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2. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline

Author

Ullmann, A.J., Aguado, J.M., Arikan-Akdagli, S., Denning, D.W., Groll, A.H., Lagrou, K., Lass-Flörl, C., Lewis, R.E., Munoz, P., Verweij, P.E., Warris, A., Ader, F., Akova, M., Arendrup, M.C., Barnes, R.A., Beigelman-Aubry, C., Blot, S., Bouza, E., Brüggemann, R.J.M., Buchheidt, D., Cadranel, J., Castagnola, E., Chakrabarti, A., Cuenca-Estrella, M., Dimopoulos, G., Fortun, J., Gangneux, J.-P., Garbino, J., Heinz, W.J., Herbrecht, R., Heussel, C.P., Kibbler, C.C., Klimko, N., Kullberg, B.J., Lange, C., Lehrnbecher, T., Löffler, J., Lortholary, O., Maertens, J., Marchetti, O., Meis, J.F., Pagano, L., Ribaud, P., Richardson, M., Roilides, E., Ruhnke, M., Sanguinetti, M., Sheppard, D.C., Sinkó, J., Skiada, A., Vehreschild, M.J.G.T., Viscoli, C., and Cornely, O.A.

Published
2018
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5. Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, non-neutropenic, adult patients: An update including COVID-19 data

Author

Bassetti, Matteo, primary, Zuccaro, Valentina, additional, Asperges, Erika, additional, Scudeller, Luigia, additional, Giacobbe, Daniele Roberto, additional, Akova, M., additional, Alastruey-Izquierdo, A., additional, Arikan-Akdagli, S., additional, Azoulay, E., additional, Blot, S., additional, Cortegiani, A., additional, Cornely, O.A., additional, Grecchi, C., additional, Lass-Flörl, C., additional, Koehler, P., additional, Cuenca-Estrella, M., additional, de Lange, D.W., additional, De Rosa, F.G., additional, De Waele, J.J., additional, Dimopoulos, G., additional, Garnacho-Montero, J., additional, Hoenigl, M., additional, Kanj, S.S., additional, Lamoth, F., additional, Maertens, J., additional, Martin-Loeches, I., additional, Muñoz, P., additional, Kullberg, B.J., additional, Agvald-Ohman, C., additional, Poulakou, G., additional, Rebuffi, C., additional, Rello, J., additional, Sanguinetti, M., additional, Taccone, F.S., additional, Timsit, J-F., additional, Torres, A., additional, Vazquez, J.A., additional, Wauters, J., additional, Calandra, T., additional, Tejada, S., additional, Karaiskos, I., additional, Peghin, M., additional, Vena, A., additional, Mortensen, K.L., additional, Lebihan, C., additional, and Mercier, T., additional

Published
2022
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9. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of systemic phaeohyphomycosis: diseases caused by black fungi

Author

Chowdhary, A., Meis, J.F., Guarro, J., de Hoog, G.S., Kathuria, S., Arendrup, M.C., Arikan-Akdagli, S., Akova, M., Boekhout, T., Caira, M., Guinea, J., Chakrabarti, A., Dannaoui, E., van Diepeningen, A., Freiberger, T., Groll, A.H., Hope, W.W., Johnson, E., Lackner, M., Lagrou, K., Lanternier, F., Lass-Flörl, C., Lortholary, O., Meletiadis, J., Muñoz, P., Pagano, L., Petrikkos, G., Richardson, M.D., Roilides, E., Skiada, A., Tortorano, A.M., Ullmann, A.J., Verweij, P.E., Cornely, O.A., and Cuenca-Estrella, M.

Published
2014
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10. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others

Author

Tortorano, A.M., Richardson, M., Roilides, E., van Diepeningen, A., Caira, M., Munoz, P., Johnson, E., Meletiadis, J., Pana, Z.-D., Lackner, M., Verweij, P., Freiberger, T., Cornely, O.A., Arikan-Akdagli, S., Dannaoui, E., Groll, A.H., Lagrou, K., Chakrabarti, A., Lanternier, F., Pagano, L., Skiada, A., Akova, M., Arendrup, M.C., Boekhout, T., Chowdhary, A., Cuenca-Estrella, M., Guinea, J., Guarro, J., de Hoog, S., Hope, W., Kathuria, S., Lortholary, O., Meis, J.F., Ullmann, A.J., Petrikkos, G., and Lass-Flörl, C.

