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Stecher, Melanie ; Schommers, Philipp Frederik ; Kollan, Christian ; Stoll, Matthias ; Kuhlendahl, Frieder ; Stellbrink, Hans‑Jürgen ; Wasmuth, Jan‑Christian ; Stephan, Christoph ; Hamacher, Laura ; Lehmann, Clara ; Boesecke, Christoph ; Bogner, Johannes ; Esser, Stefan ; Fritzsche, Carlos ; Haberl, Annette ; Hofmann, Christian ; Jensen, Björn ; Schwarze‑Zander, Carolynne ; Platten, Martin ; Fätkenheuer, Gerd ; Schmidt, Daniel ; Gunsenheimer-Bartmeyer, Barbara ; Vehreschild, Jörg Janne
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Stecher, Melanie ; Schommers, Philipp Frederik ; Kollan, Christian ; Stoll, Matthias ; Kuhlendahl, Frieder-Johan ; Stellbrink, Hans‑Jürgen ; Wasmuth, Jan‑Christian ; Stephan, Christoph ; Hamacher, Laura ; Lehmann, Clara ; Boesecke, Christoph ; Bogner, Johannes ; Esser, Stefan ; Fritzsche, Carlos ; Haberl, Annette ; Schürmann, Dirk ; Degen, Olaf ; Horst, Heinz August ; Hoffmann, Christian ; Jensen, Björn-Erik Ole ; Schwarze-Zander, Carolynne ; Platten, Martin ; Fätkenheuer, Gerd ; Schmidt, Daniel ; Gunsenheimer-Bartmeyer, Barbara ; Vehreschild, Jörg Janne
Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.
Stein, Stefan ; Ott, Marion Gabriele ; Schultze-Straßer, Stephan ; Jauch, Anna ; Burwinkel, Barbara ; Kinner, Andrea ; Schmidt, Manfred ; Krämer, Alwin ; Schwäble, Joachim ; Glimm, Hanno ; Köhl, Ulrike ; Preiss, Carolin ; Ball, Claudia ; Martin, Hans ; Göhring, Gudrun ; Schwarzwaelder, Kerstin ; Hofmann, Wolf-Karsten ; Karakaya, Kadin ; Tchatchou, Sandrine ; Yang, Rongxi ; Reinecke, Petra ; Kühlcke, Klaus ; Schlegelberger, Brigitte ; Thrasher, Adrian J. ; Hoelzer, Dieter ; Seger, Reinhard ; Kalle, Christof von ; Grez, Manuel
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.
Barucca, Gianni ; Davì, F. ; Lancioni, G. ; Mengucci, P. ; Montalto, L. ; Natali, P. P. ; Paone, N. ; Rinaldi, D. ; Scalise, L. ; Erni, W. ; Krusche, B. ; Steinacher, M. ; Walford, N. ; Cao, N. ; Liu, Z. ; Liu, C. ; Liu, B. ; Shen, X. ; Sun, S. ; Tao, J. ; Xiong, X. A. ; Zhao, G. ; Zhao, J. ; Albrecht, Malte ; Alkakhi, W. ; Bökelmann, S. ; Coen, S. ; Feldbauer, Florian ; Fink, M. ; Frech, J. ; Freudenreich, V. ; Fritsch, Miriam ; Grochowski, J. ; Hagdorn, R. ; Heinsius, Fritz-Herbert ; Held, T. ; Holtmann, Tobias ; Keshk, Iman ; Koch, H. ; Kopf, Bertram ; Kuhlmann, M. ; Kümmel, M. ; Küßner, M. ; Li, J. ; Linzen, L. ; Maldaner, Stephan ; Oppotsch, J. ; Pankonin, S. ; Pelizäus, Marc ; Pflüger, S. ; Pitka, A. ; Reher, J. ; Reicherz, G. ; Schnier, Claudius ; Steinke, M. ; Triffterer, T. ; Wenzel, C. ; Wiedner, Ulrich ; Denizli, H. ; Er, N. ; Keskin, U. ; Olgun, A. T. ; Yerlikaya, S. ; Yilmaz, A. ; Beck, R. ; Hammann, C. ; Hartmann, J. ; Ketzer, Bernhard ; Müllers, J. ; Rossbach, M. ; Salisbury, B. ; Schmidt, Christian