian ; Hohberger, Bettina ; Kähler, Katharina C. ; Knorr, Harald ; Kreuzberg-Brenner, Nicole ; Leiter-Stöppke, Ulrike ; Loquai, Carmen ; Meier, Friedegund ; Meissner, Markus ; Mohr, Peter ; Pföhler, Claudia Ursula ; Rahimi, Farnaz ; Schadendorf, Dirk ; Schell, Beatrice ; Schlaak, Max Simon ; Terheyden, Patrick ; Thoms, Kai-Martin ; Schuler-Thurner, Beatrice ; Ugurel, Selma ; Ulrich, Jens ; Utikal, Jochen ; Weichenthal, Michael ; Ziller, Fabian ; Berking, Carola ; Heppt, Markus V.
Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ2 tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.
Solà, Elsa ; Pose Mendez, Elisa ; Campion, Daniela ; Piano, Salvatore ; Roux, Olivier ; Simon-Talero, Macarena ; Uschner, Frank Erhard ; Wit, Koos de ; Zaccherini, Giacomo ; Alessandria, Carlo ; Beuers, Ulrich ; Caraceni, Paolo ; Francoz, Claire ; Mookerjee, Rajeshwar Prosad ; Trebicka, Jonel ; Vargas Blasco, Victor Manuel ; Serra, Miquel ; Torres, Ferran ; Montagnese, Sara ; Krag, Aleksander ; Hernaez, Ruben ; Korenjak, Marko ; Watson, Hugh ; Abraldes, Juan G. ; Kamath, Patrick S. ; Ginès, Pere
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Relationship between regional white matter hyperintensities and alpha oscillations in older adults
(2021)
Kumral, Deniz ; Cesnaite, Elena ; Beyer, Frauke ; Hofmann, Simon M. ; Hensch, Tilman ; Sander, Christian ; Hegerl, Ulrich ; Haufe, Stefan ; Villringer, Arno ; Witte, A. Veronica ; Nikulin, Vadim V.
Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7–13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60–80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources.
Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
(2022)
Demel, Uta M. ; Böger, Marlitt ; Yousefian, Schayan ; Grunert, Corinna ; Zhang, Le ; Hotz, Paul W. ; Gottschlich, Adrian ; Köse, Hazal ; Isaakidis, Konstandina ; Vonficht, Dominik ; Grünschläger, Florian ; Rohleder, Elena ; Wagner, Kristina ; Dönig, Judith ; Igl, Veronika ; Brzezicha, Bernadette ; Baumgartner, Francis ; Habringer, Stefan ; Löber, Jens ; Chapuy, Björn ; Weidinger, Carl Thomas Maximilian ; Kobold, Sebastian ; Haas, Simon ; Busse, Antonia B. ; Müller, Stefan ; Wirth, Matthias ; Schick, Markus ; Keller, Ulrich
Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell–mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM). Loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, and the pharmacological inhibition of SUMOylation (SUMOi) resulted in reduced activity of the transcriptional repressor scaffold attachment factor B (SAFB) and induction of the MHC-I APM. Consequently, SUMOi enhanced the presentation of antigens and the susceptibility of tumor cells to CD8+ T cell–mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T cells and thereby drove a feed-forward loop amplifying the specific antitumor immune response. In summary, we showed that activated SUMOylation allowed tumor cells to evade antitumor immunosurveillance, and we have expanded the understanding of SUMOi as a rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies.
Büntgen, Ulf ; Bagi, István ; Fekete, Oszkár ; Molinier, Virginie ; Peter, Martina ; Splivallo, Richard ; Vahdatzadeh, Maryam ; Richard, Franck ; Murat, Claude ; Tegel, Willy ; Stobbe, Ulrich ; Martínez-Peña, Fernando ; Sproll, Ludger ; Hülsmann, Lisa ; Nievergelt, Daniel ; Meier, Barbara ; Egli, Simon
Despite an increasing demand for Burgundy truffles (Tuber aestivum), gaps remain in our understanding of the fungus’ overall lifecycle and ecology. Here, we compile evidence from three independent surveys in Hungary and Switzerland. First, we measured the weight and maturity of 2,656 T. aestivum fruit bodies from a three-day harvest in August 2014 in a highly productive orchard in Hungary. All specimens ranging between 2 and 755 g were almost evenly distributed through five maturation classes. Then, we measured the weight and maturity of another 4,795 T. aestivum fruit bodies harvested on four occasions between June and October 2015 in the same truffière. Again, different maturation stages occurred at varying fruit body size and during the entire fruiting season. Finally, the predominantly unrelated weight and maturity of 81 T. aestivum fruit bodies from four fruiting seasons between 2010 and 2013 in Switzerland confirmed the Hungarian results. The spatiotemporal coexistence of 7,532 small-ripe and large-unripe T. aestivum, which accumulate to ~182 kg, differs from species-specific associations between the size and ripeness that have been reported for other mushrooms. Although size-independent truffle maturation stages may possibly relate to the perpetual belowground environment, the role of mycelial connectivity, soil property, microclimatology, as well as other abiotic factors and a combination thereof, is still unclear. Despite its massive sample size and proof of concept, this study, together with existing literature, suggests consideration of a wider ecological and biogeographical range, as well as the complex symbiotic fungus-host interaction, to further illuminate the hidden development of belowground truffle fruit bodies.
