Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647782
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647782
DOI : 10.1016/j.rmr.2017.07.017
PUBMED : 28939155

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial EIA (Bordier Affinity Products) with those of the Bio-Rad and VirionSerion EIAs. This assay is novel in the association of two recombinant antigens with somatic and metabolic antigens of A. fumigatus. In a prospective multicentre study, 436 serum samples from 147 patients diagnosed with CPA (136 sera/104 patients) or ABPA (94 sera/43 patients) and from 205 controls (206 sera) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad and VirionSerion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (p < 0.01), which was itself more sensitive than the VirionSerion kit (p=0.04). The Bordier and Bio-Rad kits had similar specificities (p=0.8), both higher than that of the VirionSerion kit (p=0.02). The areas under the ROC curves confirmed the superiority of the Bordier kit over the Bio-Rad and the VirionSerion kits (0.977, 0.951 and 0.897, respectively; p < 0.01 for each comparison). In a subset analysis of 279 sera tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; p=0.10).The use of recombinant, somatic and metabolic antigens in a single EIA improved the balance between sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
ISSN: 0095-1137

hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01282328/file/Prospective%20evaluation%20of%20a%20new%20Aspergillus.pdf
DOI : 10.1128/JCM.03261-15

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647076
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647076
DOI : 10.1016/j.rmr.2017.07.022
PUBMED : 28935495

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. METHODS: Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. RESULTS: In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. CONCLUSIONS: Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.
ISSN: 1058-4838

hal-00875190
https://hal.archives-ouvertes.fr/hal-00875190
DOI : 10.1093/cid/cis226
PUBMED : 22460967

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Revue Des Maladies Respiratoires

hal-01647079
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647079
DOI : 10.1016/j.rmr.2017.07.019
PUBMED : 28939154

Éditeur(s) : HAL CCSD
Résumé : International audience
In vitro susceptibility of 933 Candida isolates, from 16 French hospitals, to micafungin was determined using the Etest in each center. All isolates were then sent to a single center for determination of MICs by the EUCAST reference method. Overall essential agreement between the two tests was 98.5% at ±2 log2 dilutions and 90.2% at ±1 log2 dilutions. Categorical agreement was 98.2%. The Etest is a valuable alternative to EUCAST for the routine determination of micafungin MICs in medical mycology laboratories. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Antimicrobial Agents and Chemotherapy

hal-01367142
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367142
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367142/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367142/file/Multicenter%20comparison%20of%20the%20Etest.pdf
DOI : 10.1128/AAC.00630-16

Éditeur(s) : HAL CCSD
Résumé : International audience
Systemic Antifungal therapy (SAT) of invasive candidiasis (IC) needs to be started immediately upon clinical suspicion. Controversies exist then about potential harms from antifungal de-escalation (DE).(1) in cases of documented IC, early DE to fluconazole is recommended by US guidelines but discouraged in EU guidelines. in non-documented IC, no data are available to guide SAT DE. These questions are key issues however as the relationship between antifungal use and Candida antifungal resistance has been repeatedly demonstrated.
Intensive Care Medicine Experimental

hal-01334073
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334073
DOI : 10.1186/2197-425X-3-S1-A5
PUBMED : 27290057

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The present study is a contribution to the "neXt50 challenge", a coordinated effort across C-HPP teams to identify the SO most tractable missing proteins (MPs) on each chromosome. We report the targeted search of 38 theoretically detectable MPs from chromosomes 2 and 14 in Triton X-100 soluble and insoluble sperm fractions from a total of 15 healthy donors. A targeted mass spectrometry-based strategy consisting of the development of LC-PRM assays (with heavy labeled synthetic peptides) targeting 92 proteotypic peptides of the 38 selected MPs was used. Out of the 38 selected MPs, 12 were identified with two or more peptides and 3 with one peptide after extensive SDS-PAGE fractionation of the two samples and with overall low-intensity signals. The PRM data are available via ProteomeXchange in PASSEL (PASS01013). Further validation by immunohistochemistry on human testes sections and cytochemistry on sperm smears was performed for eight MPs with antibodies available from the Human Protein Atlas. Deep analysis of human sperm still allows the validation of MPs and therefore contributes to the C-HPP worldwide effort. We anticipate that our results will be of interest to the reproductive biology community because an in-depth analysis of these MPs may identify potential new candidates in the context of human idiopathic infertilities.
ISSN: 1535-3893

hal-01681656
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01681656
DOI : 10.1021/acs.jproteome.7b00374