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1. Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study

Author

Pabst, Thomas, Papayannidis, Cristina, Demirkan, Fatih, Doronin, Vadim, Fogliatto, Laura M, Guttke, Christina, Gyan, Emmanuel, Hamad, Nada, Herrera, Pilar, Hultberg, Anna, Jacobs, Julie, Johnson, Amy J, Langlois, Angélique, Ma, Xuewen, Martinelli, Giovanni, Arnan, Montserrat, Müller, Rouven, Nottage, Kerri, Ofran, Yishai, Özcan, Muhit, Samoilova, Olga, Tolbert, Jaszianne A, Trudel, Géralyn C, Xiu, Liang, Vey, Norbert, and Wei, Andrew H

Published
2023
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3. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents

Author

Riether, Carsten, Pabst, Thomas, Höpner, Sabine, Bacher, Ulrike, Hinterbrandner, Magdalena, Banz, Yara, Müller, Rouven, Manz, Markus G., Gharib, Walid H., Francisco, David, Bruggmann, Remy, van Rompaey, Luc, Moshir, Mahan, Delahaye, Tim, Gandini, Domenica, Erzeel, Ellen, Hultberg, Anna, Fung, Samson, de Haard, Hans, Leupin, Nicolas, and Ochsenbein, Adrian F.

Published
2020
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4. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

Author

Bar, Daniel, Basso, Alfredo, Fantl, Dorotea, He, Simon, Horvath, Neomi, Lee, Cindy, Rowlings, Phillip, Taylor, Kerry, Spencer, Andrew, Cochrane, Tara, Kwok, Fiona, Ramanathan, Sundreswran, Agis, Hermine, Zojer, Niklas, Kentos, Alain, Offner, Fritz, Van Droogenbroeck, Jan, Wu, Ka Lung, Maiolino, Angelo, Martinez, Gracia, Zanella, Karla, Capra, Marcelo, Araújo, Sérgio, Gregora, Evzen, Hajek, Roman, Maisnar, Vladimir, Pour, Ludek, Scudla, Vlastimil, Spicka, Ivan, Abildgaard, Niels, Andersen, Niels, Jensen, Bo Amdi, Helleberg, Carsten, Plesner, Torben, Salomo, Morten, Svirskaite, Asta, Delarue, Richard, Moreau, Philippe, Blau, Igor, Goldschmidt, Hartmut, Schieferdecker, Aneta, Teleanu, Veronica, Munder, Markus, Röllig, Christoph, Salwender, Han-Juergen, Fuhrmann, Stephan, Weisel, Katja, Duerig, Jan, Zeis, Matthias, Klein, Stefan, Reimer, Peter, Schmidt, Christian, Scheid, Christof, Mayer, Karin, Hoffmann, Martin, Sosada, Markus, Dimopoulos, Athanasios, Delimpasi, Sosana, Kyrtsonis, Mary-Christine, Anagnostopoulos, Achilleas, Nagy, Zsolt, Illés, Árpád, Egyed, Miklós, Borbényi, Zita, Mikala, Gabor, Dally, Najib, Horowitz, Netanel, Gutwein, Odit, Nemets, Anatoly, Vaxman, Iuliana, Shvetz, Olga, Trestman, Svetlana, Ruchlemer, Rosa, Nagler, Arnon, Tadmor, Tamar, Rouvio, Ory, Preis, Meir, Gay, Francesca, Cavo, Michele, De Rosa, Luca, Musto, Pellegrino, Cafro, Anna, Tosi, Patrizia, Offidani, Massimo, Corso, Alessandro, Rossi, Giuseppe, Liberati, Anna Marina, Bosi, Alberto, Suzuki, Kenshi, Iida, Shinsuke, Nakaseko, Chiaki, Ishikawa, Takayuki, Matsumoto, Morio, Nagai, Hirokazu, Sunami, Kazutaka, Chou, Takaaki, Akashi, Koichi, Takezako, Naoki, Hagiwara, Shotaro, Eom, Hyeon Seok, Jo, Deog-Yeon, Kim, Jin Seok, Lee, Jae Hoon, Min, Chang Ki, Yoon, Sung Soo, Yoon, Dok Hyun, Kim, Kihyun, Zweegman, Sonja, Levin, Mark-David, Vellenga, Edo, Minnema, Monique, Schjesvold, Fredrik, Waage, Anders, Haukås, Einar, Grosicki, Sebastian, Pluta, Andrzej, Robak, Tadeusz, Marques, Herlander, Bergantim, Rui, Campilho, Fernando, Chng, Wee Joo, Goh, Yeow Tee, McDonald, Andrew, Rapoport, Bernado, Álvarez Rivas, Miguel Angel, De Arriba de La Fuente, Felipe, González Montes, Yolanda, Martin Sanchez, Jesus, Mateos, Maria Victoria, Oriol Rocafiguera, Albert, Rosinol, Laura, San Miguel, Jesús, Pérez de Oteyza, Jaime, Encinas, Cristina, Alegre-Amor, Adrian, López-Guía, Ana, Axelsson, Per, Carlson, Kristina, Stromberg, Olga, Hansson, Markus, Hveding Blimark, Cecile, Mueller, Rouven, Chen, Chih-Cheng, Liu, Ta-Chih, Huang, Shang-Yi, Wang, Po-Nan, Na Nakorn, Thanyaphong, Prayongratana, Kannadit, Beksac, Meral, Unal, Ali, Goker, Hakan, Sonmez, Mehmet, Korenkova, Sybiryna, Chaidos, Aristeidis, Oakervee, Heather, Sati, Hamdi, Benjamin, Reuben, Wechalekar, Ashutosh, Garg, Mamta, Kaiser, Martin, Ramasamy, Karthik, Cook, Gordon, Chantry, Andrew, Jenner, Matthew, Buadi, Francis, Berryman, Robert, Janakiram, Murali, Dimopoulos, Meletios A, Weisel, Katja Christina, Pluta, Agnieszka, Chng, Wee-Joo, Mateos, Maria-Victoria, Morgan, Gareth, Suryanarayan, Kaveri, Teng, Zhaoyang, Skacel, Tomas, Palumbo, Antonio, Dash, Ajeeta B, Gupta, Neeraj, Labotka, Richard, and Rajkumar, S Vincent

