Previously unknown species of Aspergillus Gautier, M.; Normand, A.-C.; Ranque, S.
Clinical microbiology and infection,
August 2016, 2016-Aug, 2016-08-00, 20160801, 2016-08, Letnik:
22, Številka:
8
Journal Article
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The use of multi-locus DNA sequence analysis has led to the description of previously unknown ‘cryptic’ Aspergillus species, whereas classical morphology-based identification of Aspergillus remains ...limited to the section or species-complex level. The current literature highlights two main features concerning these ‘cryptic’ Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these ‘cryptic’ Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care.
Summary Background & aims Despite the clinical benefits of using standard (non-disease specific) oral nutritional supplements (ONS) in the community and care homes, there is uncertainty about their ...economic consequences. Methods A systematic review was undertaken according to recommended procedures to assess whether ONS can produce cost savings and cost-effective outcomes. Results 19 publications with and without a hospital component were identified: 9 full text papers, 9 abstracts, and 1 report with retrospective analyses of 6 randomised controlled trials. From these publications a total of 31 cost and 4 cost-effectiveness analyses were identified. Most were retrospective analyses based on clinical data from randomised controlled trials (RCTs). In 9 studies/economic models involving ONS use for <3 months, there were consistent cost savings compared to the control group (median cost saving 9.2%; P < 0.01). When used for ≥3 months, the median cost saving was 5% (P > 0.05; 5 studies). In RCTs, ONS accounted for less than 5% of the total costs and the investment in the community produced a cost saving in hospital. Meta-analysis indicated that ONS reduced hospitalisation significantly (16.5%; P < 0.001; 9 comparisons) and mortality non-significantly (Relative risk 0.86 (95% CI, 0.61, 1.22); 8 comparisons). Many clinically relevant outcomes favouring ONS were reported: improved quality of life, reduced infections, reduced minor post-operative complications, reduced falls, and functional limitations. Of the cost-effectiveness analyses involving quality adjusted life years or functional limitations, most favoured the ONS group. The care home studies (4 cost analyses; 2 cost-effectiveness analyses) had differing aims, designs and conclusions. Conclusions Overall, the reviewed studies, mostly based on retrospective cost analyses, indicate that ONS use in the community produce an overall cost advantage or near neutral balance, often in association with clinically relevant outcomes, suggesting cost effectiveness. There is a need for prospective studies designed to examine primary economic outcomes.
Summary Background & aims There is limited information about the economic impact of nutritional support despite its known clinical benefits. This systematic review examined the cost and cost ...effectiveness of using standard (non-disease specific) oral nutritional supplements (ONS) administered in the hospital setting only. Methods A systematic literature search of multiple databases, data synthesis and analysis were undertaken according to recommended procedures. Results Nine publications comprising four full text papers, two abstracts and three reports, one of which contained 11 cost analyses of controlled cohort studies, were identified. Most of these were based on retrospective analyses of randomised controlled trials designed to assess clinically relevant outcomes. The sample sizes of patients with surgical, orthopaedic and medical problems and combinations of these varied from 40 to 1.16 million. Of 14 cost analyses comparing ONS with no ONS (or routine care), 12 favoured the ONS group, and among those with quantitative data (12 studies) the mean cost saving was 12.2%. In a meta-analysis of five abdominal surgical studies in the UK, the mean net cost saving was £746 per patient (se £338; P = 0.027). Cost savings were typically associated with significantly improved outcomes, demonstrated through the following meta-analyses: reduced mortality (Risk ratio 0.650, P < 0.05; N = 5 studies), reduced complications (by 35% of the total; P < 0.001, N = 7 studies) and reduced length of hospital stay (by ∼2 days, P < 0.05; N = 5 surgical studies) corresponding to ∼13.0% reduction in hospital stay. Two studies also found ONS to be cost effective, one by avoiding development of pressure ulcers and releasing hospital beds, and the other by gaining quality adjusted life years. Conclusion This review suggests that standard ONS in the hospital setting produce a cost saving and are cost effective. The evidence base could be further strengthened by prospective studies in which the primary outcome measures are economic.