Published
2014
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11. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013

Author

Cornely, O.A., Arikan-Akdagli, S., Dannaoui, E., Groll, A.H., Lagrou, K., Chakrabarti, A., Lanternier, F., Pagano, L., Skiada, A., Akova, M., Arendrup, M.C., Boekhout, T., Chowdhary, A., Cuenca-Estrella, M., Freiberger, T., Guinea, J., Guarro, J., de Hoog, S., Hope, W., Johnson, E., Kathuria, S., Lackner, M., Lass-Flörl, C., Lortholary, O., Meis, J.F., Meletiadis, J., Muñoz, P., Richardson, M., Roilides, E., Tortorano, A.M., Ullmann, A.J., van Diepeningen, A., Verweij, P., and Petrikkos, G.

Published
2014
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15. When to change treatment of acute invasive aspergillosis: an expert viewpoint

Author

Slavin, MA, Chen, Y-C, Cordonnier, C, Cornely, OA, Cuenca-Estrella, M, Donnelly, JP, Groll, AH, Lortholary, O, Marty, FM, Nucci, M, Rex, JH, Rijnders, BJA, Thompson, GR, Verweij, PE, White, PL, Hargreaves, R, Harvey, E, Maertens, JA, Slavin, MA, Chen, Y-C, Cordonnier, C, Cornely, OA, Cuenca-Estrella, M, Donnelly, JP, Groll, AH, Lortholary, O, Marty, FM, Nucci, M, Rex, JH, Rijnders, BJA, Thompson, GR, Verweij, PE, White, PL, Hargreaves, R, Harvey, E, and Maertens, JA

Abstract

Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice. For primary treatment failure, a change in antifungal therapy should be made: (i) when mycological susceptibility testing identifies an organism from a confirmed site of infection, which is resistant to the antifungal given for primary therapy, or a resistance mutation is identified by molecular testing; (ii) at, or after, 8 days of primary antifungal treatment if there is increasing serum galactomannan, or galactomannan positivity in serum, or bronchoalveolar lavage fluid when the antigen was previously undetectable, or there is sudden clinical deterioration, or a new clearly distinct site of infection is detected; and (iii) at, or after, 15 days of primary antifungal treatment if the patient is clinically stable but with ≥2 serum galactomannan measurements persistently elevated compared with baseline or increasing, or if the original lesions on CT or other imaging, show progression by >25% in size in the context of no apparent change in immune status.

Published
2022

16. Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, non-neutropenic, adult patients: An update including COVID-19 data

Author

Bassetti, M., Zuccaro, V., Asperges, E., Scudeller, L., Giacobbe, D. R., Akova, M., Alastruey-Izquierdo, A., Arikan-Akdagli, S., Azoulay, E., Blot, S., Cortegiani, A., Cornely, O. A., Grecchi, C., Lass-Florl, C., Koehler, P., Cuenca-Estrella, M., de Lange, D. W., De Rosa, F. G., De Waele, J. J., Dimopoulos, G., Garnacho-Montero, J., Hoenigl, M., Kanj, S. S., Lamoth, F., Maertens, J., Martin-Loeches, I., Munoz, P., Kullberg, B. J., Agvald-Ohman, C., Poulakou, G., Rebuffi, C., Rello, J., Sanguinetti, Maurizio, Taccone, F. S., Timsit, J. -F., Torres, A., Vazquez, J. A., Wauters, J., Calandra, T., Tejada, S., Karaiskos, I., Peghin, M., Vena, A., Mortensen, K. L., Lebihan, C., Mercier, T., Sanguinetti M. (ORCID:0000-0002-9780-7059), Bassetti, M., Zuccaro, V., Asperges, E., Scudeller, L., Giacobbe, D. R., Akova, M., Alastruey-Izquierdo, A., Arikan-Akdagli, S., Azoulay, E., Blot, S., Cortegiani, A., Cornely, O. A., Grecchi, C., Lass-Florl, C., Koehler, P., Cuenca-Estrella, M., de Lange, D. W., De Rosa, F. G., De Waele, J. J., Dimopoulos, G., Garnacho-Montero, J., Hoenigl, M., Kanj, S. S., Lamoth, F., Maertens, J., Martin-Loeches, I., Munoz, P., Kullberg, B. J., Agvald-Ohman, C., Poulakou, G., Rebuffi, C., Rello, J., Sanguinetti, Maurizio, Taccone, F. S., Timsit, J. -F., Torres, A., Vazquez, J. A., Wauters, J., Calandra, T., Tejada, S., Karaiskos, I., Peghin, M., Vena, A., Mortensen, K. L., Lebihan, C., Mercier, T., and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