Published
2019
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5. Melphalan dose in myeloma patients ≥65 years of age undergoing high-dose therapy and autologous stem cell transplantation: a multicentric observational registry study

Author

Ghilardi, Guido, Pabst, Thomas, Jeker, Barbara, Müller, Rouven, Cairoli, Anne, Müller, Antonia M. S., Bargetzi, Mario, Hitz, Felicitas, Baldomero, Helen, Heim, Dominik, Schmidt, Adrian, Rossi, Davide, Ghielmini, Michele, Wannesson, Luciano, Lerch, Erika, Samaras, Panagiotis, Schanz, Urs, Passweg, Jakob R., Stussi, Georg, Kleber, Martina, Gerber, Bernhard, and On behalf of the Swiss Blood Stem Cell Transplantation Registry

Published
2019
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7. Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy

Author

Pabst, Thomas, Vey, Norbert, Adès, Lionel, Bacher, Ulrike, Bargetzi, Mario, Fung, Samson, Gaidano, Gianluca, Gandini, Domenica, Hultberg, Anna, Johnson, Amy, Ma, Xuewen, Müller, Rouven, Nottage, Kerri, Papayannidis, Cristina, Recher, Christian, Riether, Carsten, Shah, Priya, Tryon, Jeffrey, Xiu, Liang, Ochsenbein, Adrian F, Pabst, Thomas, Vey, Norbert, Adès, Lionel, Bacher, Ulrike, Bargetzi, Mario, Fung, Samson, Gaidano, Gianluca, Gandini, Domenica, Hultberg, Anna, Johnson, Amy, Ma, Xuewen, Müller, Rouven, Nottage, Kerri, Papayannidis, Cristina, Recher, Christian, Riether, Carsten, Shah, Priya, Tryon, Jeffrey, Xiu, Liang, and Ochsenbein, Adrian F

Abstract

Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in acute myeloid leukemia (AML). This two-part, open-label, multicenter, phase I/II trial evaluated cusatuzumab plus azacitidine in patients with newly diagnosed AML ineligible for intensive chemotherapy. Patients received a single dose of cusatuzumab at one of four dose levels (1, 3, 10, or 20 mg/kg) 14 days before starting combination therapy. In phase I dose escalation, cusatuzumab was then administered on days 3 and 17, in combination with azacitidine (75 mg/m2) on days 1-7, every 28 days. The primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. The primary objective in phase II was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients were enrolled: 12 in phase I (three per dose level; four with European LeukemiaNet 2017 adverse risk) and 26 in phase II (21 with adverse risk). An objective response (≥partial remission) was achieved by 19/38 patients (including 8/26 in phase II); 14/38 achieved complete remission. Eleven patients (37.9%) achieved an objective response among the 29 patients in phase I and phase II treated at the RP2D. At a median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. The most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Seven patients (18.4%) reported infusion-related reactions, including two with grade 3 events. Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing.

