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2. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Author

Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., Cingolani A. (ORCID:0000-0002-3793-2755), Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., and Cingolani A. (ORCID:0000-0002-3793-2755)

Abstract

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe

Published
2024

3. Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO)

Author

Kochanek, Matthias, Schalk, E., von Bergwelt-Baildon, M., Beutel, G., Buchheidt, D., Hentrich, M., Henze, L., Kiehl, M., Liebregts, T., von Lilienfeld-Toal, M., Classen, A., Mellinghoff, S., Penack, O., Piepel, C., and Böll, B.

Published
2019
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7. Influenza virus infections in patients with malignancies –– characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO)

Author

Hermann, B., Lehners, N., Brodhun, M., Boden, K., Hochhaus, A., Kochanek, M., Meckel, K., Mayer, K., Rachow, T., Rieger, C., Schalk, E., Weber, T., Schmeier-Jürchott, A., Schlattmann, P., Teschner, D., and von Lilienfeld-Toal, M.

Published
2017
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8. 1496P Trabectedin for patients with advanced soft tissue sarcoma: A non-interventional, prospective, multicenter study

Author

Grünwald, V., primary, Pink, D., additional, Egerer, G., additional, Schalk, E., additional, Augustin, M., additional, Deinzer, C.K., additional, Kob, V., additional, Reichert, D., additional, Kebenko, M., additional, Brandl, S.F., additional, Hahn, D.A., additional, Lindner, L.H., additional, Hoiczyk, M., additional, Ringsdorf, U., additional, Hanker, L., additional, Hempel, D., additional, Pontes, M.J., additional, Wismann, T., additional, and Ivanyi, P., additional

Published
2022
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10. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), and Dragonetti G.

Abstract

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. Ho

Published
2021

12. Baseline Chest Computed Tomography as Standard of Care in High-Risk Hematology Patients

Author

Stemler, J., Bruns, C., Mellinghoff, S.C., Alakel, N., Akan, H., Ananda-Rajah, M., Auberger, J., Bojko, P., Chandrasekar, P.H., Chayakulkeeree, M., Cozzi, J.A., Kort, E.A. de, Groll, A.H., Heath, C.H., Henze, L., Hernandez Jimenez, M., Kanj, S.S., Khanna, N., Koldehoff, M., Lee, D.G., Mager, A., Marchesi, F., Martino-Bufarull, R., Nucci, M., Oksi, J., Pagano, L., Phillips, B., Prattes, J., Pyrpasopoulou, A., Rabitsch, W., Schalk, E., Schmidt-Hieber, M., Sidharthan, N., Soler-Palacin, P., Stern, A., Weinbergerova, B., El Zakhem, A., Cornely, O.A., Koehler, P., Stemler, J., Bruns, C., Mellinghoff, S.C., Alakel, N., Akan, H., Ananda-Rajah, M., Auberger, J., Bojko, P., Chandrasekar, P.H., Chayakulkeeree, M., Cozzi, J.A., Kort, E.A. de, Groll, A.H., Heath, C.H., Henze, L., Hernandez Jimenez, M., Kanj, S.S., Khanna, N., Koldehoff, M., Lee, D.G., Mager, A., Marchesi, F., Martino-Bufarull, R., Nucci, M., Oksi, J., Pagano, L., Phillips, B., Prattes, J., Pyrpasopoulou, A., Rabitsch, W., Schalk, E., Schmidt-Hieber, M., Sidharthan, N., Soler-Palacin, P., Stern, A., Weinbergerova, B., El Zakhem, A., Cornely, O.A., and Koehler, P.

Abstract

Contains fulltext : 218254.pdf (publisher's version ) (Open Access), Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5-15%) and non-BCT centers (7%; IQR 5-10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.

Published
2020

13. Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Author

Schmidt-Hieber, M., Bierwirth, J., Buchheidt, D., Cornely, O. A., Hentrich, M., Maschmeyer, G., Schalk, E., Vehreschild, J. J., Vehreschild, Maria J. G. T., Schmidt-Hieber, M., Bierwirth, J., Buchheidt, D., Cornely, O. A., Hentrich, M., Maschmeyer, G., Schalk, E., Vehreschild, J. J., and Vehreschild, Maria J. G. T.