Not available

Published
2022

17. ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients

Author

Cornely, O.A., Bassetti, M., Calandra, T., Garbino, J., Kullberg, B.J., Lortholary, O., Meersseman, W., Akova, M., Arendrup, M.C., Arikan-Akdagli, S., Bille, J., Castagnola, E., Cuenca-Estrella, M., Donnelly, J.P., Groll, A.H., Herbrecht, R., Hope, W.W., Jensen, H.E., Lass-Florl, C., Petrikkos, G., Richardson, M.D., Roilides, E., Verweij, P.E., Viscoli, C., and Ullmann, A.J.

Published
2012
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19. ESCMID guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT)

Author

Ullmann, A.J., Akova, M., Herbrecht, R., Viscoli, C., Arendrup, M.C., Arikan-Akdagli, S., Bassetti, M., Bille, J., Calandra, T., Castagnola, E., Cornely, O.A., Donnelly, J.P., Garbino, J., Groll, A.H., Hope, W.W., Jensen, H.E., Kullberg, B.J., Lass-Flörl, C., Lortholary, O., Meersseman, W., Petrikkos, G., Richardson, M.D., Roilides, E., Verweij, P.E., and Cuenca-Estrella, M.

Published
2012
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20. ESCMID guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp.

Author

Hope, W.W., Castagnola, E., Groll, A.H., Roilides, E., Akova, M., Arendrup, M.C., Arikan-Akdagli, S., Bassetti, M., Bille, J., Cornely, O.A., Cuenca-Estrella, M., Donnelly, J.P., Garbino, J., Herbrecht, R., Jensen, H.E., Kullberg, B.J., Lass-Flörl, C., Lortholary, O., Meersseman, W., Petrikkos, G., Richardson, M.D., Verweij, P.E., Viscoli, C., and Ullmann, A.J.

Published
2012
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21. ESCMID guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS

Author

Lortholary, O., Petrikkos, G., Akova, M., Arendrup, M.C., Arikan-Akdagli, S., Bassetti, M., Bille, J., Calandra, T., Castagnola, E., Cornely, O.A., Cuenca-Estrella, M., Donnelly, J.P., Garbino, J., Groll, A.H., Herbrecht, R., Hope, W.W., Jensen, H.E., Kullberg, B.J., Lass-Flörl, C., Meersseman, W., Richardson, M.D., Roilides, E., Verweij, P.E., Viscoli, C., and Ullmann, A.J.

Published
2012
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22. ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures

Author

Cuenca-Estrella, M., Verweij, P. E, Arendrup, M. C, Arikan-Akdagli, S., Bille, J., Donnelly, J. P, Jensen, H. E, Lass-Flörl, C., Richardson, M. D, Akova, M., Bassetti, M., Calandra, T., Castagnola, E., Cornely, O. A, Garbino, J., Groll, A. H, Herbrecht, R., Hope, W. W, Kullberg, B. J, Lortholary, O., Meersseman, W., Petrikkos, G., Roilides, E., Viscoli, C., and Ullmann, A. J

Published
2012
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23. ESCMID guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases

Author

Ullmann, A.J., Cornely, O.A., DonneNy, J.P., Akova, M., Arendrup, M.C., Arikan-Akdagli, S., Bassetti, M., Bille, J., Calandra, T., Castagnola, E., Garbino, J., Groll, A.H., Herbrecht, R., Hope, W.W., Jensen, H.E., Kullberg, B.J., Lass-Flörl, C., Lortholary, O., Meersseman, W., Petrikkos, G., Richardson, M.D., Roilides, E., Verweij, P.E., Viscoli, C., and Cuenca-Estrella, M.