Joachim ; Thoma, U. ; Urban, M. ; Bianconi, A. ; Bragadireanu, Mario ; Pantea, D. ; Domagala, M. ; Filo, G. ; Lisowski, E. ; Lisowski, F. ; Michałek, M. ; Poznański, P. ; Płażek, J. ; Korcyl, K. ; Kozela, A. ; Lebiedowicz, P. ; Pysz, K. ; Schäfer, W. ; Szczurek, A. ; Firlej, M. ; Fiutowski, T. ; Idzik, M. ; Moron, J. ; Swientek, K. ; Terlecki, P. ; Korcyl, G. ; Lalik, R. ; Malige, A. ; Moskal, P. ; Nowakowski, K. ; Przygoda, W. ; Rathod, N. ; Rudy, Z. ; Salabura, P. ; Smyrski, J. ; Augustin, I. ; Böhm, R. ; Lehmann, I. ; Schmitt, L. ; Varentsov, V. ; Al-Turany, Mohammad ; Belias, A. ; Deppe, H. ; Dzhygadlo, R. ; Flemming, H. ; Gerhardt, A. ; Götzen, Klaus ; Heinz, Andreas ; Jiang, P. ; Karabowicz, R. ; Koch, S. ; Kurilla, U. ; Lehmann, D. ; Lühning, J. ; Lynen, U. ; Orth, H. ; Peters, Klaus ; Saito, T. ; Schepers, G. ; Schmidt, C. J. ; Schwarz, C. ; Schwiening, J. ; Täschner, Alexander ; Traxler, M. ; Voss, B. ; Wieczorek, P. ; Abazov, V. ; Alexeev, G. ; Arefiev, V. A. ; Astakhov, V. ; Barabanov, M. Yu. ; Batyunya, B. V. ; Dodokhov, V. Kh. ; Efremov, A. ; Fechtchenko, A. ; Galoyan, A. ; Golovanov, G. ; Koshurnikov, E. K. ; Lobanov, Y. Yu. ; Olshevskiy, A. G. ; Piskun, A. A. ; Samartsev, A. ; Shimanski, S. ; Skachkov, N. B. ; Skachkova, A. N. ; Strokovsky, E. A. ; Tokmenin, V. ; Uzhinsky, V. ; Verkheev, A. ; Vodopianov, A. ; Zhuravlev, N. I. ; Branford, D. ; Watts, D. ; Böhm, M. ; Eyrich, W. ; Lehmann, A. ; Miehling, D. ; Pfaffinger, M. ; Quin, N. ; Robison, L. ; Seth, K. ; Xiao, T. ; Bettoni, Diego ; Ali, A. ; Hamdi, A. ; Himmelreich, Mathilde ; Krebs, M. ; Nakhoul, S. ; Nerling, Frank ; Belousov, A. ; Kisel, Ivan ; Kozlov, Grigory ; Pugach, M. ; Zyzak, Maksym ; Bianchi, Nicola ; Gianotti, Paola ; Lucherini, V. ; Bracco, G. ; Bettner, Y. ; Bodenschatz, S. ; Brinkmann, K. T. ; Brück, L. ; Diehl, S. ; Dormenev, V. ; Düren, M. ; Erlen, T. ; Föhl, K. ; Hahn, C. ; Hayrapetyan, A. ; Hofmann, J. ; Kegel, S. ; Kesselkaul, M. ; Köseoglu, I. ; Kripko, A. ; Kühn, Wolfgang ; Lange, Jens Sören ; Metag, V. ; Moritz, M. ; Nanova, M. ; Novotny, R. ; Orsich, P. ; Pereira-de-Lira, J. ; Peter, M. ; Sachs, M. ; Schmidt, M. ; Schubert, R. ; Stenzel, H. ; Straube, M. ; Strickert, M. ; Thöring, U. ; Wasem, T. ; Wohlfahrt, B. ; Zaunick, H. G. ; Tomasi-Gustafsson, E. ; Glazier, D. ; Ireland, D. ; Seitz, B. ; Deepak, P. N. ; Kulkarni, A. ; Kappert, R. ; Kavatsyuk, Myroslav O. ; Loehner, H. ; Messchendorp, Johannes Gerhardus ; Rodin, Viktor ; Schakel, P. ; Vejdani, S. ; Dutta, K. ; Kalita, K. ; Huang, G. ; Liu, D. ; Peng, H. ; Qi, H. ; Sun, Y. ; Zhou, X. ; Kunze, M. ; Azizi, K. ; Tavukoglu, Z. ; Derichs, A. ; Dosdall, R. ; Esmail, W. ; Gillitzer, A. ; Goldenbaum, F. ; Grunwald, D. ; Jokhovets, L. ; Kannika, J. ; Kulessa, P. ; Orfanitski, S. ; Pérez