Acharya, Shreyasi ; Adamová, Dagmar ; Adler, Alexander ; Adolfsson, Jonatan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Akbar, Zaenal ; Akindinov, Alexander ; Al-Turany, Mohammad ; Albuquerque, Danilo Silva de ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Ali, Yasir ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Dimitra ; Andronic, Anton ; Angeletti, Massimo ; Anguelov, Venelin ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arratia, Miguel ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Aziz, Sizar ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bala, Renu ; Balbino, Alessandro ; Baldisseri, Alberto ; Ball, Markus ; Banerjee, Debjani ; Barbera, Roberto ; Barioglio, Luca ; Barlou, Maria ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Ramillien Barret, Valerie ; Bartels, Clara ; Barth, Klaus ; Bartsch, Esther ; Baruffaldi, Filippo ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Batyunya, Boris ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Beattie, Caitlin ; Belikov, Iouri ; Bell Hechavarria, Ailec de la Caridad ; Bellini, Francesca ; Bellwied, Rene ; Belokurova, Svetlana ; Belyaev, Vladimir ; Bencédi, Gyula ; Beolè, Stefania ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berdnikova, Anastasia ; Berényi, Dániel ; Bergmann, Luisa ; Besoiu, Mihaela Gabriela ; Betev, Latchezar ; Bhaduri, Partha Pratim ; Bhasin, Anju ; Bhat, Inayat Rasool ; Bhat, Mohammad Asif ; Bhattacharjee, Buddhadeb ; Bhattacharya, Purba ; Bianchi, Antonio ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Saikat ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blidaru, Mihail-Bogdan ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bogdanov, Alexey A. ; Boi, Stefano ; Bok, Jeongsu ; Boldizsar, László ; Bolozdynya, Alexander I. ; Bombara, Marek ; Bonomi, Germano ; Borel, Hervé ; Borissov, Alexander ; Bossi, Hannah ; Botta, Elena ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broz, Michal ; Bruno, Giuseppe Eugenio ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bugnon, Ophélie ; Bühler, Paul ; Bunčić, Predrag ; Buthelezi, Edith Zinhle ; Bashir Butt, Jamila ; Bysiak, Sebastian Adam ; Caffarri, Davide ; Caliva, Alberto ; Calvo Villar, Ernesto ; Mejia Camacho, Juan Manuel ; Soto Camacho, Rabi ; Camerini, Paolo ; Canedo, Fabio de Moraes Canedo ; Capon, Aaron Allan ; Carnesecchi, Francesca ; Caron, Robin Albert Andre ; Castillo Castellanos, Javier Ernesto ; Casula, Ester Anna Rita ; Catalano, Fabio ; Ceballos Sanchez, Cesar ; Chakraborty, Pritam ; Chandra, Sinjini ; Chang, Wan ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; Chauvin, Alex Henri Jean ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Cho, Soyeon ; Chochula, Peter ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Ciupek, Michael Rudolf ; Clai, Giulia ; Cleymans, Jean Willy Andre ; Colamaria, Fabio Filippo ; Colburn, Jonathan Samuel ; Colella, Domenico ; Collu, Alberto ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Crochet, Philippe ; Cuautle Flores, Eleazar ; Cui, Pengyao ; Cunqueiro Mendez, Leticia ; 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Erokhin, Andrey ; Ersdal, Magnus Rentsch ; Espagnon, Bruno ; Eulisse, Giulio ; Evans, David ; Evdokimov, Sergey ; Fabbietti, Laura ; Faggin, Mattia ; Faivre, Julien ; Fan, Feng ; Fantoni, Alessandra ; Fasel, Markus ; Fecchio, Pietro ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferrero, Andrea ; Ferretti, Alessandro ; Festanti, Andrea ; Feuillard, Victor Jose Gaston ; Figiel, Jan ; Filchagin, Sergey ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Fiorenza, Gabriele ; Flor, Fernando Antonio ; Flores, Amanda Nicole ; Foertsch, Siegfried Valentin ; Foka, Panagiota ; Fokin, Sergey ; Fragiacomo, Enrico ; Fuchs, Ulrich ; Furget, Christophe ; Furs, Artur ; Fusco Girard, Mario ; Gaardhoeje, Jens Joergen ; Gagliardi, Martino ; Gago Medina, Alberto Martín ; Gal, Arthur Willem Jean ; Duarte Galvan, Carlos ; Ganoti, Paraskevi ; Garabatos Cuadrado, Jose ; Alvarado Garcia, Jesús Ricardo ; Garcia-Solis, Edmundo Javier ; Garg, Kunal ; Gargiulo, Corrado ; Garibli, Aydan ; Garner, Katharina ; Gasik, Piotr ; Gauger, Erin Frances ; Ducati, Maria Beatriz de Leone Gay ; Germain, Marie ; Ghosh, Jhuma ; Ghosh, Premomoy ; Ghosh, Sanjay Kumar ; Giacalone, Marco ; Gianotti, Paola ; Giubellino, Paolo ; Giubilato, Piero ; Glaenzer, Aude Marie Camille ; Glässel, Peter ; Gonzalez, Victor ; González Trueba, Laura Helena ; Gorbunov, Sergey ; Görlich, Lidia Maria ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Graham, Katie Leanne ; Greiner, Leo Clifford ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoryev, Vladislav ; Grigoryan, Ara ; Grigoryan, Smbat ; Groettvik, Ola Slettevoll ; Grosa, Fabrizio ; Große-Oetringhaus, Jan Fiete ; Grosso, Raffaele ; Guernane, Rachid ; Guilbaud, Maxime Rene Joseph ; Guittiere, Manuel ; Gulbrandsen, Kristjan Herlache ; Gunji, Taku ; Gupta, Anik ; Gupta, Ramni ; Bautista Guzman, Irais ; Haake, Rüdiger ; Habib, Michael Karim ; Hadjidakis, Cynthia Marie ; Hamagaki, Hideki ; Hamar, Gergö ; Hamid, Mohammed ; Hannigan, Ryan ; Haque, Md Rihan ; Gromada, Alena ; Harris, John William ; Harton, Austin Vincent ; Hasenbichler, Jan Anton ; Hassan, Hadi ; Hatzifotiadou, Despina ; Hauer, Philip ; Havener, Laura Brittany ; Hayashi, Shinichi ; Heckel, Stefan Thomas ; Hellbär, Ernst ; Helstrup, Håvard ; Herman, Tomáš ; Gonzalez Hernandez, Emma ; Herrera Corral, Gerardo Antonio ; Herrmann, Florian ; Hetland, Kristin Fanebust ; Hillemanns, Hartmut ; Hills, Christopher ; Hippolyte, Boris ; Hohlweger, Bernhard ; Honermann, Jan ; Hong, Geunhee ; Horak, David ; Hornung, Sebastian ; Hosokawa, Ritsuya ; Hristov, Peter ; Huang, Chun-Lu ; Hughes, Charles ; Huhn, Patrick ; Humanic, Thomas J. ; Hushnud, Hushnud ; Husova, Lucia Anna ; Hussain, Nur ; Hutter, Dirk ; Iddon, James Philip ; Ilkaev, Radiy ; Ilyas, Hira ; Inaba, Motoi ; Innocenti, Gian Michele ; Ippolitov, Mikhail ; Isakov, Artem ; Islam, Md Samsul ; Ivanov, Marian ; Ivanov, Vladimir ; Izucheev, Vladimir ; Jacak, Barbara ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadlovska, Slavka ; Jadlovsky, Jan ; Jaelani, Syaefudin ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Janik, Malgorzata Anna ; Janson, Thomas ; Jercic, Marko ; Jevons, Oliver Thomas ; Jin, Muqing ; Jonas, Florian ; Jones, Peter Graham ; Jung, Jerome ; Jung, Michael ; Jusko, Anton ; Kalinak, Peter ; Kalweit, Alexander Philipp ; Kaplin, Vladimir ; Kar, Somnath ; Karasu Uysal, Ayben ; Karatović, David ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karczmarczyk, Przemyslaw ; Karpechev, Evgeny ; Kazantsev, Andrey ; Kebschull, Udo ; Keidel, Ralf ; Keil, Markus ; Ketzer, Bernhard ; Khabanova, Zhanna ; Khan, Ahsan Mehmood ; Khan, Shaista ; Khanzadeev, Alexei ; Kharlov, Yury ; Khatun, Anisa ; Khuntia, Arvind ; Kileng, Bjarte ; Kim, Beomkyu ; Kim, Daehyeok ; Kim, Dong Jo ; Kim, Eun Joo ; Kim, Hyeonjoong ; Kim, Jaehyun ; Kim, Jin Sook ; Kim, Jiyoung ; Kim, Jungeol ; Kim, Junlee ; Kim, Minjung ; Kim, Se Yong ; Kim, Taejun ; Kim, Taesoo ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Klay, Jennifer Lynn ; Klein, Jochen ; Klein, Spencer Robert ; Klein-Bösing, Christian ; Kleiner, Matthias ; Klemenz, Thomas ; Kluge, Alexander ; Knospe, Anders Garritt ; Kobdaj, Chinorat ; Köhler, Markus Konrad ; Kollegger, Thorsten ; Kondratyev, Andrey ; Kondratyeva, Natalia V. ; Kondratyuk, Evgeny ; König, Joshua Leon ; Königstorfer, Stephan Alexander ; Konopka, Piotr Jan ; Kornakov, Georgy ; Koryciak, Sebastian Dominik ; Koska, Lukas ; Kovalenko, Oleksandr ; Kovalenko, Vladimir ; Kowalski, Marek ; Králik, Ivan ; Kravčáková, Adela ; Kreis, Lukas ; Krivda, Marian ; Krizek, Filip ; Krizkova Gajdosova, Katarina ; Kroesen, Martin ; Krüger, Mario ; Kryshen, Evgeny ; Krzewicki, Mikolaj ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kumaoka, Takuya ; Kumar, Lokesh ; Kundu, Sourav ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kushpil, Svetlana ; Kvapil, Jakub ; Kweon, Min Jung ; Kwon, Jiyeon ; Kwon, Youngil ; La Pointe, Sarah Louise ; La Rocca, Paola ; Lai, Yue Shi ; Lakrathok, Anantachai ; Lamanna, Massimo ; Langoy, Rune ; Lapidus, Kirill ; Larionov, Pavel ; Laudi, Elisa ; Lautner, Lukas ; Lavicka, Roman ; Lazareva, Tatiana V. ; Lea, Ramona ; Lee, Joonil ; Lee, Seongjoo ; Lehrbach, Johannes ; Lemmon, Roy Crawford ; Leon Monzon, Ildefonso ; Lesser, Ezra Douglas ; Lettrich, Michael ; Lévai, Peter ; Li, Xiaomei ; Li, Xing Long ; Lien, Jørgen André ; Lietava, Roman ; Lim, Bong-Hwi ; Lim, Sanghoon ; Lindenstruth, Volker ; Lindner, Amelia ; Lippmann, Christian ; Liu, Alwina Ruixin ; Liu, Jian ; Lofnes, Ingrid Mckibben ; Loginov, Vitaly ; Loizides, Constantinos ; Lončar, Petra ; López, Jorge Andres ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Ma, Yu-Gang ; Maevskaya, Alla ; Mager, Magnus ; Mahmood, Sohail Musa ; Mahmoud, Tariq ; Maire, Antonin ; Majka, Richard Daniel ; Malaev, Mikhail ; Malik, Qasim Waheed ; Malinina, Liudmila ; Mal'Kevich, Dmitry ; Mallick, Neelkamal ; Malzacher, Peter ; Mandaglio, Giuseppe ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marin, Ana ; Markert, Christina ; Marquard, Marco ; Martin, Nicole Alice ; Martinengo, Paolo ; Martinez, Jacobb Lee ; Martínez Hernández, Mario Iván ; Martínez Garcia, Ginés ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Mastroserio, Annalisa ; Mathis, Andreas Michael ; Matonoha, Oliver ; Matuoka, Paula Fernanda Toledo ; Matyja, Adam Tomasz ; Mayer, Christoph ; Mazzaschi, Francesco ; Mazzilli, Marianna ; Mazzoni, Alessandra Maria ; Mechler, Adrian Florin ; Meddi, Franco ; Melikyan, Yury ; Menchaca-rocha, Arturo Alejandro ; Cai, Mengke ; Meninno, Elisa ; Sasikumar Menon, Anjaly ; Meres, Michal ; Mhlanga, Sibaliso ; Miake, Yasuo ; Micheletti, Luca ; Migliorin, Lucrezia Camilla ; Mihaylov, Dimitar ; Mikhaylov, Konstantin ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Modak, Abhi ; Mohammadi, Naghmeh ; Mohanty, Auro Prasad ; Mohanty, Bedangadas ; Khan, Mohammed Mohisin ; Moravcova, Zuzana ; Mordasini, Cindy ; Godoy, Denise Aparecida Moreira de ; Perez Moreno, Luis Alberto ; Morozov, Igor ; Morsch, Andreas ; Mrnjavac, Teo ; Muccifora, Valeria ; Mudnic, Eugen ; Muhlheim, Daniel ; Muhuri, Sanjib ; Mulligan, James Declan ; Mulliri, Alice ; Gameiro Munhoz, Marcelo ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myers, Corey James ; Myrcha, Julian Wojciech ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Naru, Muhammad Umair ; Nassirpour, Adrian Fereydon ; Nattrass, Christine ; Nayak, Ranjit ; Nazarenko, Sergey ; Neagu, Alexandra ; Nellen, Lukas ; Nesbo, Simon Voigt ; Nešković, Gvozden ; Nesterov, Dmitrii ; Nielsen, Borge Svane ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Noh, Seoyoung ; Nomokonov, Petr V. ; Norman, Jaime ; Novitzky, Norbert ; Nowakowski, Piotr ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Ogino, Masanori ; Ohlson, Alice ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Önnerstad, Anna ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Osako, Takumi ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paic, Guy ; Pan, Jinjin ; Panebianco, Stefano Matthias ; Pareek, Pooja ; Park, Jonghan ; Parkkila, Jasper Elias ; Parmar, Sonia ; Pathak, Surya Prakash ; Paul, Biswarup ; Pazzini, Jacopo ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Perrin, Sébastien ; Pestov, Yury N. ; Petráček, Vojtech ; Petrovici, Mihai A. ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Poghosyan, Martin G. ; Polishchuk, Boris ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf, Sarah Julie ; Porter, R. 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Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, Song ; Zhang, Xiaoming ; Zhang, Yifei ; Zherebchevskii, Vladimir ; Yu, Zhi ; Zhou, Daicui ; Zhou, You ; Zhu, Jianhui ; Zhu, Ya ; Zichichi, Antonino ; Zinovjev, Gennady M. ; Zurlo, Nicola
Deuteron production in high-energy collisions is sensitive to the space–time evolution of the collision system, and is typically described by a coalescence mechanism. For the first time, we present results on jet-associated deuteron production in pp collisions at √s = 13 TeV, providing an opportunity to test the established picture for deuteron production in events with a hard scattering. Using a trigger particle with high transverse-momentum (pT > 5 GeV/c) as a proxy for the presence of a jet at midrapidity, we observe a measurable population of deuterons being produced around the jet proxy. The associated deuteron yield measured in a narrow angular range around the trigger particle differs by 2.4–4.8 standard deviations from the uncorrelated background. The data are described by PYTHIA model calculations featuring baryon coalescence.
