Specificity of mannan antigen and anti-mannan antibody screening in patients with haematological malignancies at risk for fungal infection.

Combination of mannan antigen and anti-mannan antibody (Mn/A-Mn) testing has been reported a useful and specific strategy for diagnosis of invasive Candida infections (ICIs). We evaluated Mn/A-Mn as a screening tool in patients with haematological malignancies. This clinical prospective study was performed at the Division of Hematology, Medical University Graz, Austria between July and December 2012. Patients at risk for fungal infection were included into the study and twice weekly screened by Mn/A-Mn testing, yielding 650 samples. Of overall 67 patients 66 had no evidence for ICI. From those, 153/640 serum samples (23.9%) were positive for mannan Ab, and nine (1.4%) for Ag. Most false positive Ab results were observed among 375 samples from patients without haematopoietic stem cell transplantation (34.9% resulted positive). Combined specificity of Mn/A-Mn was 74.8%. Of 10 samples obtained in the single patient with candidemia, five were positive for mannan Ag (from the day of diagnosis up to 40 days after detection of candidemia) and none for Ab. In conclusion, mannan Ab screening yielded a high number of false positive results. While mannan Ag was found to be highly specific and may have potential for diagnostic driven testing, mannan Ab testing cannot be recommended based on our study results.

Monoglyceride lipase deficiency modulates endocannabinoid signaling and improves plaque stability in ApoE-knockout mice.

BACKGROUND AND AIMS: Monoglyceride lipase (MGL) catalyzes the final step of lipolysis by degrading monoglyceride (MG) to glycerol and fatty acid. MGL also hydrolyzes and thereby deactivates 2-arachidonoyl glycerol (2-AG), the most abundant endocannabinoid in the mammalian system. 2-AG acts as full agonist on cannabinoid receptor type 1 (CB1R) and CB2R, which are mainly expressed in brain and immune cells, respectively. Thus, we speculated that in the absence of MGL, increased 2-AG concentrations mediate CB2R signaling in immune cells to modulate inflammatory responses, thereby affecting the development of atherosclerosis. METHODS AND RESULTS: We generated apolipoprotein E (ApoE)/MGL double-knockout (DKO) mice and challenged them with Western-type diet for 9 weeks. Despite systemically increased 2-AG concentrations in DKO mice, CB2R-mediated signaling remains fully functional, arguing against CB2R desensitization. We found increased plaque formation in both en face aortae (1.3-fold, p = 0.028) and aortic valve sections (1.5-fold, p = 0.0010) in DKO mice. Interestingly, DKO mice also presented reduced lipid (12%, p = 0.031) and macrophage content (18%, p = 0.061), elevated intraplaque smooth muscle staining (1.4-fold, p = 0.016) and thicker fibrous caps (1.8-fold, p = 0.0032), together with a higher ratio of collagen to necrotic core area (2.5-fold, p = 0.0003) and expanded collagen content (1.6-fold, p = 0.0007), which suggest formation of less vulnerable atherosclerotic plaques. Treatment with a CB2R inverse agonist prevents these effects in DKO mice, demonstrating that the observed plaque phenotype in DKO mice originates from CB2R activation. CONCLUSION: Loss of MGL modulates endocannabinoid signaling in CB2R-expressing cells, which concomitantly affects the pathogenesis of atherosclerosis. We conclude that despite larger lesion size loss of MGL improves atherosclerotic plaque stability. Thus, pharmacological MGL inhibition may be a novel intervention to reduce plaque rupture.

Impact of galactomannan testing on the prevalence of invasive aspergillosis in patients with hematological malignancies.

Galactomannan (GM) is a polysaccharide component of the cell wall of Aspergillus spp. and is released into the host's circulation by growing hyphae. GM testing of patients with hematological malignancies has been rarely considered in recent epidemiologic studies of invasive mould infections (IMIs). The aim of the investigation was to analyze the impact of GM testing on the reported prevalence of IMI by comparing detection rates of IMI before and after the introduction of this diagnostic procedure. Prevalence of IMI was assessed by conducting a prospective single-centre study over seven months in 2010. Results obtained were then compared to those obtained with a representative collection of patients assessed by the same investigators at the same institution over seven months in 2007, i.e., prior to the introduction of GM testing. We found that, in general, detection rates of invasive aspergillosis (IA) and invasive mould infections increased significantly after the introduction of GM analysis. This study may therefore indicate that GM testing has a significant impact on the reported prevalence of IMI. Broad usage of such testing in patients with hematological malignancies may be able to produce a realistic picture of IMI rates when current diagnostic criteria are applied.