The clinical diagnosis of mould infections currently involves complex species identification based on morphological criteria, which is often prone to error. Employing an extensive mould species ...reference spectral library (up to 2832 reference spectra, corresponding to 708 strains from 347 species), we assessed the extent to which matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) enhanced the accuracy of species identification. MALDI-TOF MS data were validated against morphology-based and DNA sequence-based results with 262 clinical isolates collected over a 4-month period in 2013. The implementation of MALDI-TOF MS resulted in a dramatic improvement in mould identification at the species level (from 78.2% to 98.1%) and a marked reduction in the misidentification rate (from 9.8% to 1.2%). We then compared the mould identification results obtained before (i.e. 2011) and after (i.e. 2013) the implementation of MALDI-TOF MS in routine identification procedures, which showed an improvement from 64.57% to 100%. Reassessment of a set of isolates from 2011 with this procedure, including MALDI-TOF MS, yielded an increase in species diversity from 16 to 42 species. Finally, application of this procedure during a 16-month period (2012–2013) enabled the identification of 1094 of 1107 (98.8%) clinical mould isolates corresponding to 107 distinct species. MALDI-TOF MS-based mould species identification may soon challenge traditional techniques in the clinical laboratory, as patient prognosis is largely contingent on rapid and accurate diagnosis.
Introduction Le syndrome des ovaires polykystiques (SOPK) constitue un bon modèle pour l’étude des altérations métaboliques dans les maladies complexes vu qu’il est caractérisé par des degrés ...variables d’obésité et de résistance à l’insuline et comporte un terrain génétique de prédisposition. Patients et méthodes Dans le programme Européen MEDIGENE (FP7– 279171), coordonné par l’UM-1 Montpellier (France), nous avons exploré le gène DUSP9 (dual specificity phosphatase 9) dans une population de femmes (n = 413) d’Europe Centrale (Roumanie) atteinte de SOPK selon les critères de Rotterdam. La cartographie dense du gène a comporté le SNP leader rs5945326 A/G ainsi que 5 autres SNP du même locus : rs5945327 (T/C), rs60186537 (C/T), rs55909671 (G/A), rs5987114 (G/A) et rs55714157 (T/C). Nous avons également génotypé le SNP proxy rs3020789 (C/T). Le génotypage a été réalisé par KASPar et par séquençage direct tandis que la reconstruction des haplotypes a été réalisée par PHASE. Enfin, l’étude statistique a été effectuée par StatView. Résultats Nous avons reconstitué cinq haplotypes (H1 à H5) dans la population dont un seul (H5) porte l’allèle G de rs5945326. La régression logistique a montré l’association de l’homozygote GG de rs5945326 (P < 0,031 ; OR = 0,18 IC95 % 0,04–0,86) et de l’homozygote CC rs3020789 (P < 0,039 ; OR = 0,11 IC95 % 0,01–0,90) à un effet protecteur contre l’obésité. Nous avons également observé l’absence du génotype GG de rs5945326 de la forme la plus grave du SOPK avec Acanthosis nigricans et syndrome métabolique (P < 0,012). L’analyse haplotypique a montré des résultats similaires. Conclusion Ces données montrent que DUSP9 est très influent dans le SOPK, cela parmi plusieurs gènes testés dans cette population. La localisation du gène sur le chromosome X et son rôle dans l’action de l’insuline font de lui un excellent candidat pour expliquer les formes les plus sévères du SOPK avec Acanthosis nigricans et syndrome métabolique.
Objectif Les altérations du catabolisme des aminoacides branchés (AABC) sont impliquées dans la pathogénie du syndrome métabolique. Le syndrome des ovaires polykystiques (SOPK) caractérisé par des ...degrés d’insulinorésistance et des taux plasmatiques d’AABC élevés constitue un modèle adéquat pour l’étude des gènes de susceptibilité liés au catabolisme d’AABC. Parmi les gènes les plus candidats l’ isovaleryl-CoA dehydrogenase ( IVD ). Dans ce travail, nous avons exploré l’association des marqueurs SNP du gène IVD dans une population de femmes avec SOPK d’Europe Centrale. Patients et méthodes Nous avons étudié 401 femmes avec SOPK (critères de Rotterdam 2003) et 143 contrôles, par le SNP leader rs10518693 (C/T), génotypé par KASPar, et criblé chez 55 patients SOPK et 48 contrôles 9 SNP du gène via la technologie Affymetrix. Le profil de déséquilibre de liaison (DL) était étudié par HAPLOVIEW et l’association génétique par régression logistique. Résultats Le génotype TT de rs10518693 s’associe au SOPK le plus insulinorésistant ( p = 0,02, OR 2,55 1,13–5,75) et corrèle avec des taux plus bas d’HDL ( p = 0,017). Parmi les 9 SNP identifiés par criblage dense, le SNP rs11633883 est proxy du leader (G du proxy correspond à T pathogène du leader). La cartographie a montré un DL élevé permettant de construire 8 haplotypes par PHASE. L’haplotype H6 (GAGGAGATG) s’associe au SOPK le plus insulinorésistant ( p = 0,02, OR 3,08 1,13–8,36) et corrèle avec des taux plus élevés d’HOMAIR ( p = 0,0165) et d’insulinémie à jeun ( p = 0,0017) chez les SOPK. Conclusion L’association de l’IVD au SOPK suggère son rôle comme marqueur de l’insulinorésistance dans la maladie.