Published
2023

8. Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy

Author

Pabst, Thomas, primary, Vey, Norbert, additional, Adès, Lionel, additional, Bacher, Ulrike, additional, Bargetzi, Mario, additional, Fung, Samson, additional, Gaidano, Gianluca, additional, Gandini, Domenica, additional, Hultberg, Anna, additional, Johnson, Amy, additional, Ma, Xuewen, additional, Müller, Rouven, additional, Nottage, Kerri, additional, Papayannidis, Cristina, additional, Recher, Christian, additional, Riether, Carsten, additional, Shah, Priya, additional, Tryon, Jeffrey, additional, Xiu, Liang, additional, and Ochsenbein, Adrian F., additional

Published
2023
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10. Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study

Author

Tamò, Raphaël; https://orcid.org/0000-0002-2098-9392, Turk, Teja; https://orcid.org/0000-0003-3065-8578, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Shah, Cyril, Bischoff-Ferrari, Heike A, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Battegay, Edouard; https://orcid.org/0000-0001-9202-5034, Giovanoli, Pietro, Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071, Kohler, Malcolm; https://orcid.org/0000-0003-1800-8003, Müller, Rouven, Petry, Heidi; https://orcid.org/0000-0001-5220-4273, Ruschitzka, Frank; https://orcid.org/0000-0001-5972-0596, McGeer, Allison, Sax, Hugo; https://orcid.org/0000-0002-1532-2198, Weber, Rainer, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kuster, Stefan P; https://orcid.org/0000-0002-0525-6529, Tamò, Raphaël; https://orcid.org/0000-0002-2098-9392, Turk, Teja; https://orcid.org/0000-0003-3065-8578, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Shah, Cyril, Bischoff-Ferrari, Heike A, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Battegay, Edouard; https://orcid.org/0000-0001-9202-5034, Giovanoli, Pietro, Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071, Kohler, Malcolm; https://orcid.org/0000-0003-1800-8003, Müller, Rouven, Petry, Heidi; https://orcid.org/0000-0001-5220-4273, Ruschitzka, Frank; https://orcid.org/0000-0001-5972-0596, McGeer, Allison, Sax, Hugo; https://orcid.org/0000-0002-1532-2198, Weber, Rainer, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, and Kuster, Stefan P; https://orcid.org/0000-0002-0525-6529

Abstract

OBJECTIVE: Nosocomial transmission of influenza is a major concern for infection control. We aimed to dissect transmission dynamics of influenza, including asymptomatic transmission events, in acute care. DESIGN: Prospective surveillance study during 2 influenza seasons. SETTING: Tertiary-care hospital. PARTICIPANTS: Volunteer sample of inpatients on medical wards and healthcare workers (HCWs). METHODS: Participants provided daily illness diaries and nasal swabs for influenza A and B detection and whole-genome sequencing for phylogenetic analyses. Contacts between study participants were tracked. Secondary influenza attack rates were calculated based on spatial and temporal proximity and phylogenetic evidence for transmission. RESULTS: In total, 152 HCWs and 542 inpatients were included; 16 HCWs (10.5%) and 19 inpatients (3.5%) tested positive for influenza on 109 study days. Study participants had symptoms of disease on most of the days they tested positive for influenza (83.1% and 91.9% for HCWs and inpatients, respectively). Also, 11(15.5%) of 71 influenza-positive swabs among HCWs and 3 (7.9%) of 38 influenza-positive swabs among inpatients were collected on days without symptoms; 2 (12.5%) of 16 HCWs and 2 (10.5%) of 19 inpatients remained fully asymptomatic. The secondary attack rate was low: we recorded 1 transmission event over 159 contact days (0.6%) that originated from a symptomatic case. No transmission event occurred in 61 monitored days of contacts with asymptomatic influenza-positive individuals. CONCLUSIONS: Influenza in acute care is common, and individuals regularly shed influenza virus without harboring symptoms. Nevertheless, both symptomatic and asymptomatic transmission events proved rare. We suggest that healthcare-associated influenza prevention strategies that are based on preseason vaccination and barrier precautions for symptomatic individuals seem to be effective.

Published
2022

11. Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward

Author

Zeeb, Marius, Weissberg, Dana; https://orcid.org/0000-0001-7481-5729, Rampini, Silvana K; https://orcid.org/0000-0002-4788-438X, Müller, Rouven, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Zingg, Walter, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Wolfensberger, Aline; https://orcid.org/0000-0001-9028-0007, Zeeb, Marius, Weissberg, Dana; https://orcid.org/0000-0001-7481-5729, Rampini, Silvana K; https://orcid.org/0000-0002-4788-438X, Müller, Rouven, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Zingg, Walter, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Wolfensberger, Aline; https://orcid.org/0000-0001-9028-0007

Abstract

We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but working shifts with presymptomatic healthcare coworkers did.

