Introduction: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking.
Methods: We performed a prospective case-control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Cases were subjects with hematological diagnoses who met established revised definitions for proven or probable IPA established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG, 2008), without the use of BAL GM results. Exclusion criteria included the use of piperacillin/tazobactam and use of antifungals that were active against spp. before bronchoscopy. There were two control groups: patients with hematological diagnoses not meeting definitions for proven or probable IPA and patients with nonhematological diagnoses with no evidence of aspergillosis. Following bronchoscopy and BAL, GM testing was performed using the Platelia seroassay in accordance with the manufacturer's instructions.
Results: There were 51 cases and 20 controls. Cases had higher BAL fluid GM OD indices (ODIs) (mean: 1.27 and range: 0.4-3.78) compared with controls (mean: 0.26 and range: 0.09-0.35). Receiver operating characteristic analysis demonstrated an optimum ODI cutoff of 1.0, with high specificity (100%) and sensitivity (87.5%) for diagnosing IPA.
Conclusions: Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.
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http://dx.doi.org/10.4103/JLP.JLP_127_16 | DOI Listing |
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Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory for Stem Cell Therapy, Faculty of Medicine, Tsukuba University, Ibaraki, Japan. Electronic address:
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Division of Hematology/Oncology, The University of Texas Health Sciences Center at Houston, McGovern Medical School, 6431 Fannin Street, MSB 5.216, Houston, TX, 77030, USA.
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Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
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Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan.
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Division of Hematology, Second Xiang-ya Hospital, Central South University, Changsha, China.
Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.
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