ϒ production and nuclear modification at forward rapidity in Pb–Pb collisions at √sNN = 5.02TeV
(2021)
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Mao, Yaxian ; Marchisone, Massimiliano ; Mareš, Jiří ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marín, Ana ; Markert, Christina ; Marquard, Marco ; Martin, Nicole Alice ; Martinengo, Paolo ; Martinez, Jacobb Lee ; Martínez Hernández, Mario Iván ; Martínez Garcia, Ginés ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Mastroserio, Annalisa ; Mathis, Andreas Michael ; Matonoha, Oliver ; Matuoka, Paula Fernanda Toledo ; Matyja, Adam Tomasz ; Mayer, Christoph ; Mazzaschi, Francesco ; Mazzilli, Marianna ; Mazzoni, Alessandra Maria ; Mechler, Adrian Florin ; Meddi, Franco ; Melikyan, Yury ; Menchaca-Rocha, Arturo Alejandro ; Meninno, Elisa ; Sasikumar Menon, Anjaly ; Meres, Michal ; Mhlanga, Sibaliso ; Miake, Yasuo ; Micheletti, Luca ; Migliorin, Lucrezia Camilla ; Mihaylov, Dimitar ; Mikhaylov, Konstantin ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Modak, Abhi ; Mohammadi, Naghmeh ; Mohanty, Auro Prasad ; Mohanty, Bedangadas ; Mohisin Khan, Mohammed ; Moravcova, Zuzana ; Mordasini, Cindy ; Godoy, Denise Aparecida Moreira de ; Perez Moreno, Luis Alberto ; Morozov, Igor ; Morsch, Andreas ; Mrnjavac, Teo ; Muccifora, Valeria ; Mudnic, Eugen ; Mühlheim, Daniel ; Muhuri, Sanjib ; Mulligan, James Declan ; Mulliri, Alice ; Munhoz, Marcelo Gameiro ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myers, Corey James ; Myrcha, Julian Wojciech ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Naru, Muhammad Umair ; Nassirpour, Adrian Fereydon ; Nattrass, Christine ; Nazarenko, Sergey ; Neagu, Alexandra ; Nellen, Lukas ; Nesbo, Simon Voigt ; Nešković, Gvozden ; Nesterov, Dmitrii ; Nielsen, Borge Svane ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Noh, S. ; Nomokonov, Petr V. ; Norman, Jaime ; Novitzky, Norbert ; Nowakowski, Piotr ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Ogino, Masanori ; Ohlson, Alice ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Onnerstad, B.S. ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Osako, Takumi ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oyama, Ken ; Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paić, Guy ; Pan, Jinjin ; Panebianco, Stefano Matthias ; Pareek, Pooja ; Park, Jonghan ; Parkkila, Jasper Elias ; Parmar, Sonia ; Pathak, Surya Prakash ; Paul, Biswarup ; Pazzini, J. ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Perrin, Sébastien ; Pestov, Yury N. ; Petráček, Vojtech ; Petrovici, Mihai A. ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Poghosyan, Martin G. ; Polichtchouk, Boris ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf-Houssais, Sarah Julie ; Porter, Jeffrey Brent ; Pozdniakov, Valeriy ; Prasad, Sidharth Kumar ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Qiu, Shi ; Quaglia, Luca ; Quishpe, Raquel Estefania ; Ragoni, Simone ; Rak, Jan ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rodríguez Ramírez, Saúl Aníbal ; Torres Ramos, Arianna Grisel ; Raniwala, Rashmi ; Raniwala, Sudhir ; Räsänen, Sami Sakari ; Rath, Rutuparna ; Ravasenga, Ivan ; Read, Kenneth Francis ; Redelbach, Andreas Ralph ; Redlich, Krzysztof ; Rehman, Attiq ur ; Reichelt, Patrick ; Reidt, Felix ; Renfordt, Rainer Arno Ernst ; Rescakova, Zuzana ; Reygers, Klaus ; Riabov, Andrei ; Riabov, Viktor G. ; Richert, Tuva Ora Herenui ; Richter, Matthias Rudolph ; Riedler, Petra ; Riegler, Werner ; Riggi, Francesco ; Ristea, Cătălin-Lucian ; Rode, Sudhir Pandurang ; Rodrı́guez Cahuantzi, Mario ; Røed, Ketil ; Rogalev, Roman ; Rogochaya, Elena ; Rogoschinski, Tim Sebastian ; Rohr, David ; Röhrich, Dieter ; Fierro Rojas, Pablo ; Rokita, Przemyslaw Stefan ; Ronchetti, Federico ; Rosano, Antonina ; Dominguez Rosas, Edgar ; Rossi, Andrea ; Rotondi, Alberto ; Roy, Ankhi ; Roy, Pradip Kumar ; Vazquez Rueda, Omar ; Rui, Rinaldo ; Rumyantsev, Boris ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej ; Rytkönen, Heidi Maria ; Saarimäki, Oskari Antti Matti ; Sadek, Rita ; Sadovskiy, Sergey ; Sætre, Jon-are ; Šafařík, Karel ; Saha, Sumit Kumar ; Saha, Swati ; Sahoo, Baidyanath ; Sahoo, Pragati ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Dushmanta ; Sahu, Pradip Kumar ; Saini, Jogender ; Sakai, Shingo ; Sambyal, Sanjeev Singh ; Samsonov, Vladimir ; Sarkar, Debojit ; Sarkar, Nachiketa ; Sarma, Pranjal ; Mantovani Sarti, Valentina ; Sas, Mike Henry Petrus ; Schambach, Joachim ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schmah, Alexander ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmier, Austin Robert ; Schotter, Romain ; Schukraft, Jürgen ; Schutz, Yves Roland ; Schwarz, Kilian ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jin Joo ; Serebryakov, Dmitry ; Šerkšnytė, Laura ; Sevcenco, Adrian ; Shabanov, Arseniy ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shaikh, Wadut ; Shangaraev, Artem ; Sharma, A. ; Sharma, H. ; Sharma, M. ; Sharma, Natasha ; Sharma, Sheetal ; Sheibani, Oveis ; Sheikh, Ashik Ikbal ; Shigaki, Kenta ; Shimomura, Maya ; Shirinkin, Sergey ; Shou, Qiye ; Sibiriak, Yury ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silvermyr, David Olle Rickard ; Simatovic, Goran ; Simonetti, Giuseppe ; Singh, Bhawani ; Singh, R. ; Singh, R. ; Singh, R. ; Singh, Vivek Kumar ; Singhal, Vikas ; Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Slupecki, Maciej ; Smirnov, Nikolai ; Snellings, Raimond ; Soncco Meza, Carlos ; Song, Jihye ; Songmoolnak, Arnon ; Soramel, Francesca ; Sorensen, Soren Pontoppidan ; Sputowska, Iwona Anna ; Stachel, Johanna ; Stan, Ionel ; Steffanic, Patrick John ; Stiefelmaier, Stephan ; Stocco, Diego ; Storetvedt, Maksim Melnik ; Dello Stritto, Luigi ; Pliatskas Stylianidis, Christos ; Suaide, Alexandre Alarcon do Passo ; Sugitate, Toru ; Suire, Christophe Pierre ; Šuljić, Miljenko ; Sultanov, Rishat ; Šumbera, Michal ; Sumberia, Vikash ; Sumowidagdo, Suharyo ; Swain, Sagarika ; Szabo, Alexander ; Szarka, Imrich ; Tabassam, Uzma ; Taghavi, Seyed Farid ; Taillepied, Guillaume ; Takahashi, Jun ; Tambave, Ganesh Jagannath ; Tang, Siyu ; Tang, Zebo ; Tarhini, Mohamad ; Tarzila, Madalina-Gabriela ; Tauro, Arturo ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terlizzi, Livia ; Terrevoli, Cristina ; Tersimonov, Georgy ; Thakur, Sanchari ; Thomas, Deepa ; Thoresen, Freja ; Tieulent, Raphael Noel ; Tikhonov, Anatoly ; Timmins, Anthony Robert ; Tkacik, Milan ; Toia, Alberica ; Topilskaya, Nataliya ; Toppi, Marco ; Torales Acosta, Fernando ; Rojas Torres, Solangel ; Trifiró, Antonio ; Tripathy, Sushanta ; Tripathy, Tulika ; Trogolo, Stefano ; Trombetta, Giuseppe ; Tropp, Lukas ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Trzcinski, Tomasz Piotr ; Trzeciak, Barbara Antonina ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Umaka, Ejiro Naomi ; Uras, Antonio ; Usai, Gianluca ; Vala, Martin ; Valle, Nicolò ; Vallero, Sara ; Kolk, Naomi van der ; Doremalen, Lennart Vincent Rogier van ; Leeuwen, Marco van ; Vyvre, Pierre vande ; Varga, Dezsö ; Varga, Zoltán ; Varga-Kofarago, Monika ; Vargas Treviño, Maria Aurora Diozcora ; Vasileiou, Maria ; Vasiliev, Andrey ; Vázquez Doce, Oton ; Vechernin, Vladimir ; Vercellin, Ermanno ; Vergara Limón, Sergio ; Vermunt, Lucas Anne ; Vértesi, Róbert ; Verweij, Marta ; Vicković, Linda ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Vino, Gioacchino ; Vinogradov, Alexander A. ; Virgili, Tiziano ; Vislavicius, Vytautas ; Vodopyanov, Alexander ; Völkel, Benedikt ; Völkl, Martin Andreas ; Voloshin, Kirill ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Voscek, Dominik ; Vrláková, Janka ; Wagner, Boris ; Weber, Michael ; Wegrzynek, Adam Tadeusz ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Wiechula, Jens ; Wikne, Jon ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy ; Willems, Guido Alexander ; Willsher, Emily Jade ; Windelband, Bernd ; Winn, Michael Andreas ; Witt, William Edward ; Wright, Josephina Rae ; Wu, Y. ; Xu, Ran ; Yalcin, Serpil ; Yamaguchi, Yorito ; Yamakawa, Kosei ; Yang, S. ; Yano, Satoshi ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-Kwon ; Yoon, Jin-Hee ; Yuan, S. ; Yüncü, Alperen ; Yurchenko, Volodymyr ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zaviyalov, Nikolaj ; Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, S. ; Zhang, Xiaoming ; Zhang, Y. ; Zherebchevskii, Vladimir ; Zhi, Y. ; Zhou, Daicui ; Zhou, You ; Zhu, Jianhui ; Zhu, Y. ; Zichichi, Antonino ; Zinovjev, Gennady M. ; Zurlo, Nicola
The production of ϒ mesons in Pb–Pb collisions at a centre-of-mass energy per nucleon pair √sNN = 5.02 TeV is measured with the muon spectrometer of the ALICE detector at the LHC. The yields as well as the nuclear modification factors are determined in the forward rapidity region 2.5 < y < 4.0, as a function of rapidity, transverse momentum and collision centrality. The results show that the production of the ϒ(1S) meson is suppressed by a factor of about three with respect to the production in proton–proton collisions. For the first time, a significant signal for the ϒ(2S) meson is observed at forward rapidity, indicating a suppression stronger by about a factor 2–3 with respect to the ground state. The measurements are compared with transport, hydrodynamic, comover and statistical hadronisation model calculations.