Abstract

Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.

Published
2018

14. Consensus statement for cancer patients requiring intensive care support

Author

Kiehl, M. G., Beutel, G., Boell, B., Buchheidt, D., Forkert, R., Fuhrmann, V., Knoebl, P., Kochanek, M., Kroschinsky, F., La Rosee, P., Liebregts, T., Lueck, C., Olgemoeller, U., Schalk, E., Shimabukuro-Vornhagen, A., Sperr, W. R., Staudinger, T., Baildon, M. von Bergwelt, Wohlfarth, P., Zeremski, V., Schellongowski, P., Kiehl, M. G., Beutel, G., Boell, B., Buchheidt, D., Forkert, R., Fuhrmann, V., Knoebl, P., Kochanek, M., Kroschinsky, F., La Rosee, P., Liebregts, T., Lueck, C., Olgemoeller, U., Schalk, E., Shimabukuro-Vornhagen, A., Sperr, W. R., Staudinger, T., Baildon, M. von Bergwelt, Wohlfarth, P., Zeremski, V., and Schellongowski, P.

Abstract

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.

Published
2018

15. CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation) - Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Author

Schmidt-Hieber, Martin, Silling, Gerda, Wolf, H. H., Ruhnke, M., Schwartz, S., Maschmeyer, G., Schalk, E., Heinz, W., Panse, Jens, Penack, O., Christopeit, M., Buchheidt, D., Meyding-Lamadé, U., and Hähnel, S.

Abstract

Annals of oncology 27(7), 1207-1225 (2016). doi:10.1093/annonc/mdw155, Published by Oxford Univ. Press, Oxford

Published
2016
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17. Prophylactic exchange of central venous catheters (CVC) for prevention of CVC-related bloodstream infections (CRBSI) in patients with haematological malignancies: indirect evidence from pooled data of the SECRECY registry and the COAT study

Author

Schalk, E., Biehl, L. M., Faerber, J., Huth, A., Panse, J., Kraemer, C., Hentrich, M., Engelhardt, M., Schaefer-Eckart, K., Kofla, G., Kiehl, M., Wendtner, C. -M, Karthaus, M., Comely, O. A., Fischer, T., Vehreschild, M. J. G. T., Schalk, E., Biehl, L. M., Faerber, J., Huth, A., Panse, J., Kraemer, C., Hentrich, M., Engelhardt, M., Schaefer-Eckart, K., Kofla, G., Kiehl, M., Wendtner, C. -M, Karthaus, M., Comely, O. A., Fischer, T., and Vehreschild, M. J. G. T.

Published
2016

18. Influenza virus infections in patients with malignancies: Characteristics and outcome of the spring season 2015-final analysis by the infectious diseases working party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

Author

Teschner, D., Hermann, B., Lehners, N., Brodhun, M., Hochhaus, A., Boden, K., Kochanek, M., Meckel, K., Mayer, K., Rachow, T., Rieger, C., Schalk, E., Schmeier-Juerchott, A., Weber, T., Schlattmann, P., von Lilienfeld-Toal, M., Teschner, D., Hermann, B., Lehners, N., Brodhun, M., Hochhaus, A., Boden, K., Kochanek, M., Meckel, K., Mayer, K., Rachow, T., Rieger, C., Schalk, E., Schmeier-Juerchott, A., Weber, T., Schlattmann, P., and von Lilienfeld-Toal, M.

Published
2016

19. Influenza virus infections in patients with malignancies –– characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO)

Author

Hermann, B., primary, Lehners, N., additional, Brodhun, M., additional, Boden, K., additional, Hochhaus, A., additional, Kochanek, M., additional, Meckel, K., additional, Mayer, K., additional, Rachow, T., additional, Rieger, C., additional, Schalk, E., additional, Weber, T., additional, Schmeier-Jürchott, A., additional, Schlattmann, P., additional, Teschner, D., additional, and von Lilienfeld-Toal, M., additional

Published
2016
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22. Weichtteiltumoren

Author

Schalk, E., primary, Garlipp, B., additional, Bruns, C.J., additional, and Fischer, T., additional

Published
2015
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27. An experimental study of the load and heat influence from combustion on engine friction.