Published
2022

12. Midostaurin in Patients (Pts) with Newly Diagnosed FLT3-Mutation Negative Acute Myeloid Leukemia (AML): Final Results and Measurable Residual Disease (MRD) Analyses from the Unify Trial

Author

Cloos, Jacqueline J, primary, Montesinos, Pau, additional, Fiedler, Walter, additional, Müller, Rouven, additional, Krauter, Jürgen, additional, Sica, Simona, additional, Westermann, Jörg, additional, Heidinga, Maaike E, additional, Ngai, Lok Lam, additional, Oussoren-Brockhoff, Yvonne J.M, additional, Döhner, Hartmut, additional, Levis, Mark, additional, Ossenkoppele, Gert J., additional, Stone, Richard M., additional, Koenen, Giedre, additional, Bengoudifa, Bourras-Rezki, additional, Cheng, Yuan, additional, Medts, Thierry, additional, Heidinger, Valerie, additional, Sachs, Carolin, additional, and Sierra, Jorge, additional

Published
2021
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14. Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study

Author

Tamò, Raphaël, primary, Turk, Teja, additional, Böni, Jürg, additional, Kouyos, Roger D., additional, Schmutz, Stefan, additional, Huber, Michael, additional, Shah, Cyril, additional, Bischoff-Ferrari, Heike A., additional, Distler, Oliver, additional, Battegay, Edouard, additional, Giovanoli, Pietro, additional, Guckenberger, Matthias, additional, Kohler, Malcolm, additional, Müller, Rouven, additional, Petry, Heidi, additional, Ruschitzka, Frank, additional, McGeer, Allison, additional, Sax, Hugo, additional, Weber, Rainer, additional, Trkola, Alexandra, additional, and Kuster, Stefan P., additional

Published
2021
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15. Absenteeism and presenteeism in healthcare workers due to respiratory illness

Author

Kuster, Stefan P., primary, Böni, Jürg, additional, Kouyos, Roger D., additional, Huber, Michael, additional, Schmutz, Stefan, additional, Shah, Cyril, additional, Bischoff-Ferrari, Heike A., additional, Distler, Oliver, additional, Battegay, Edouard, additional, Giovanoli, Pietro, additional, Guckenberger, Matthias, additional, Kohler, Malcolm, additional, Müller, Rouven, additional, Petry, Heidi, additional, Ruschitzka, Frank, additional, McGeer, Allison, additional, Coleman, Brenda L., additional, Sax, Hugo, additional, Weber, Rainer, additional, and Trkola, Alexandra, additional

Published
2020
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21. MEMSID: Results from a phase 2 pilot study on memantine treatment for sickle cell disease

Author

Hegemann, Inga, Sasselli, Clelia, Valeri, Fabio, Makhro, Asya, Müller, Rouven, Bogdanova, Anna; https://orcid.org/0000-0003-0502-5381, Manz, Markus G, Gassmann, Max; https://orcid.org/0000-0003-2750-8878, Goede, Jeroen S, Hegemann, Inga, Sasselli, Clelia, Valeri, Fabio, Makhro, Asya, Müller, Rouven, Bogdanova, Anna; https://orcid.org/0000-0003-0502-5381, Manz, Markus G, Gassmann, Max; https://orcid.org/0000-0003-2750-8878, and Goede, Jeroen S

Published
2020

23. Spatially Resolved Immobilization of Metallopolymers : Spiropyrans for Light Sensitive Metal Complexes and STED-inspired Laser Lithography

Author

Müller, Rouven and Müller, Rouven

Abstract

In the course of the present thesis, the first method for the spatially resolved surface immobilization of various metallopolymers on a single surface was developed, employing the versatile NITEC photochemistry. The in-depth analysis of the photoligation process identified crucial parameters for the successful immobilization of the metallopolymers, which are also valid for all other photo triggered surface ligation protocols. ToF-SIMS and spatially resolved XPS analysis of the prepared surfaces demonstrated the preserved chemical composition of the fabricated metallopolymer surfaces. In the second part of the thesis, the photochemistry of spiro(thio)pyrans was investigated for the formation of light-sensitive spiropyran-metal complexes, as well as the creation of a photoresist for the application in STED-inspired lithography. The irradiation of an NMR tube inside the NMR spectrometer in so-called LED-NMR experiments was introduced for the investigation of the prepared spiropyran-metal complexes. Finally, the photo triggered reaction of the spirothiopyran photoswitch with an electron deficient maleimide was used for the spatial encoding of surfaces for the first time. In addition, the preparation of a spirothiopyran-based photoresist enabled the writing of structures below the diffraction limit, with the thinnest lines written with STED-inspired lithography to date.

Published
2019

24. Spatially resolved immobilization of metallopolymers – Spiropyrans for light sensitive metal complexes and STED-inspired laser lithography

Author

Müller, Rouven and Barner-Kowollik, C.