Published
2012
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26. European expert opinion on the management of invasive candidiasis in adults

Author

Kullberg, B.J., Verweij, P.E., Akova, M., Arendrup, M.C., Bille, J., Calandra, T., Cuenca-Estrella, M., Herbrecht, R., Jacobs, F., Kalin, M., Kibbler, C.C., Lortholary, O., Martino, P., Meis, J.F., Muñoz, P., Odds, F.C., De Pauw, B.E., Rex, J.H., Roilides, E., Rogers, T.R., Ruhnke, M., Ullmann, A.J., Uzun, Ö., Vandewoude, K., Vincent, J.-L., and Donnelly, J.P.

Published
2011
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28. Impact of fluconazole susceptibility on the outcome of patients with candidaemia: data from a population-based surveillance

Author

Padilla, B., Muñoz, P., Guinea, J., Paño Pardo, J.R., García-Rodríguez, J., Cerrada, C.G., Fortún, J., Martín, P., Gómez, E., Ryan, P., Campelo, C., de los Santos Gil, I., Buendía, V., Gorricho, B.P., Alonso, M., Sanz, F.S., Aguado, J.M., Merino, P., González Romo, F., Gorgolas, M., Gadea, I., Losa, J.E., Delgado-Iribarren, A., Ramos, A., Romero, Y., Romero, I.S., Zaragoza, O., Cuenca-Estrella, M., Rodríguez-Baño, J., Suarez, A.I., Loza, A., Aller García, A.I., Martín-Mazuelos, E., Pérez de Pipaón, M.R., Garnacho, J., Ortiz, C., Chávez, M., Maroto, F.L., Salavert, M., Pemán, J., Blanquer, J., Navarro, D., Camarena, J.J., Zaragoza, R., Abril, V., Gimeno, C., Hernández, S., Ezpeleta, G., Bereciartua, E., Hernández Almaraz, J.L., Montejo, M., Rivas, R.A., Ayarza, R., Planes, A.M., Camps, I.R., Almirante, B., Mensa, J., Almela, M., Gurgui, M., Sánchez-Reus, F., Martínez-Montauti, J., Sierra, M., Horcajada, J.P., Sorli, L., Gómez, J., Gené, A., Urrea, M., Mularoni, A., Valerio, M., Díaz-Martín, A., Puchades, F., Fernández-Ruiz, M., Lora-Pablos, D., Zaragoza, Ó., and Puig-Asensio, M.

Published
2017
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29. Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia

Author

Padilla, B., Muñoz, P., Guinea, J., Paño Pardo, J.R., García-Rodríguez, J., García Cerrada, C., Fortún, J., Martín, P., Gómez, E., Ryan, P., Campelo, C., de los Santos Gil, I., Buendía, V., Gorricho, B.P., Alonso, M., Sanz, F.S., Aguado, J.M., Merino, P., González Romo, F., Gorgolas, M., Gadea, I., Losa, J.E., Delgado-Iribarren, A., Ramos, A., Romero, Y., Sánchez Romero, I., Zaragoza, O., Cuenca-Estrella, M., Rodriguez-Baño, J., Isabel Suarez, A., Loza, A., Aller García, A.I., Martín-Mazuelos, E., Pérez de Pipaón, M.R., Garnacho, J., Ortiz, C., Chávez, M., Maroto, F.L., Salavert, M., Pemán, J., Blanquer, J., Navarro, D., Camarena, J.J., Zaragoza, R., Abril, V., Gimeno, C., Hernáez, S., Ezpeleta, G., Bereciartua, E., Hernández Almaraz, J.L., Montejo, M., Rivas, R.A., Ayarza, R., Planes, A.M., Camps, I.R., Almirante, B., Mensa, J., Almela, M., Gurgui, M., Sánchez-Reus, F., Martinez-Montauti, J., Sierra, M., Horcajada, J.P., Sorli, L., Gómez, J., Gené, A., Urrea, M., Valerio, M., Díaz-Martín, A., Puchades, F., Mularoni, A., Rueda, C., and Puig-Asensio, M.