Author

Allmaier, H., Knauder, C., Salhofer, S., Reich, F. M., Schalk, E., Ofner, H., and Wagner, A.

Abstract

The friction power losses of a turbo-charged heavy-duty diesel engine of the 13 litre class are investigated both by fired engine tests as well as by pressurized motoring tests. During pressurized motoring compressed air is applied to the engine intake which creates loads comparable with fired operation but without the strong and changing thermal influence of combustion. By using this combined approach the influence of the load and the thermal influence of the combustion can be studied separately for the first time. It is found that pressurized motoring yields comparable but generally a bit higher friction power losses as in fired operation. In particular, for full load operation, the agreement between the two methods is very good which supports the reasoning that for full load operation the mechanical load is the dominant factor for the friction power losses. However, for part load operation significant differences arise. Without the thermal influence from combustion, increasing the load on the engine leads to a rather linear increase in the friction power losses as is seen from pressurized motoring. This is in contrast to the fired engine tests, where the friction power losses stay almost constant over a rather large range of part loads and only increase for full load operation. It is argued that the reason for this different behaviour is the thermal impact from combustion. [ABSTRACT FROM AUTHOR]

Published
2016
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28. Two Collections of Finds from Burial Mounds in Ukraine (National Museum of Natural History, Smithsonian Institution, Washington, DC).

Author

Schalk, E.

Subjects
MOUNDS (Archaeology), ARCHAEOLOGICAL research, BRONZE Age
Abstract

Copyright of Stratum Plus Journal is the property of P.P. Stratum plus and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2015

31. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract

Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2021

32. Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile-a German multicentre cohort study.

Author

Conrad J, Giesbrecht K, Aguilar RC, Gräfe SK, Ullah A, Hunfeld KP, Lübbert C, Pützfeld S, Reuken PA, Schmitz-Rode M, Schalk E, Schmidt-Wilcke T, Schmiedel S, Solbach P, and Vehreschild MJGT

Subjects
Humans, Male, Female, Aged, Germany, Middle Aged, Cohort Studies, Aged, 80 and over, Recurrence, Treatment Outcome, Proportional Hazards Models, Adult, Vancomycin therapeutic use, Metronidazole therapeutic use, Clostridium Infections drug therapy, Clostridium Infections mortality, Clostridium Infections microbiology, Anti-Bacterial Agents therapeutic use, Clostridioides difficile drug effects
Abstract

Objectives: The objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study., Methods: The IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections., Results: Of the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33-0.65]; non-severe: HR 0.39; [95% CI, 0.24-0.60]; severe: HR 0.52; [95% CI, 0.28-0.95])., Discussion: Our analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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33. Lautropia mirabilis sepsis in immunodeficiency: first report and genomic features.

Author

Genseke S, Berisha M, Teerstegen A, Meyer B, Kaasch AJ, Färber J, Schalk E, Zautner AE, Esser T, and Kahlfuß S

Abstract

Purpose: Lautropia mirabilis is a Gram-negative, facultative anaerobic coccus, which has been detected mainly in respiratory sites of immunodeficient patients suffering from HIV or cystic fibrosis. To date, knowledge about the pathogenicity of L. mirabilis is spare due to the small numbers of documented cases., Methods: We present a literature review and report the case of a 39-year-old female diagnosed with common variable immunodeficiency (CVID) with IgG and IgA deficiency suffering from a sepsis with L. mirabilis. As no fully closed L. mirabilis genome besides the type strain was available to date, we additionally performed complete genome sequencing of L. mirabilis., Results: The patient was admitted to our hospital with recurrent episodes of fever. Here, we detected L. mirabilis in two different blood cultures. The bacterium was tested susceptible to and treated with meropenem. As the origin of L. mirabilis sepsis, we observed an active periodontitis likely due to impaired IgA levels and mucosal insufficiency as a consequence of CVID. Whole genome sequencing of L. mirabilis revealed several genes important for host cell invasion and intracellular survival of the pathogen., Conclusions: Our case highlights the importance of L. mirabilis in immunocompromised patients also in other compartments than the respiratory tract., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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35. Multiple unfolded protein response pathways cooperate to link cytosolic dsDNA release to stimulator of interferon gene activation.

