However, these trends were observed in a background of declining autopsy rates over the 20-year span of the study, consistent with the global trends of the vanishing ‘non-forensic autopsy’ in contemporary medicine.[18,

19] Multiple factors have been cited for the decline in autopsy rates, including public preferences, requirement for informed consent, concerns for limiting an institutional medical liability and the cost reimbursement for performing autopsies.[19] Therefore, a large proportion of IFIs in the later years of our study, particularly those caused by cryptic pathogens associated with fatal outcomes, may have been under-represented in our analysis. This study Z-VAD-FMK nmr also reflects the progress achieved with an ICG-001 nmr earlier

diagnosis of IFIs in haematological malignancy patients. In the first 5 years of the study, 84% of the IFIs were evident only at autopsy and did not meet the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria for ante mortem diagnosis of proven infection.[16, 20] By 2004–2008, this number had decreased to 49% of cases (P < 0.001). Improvements in ante mortem diagnosis of IFIs corresponded to the introduction of improved culture methods for fungi[21, 22] in our institution as well as the routine use of the Aspergillus ELISA galactomannan assay. However, our autopsy data also revealed that 5 of 11 (45%) patients with proven aspergillosis had repeatedly negative galactomannan test results prior to death – thus underscoring the importance of autopsy evidence for evaluating the Casein kinase 1 performance of new diagnostic tests.[23] We also documented major shifts in the patterns of underlying immunosuppression associated with IFI in haematological malignancy patients over the 20-year study period. In the first 5 years of the study, severe neutropenia (polymorphonuclear

neutrophil < 100 cells mm−3) was a predisposing condition in 90% of subjects, but declined to 44% by 2004–2008, P < 0.001. However, the use of high-dose corticosteroids increased during the study from 21% in 1989–1993, to 81% of patients in 2004–2008, P < 0.001. The shift from neutropenia to corticosteroid therapy as the predominant risk factor for IFIs in this population is consistent with the increased use of non-myeloablative conditioning for HSCT recipients, as well as targeted therapies or immunobiologicals for salvage chemotherapy in patients with haematological malignancies.[24, 25] In animal infection models and to some degree humans,[9] the pathogenesis of invasive pulmonary aspergillosis differs considerably when infection is established in the setting of neutropenia as compared with high-dose corticosteroid therapy.