{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:47:04Z","timestamp":1791985624561,"version":"4.4.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Timely diagnosis of invasive aspergillosis (IA) is hindered by moderate sensitivity of conventional diagnostic methods. Increasing plasma input volumes has been shown to improve sensitivity of plasma polymerase chain reaction (PCR), and using plasma-derived fungal exosomes (nanosized extracellular vesicles) may do the same. This study aimed to determine whether using large plasma input volumes and exosome-derived DNA enhances the diagnostic performance of\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      PCR. We included hematology patients from whom plasma was collected within 48 h of bronchoalveolar lavage in the prospective multicenter ARPO-study (NCT06069505); plasma from healthy donors served as controls. Sensitivity, specificity, positive predictive values, and negative predictive values of the PCR on DNA extracted from plasma-derived exosomes, large plasma volumes of around 4.0 mL, and small plasma volumes of 0.2 mL were assessed using the European Organization for Research and Treatment of Cancer\/Mycoses Study Group Education and Research Consortium diagnostic criteria. The IA prevalence was 34.2% (38\/111), and the median plasma volume used in the large-volume group was 4.0 mL (IQR 3.1 mL\u20134.0 mL).\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      large-volume plasma PCR yielded 22 positive results with a sensitivity of 52.6%, significantly higher than with small plasma volume (29.7%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.039) without loss of specificity (97.2%), improving further in patients not receiving versus receiving mold-active antifungals (66.7% versus 40.0%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.013). Sensitivity of the PCR on plasma-derived exosomes was low (29.4%).\n                      <jats:italic toggle=\"yes\">A. flavus<\/jats:italic>\n                      DNA was detected in five patients and three healthy controls; all were considered false positives. DNA extraction from larger plasma volumes improved the detection of\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      . The sensitivity of plasma-derived exosomes was limited; their use is not recommended.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Invasive fungal infection caused by\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      remains a life-threatening complication in patients with hematological malignancies, while early diagnosis is often challenging with the current tools. This study demonstrates that increasing the volume of blood plasma used for fungal DNA detection significantly improves diagnostic sensitivity without compromising specificity. As blood sampling is less invasive than bronchoalveolar lavage, a more sensitive plasma-based approach may facilitate earlier detection and initiation of targeted therapy when utilizing a diagnostic-driven approach. Our findings provide practical guidance for optimizing molecular diagnostic protocols in clinical laboratories.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jcm.00703-26","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:02:16Z","timestamp":1790341336000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Performance of large-volume plasma PCR for the diagnosis of invasive aspergillosis: a multicenter retrospective cohort study"],"prefix":"10.1128","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-1353","authenticated-orcid":true,"given":"Hanne","family":"Lamberink","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018906e22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine, Section of Infectious Diseases, Erasmus MC University Medical Center","place":["Rotterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/018906e22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center","place":["Rotterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6535-2213","authenticated-orcid":true,"given":"Ga-Lai M.","family":"Chong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018906e22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center","place":["Rotterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9418-8256","authenticated-orcid":true,"given":"Sammy","family":"Huygens","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sint-Jan Brugge-Oostende General Hospital","place":["Bruges, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-4304","authenticated-orcid":true,"given":"Mickey","family":"Konings","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018906e22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center","place":["Rotterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5011-6640","authenticated-orcid":true,"given":"Thomas","family":"de Corte","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ghent University Hospital","place":["Ghent, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/00cv9y106","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-8783","authenticated-orcid":true,"given":"Wendy W. 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