Published
2017
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33. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score–derived analysis of a population-based, multicentre prospective cohort

Author

Padilla, B., Muñoz, P., Guinea, J., Paño Pardo, J.R., García-Rodríguez, J., García Cerrada, C., Fortún, J., Martín, P., Gómez, E., Ryan, P., Campelo, C., de los Santos Gil, I., Buendía, V., Pérez Gorricho, B., Alonso, M., Sanz Sanz, F., María Aguado, J., Merino, P., González Romo, F., Gorgolas, M., Gadea, I., Losa, J.E., Delgado-Iribarren, A., Ramos, A., Romero, Y., Sánchez Romero, I., Zaragoza, O., Cuenca-Estrella, M., Rodríguez-Baño, J., Suarez, A.I., Loza, A., Aller García, A.I., Martín-Mazuelos, E., Pérez de Pipaón, M.R., Garnacho, J., Ortiz, C., Chávez, M., Maroto, F.L., Salavert, M., Pemán, J., Blanquer, J., Navarro, D., Camarena, J.J., Zaragoza, R., Abril, V., Gimeno, C., Hernáez, S., Ezpeleta, G., Bereciartua, E., Hernández Almaraz, J.L., Montejo, M., Rivas, R.A., Ayarza, R., Planes, A.M., Ruiz Camps, I., Almirante, B., Mensa, J., Almela, M., Gurgui, M., Sánchez-Reus, F., Martinez-Montauti, J., Sierra, M., Horcajada, J.P., Sorli, L., Gómez, J., Gené, A., Urrea, M., Valerio, M., Díaz-Martín, A., Puchades, F., Mularoni, A., López-Cortés, L.E., Garnacho-Montero, J., Puig-Asensio, M., and Ruiz-Camps, I.

Published
2016
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34. Polymorphisms within the TNFSF4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the context of the aspbiomics consortium

Author

Sanchez-Maldonado, J. M., Moniz-Diez, A., Ter Horst, R., Campa, D., Cabrera-Serrano, A. J., Martinez-Bueno, M., Garrido-Collado, M. P., Hernandez-Mohedo, F., Fernandez-Puerta, L., Lopez-Nevot, M. A., Cunha, C., Gonzalez-Sierra, P. A., Springer, J., Lackner, M., Alcazar-Fuoli, L., Fianchi, L., Aguado, J. M., Pagano, L., Lopez-Fernandez, E., Clavero, E., Potenza, L., Luppi, M., Moratalla, L., Solano, C., Sampedro, A., Cuenca-Estrella, M., Lass-Florl, C., Canzian, F., Loeffler, J., Li, Y., Einsele, H., Netea, M. G., Vazquez, L., Carvalho, A., Jurado, M., Sainz, J., Fianchi L., Pagano L. (ORCID:0000-0001-8287-928X), Sanchez-Maldonado, J. M., Moniz-Diez, A., Ter Horst, R., Campa, D., Cabrera-Serrano, A. J., Martinez-Bueno, M., Garrido-Collado, M. P., Hernandez-Mohedo, F., Fernandez-Puerta, L., Lopez-Nevot, M. A., Cunha, C., Gonzalez-Sierra, P. A., Springer, J., Lackner, M., Alcazar-Fuoli, L., Fianchi, L., Aguado, J. M., Pagano, L., Lopez-Fernandez, E., Clavero, E., Potenza, L., Luppi, M., Moratalla, L., Solano, C., Sampedro, A., Cuenca-Estrella, M., Lass-Florl, C., Canzian, F., Loeffler, J., Li, Y., Einsele, H., Netea, M. G., Vazquez, L., Carvalho, A., Jurado, M., Sainz, J., Fianchi L., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G allele showed increased numbers of CD38+IgM-IgD-plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2rs17013271T allele had decreased numbers of CD27-IgM-IgD-B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16-cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.

Published
2021

36. EUCAST Definitive Document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts: Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST)∗

Author

Rodriguez-Tudela, J.L., Arendrup, M.C., Barchiesi, F., Bille, J., Chryssanthou, E., Cuenca-Estrella, M., Dannaoui, E., Denning, D.W., Donnelly, J.P., Dromer, F., Fegeler, W., Lass-Flörl, C., Moore, C., Richardson, M., Sandven, P., Velegraki, A., and Verweij, P.