Author

Hu T, Liu Y, Fleck J, King C, Schalk E, Zhang Z, Mehle A, and Smith JA

Subjects
Humans, Animals, Mice, DNA metabolism, Protein Serine-Threonine Kinases metabolism, Signal Transduction, eIF-2 Kinase metabolism, Endoribonucleases metabolism, X-Box Binding Protein 1 metabolism, X-Box Binding Protein 1 genetics, Thapsigargin pharmacology, Reactive Oxygen Species metabolism, Transcriptional Activation, DNA, Mitochondrial metabolism, Unfolded Protein Response, Nucleotidyltransferases metabolism, Cytosol metabolism, Membrane Proteins metabolism, Membrane Proteins genetics, Interferon-beta metabolism, Endoplasmic Reticulum Stress
Abstract

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-β induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-β, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-β mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-β via mitochondrial dsDNA release., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Liu, Fleck, King, Schalk, Zhang, Mehle and Smith.)

Published
2024
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37. Multiple Unfolded Protein Response pathways cooperate to link cytosolic dsDNA release to Stimulator of Interferon Gene (STING) activation.

Author

Hu T, Liu Y, Fleck J, King C, Schalk E, Zhang Z, Mehle A, and Smith JA

Abstract

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-β induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-β, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-β mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-β via mitochondrial dsDNA release.

Published
2024
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40. Chlorhexidine gluconate-coated gel pad dressings for prevention of central venous catheter-related bloodstream infections in patients with hematologic diseases or autologous stem cell transplantation: A registry-based matched-pair analysis.

Author

Teschner D, Berisha M, Panse J, Schmitt T, Fiegle E, Naendrup JH, Neitz J, Schmidt-Hieber M, Hentrich M, Böll B, and Schalk E

Subjects
Adult, Humans, Matched-Pair Analysis, Transplantation, Autologous, Bandages, Central Venous Catheters adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Catheter-Related Infections diagnosis, Catheter-Related Infections epidemiology, Catheter-Related Infections etiology, Sepsis, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Catheterization, Central Venous adverse effects
Abstract

Objectives: Chlorhexidine gluconate (CHG)-coated gel pad dressings for central venous catheter (CVC) may prevent CVC-related bloodstream infections (CRBSI). However, real-world data showing beneficial effects in patients with hematologic malignancies are scarce., Methods: In a matched-pair analysis with data from a multicenter CVC registry, non-tunneled jugular and subclavian vein CVC in adults with hematologic malignancies or germ cell tumors (including patients receiving autologous hematopoietic stem cell transplantation [ASCT]) with CHG were compared with non-CHG dressings. The primary endpoint was definite CRBSI rate within 14 days (dCRBSI14) of CVC insertion; secondary endpoints were combined rate of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), and CRBSI incidences of all estimates., Results: In total, 2070 CVCs were assessed. There was no statistically significant difference in dCRBSI14 (2.3% vs. 3.5%) between patients with and without CHG gel dressings. Likewise, with regards to dpCRBSI14 (6.2% vs. 6.3%) and the overall dpCRBSI rate (9.2% vs. 10.5%), no significant difference was detected. Furthermore, dCRBSI14 incidence (2.0 vs. 3.2/1000 CVC days), dpCRBSI14 incidence (5.4 vs. 5.6/1000 CVC days), and overall CRBSI incidence (5.5 vs. 6.0/1000 CVC days) showed no significant differences., Conclusions: CRBSI rates were not reduced by the use of CHG gel dressings in patients with hematologic malignancies and/or ASCT., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Published
2023
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42. AML consolidation therapy: timing matters.