Subjects
surface immobilized, X-ray photoelectron spectroscopy, photoresist, Job plot, photo triggered, merocyanin, nitrile imine-mediated tetrazole-ene cycloaddition, spatially-resolved, post-modification, grafting-to, metal complex, thiol-Michael, light-sensitive, photo-chemical, photochromic, ligation, platinum, lithographic encoding, multifunctional, tetrazole, time-of-flight secondary ion mass spectrometry, two-photon excitation, silicon wafer, photoligation, phenacylsulfide, zinc, XPS mapping, ligand monomer, metallopolymer, sub-diffraction, STED, NITEC, polymerization, ddc:540, Diels–Alder, XPS imaging, lithography, spiropyran-metal complexes, 3D microstructures, RAFT, supramolecular, photo, DLW, lanthanum, Job’s method of continuous variations, light sensitive, Chemistry & allied sciences, polymer, Newman–Kwart, trifunctional, triphenylphosphine, nickel, LED-NMR, photocaged, spirothiopyran, XPS, surface, STED inspired, photochemical, diffraction limit, STED-inspired, calcium, photoswitch, self-assembled monolayers, photo-caged, hetero Diels–Alder, gold, palladium, maleimide, photo-triggered, spiropyran, direct laser writing, bifunctional, bipyridine, reversible-addition-fragmentation chain-transfer, Beer–Lambert law, dithiobenzoate, photo-ligation, immobilization, postmodification, o-quinodimethane, ToF-SIMS, surface-immobilized, surface characterization
Abstract

In the course of the present thesis, the first method for the spatially resolved surface immobilization of various metallopolymers on a single surface was developed, employing the versatile NITEC photochemistry. The in-depth analysis of the photoligation process identified crucial parameters for the successful immobilization of the metallopolymers, which are also valid for all other photo triggered surface ligation protocols. ToF-SIMS and spatially resolved XPS analysis of the prepared surfaces demonstrated the preserved chemical composition of the fabricated metallopolymer surfaces. In the second part of the thesis, the photochemistry of spiro(thio)pyrans was investigated for the formation of light-sensitive spiropyran-metal complexes, as well as the creation of a photoresist for the application in STED-inspired lithography. The irradiation of an NMR tube inside the NMR spectrometer in so-called LED-NMR experiments was introduced for the investigation of the prepared spiropyran-metal complexes. Finally, the photo triggered reaction of the spirothiopyran photoswitch with an electron deficient maleimide was used for the spatial encoding of surfaces for the first time. In addition, the preparation of a spirothiopyran-based photoresist enabled the writing of structures below the diffraction limit, with the thinnest lines written with STED-inspired lithography to date.

Published
2019
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25. Targeting CD70 with Cusatuzumab Eliminates Acute Myeloid Leukemia Stem Cells in Humans

Author

Ochsenbein, Adrian F, primary, Pabst, Thomas, primary, Höpner, Sabine, primary, Bacher, Vera Ulrike, primary, Hinterbrandner, Magdalena, primary, Banz, Yara, primary, Müller, Rouven, primary, Manz, Markus G., primary, Gharib, Walid, primary, Francisco, David, primary, Bruggmann, Rémy, primary, Van Rompaey, Luc, primary, Moshir, Mahan, primary, Delahaye, Tim, primary, Gandini, Domenica, primary, Erzeel, Ellen, primary, Hultberg, Anna, primary, Fung, Samson, primary, De Haard, Hans, primary, Leupin, Nicolas, primary, and Riether, Carsten, primary

Published
2019
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27. Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study

Author

Tamò, Raphaël, Turk, Teja, Böni, Jürg, Kouyos, Roger D., Schmutz, Stefan, Huber, Michael, Shah, Cyril, Bischoff-Ferrari, Heike A., Distler, Oliver, Battegay, Edouard, Giovanoli, Pietro, Guckenberger, Matthias, Kohler, Malcolm, Müller, Rouven, Petry, Heidi, Ruschitzka, Frank, McGeer, Allison, Sax, Hugo, Weber, Rainer, Trkola, Alexandra, and Kuster, Stefan P.