Published
2008
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44. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis

Author

Lupiañez, C B, Martínez-Bueno, M, Sánchez-Maldonado, J M, Badiola, J, Cunha, C, Springer, J, Lackner, M, Segura-Catena, J, Canet, L M, Alcazar-Fuoli, L, López-Nevot, M A, Fianchi, L, Aguado, J M, Pagano, L, López-Fernández, E, Alarcón-Riquelme, M, Potenza, L, Gonçalves, S M, Luppi, M, Moratalla, L, Solano, C, Sampedro, A, González-Sierra, P, Cuenca-Estrella, M, Lagrou, K, Maertens, J A, Lass-Flörl, C, Einsele, H, Vazquez, L, PCRAGA Study Group, Loeffler, J, Ríos-Tamayo, R, Carvalho, A, Jurado, M, and Sainz, J

Subjects
0301 basic medicine, host immunity, Genotype, 030106 microbiology, Immunology, Population, CX3C Chemokine Receptor 1, Single-nucleotide polymorphism, ARNT2, CX3CR1, genetic susceptibility, invasive aspergillosis, Biology, Aspergillosis, Microbiology, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, medicine, Genetic predisposition, Basic Helix-Loop-Helix Transcription Factors, Humans, Genetic Predisposition to Disease, Allele, education, Invasive Pulmonary Aspergillosis, education.field_of_study, Haplotype, Aryl Hydrocarbon Receptor Nuclear Translocator, PCRAGA Study Group, medicine.disease, Hematologic Diseases, 3. Good health, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Infectious Diseases, Aspergillus, Case-Control Studies, Expression quantitative trait loci, Parasitology
Abstract

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development. ispartof: INFECTION AND IMMUNITY vol:88 issue:4 ispartof: location:United States status: published

Published
2020

48. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

Author

Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach, W.J., Baddley, J.W., Verweij, P.E., Clancy, C.J., Wingard, J.R., Lockhart, S.R., Groll, A.H., Sorrell, T.C., Bassetti, M., Akan, H., Alexander, B.D., Andes, D., Azoulay, E., Bialek, R., Bradsher, R.W., Bretagne, S., Calandra, T., Caliendo, A.M., Castagnola, E., Cruciani, M., Cuenca-Estrella, M., Decker, C.F., Desai, S.R., Fisher, B., Harrison, T., Heussel, C.P., Jensen, H.E., Kibbler, C.C., Kontoyiannis, D.P., Kullberg, B.J., Lagrou, K., Lamoth, F., Lehrnbecher, T., Loeffler, J., Lortholary, O., Maertens, J., Marchetti, O., Marr, K.A., Masur, H., Meis, J.F.G.M., Morrisey, C.O., Nucci, M., Ostrosky-Zeichner, L., Pagano, L., Patterson, T.F., Perfect, J.R., Racil, Z., Roilides, E., Ruhnke, M., Schaefer-Prokop, C.M., Shoham, S., Slavin, M.A., Stevens, David A., Thompson, G.R., Vazquez, J.A., Viscoli, C., Walsh, T.J., Warris, A., Wheat, L.J., White, P.L., Zaoutis, T.E., Pappas, P.G., Donnelly, J.P., Chen, S.C., Kauffman, C.A., Steinbach, W.J., Baddley, J.W., Verweij, P.E., Clancy, C.J., Wingard, J.R., Lockhart, S.R., Groll, A.H., Sorrell, T.C., Bassetti, M., Akan, H., Alexander, B.D., Andes, D., Azoulay, E., Bialek, R., Bradsher, R.W., Bretagne, S., Calandra, T., Caliendo, A.M., Castagnola, E., Cruciani, M., Cuenca-Estrella, M., Decker, C.F., Desai, S.R., Fisher, B., Harrison, T., Heussel, C.P., Jensen, H.E., Kibbler, C.C., Kontoyiannis, D.P., Kullberg, B.J., Lagrou, K., Lamoth, F., Lehrnbecher, T., Loeffler, J., Lortholary, O., Maertens, J., Marchetti, O., Marr, K.A., Masur, H., Meis, J.F.G.M., Morrisey, C.O., Nucci, M., Ostrosky-Zeichner, L., Pagano, L., Patterson, T.F., Perfect, J.R., Racil, Z., Roilides, E., Ruhnke, M., Schaefer-Prokop, C.M., Shoham, S., Slavin, M.A., Stevens, David A., Thompson, G.R., Vazquez, J.A., Viscoli, C., Walsh, T.J., Warris, A., Wheat, L.J., White, P.L., Zaoutis, T.E., and Pappas, P.G.

