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- Hoenigl, M., et al.
(författare)
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Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study
- 2023
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Ingår i: Lancet. Infectious Diseases. - : Elsevier BV. - 1473-3099 .- 1474-4457. ; 23:6, s. 751-761
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.Methods In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.Findings 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1 & BULL;08 [95% CI 1 & BULL;04-1 & BULL;11; p<0 & BULL;0001] in patients with a central venous catheter and 1 & BULL;09 [1 & BULL;05-1 & BULL;13; p<0 & BULL;0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.Interpretation Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.
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- Vogl, G, et al.
(författare)
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Immune evasion by acquisition of complement inhibitors: The mould Aspergillus binds both factor H and C4b binding protein
- 2008
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Ingår i: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 45:5, s. 1485-1493
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic fungi represent a major threat particularly to immunocompromised hosts, leading to severe, and often lethal, systemic opportunistic infections. Although the impaired immune status of the host is clearly the most important factor leading to disease, virulence factors of the fungus also play a role. Factor H (FH) and its splice product FHL-1 represent the major fluid phase inhibitors of the alternative pathway of complement, whereas C4b-binding protein (C4bp) is the main fluid phase inhibitor of the classical and lectin pathways. Both proteins can bind to the surface of various human pathogens conveying resistance to complement destruction and thus contribute to their pathogenic potential. We have recently shown that Candida albicans evades complement by binding both Factor H and C4bp. Here we show that moulds such as Aspergillus spp. bind Factor H, the splicing variant FHL-1 and also C4bp. Immunofluorescence and flow cytometry studies show that the binding of Factor H and C4bp to Aspergillus spp. appears to be even stronger than to Candida spp. and that different, albeit possibly nearby, binding moieties mediate this surface attachment.
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- Lindwall, Greta, et al.
(författare)
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Simulation of TTT Curves for Additively Manufactured Inconel 625
- 2019
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Ingår i: Metallurgical and Materials Transactions. A. - : SPRINGER. - 1073-5623 .- 1543-1940. ; 50A:1, s. 457-467
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Tidskriftsartikel (refereegranskat)abstract
- The ability to use common computational thermodynamic and kinetic tools to study the microstructure evolution in Inconel 625 (IN625) manufactured using the additive manufacturing (AM) technique of laser powder-bed fusion is evaluated. Solidification simulations indicate that laser melting and re-melting during printing produce highly segregated interdendritic regions. Precipitation simulations for different degrees of segregation show that the larger the segregation, i.e., the richer the interdendritic regions are in Nb and Mo, the faster the -phase (Ni3Nb) precipitation. This is in accordance with the accelerated precipitation observed experimentally during post-build heat treatments of AM IN625 compared to wrought IN625. The -phase may be undesirable since it can lead to detrimental effects on the mechanical properties. The results are presented in the form of a TTT diagram and agreement between the simulated diagram and the experimental TTT diagram demonstrate how these computational tools can be used to guide and optimize post-build treatments of AM materials.
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