Abstract

AbstractObjective:Nosocomial transmission of influenza is a major concern for infection control. We aimed to dissect transmission dynamics of influenza, including asymptomatic transmission events, in acute care.Design:Prospective surveillance study during 2 influenza seasons.Setting:Tertiary-care hospital.Participants:Volunteer sample of inpatients on medical wards and healthcare workers (HCWs).Methods:Participants provided daily illness diaries and nasal swabs for influenza A and B detection and whole-genome sequencing for phylogenetic analyses. Contacts between study participants were tracked. Secondary influenza attack rates were calculated based on spatial and temporal proximity and phylogenetic evidence for transmission.Results:In total, 152 HCWs and 542 inpatients were included; 16 HCWs (10.5%) and 19 inpatients (3.5%) tested positive for influenza on 109 study days. Study participants had symptoms of disease on most of the days they tested positive for influenza (83.1% and 91.9% for HCWs and inpatients, respectively). Also, 11(15.5%) of 71 influenza-positive swabs among HCWs and 3 (7.9%) of 38 influenza-positive swabs among inpatients were collected on days without symptoms; 2 (12.5%) of 16 HCWs and 2 (10.5%) of 19 inpatients remained fully asymptomatic. The secondary attack rate was low: we recorded 1 transmission event over 159 contact days (0.6%) that originated from a symptomatic case. No transmission event occurred in 61 monitored days of contacts with asymptomatic influenza-positive individuals.Conclusions:Influenza in acute care is common, and individuals regularly shed influenza virus without harboring symptoms. Nevertheless, both symptomatic and asymptomatic transmission events proved rare. We suggest that healthcare-associated influenza prevention strategies that are based on preseason vaccination and barrier precautions for symptomatic individuals seem to be effective.

Published
2022
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28. Investigating the Photochemistry of Spiropyran Metal Complexes with Online LED-NMR

Author

Feuerstein, Thomas J., Müller, Rouven, Barner-Kowollik, Christopher, Roesky, Peter W., Feuerstein, Thomas J., Müller, Rouven, Barner-Kowollik, Christopher, and Roesky, Peter W.

Abstract

As one of the best studied photoswitches, spiropyrans (SPs) have attracted significant interest in the scientific community. Among the many stimuli to alter the isomerization into the merocyanine (MC) isomer, such as temperature, pH, solvent polarity, redox potential, or mechanical force, the ability of the MC form to act as a ligand site for metal complexation has recently raised new attention. We herein synthesize hitherto undescribed coordination compounds of 8-methoxy-1′,3′,3′-trimethyl-6-nitrospiro-[chromene-2,2′-indoline] with s-block ([Ca(MC)4](ClO4)2), d-block ([Zn(MC)2(MeCN)2](ClO4)2, [Ni(MC)2(MeCN)2](ClO4)2), as well as f-block ([La(NO3)3(MC)2]) metals. All complexes are structurally described by X-ray crystallography and systematically investigated in solution via Job's method of continuous variations (Job plots), as well as online NMR spectroscopic kinetic experiments with in situ irradiation of the analyte solution inside the NMR spectrometer (LED-NMR). We can unambiguously identify the photoresponsive nature of the complexes in solution, which is a crucial step toward the application of these promising molecules in material science.

Published
2019

30. inv(16) and NPM1mut AMLs engraft human cytokine knock-in mice

Author

Ellegast, Jana M., Rauch, Philipp J., Kovtonyuk, Larisa V., Müller, Rouven, Wagner, Ulrich, Saito, Yasuyuki, Wildner-Verhey van Wijk, Nicole, Fritz, Christine, Rafiei, Anahita, Lysenko, Veronika, Dudkiewicz, Ewa, Theocharides, Alexandre P., Soldini, Davide, Goede, Jeroen S., Flavell, Richard A., and Manz, Markus G.

Published
2016
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33. Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial

Author

Ochsenbein, Adrian F, primary, Riether, Carsten, additional, Bacher, Ulrike, additional, Müller, Rouven, additional, Höpner, Sabine, additional, Banz, Yara, additional, Hinterbrandner, Magdalena, additional, Bargetzi, Mario, additional, Manz, Markus G., additional, Van Rompaey, Luc, additional, Moshir, Mahan, additional, Delahaye, Tim, additional, Gandini, Domenica, additional, Erzeel, Ellen, additional, Hultberg, Anna, additional, Fung, Samson, additional, De Haard, Hans, additional, Leupin, Nicolas, additional, and Pabst, Thomas, additional

Published
2018
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34. Absenteeism and presenteeism in healthcare workers due to respiratory illness

Author

Kuster, Stefan P., Böni, Jürg, Kouyos, Roger D., Huber, Michael, Schmutz, Stefan, Shah, Cyril, Bischoff-Ferrari, Heike A., Distler, Oliver, Battegay, Edouard, Giovanoli, Pietro, Guckenberger, Matthias, Kohler, Malcolm, Müller, Rouven, Petry, Heidi, Ruschitzka, Frank, McGeer, Allison, Coleman, Brenda L., Sax, Hugo, Weber, Rainer, and Trkola, Alexandra