Kalvelage, Christina ; Zacharowski, Kai ; Bauhofer, Artur ; Gockel, Ulrich ; Adamzik, Michael ; Nierhaus, Axel ; Kujath, Peter ; Eckmann, Christian ; Pletz, Mathias Wilhelm Rudolf ; Bracht, Hendrik ; Simon, Tim-Philipp ; Winkler, Michael ; Kindgen-Milles, Detlef ; Albertsmeier, Markus ; Weigand, Markus ; Ellger, Björn ; Ragaller, Maximilian ; Ullrich, Roman ; Marx, Gernot
Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum).
Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival.
Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine.
Trial registration: EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017.
Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).
Apheresis therapies for NMOSD attacks : a retrospective study of 207 therapeutic interventions
(2018)
Kleiter, Ingo ; Gahlen, Anna ; Borisow, Nadja ; Fischer, Katrin ; Wernecke, Klaus-Dieter ; Hellwig, Kerstin ; Pache, Florence ; Ruprecht, Klemens ; Havla, Joachim ; Kümpfel, Tania ; Aktas, Orhan ; Hartung, Hans-Peter ; Ringelstein, Marius ; Geis, Christian ; Kleinschnitz, Christoph ; Berthele, Achim ; Hemmer, Bernhard ; Angstwurm, Klemens ; Stellmann, Jan-Patrick ; Schuster, Simon ; Stangel, Martin ; Lauda, Florian ; Tumani, Hayrettin ; Mayer, Christoph ; Krumbholz, Markus ; Zeltner, Lena ; Ziemann, Ulf ; Linker, Ralf ; Schwab, Matthias ; Marziniak, Martin ; Then Bergh, Florian ; Hofstadt-van Oy, Ulrich ; Neuhaus, Oliver ; Zettl, Uwe K. ; Faiss, Jürgen Hartmut ; Wildemann, Brigitte ; Paul, Friedemann ; Jarius, Sven ; Trebst, Corinna
Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).
Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody–seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome.
Results: Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04–144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89–0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76–631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03–21.62, p = 0.046).
Conclusions: Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques.
Classification of evidence: This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.
Grote, Jessica ; Krysciak, Dagmar ; Petersen, Katrin ; Güllert, Simon ; Schmeißer, Christel ; Förstner, Konrad Ulrich ; Krishnan, Hari B. ; Schwalbe, Harald ; Kubatova, Nina ; Streit, Wolfgang R.
Plant-released flavonoids induce the transcription of symbiotic genes in rhizobia and one of the first bacterial responses is the synthesis of so called Nod factors. They are responsible for the initial root hair curling during onset of root nodule development. This signal exchange is believed to be essential for initiating the plant symbiosis with rhizobia affiliated with the Alphaproteobacteria. Here, we provide evidence that in the broad host range strain Sinorhizobium fredii NGR234 the complete lack of quorum sensing molecules results in an elevated copy number of its symbiotic plasmid (pNGR234a). This in turn triggers the expression of symbiotic genes and the production of Nod factors in the absence of plant signals. Therefore, increasing the copy number of specific plasmids could be a widespread mechanism of specialized bacterial populations to bridge gaps in signaling cascades.