Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies

Abstract

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 Aspergillus 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 Aspergillus 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.

Intravenous Transplantation of Mesenchymal Stem Cells Reduces the Number of Infiltrated Ly6C+ Cells but Enhances the Proportions Positive for BDNF, TNF-1α, and IL-1β in the Infarct Cortices of dMCAO Rats

“…We have shown that in the ipsilateral ischemia core cortex, Iba-1 + cells are one of the main sources for the production of BDNF [ 7 ]. Other cell types, such as CD68 + microglia, and NeuN + neurons, are partly responsible for production of BDNF, even after the induction of ischemia.…”

“…The performance of allogeneic bone marrow MSC culture, cell transplantation, dMCAO model establishment, and behavioral tests have been described in our previous study [ 7 ]. In brief, 1 × 10 6 MSCs in 1 mL 0.9% saline were administered via intravenous injection one hour after ischemia.…”

“…Immunohistochemistry and cell counting were performed as previously described [ 7 ]. In brief, floating brain sections were incubated in 0.3% Triton-100 PBS for 30 min and blocked with 2% donkey serum in PBS for 30 min at room temperature (RT).…”

“…We have previously shown a rapid accumulation of ionized calcium binding adaptor molecule-1- (Iba-1-) positive microglia in the injured cerebral cortex two days after dMCAO in rats [ 7 ]. After intravenous MSC transplantation, the concentrations of neurotrophin BDNF and proinflammatory cytokines TNF- α and IL-1 β are all increased [ 7 ]. It will be interesting to examine the respective contribution from microglial vs. infiltrated cells in production of BDNF, TNF- α , and IL-1 β .…”

“…We have previously found that in the ischemic brain, BDNF is expressed in NeuN-positive neurons and CD68-positive microglia/macrophages in the peri-infarct areas, but mainly by Iba-1-positive microglia in the infarct core [ 7 ]. Whether BDNF production can be derived from infiltrated cells and regulatable by MSC treatment is still unclear, and the current study will try to address these questions as well.…”