Author

Reimann AM, Schalk E, Jost F, Mougiakakos D, Weber D, Döhner H, Récher C, Dumas PY, Ditzhaus M, Fischer T, and Sager S

Abstract

Purpose: Infections due to severe neutropenia are the most common therapy-associated causes of mortality in patients with acute myeloid leukemia (AML). New strategies to lessen the severity and duration of neutropenia are needed., Methods: Cytarabine is commonly used for AML consolidation therapy; we compared high- and intermediate-dose cytarabine administration on days 1, 2, and 3 (AC-123) versus days 1, 3, and 5 (AC-135) in consolidation therapy of AML. Recently, clinical trials demonstrated that high-dose AC-123 resulted in a shortened white blood cell (WBC) recovery time compared with high-dose AC-135. Our main hypothesis is that this is also the case for different cytarabine dosage, granulocyte colony-stimulating factor (G-CSF) administration, and cycle lengths. We analyzed 334 treatment schedules on virtual cohorts of digital twins., Results: Comparison of 32,565 simulated consolidation cycles resulted in a reduction in the WBC recovery time for AC-123 in 99.6% of the considered cycles (median reduction 3.5 days) without an increase in the number of leukemic blasts (lower value in 94.2% of all cycles), compared to AC-135., Conclusion: Our numerical study supports the use of AC-123 plus G-CSF as standard conventional AML consolidation therapy to reduce the risk for life-threatening infectious complications., (© 2023. The Author(s).)

Published
2023
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43. Tigecycline as salvage treatment of febrile neutropenia in patients with haematological malignancies-a retrospective single-centre analysis of 200 cases.

Author

Geßner D, Berisha M, Esser T, and Schalk E

Subjects
Male, Humans, Female, Tigecycline therapeutic use, Salvage Therapy, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Anti-Bacterial Agents therapeutic use, Hematologic Neoplasms complications, Hematologic Neoplasms drug therapy, Febrile Neutropenia drug therapy, Febrile Neutropenia complications
Abstract

Tigecycline has been used to treat patients with febrile neutropenia (FN). This study aims to analyse the effectiveness of tigecycline as salvage treatment of FN. Patients records from 09/2004 to 04/2019 were reviewed. Cases were eligible if fever persisted/recurred (p/r-FN) after 3 days of second-line treatment with a carbapenem, and were divided into three groups: switch to tigecycline (TGC group), switch to other antibiotics (OAB group), and no switch (W&W group). The primary endpoint was response rate (defervescence for ≥ 7 days or at least until discharge); the key secondary endpoint was 30-day mortality rate. Two hundred cases from 176 patients (median 59 years; 53.5% men) treated were included, mostly acute myeloid leukaemias (61.0%). 45.5% of cases were in the TGC group (in combination with an anti-pseudomonal antibiotic, mostly ceftazidime [95.6%]); 35.5% were in the OAB and 19.0% in the W&W group. There was no significant difference in response rates (TGC, 73.6%; OAB, 62.0%; W&W, 78.9%; p = 0.12) or 30-day mortality rates (TGC, 7.7%; OAB, 7.0%; W&W, 5.3%; p = 0.94). Tigecycline plus an anti-pseudomonal antibiotic does not improve response or 30-day mortality rate compared to other antibiotics in patients with p/r-FN. Also, in some cases, no switch in antibiotics may be necessary at all., (© 2023. The Author(s).)

Published
2023
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44. Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

Author

Stemler J, Mellinghoff SC, Khodamoradi Y, Sprute R, Classen AY, Zapke SE, Hoenigl M, Krause R, Schmidt-Hieber M, Heinz WJ, Klein M, Koehler P, Liss B, Koldehoff M, Buhl C, Penack O, Maschmeyer G, Schalk E, Lass-Flörl C, Karthaus M, Ruhnke M, Cornely OA, and Teschner D

Subjects
Humans, Antifungal Agents therapeutic use, Cytochrome P-450 CYP3A, Medical Oncology, Triazoles therapeutic use, Invasive Fungal Infections drug therapy, Invasive Fungal Infections prevention & control, Invasive Fungal Infections microbiology, Communicable Diseases drug therapy, Hematologic Neoplasms complications, Hematologic Neoplasms drug therapy, Hematology
Abstract

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Published
2023
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45. Impact of the insertion site of central venous catheters on central venous catheter-related bloodstream infections in patients with cancer: results from a large prospective registry.