Abstract

Contains fulltext : 225781.pdf (Publisher’s version ) (Open Access), BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Published
2020

49. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium

Author

Donnelly, JP, Chen, SC, Kauffman, CA, Steinbach, WJ, Baddley, JW, Verweij, PE, Clancy, CJ, Wingard, JR, Lockhart, SR, Groll, AH, Sorrell, TC, Bassetti, M, Akan, H, Alexander, BD, Andes, D, Azoulay, E, Bialek, R, Bradsher, RW, Bretagne, S, Calandra, T, Caliendo, AM, Castagnola, E, Cruciani, M, Cuenca-Estrella, M, Decker, CF, Desai, SR, Fisher, B, Harrison, T, Heussel, CP, Jensen, HE, Kibbler, CC, Kontoyiannis, DP, Kullberg, B-J, Lagrou, K, Lamoth, F, Lehrnbecher, T, Loeffler, J, Lortholary, O, Maertens, J, Marchetti, O, Marr, KA, Masur, H, Meis, JF, Morrisey, CO, Nucci, M, Ostrosky-Zeichner, L, Pagano, L, Patterson, TF, Perfect, JR, Racil, Z, Roilides, E, Ruhnke, M, Prokop, CS, Shoham, S, Slavin, MA, Stevens, DA, Thompson, GR, Vazquez, JA, Viscoli, C, Walsh, TJ, Warris, A, Wheat, LJ, White, PL, Zaoutis, TE, Pappas, PG, Donnelly, JP, Chen, SC, Kauffman, CA, Steinbach, WJ, Baddley, JW, Verweij, PE, Clancy, CJ, Wingard, JR, Lockhart, SR, Groll, AH, Sorrell, TC, Bassetti, M, Akan, H, Alexander, BD, Andes, D, Azoulay, E, Bialek, R, Bradsher, RW, Bretagne, S, Calandra, T, Caliendo, AM, Castagnola, E, Cruciani, M, Cuenca-Estrella, M, Decker, CF, Desai, SR, Fisher, B, Harrison, T, Heussel, CP, Jensen, HE, Kibbler, CC, Kontoyiannis, DP, Kullberg, B-J, Lagrou, K, Lamoth, F, Lehrnbecher, T, Loeffler, J, Lortholary, O, Maertens, J, Marchetti, O, Marr, KA, Masur, H, Meis, JF, Morrisey, CO, Nucci, M, Ostrosky-Zeichner, L, Pagano, L, Patterson, TF, Perfect, JR, Racil, Z, Roilides, E, Ruhnke, M, Prokop, CS, Shoham, S, Slavin, MA, Stevens, DA, Thompson, GR, Vazquez, JA, Viscoli, C, Walsh, TJ, Warris, A, Wheat, LJ, White, PL, Zaoutis, TE, and Pappas, PG

Abstract

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Published
2020

50. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis

Author

Lupianez, C. B., Martinez-Bueno, M., Sanchez-Maldonado, J. M., Badiola, J., Cunha, C., Springer, J., Lackner, M., Segura-Catena, J., Canet, L. M., Alcazar-Fuoli, L., Lopez-Nevot, M. A., Fianchi, Luana, Aguado, J. M., Pagano, Livio, Lopez-Fernandez, E., Alarcon-Riquelme, M., Potenza, L., Goncalves, S. M., Luppi, M., Moratalla, L., Solano, C., Sampedro, A., Gonzalez-Sierra, P., Cuenca-Estrella, M., Lagrou, K., Maertens, J. A., Lass-Florl, C., Einsele, H., Vazquez, L., Loeffler, J., Rios-Tamayo, R., Carvalho, A., Jurado, M., Sainz, J., Fianchi L., Pagano L. (ORCID:0000-0001-8287-928X), Lupianez, C. B., Martinez-Bueno, M., Sanchez-Maldonado, J. M., Badiola, J., Cunha, C., Springer, J., Lackner, M., Segura-Catena, J., Canet, L. M., Alcazar-Fuoli, L., Lopez-Nevot, M. A., Fianchi, Luana, Aguado, J. M., Pagano, Livio, Lopez-Fernandez, E., Alarcon-Riquelme, M., Potenza, L., Goncalves, S. M., Luppi, M., Moratalla, L., Solano, C., Sampedro, A., Gonzalez-Sierra, P., Cuenca-Estrella, M., Lagrou, K., Maertens, J. A., Lass-Florl, C., Einsele, H., Vazquez, L., Loeffler, J., Rios-Tamayo, R., Carvalho, A., Jurado, M., Sainz, J., Fianchi L., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1

Published
2020

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