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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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| 4. |
- Kiiveri, K., et al.
(författare)
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CODEX weak lensing mass catalogue and implications on the mass-richness relation
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 502:1, s. 1494-1526
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Tidskriftsartikel (refereegranskat)abstract
- The COnstrain Dark Energy with X-ray clusters (CODEX) sample contains the largest flux limited sample of X-ray clusters at 0.35 < z < 0.65. It was selected from ROSAT data in the 10 000 square degrees of overlap with BOSS, mapping a total number of 2770 high-z galaxy clusters. We present here the full results of the CFHT CODEX programme on cluster mass measurement, including a reanalysis of CFHTLS Wide data, with 25 individual lensing-constrained cluster masses. We employ LENSFIT shape measurement and perform a conservative colour–space selection and weighting of background galaxies. Using the combination of shape noise and an analytic covariance for intrinsic variations of cluster profiles at fixed mass due to large-scale structure, miscentring, and variations in concentration and ellipticity, we determine the likelihood of the observed shear signal as a function of true mass for each cluster. We combine 25 individual cluster mass likelihoods in a Bayesian hierarchical scheme with the inclusion of optical and X-ray selection functions to derive constraints on the slope α, normalization β, and scatter σln λ|μ of our richness–mass scaling relation model in log-space: |${\langle {\rm In}\,\, \lambda\!\!\mid\!\!\mu\rangle = \alpha\mu + \beta,} $| with μ = ln (M200c/Mpiv), and Mpiv = 1014.81M⊙. We find a slope |$\alpha = 0.49^{+0.20}_{-0.15}$|, normalization |$\exp (\beta) = 84.0^{+9.2}_{-14.8}$|, and |$\sigma _{\ln \lambda | \mu } = 0.17^{+0.13}_{-0.09}$| using CFHT richness estimates. In comparison to other weak lensing richness–mass relations, we find the normalization of the richness statistically agreeing with the normalization of other scaling relations from a broad redshift range (0.0 < z < 0.65) and with different cluster selection (X-ray, Sunyaev–Zeldovich, and optical).
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| 5. |
- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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| 6. |
- Cattaneo, C, et al.
(författare)
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Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.
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| 8. |
- van Osch, G. J., et al.
(författare)
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Cartilage repair: past and future--lessons for regenerative medicine
- 2009
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Ingår i: Journal of Cellular and Molecular Medicine. - 1582-4934. ; 13:5, s. 792-810
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Tidskriftsartikel (refereegranskat)abstract
- Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissue-related outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general.
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