Abstract

AbstractObjective:To assess influenza symptoms, adherence to mask use recommendations, absenteesm and presenteeism in acute care healthcare workers (HCWs) during influenza epidemics.Methods:The TransFLUas influenza transmission study in acute healthcare prospectively followed HCWs prospectively over 2 consecutive influenza seasons. Symptom diaries asking for respiratory symptoms and adherence with mask use recommendations were recorded on a daily basis, and study participants provided midturbinate nasal swabs for influenza testing.Results:In total, 152 HCWs (65.8% nurses and 13.2% physicians) were included: 89.1% of study participants reported at least 1 influenza symptom during their study season and 77.8% suffered from respiratory symptoms. Also, 28.3% of HCW missed at least 1 working day during the study period: 82.6% of these days were missed because of symptoms of influenza illness. Of all participating HCWs, 67.9% worked with symptoms of influenza infection on 8.8% of study days. On 0.3% of study days, symptomatic HCWs were shedding influenza virus while at work. Among HCWs with respiratory symptoms, 74.1% adhered to the policy to wear a mask at work on 59.1% of days with respiratory symptoms.Conclusions:Respiratory disease is frequent among HCWs and imposes a significant economic burden on hospitals due to the number of working days lost. Presenteesm with respiratory illness, including influenza, is also frequent and poses a risk for patients and staff.Trial registration:NCT02478905 (clinicaltrials.gov)

Published
2021
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37. Lymphadenopathy driven by TCR-Vγ8Vδ1 T-cell expansion in FAS-related autoimmune lymphoproliferative syndrome

Author

Vavassori, Stefano, primary, Galson, Jacob D., additional, Trück, Johannes, additional, van den Berg, Anke, additional, Tamminga, Rienk Y. J., additional, Magerus-Chatinet, Aude, additional, Pellé, Olivier, additional, Camenisch Gross, Ulrike, additional, Marques Maggio, Ewerton, additional, Prader, Seraina, additional, Opitz, Lennart, additional, Nüesch, Ursina, additional, Mauracher, Andrea, additional, Volkmer, Benjamin, additional, Speer, Oliver, additional, Suda, Luzia, additional, Röthlisberger, Benno, additional, Zimmermann, Dieter Robert, additional, Müller, Rouven, additional, Diepstra, Arjan, additional, Visser, Lydia, additional, Haralambieva, Eugenia, additional, Neven, Bénédicte, additional, Rieux-Laucat, Frédéric, additional, and Pachlopnik Schmid, Jana, additional

Published
2017
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39. Inv(16) AML Engrafts Human Cytokine Knock-in Mice

Author

Rauch, Philipp J, primary, Ellegast, Jana M, additional, Kovtonyuk, Larisa V, additional, Wagner, Ulrich, additional, Müller, Rouven, additional, Saito, Yasuyuki, additional, Wildner-Verhey van Wijk, Nicole, additional, Fritz, Christine, additional, Rafiei, Anahita, additional, Lysenko, Veronika, additional, Dudkiewicz, Ewa, additional, Soldini, Davide, additional, Goede, Jeroen S, additional, Flavell, Richard, additional, and Manz, Markus G, additional

Published
2016
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40. The HIV Protease Inhibitor Nelfinavir in Combination with Bortezomib and Dexamethasone (NVd) Has Excellent Activity in Patients with Advanced, Proteasome Inhibitor-Refractory Multiple Myeloma: A Multicenter Phase II Trial (SAKK 39/13)

Author

Driessen, Christoph, primary, Müller, Rouven, additional, Novak, Urban, additional, Cantoni, Nathan, additional, Betticher, Daniel, additional, Mach, Nicolas, additional, Gregor, Michael, additional, Samaras, Panagiotis, additional, Berset, Catherine, additional, Rondeau, Stephanie, additional, Hawle, Hanne, additional, Hitz, Felicitas, additional, Pabst, Thomas, additional, and Zander, Thilo, additional

Published
2016
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43. Microarray‐based comparative genomic hybridisation reveals additional recurrent aberrations in adult patients evaluated for myelodysplastic syndrome with normal karyotype.

Author

Ouahchi, Ines, Zhang, Luduo, Benitez Brito, Ramon, Benz, Rudolf, Müller, Rouven, Bonadies, Nicolas, and Tchinda, Joëlle

Subjects
MYELODYSPLASTIC syndromes, COMPARATIVE genomic hybridization, CHROMOSOME banding, PATIENTS, BONE marrow diseases
Abstract

The article examines additional information obtained using microarray-based comparative genomic hybridisation compared to chromosome banding analysis in large cohort of patients undergoing primary diagnostic tests for suspected myelodysplastic syndromes (MDS). Chromosome banding analysis succeeded in nearly ninety-seven percent confirmed MDS.

Published
2019
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46. Exploiting λ‐Orthogonal Photoligation for Layered Surface Patterning.