Author

Hentrich M, Böll B, Teschner D, Panse J, Schmitt T, Naendrup JH, Schmidt-Hieber M, Neitz J, Fiegle E, and Schalk E

Subjects
Humans, Subclavian Vein, Central Venous Catheters adverse effects, Catheterization, Central Venous adverse effects, Neoplasms complications, Sepsis etiology, Catheter-Related Infections epidemiology, Catheter-Related Infections etiology
Abstract

Purpose: Overall, insertion of central venous catheter (CVC) into femoral veins (FV) has been shown to be associated with a higher risk of infection compared with subclavian and internal jugular (IJV/SCV) CVC, but no data are available on the impact of the FV insertion site on the CVC-related bloodstream infections (CRBSI) risk in patients with cancer. The objective of the study is to compare CRBSI rates and incidences of FV with those of internal jugular and subclavian vein (IJV/SCV CVC) as observed in the prospective SECRECY registry., Methods: SECRECY is an ongoing observational, prospective, clinical CRBSI registry active in six departments of hematology/oncology in Germany. Each case of FV CVC was matched at a ratio of 1:1 to a case with IJV/SCV CVC. The propensity score was estimated using a multivariable logistic regression model adjusting for age, sex, cancer type, and duration of indwelling catheter., Results: Of 4268 CVCs included in this analysis, 52 (1.2%) were inserted into the FV and 4216 (98.8%) into the IJV/SCV. 52 cases of FV CVC were matched with 52 IJV/SCV CVC. There was no significant difference in the CRBSI rate (3.8% vs. 9.6%), the CRBSI incidence (5.7 vs. 14.2/1000 CVC days), and the median CVC time (5.5 vs. 5 days) between the FV and the IJV/SCV group., Conclusion: Based on this data, inserting FV CVCs in patients with cancer does, at least in the short-term, not appear to be associated with an increased risk of CRBSI as compared to IJV/SCV CVC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Published
2023
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47. Which trial do we need? Scheduled central venous catheter removal vs. routine clinical care for prevention of central venous catheter-related bloodstream infections in patients with haematologic malignancies.

Author

Schalk E and Panse J

Subjects
Humans, Central Venous Catheters adverse effects, Catheterization, Central Venous adverse effects, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Sepsis prevention & control, Sepsis microbiology, Catheter-Related Infections microbiology, Bacteremia prevention & control
Published
2023
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48. AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants.

Author

Giesen N, Busch E, Schalk E, Beutel G, Rüthrich MM, Hentrich M, Hertenstein B, Hirsch HH, Karthaus M, Khodamoradi Y, Koehler P, Krüger W, Koldehoff M, Krause R, Mellinghoff SC, Penack O, Sandherr M, Seggewiss-Bernhardt R, Spiekermann K, Sprute R, Stemler J, Weissinger F, Wörmann B, Wolf HH, Cornely OA, Rieger CT, and von Lilienfeld-Toal M

Subjects
Humans, SARS-CoV-2, Vaccination, COVID-19 prevention & control, COVID-19 complications, Neoplasms therapy, Neoplasms drug therapy, Communicable Diseases complications, Communicable Diseases drug therapy
Abstract

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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49. Overweight or obesity are not risk factors for central venous catheter-related bloodstream infections in patients with hematological malignancies.

Author

Schalk E and Hentrich M

Subjects
Humans, Overweight complications, Overweight epidemiology, Obesity complications, Obesity epidemiology, Central Venous Catheters adverse effects, Catheter-Related Infections etiology, Catheterization, Central Venous adverse effects, Hematologic Neoplasms complications, Sepsis etiology
Published
2022
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50. Central venous catheter-related bloodstream infections in patients with haematological malignancies during the SARS-CoV-2 pandemic.

Author

Schalk E, Schmitt T, Panse J, Fiegle E, Naendrup JH, Schmidt-Hieber M, Böll B, Hentrich M, Teschner D, and Mougiakakos D

Subjects
Humans, SARS-CoV-2, Pandemics, Central Venous Catheters adverse effects, COVID-19, Catheterization, Central Venous adverse effects, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Sepsis, Bacteremia epidemiology, Bacteremia etiology
Published
2022
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