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

      research-article
      1 , 2 , 3 , * , 1 , 2 , 3 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 1 , 2 , 3 , 43 , 1 , 2
      Journal of Fungi
      MDPI
      invasive aspergillosis, antifungal prophylaxis, infection in hematology

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          Abstract

          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.

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          Most cited references26

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          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

          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.
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            The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study.

            The aim of this study was to evaluate the incidence and outcome of invasive fungal infections (IFI) in patients with hematologic malignancies. This was a retrospective cohort study of patients admitted between 1999 and 2003 to 18 hematology wards in Italy. Each participating center provided information on all patients with newly diagnosed hematologic malignancies admitted during the survery period and on all episodes of IFI experienced by these patients. The cohort was formed of 11,802 patients with hematologic malignacies: acute leukemia (myeloid 3012, lymphoid 1173), chronic leukemia (myeloid 596, lymphoid 1104), lymphoma (Hodgkin's 844, non-Hodgkin's 3457), or multiple myeloma (1616). There were 538 proven or probable IFI (4.6%); 373 (69%) occurred in patients with acute myeloid leukemia. Over half (346/538) were caused by molds (2.9%), in most cases Aspergillus spp. (310/346). The 192 yeast infections (1.6%) included 175 cases of candidemia. Overall and IFI-attributable mortality rates were 2% (209/11802) and 39% (209/538), respectively. The highest IFI-attributable mortality rates were associated with zygomycosis (64%) followed by fusariosis (53%), aspergillosis (42%), and candidemia (33%). Patients with hematologic malignancies are currently at higher risk of IFI caused by molds than by yeasts, and the incidence of IFI is highest among patients with acute myeloid leukemia. Aspergillus spp are still the most common pathogens, followed by Candida spp. Other agents are rare. The attributable mortality rate for aspergillosis has dropped from 60-70% to approximately 40%. Candidemia-related mortality remains within the 30-40% range reported in literature although the incidence has decreased.
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              Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry.