Author

Lederhose, Paul, Blinco, James P., Barner‐Kowollik, Christopher, Abt, Doris, Welle, Alexander, and Müller, Rouven

Subjects
CHEMICAL reagents, SPECTROMETERS, CHROMATOGRAPHIC analysis, LIGHT emitting diodes, TEMPERATURE
Abstract

Abstract: We exploit λ‐orthogonal photoligation of nitrile imine‐mediated tetrazole‐ene cycloaddition (NITEC) chemistry to generate complex, interconnected surface modifications via a simple layered surface patterning approach. By judicious choice of activating chromophores, we introduce a one pot reaction where nitrile imine formation can be triggered independently of other tetrazoles present. When irradiated with visible light, a tetrazole bearing a pyrene chromophore undergoes quantitative elimination of nitrogen to release nitrile imine (which subsequently undergoes trapping with a dipolarophile in a 1,3 dipolar cycloaddition) whereas a tetrazole bearing a phenyl moiety remains unreacted. Subsequent irradiation of the solution with UV light yields the N‐phenyl containing nitrile imine quantitatively, while the pyrene pyrazoline adduct remains unchanged. This λ‐orthogonal photoligation was subsequently exploited for the generation of layered patterned surfaces. Specifically, the visible light active tetrazole was grafted to a silicon wafer and subsequently photolithographically patterned with a dipolarophile modified with a UV‐active tetrazole. Various electron deficient olefins were then patterned in a spatially resolved manner relying on different light activation. The desired functionality was successfully imaged on the silicon wafers using time‐of‐flight–secondary ion mass spectrometry (ToF‐SIMS), demonstrating that a powerful mask‐less lithographic platform technology has been established. [ABSTRACT FROM AUTHOR]

Published
2018
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47. Modelling of a genetically diverse evolution of Systemic Mastocytosis with Chronic Myelomonocytic Leukemia (SM-CMML) by next generation sequencing

Author

Rechsteiner, Markus, Müller, Rouven, Reineke, Tanja, Goede, Jeroen, Bohnert, Annette, Zhong, Qing, Manz, Markus G, Moch, Holger, Wild, Peter J, Zimmermann, Dieter R, Tinguely, Marianne, Rechsteiner, Markus, Müller, Rouven, Reineke, Tanja, Goede, Jeroen, Bohnert, Annette, Zhong, Qing, Manz, Markus G, Moch, Holger, Wild, Peter J, Zimmermann, Dieter R, and Tinguely, Marianne

Abstract

BACKGROUND Systemic mastocytosis (SM) is a heterogenous, clonal mast cell (MC) proliferation, rarely associated with clonal hematologic non-mast cell lineage disease (SM-AHNMD). KIT (D816V) is regarded as driver-mutation in SM-AHNMD. METHODS DNA isolated from peripheral blood (PB) of an SM-CMML patient was investigated with targeted next generation sequencing. Variants were verified by Sanger sequencing and further characterized in the SM part of the bone marrow trephine (BMT), normal tissue, and FACS sorted PB cell subpopulations. FINDINGS Low coverage deep-sequencing (mean 10x) on a GS 454 Junior revealed two as yet unreported SNVs (CBFA2T3 and CLTCL1), both germ-line mutations. High coverage (mean 1674x) targeted re-sequencing on an Ion Proton revealed 177 variants in coding regions. Excluding SNPs, the final list comprised 11 variants. Among these, TET2 (p.Thr1027fs, p.Cys1263Ser) and RUNX1 (p.Asn109Ser) were identified in in the peripheral blood and the SM part of BMT, but not in normal tissue. Furthermore, Sanger sequencing of PB cells revealed similar signal intensities for both TET2 mutations in FACS sorted CD34+ precursor cells and CD16+ granulocytes comparable to signals in the SM part of BMT. In contrast, RUNX1 exhibited a double intensity in CD34+ cells compared to the SM part of BMT and a homozygous variant signal in granulocytes. Both TET2 and RUNX1 mutations were not detectable in B- and T-cells. CONCLUSION We present a heterozygous triple-mutation pattern (KIT, TET2, RUNX1) in mast cells (SM disease part) with additional LOH of RUNX1 in granulocytes (CMML disease part). These identified mutations allow a more detailed insight into a multistep pathogenesis which suggests a common tumor progenitor in SM-CMML.

Published
2014

50. Modelling of a genetically diverse evolution of Systemic Mastocytosis with Chronic Myelomonocytic Leukemia (SM-CMML) by Next Generation Sequencing

Author

Rechsteiner, Markus, primary, Müller, Rouven, additional, Reineke, Tanja, additional, Goede, Jeroen, additional, Bohnert, Annette, additional, Zhong, Qing, additional, Manz, Markus G, additional, Moch, Holger, additional, Wild, Peter J, additional, Zimmermann, Dieter R, additional, and Tinguely, Marianne, additional

Published
2014
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