Andrade, G. ; Prasuhn, D. ; Prencipe, E. ; Pütz, J. ; Ritman, J. ; Rosenthal, E. ; Schadmand, S. ; Schmitz, R. ; Scholl, A. ; Sefzick, T. ; Serdyuk, V. ; Stockmanns, T. ; Veretennikov, D. ; Wintz, P. ; Wüstner, P. ; Xu, H. ; Zhou, Y. ; Cao, X. ; Hu, Q. ; Li, Z. ; Li, H. ; Liang, Y. ; Ma, X. ; Rigato, V. ; Isaksson, L. ; Achenbach, P. ; Corell, O. ; Denig, Achim ; Distler, M. ; Hoek, M. ; Lauth, W. ; Leithoff, H. H. ; Liu, Z. ; Merkel, H. ; Müller, U. ; Pochodzalla, J. ; Schlimme, S. ; Sfienti, C. ; Thiel, M. ; Zambrana, M. ; Ahmed, Samer ; Bleser, S. ; Bölting, M. ; Capozza, L. ; Dbeyssi, A. ; Ehret, A. ; Klasen, R. ; Kliemt, Ralf ; Maas, F. ; Motzko, C. ; Noll, O. ; Piñeiro, D. Rodríguez ; Schupp, F. ; Steinen, M. ; Wolff, S. ; Zimmermann, I. ; Fedorov, A. ; Kazlou, D. ; Korzhik, M. ; Missevitch, O. ; Balanutsa, P. ; Chernetsky, V. ; Demekhin, A. ; Dolgolenko, A. ; Fedorets, P. ; Gerasimov, A. ; Golubev, A. ; Goryachev, V. ; Kantsyrev, Alexey V. ; Kirin, D. Y. ; Kristi, N. ; Ladygina, E. ; Luschevskaya, E. ; Matveev, V. A. ; Panjushkin, V. ; Stavinskiy, A. V. ; Balashoff, A. ; Boukharov, A. ; Malyshev, O. ; Basant, K. N. ; Kumawat, H. ; Roy, B. ; Saxena, Alok ; Yogesh, S. ; Bonaventura, D. ; Brand, P. ; Fritzsch, C. ; Grieser, S. ; Hargens, C. ; Hergemöller, A. K. ; Hetz, B. ; Hüsken, Nils ; Kellers, J. ; Khoukaz, Alfons ; Mannweiler, C. ; Vestrick, S. ; Bumrungkoh, D. ; Herold, Christoph ; Khosonthongkee, K. ; Kobdaj, Chinorat ; Limphirat, A. ; Manasatitpong, K. ; Nasawad, T. ; Pongampai, S. ; Simantathammakul, T. ; Srisawad, P. ; Wongprachanukul, N. ; Yan, Y. ; Yu, C. ; Zhang, X. ; Zhu, W. ; Blinov, A. E. ; Kononov, S. ; Kravchenko, E. A. ; Antokhin, E. ; Barnyakov, A. Yu. ; Beloborodov, K. ; Blinov, V. E. ; Kuyanov, I. A. ; Pivovarov, S. ; Pyata, E. ; Tikhonov, Y. ; Hunter, G. ; Lattery, M. ; Pace, H. ; Boca, Gianluigi ; Duda, D. ; Finger, M. ; Finger, M. ; Kveton, A. ; Pesek, M. ; Peskova, M. ; Prochazka, I. ; Slunecka, M. ; Volf, M. ; Gallus, P. ; Jary, V. ; Korchak, O. ; Marcisovsky, M. ; Neue, G. ; Novy, J. ; Tomasek, L. ; Tomasek, M. ; Virius, M. ; Vrba, V. ; Abramov, V. ; Bukreeva, S. ; Chernichenko, S. ; Derevschikov, A. ; Ferapontov, V. ; Goncharenko, Y. ; Levin, A. ; Maslova, E. ; Melnik, Y. ; Meščanin, Aleksei P. ; Minaev, N. ; Mochalov, V. ; Moiseev, V. ; Morozov, D. ; Nogach, L. ; Poslavskiy, S. ; Ryazantsev, A. ; Ryzhikov, S. ; Semenov, P. ; Shein, I. ; Uzunian, A. ; Vasiliev, Andrey ; Yakutin, A. ; Roy, U. ; Yabsley, B. ; Belostotski, S. ; Fedotov, G. ; Gavrilov, G. ; Izotov, A. ; Manaenkov, S. ; Miklukho, O. ; Zhdanov, A. ; Atac, A. ; Bäck, T. ; Cederwall, B. ; Makonyi, K. ; Preston, M. ; Tegner, P. E. ; Wölbing, D. ; Gandhi, K. ; Rai, A. K. ; Godre, S. ; Crede, V. ; Dobbs, S. ; Eugenio, P. ; Lersch, D. ; Calvo, D. ; De Remigis, P. ; Filippi, A. ; Mazza, G. ; Rivetti, Angelo ; Wheadon, R. ; Bussa, M. P. ; Spataro, Stefano ; Iazzi, F. ; Lavagno, A. ; Martin, A. ; Akram, A. ; Calen, H. ; Ikegami Andersson, Walter ; Johansson, Tord ; Kupsc, Andrzej ; Marciniewski, P. ; Papenbrock, Michael ; Regina, J. ; Rieger, J. ; Schönning, K. ; Wolke, M. ; Pothodi Chackara, V. ; Chlopik, A. ; Kesik, G. ; Melnychuk, D. ; Tarasiuk, J. ; Wojciechowski, M. ; Wronka, S. ; Zwieglinski, B. ; Amsler, C. ; Bühler, Paul ; Marton, J. ; Nalti, W. ; Steinschaden, D. ; Widmann, Eberhard ; Zimmermann, S. ; Zmeskal, Johann
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Koch, Vitali ; Conrades, Lena Marie ; Grünewald, Leon David ; Eichler, Katrin ; Martin, Simon ; Booz, Christian ; D'Angelo, Tommaso ; Yel, Ibrahim ; Bernatz, Simon ; Mahmoudi, Scherwin ; Albrecht, Moritz Hans Ernst ; Scholtz, Jan-Erik ; Scholtz, Jan-Erik ; Thalhammer, Axel ; Zangos, Stephan ; Vogl, Thomas J. ; Gruber-Rouh, Tatjana
This prospective study sought to evaluate potential savings of radiation dose to medical staff using real-time dosimetry coupled with visual radiation dose feedback during angiographic interventions. For this purpose, we analyzed a total of 214 angiographic examinations that consisted of chemoembolizations and several other types of therapeutic interventions. The Unfors RaySafe i2 dosimeter was worn by the interventionalist at chest height over the lead protection. A total of 110 interventions were performed with real-time radiation dosimetry allowing the interventionalist to react upon higher x-ray exposure and 104 examinations served as the comparative group without real-time radiation monitoring. By using the real-time display during interventions, the overall mean operator radiation dose decreased from 3.67 (IQR, 0.95–23.01) to 2.36 μSv (IQR, 0.52–12.66) (−36%; p = 0.032) at simultaneously reduced operator exposure time by 4.5 min (p = 0.071). Dividing interventions into chemoembolizations and other types of therapeutic interventions, radiation dose decreased from 1.31 (IQR, 0.46-3.62) to 0.95 μSv (IQR, 0.53-3.11) and from 24.39 (IQR, 12.14-63.0) to 10.37 μSv (IQR, 0.85-36.84), respectively, using live-screen dosimetry (p ≤ 0.005). Radiation dose reductions were also observed for the participating assistants, indicating that they could also benefit from real-time visual feedback dosimetry during interventions (−30%; p = 0.039). Integration of real-time dosimetry into clinical processes might be useful in reducing occupational radiation exposure time during angiographic interventions. The real-time visual feedback raised the awareness of interventionalists and their assistants to the potential danger of prolonged radiation exposure leading to the adoption of radiation-sparing practices. Therefore, it might create a safer environment for the medical staff by keeping the applied radiation exposure as low as possible.