              The study investigated the epidemiology and outcome of invasive aspergillosis (IA), an important cause of morbidity and mortality in immunocompromised patients. Cases of proven/probable IA from the Prospective Antifungal Therapy Alliance (PATH Alliance(®)) registry - a prospective surveillance network comprising 25 centers in the United States and Canada that collected data on invasive fungal infections from 2004 to 2008 - were analyzed with respect to clinical outcome. Nine hundred and sixty patients with IA were enrolled, the most frequent underlying disease being hematologic malignancy (n=464 [48.3%]). Two hundred and eighty patients (29.2%) received solid organ transplant; 268 patients (27.9%) underwent hematopoietic stem cell transplantation. Identified isolates included Aspergillus fumigatus (72.6%), Aspergillus flavus (9.9%), Aspergillus niger (8.7%) and Aspergillus terreus (4.3%). The lung was most frequently affected. Following diagnosis, 47% patients received monotherapy - voriconazole (70%), an amphotericin B formulation (13.8%), or an echinocandin (10.5%) - while 279 patients (29%) received combination therapy. Twelve-week overall survival was 64.4%. In this series of patients with IA, the lung was the predominant focus of infection, A. fumigatus was the major species isolated, and overall survival appeared slightly improved compared with previous reports. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                J Fungi (Basel)
                J Fungi (Basel)
                jof
                Journal of Fungi
                MDPI
                2309-608X
                13 March 2020
                March 2020
                : 6
                : 1
                : 36
                Affiliations
                [1 ]Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; caroline.bruns@ 123456uk-koeln.de (C.B.); sibylle.mellinghoff@ 123456uk-koeln.de (S.C.M.); oliver.cornely@ 123456uk-koeln.de (O.A.C.); philipp.koehler@ 123456uk-koeln.de (P.K.)
                [2 ]Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
                [3 ]German Centre for Infection Research, Partner Site Bonn-Cologne, 50937 Cologne, Germany
                [4 ]Department of Internal Medicine I, University Hospital of Dresden, 01307 Dresden, Germany; nael.alakel@ 123456uniklinikum-dresden.de
                [5 ]Hematology Clinical Research Unit, Cebeci Hospital, Ankara University Faculty of Medicine, 06100 Ankara, Turkey; hamdiakan@ 123456gmail.com
                [6 ]Dept of Infectious Diseases and General Medical Unit, Alfred Health & Central Clinical School, Monash University, Melbourne 3004, Australia; michelle.ananda-rajah@ 123456monash.edu
                [7 ]Onkologische Schwerpunktpraxis Freilassing, 83395 Freilassing, Germany; auberger@ 123456onko-endo.de
                [8 ]Department of Hematology and Oncology, Red Cross Hospital Munich, 80634 Munich, Germany; peter.bojko@ 123456swmbrk.de
                [9 ]Division of Infectious Diseases, Wayne State University School of Medicine, Karmanos Cancer Center, Detroit, MI 48201, USA; pchandrasekar@ 123456med.wayne.edu
                [10 ]Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; methee.cha@ 123456mahidol.ac.th
                [11 ]Hematology Department, Hospital Provincial Del Centenario, Rosario 2000, Argentina; joseacozzi@ 123456hotmail.com
                [12 ]Department of Hematology, Radboud University Medical Center, 6500 Nijmegen, The Netherlands; Elizabeth.Dekort@ 123456Radboudumc.nl
                [13 ]Infectious Disease Research Program, Center for Bone Marrow Transplantation and, Department of Pediatric Hematology and Oncology, University Children’s Hospital, 48149 Münster, Germany; grollan@ 123456ukmuenster.de
                [14 ]Department of Microbiology (PathWest Laboratory Medicine, WA, FSH Network), Perth 6000, Australia; chris.heath@ 123456health.wa.gov.au
                [15 ]Depts. of Infectious Diseases, Fiona Stanley Hospital & Royal Perth Hospital, Perth 6000, Australia
                [16 ]Faculty of Health & Medical Sciences, University of Western Australia, Murdoch/Perth, Murdoch 6150, Australia
                [17 ]Department of Medicine, Clinic III – Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany; larissa.henze@ 123456med.uni-rostock.de
                [18 ]Head of the bone marrow unit, Hospital City Dr. Enrique Tejera, 2001 Valencia, Venezuela; mhernanj@ 123456gmail.com
                [19 ]Departament of Medicine, Facultad de Ciencias de la Salud, University of Carabobo, 2001 Valencia, Venezuela
                [20 ]Division of Infectious Diseases, Infection Control Program, Antimicrobial Stewardship Program, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; sk11@ 123456aub.edu.lb
                [21 ]Division of Infection Diseases and Hospital Epidemiology, University and University Hospital of Basel, 4031 Basel, Switzerland; nina.khanna@ 123456usb.ch
                [22 ]Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; michael.koldehoff@ 123456uk-essen.de
                [23 ]Division of infectious Diseases, Department of Internal Medicine, Catholic Hematology Hospital & Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 06591 Seoul, Korea; symonlee@ 123456catholic.ac.kr
                [24 ]Department of Diagnostic and Interventional Radiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany; Alina.mager@ 123456uk-koeln.de
                [25 ]Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy; francesco.marchesi@ 123456ifo.gov.it
                [26 ]Servei d’Hematologia Clinica, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; rmartino@ 123456santpau.cat
                [27 ]Department of Internal Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-901, Brazil; mnucci@ 123456hucff.ufrj.br
                [28 ]Department of Infectious Diseases, Turku University Hospital and University of Turku, 20521 Turku, Finland; Jarmo.Oksi@ 123456tyks.fi
                [29 ]Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico A. Gemelli -IRCCS, 00169 Rome, Italy; Livio.Pagano@ 123456unicatt.it
                [30 ]Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
                [31 ]Leeds Children’s Hospital, Leeds General Infirmary, Leeds Teaching Hospitals, NHS Trust, Leeds LS1 3EX, UK; bob.phillips@ 123456york.ac.uk
                [32 ]Centre for Reviews and Dissemination, Alcuin College, University of York, York YO10 5DD, UK
                [33 ]Department of Internal Medicine, Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, 8036 Graz, Austria; juergen.prattes@ 123456medunigraz.at
                [34 ]Infectious Diseases Unit, Hippokration Hospital, 54642 Thessaloniki, Greece; a.pyrpasopoulou@ 123456doctors.org.uk
                [35 ]Department of Internal Medicine I, Bone Marrow Transplant-Unit, Medical University of Vienna, 1090 Vienna, Austria; werner.rabitsch@ 123456meduniwien.ac.at
                [36 ]Department of Hematology and Oncology, Otto-von-Guericke University Magdeburg, Medical Center, 39120 Magdeburg, Germany; enrico.schalk@ 123456med.ovgu.de
                [37 ]2. Medizinische Klinik, Carl-Thiem-Klinikum Cottbus, 03048 Cottbus, Germany; m.schmidt_hieber@ 123456ctk.de
                [38 ]Department of Clinical Haematology, Amrita Institute of Medical Sciences, Kochi 682041, India; neerajsidh@ 123456gmail.com
                [39 ]Pediatric Infectious Diseases and Immunodeficiencies Unit. Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain; psoler@ 123456vhebron.net
                [40 ]Infectious Diseases institute, Rambam Health Care Campus, 3109601 Haifa, Israel; a_shteren@ 123456rambam.health.gov.il
                [41 ]Department of Internal Medicine–Hematology and Oncology, Masaryk University and University Hospital Brno, 62500 Brno, Czech Republic; weinbergerova.barbora@ 123456fnbrno.cz
                [42 ]Division of Infectious Diseases, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon; az51@ 123456aub.edu.lb
                [43 ]Clinical Trials Centre Cologne, ZKS Köln, 50935 Cologne, Germany
                Author notes
                [* ]Correspondence: jannik.stemler@ 123456uk-koeln.de ; Tel.: +49(0)-221-478-32884
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9152-2469
                https://orcid.org/0000-0003-3669-5564
                https://orcid.org/0000-0001-7164-3108
                https://orcid.org/0000-0002-4582-4914
                https://orcid.org/0000-0002-7162-3470
                https://orcid.org/0000-0003-0125-9543
                https://orcid.org/0000-0001-7850-6931
                https://orcid.org/0000-0001-6104-3643
                https://orcid.org/0000-0002-8738-5884
                https://orcid.org/0000-0001-7650-2718
                https://orcid.org/0000-0003-4867-0014
                https://orcid.org/0000-0001-8287-928X
                https://orcid.org/0000-0002-4938-9673
                https://orcid.org/0000-0001-5751-9311
                https://orcid.org/0000-0003-1892-5098
                https://orcid.org/0000-0002-0115-8104
                https://orcid.org/0000-0002-0346-5570
                https://orcid.org/0000-0002-8659-8108
                https://orcid.org/0000-0001-9599-3137
                https://orcid.org/0000-0002-7386-7495
                Article
                jof-06-00036
                10.3390/jof6010036
                7151030
                32183235
                130a4e27-9535-4267-9141-d76751b528f1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 January 2020
                : 11 March 2020
                Categories
                Article

                invasive aspergillosis,antifungal prophylaxis,infection in hematology

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