The purpose of this study was to compare the efficiency of mould identification of two matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) systems – Vitek MS ...(VMS) and Microflex LT (MLT) – and the MSI application.
Moulds were collected retrospectively and prospectively to display epidemiological diversity of a microbiology laboratory. All of them were identified via sequencing. Strains were then identified using the VMS v3.0, the MLT, and the MSI software applied on MLT spectra. Rates of correct identifications to the species, to the complex, and to the genus level were compared with the molecular reference standard.
A total of 102 isolates were collected. The rate of correct identification to the species level with the MLT was 42.2% (43/102) with a threshold of 1.7 (vs. 16.7% (17/102) with a threshold of 2.0, p < 0.05). The VMS performed better than the MLT with a threshold of 1.7 for species (49.0% (50/102), p 0.33) and complex level identifications (71.6% (73/102) vs. 54.9% (56/102), p < 0.05). However the highest performances were observed when the MLT spectra were analysed via the Mass Spectrometry Identification (MSI) software reaching 90.2% (92/102) of correct identification to the species, 92.2% (94/102) to the species complex and 94.1% (96/102) to the genus level.
The VMS performed better than the MLT for mould identification. However, it remains of utmost importance to expand commercial databases, as performances of the MLT highly improved when using the MSI software and its extended database, reaching far above the VMS system. Thus the VMS could benefit from the use of this online tool.
, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been ...recently reclassified into the
section
However, little is yet known among the section
about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as
were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The MICs of itraconazole, voriconazole, posaconazole, isavuconazole, and amphotericin B were determined by both the EUCAST and gradient concentration strip methods.
(
= 51, 45.5%) and
(
= 50, 44.6%) were the most common species while
accounted for only 6.3% (
= 7). The MICs of azole drugs were higher for
than for
The MIC of amphotericin B was 2 mg/liter or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by the gradient concentration strip method, with the latter being lower than the former (Spearman's rank correlation tests ranging from 0.01 to 0.25 depending on the antifungal agent;
> 0.4). In conclusion,
should be considered as a minority species in the section
The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and the gradient concentration strip methods require further investigation.
Changes in sensorimotor function and increased trunk muscle fatigability have been identified in patients with chronic low back pain (cLBP). This study assessed the control of trunk force production ...in conditions with and without local erector spinae muscle vibration and evaluated the influence of muscle fatigue on trunk sensorimotor control.
Twenty non-specific cLBP patients and 20 healthy participants were asked to perform submaximal isometric trunk extension torque with and without local vibration stimulation, before and after a trunk extensor muscle fatigue protocol. Constant error (CE), variable error (VE) as well as absolute error (AE) in peak torque were computed and compared across conditions. Trunk extensor muscle activation during isometric contractions and during the fatigue protocol was measured using surface electromyography (sEMG).
Force reproduction accuracy of the trunk was significantly lower in the patient group (CE = 9.81 ± 2.23 Nm; AE = 18.16 ± 3.97 Nm) than in healthy participants (CE = 4.44 ± 1.68 Nm; AE = 12.23 ± 2.44 Nm). Local erector spinae vibration induced a significant reduction in CE (4.33 ± 2.14 Nm) and AE (13.71 ± 3.45 Nm) mean scores in the patient group. Healthy participants conversely showed a significant increase in CE (8.17 ± 2.10 Nm) and AE (16.29 ± 2.82 Nm) mean scores under vibration conditions. The fatigue protocol induced erector spinae muscle fatigue as illustrated by a significant decrease in sEMG median time-frequency slopes. Following the fatigue protocol, patients with cLBP showed significant decrease in sEMG root mean square activity at L4-5 level and responded in similar manner with and without vibration stimulation in regard to CE mean scores.
Patients with cLBP have a less accurate force reproduction sense than healthy participants. Local muscle vibration led to significant trunk neuromuscular control improvements in the cLBP patients before and after a muscle fatigue protocol. Muscle vibration stimulation during motor control exercises is likely to influence motor adaptation and could be considered in the treatment of cLBP. Further work is needed to clearly identify at what levels of the sensorimotor system these gains are achievable.
RAS mutations are currently sought for in tumor samples, which takes a median of almost 3weeks in western European countries. This creates problems in clinical situations that require urgent ...treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort.
Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision±0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary.
From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 95% confidence interval (CI), 0.64–0.77 and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84–0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results odds ratio=0.11 (95% CI, 0.06–0.21). In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers.
This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients.
Clinicaltrials.gov, NCT02502656.
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