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Schwarzinger M.,French Institute of Health and Medical Research | Schwarzinger M.,University Paris Diderot | Schwarzinger M.,A+ Network | Schwarzinger M.,Stanford University | And 8 more authors.
PLoS ONE | Year: 2013

Background: The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. Methods: We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. Results: The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). Conclusions: The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay. © 2013 Schwarzinger et al. Source


Robin C.,Henri Mondor Teaching Hospital | Robin C.,University Paris Est Creteil | Alanio A.,Parasitology Mycology Laboratory | Alanio A.,University of Paris Pantheon Sorbonne | And 3 more authors.
Current Opinion in Hematology | Year: 2014

Purpose of review This study focuses on the epidemiology and management of mucormycosis in hematopoietic stem cell transplant patients, a life-threatening mold infection whose incidence has increased over the past decades. Recent findings Mucormycosis may occur in hematopoietic stem cell transplant recipients with severe graft-versus-host disease, steroids, neutropenia, iron overload, diabetes, and malnutrition, or those who received antifungals not active against Mucorales. Its incidence in allogeneic hematopoietic stem cell transplant is around 0.3%. As Mucorales are not susceptible to voriconazole and candins, and as mucormycosis often mimics aspergillosis, it is extremely important to have a precise diagnostic to correctly manage the patient. The reversed halo sign on chest computed tomography has been associated to mucormycosis in neutropenic patients, but is not pathognomonic. Direct fungal identification is crucial. Molecular approaches are developed that may be extremely useful for early diagnosis. Summary Although randomized trials are quite impossible to run, due to the rarity of the disease, the recent numerous data have allowed the elaboration of European guidelines for the management of mucormycosis. Lipid formulations of amphotericin B, and especially liposomal amphotericin B at high doses (5-10mg/kg/day), are the standard treatment, combined with surgery and control of favoring factors. The prognosis is poor, and any delay in the initiation of therapy may impact on outcome. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Pallud J.,Sainte Anne Hospital | Pallud J.,University of Paris Descartes | Pallud J.,Institute Pasteur Paris | Audureau E.,Henri Mondor Teaching Hospital | And 38 more authors.
Neuro-Oncology | Year: 2015

Background. The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care. Me th od s. Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted. Results. The median progression-free survival was 12.0 months (95% CI: 10.712.6) in the implantation group and 10.0 months (9.010.0) in the standard group and the median overall survival was 20.4 months (19.022.7) and 18.0 months (17.019.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.630.92], P =.005) and after propensity matching (HR, 0.74 [95% CI: 0.600.92], P =.008), whereas no significant difference was found for overall survival (HR, 0.95 [0.801.13], P =.574; HR, 1.06 [0.871.29], P =.561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.440.76], P <.0001; HR, 0.54 [0.410.70], P <.0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.400.78], P <.0001; HR, 0.46 [95% CI: 0.330.64], P <.0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival. Conclusions. Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit. © 2015 The Author(s). Source


Ducat A.,University Pierre and Marie Curie | Sariali E.,University Pierre and Marie Curie | Lebel B.,Cote de Nacre Teaching Hospital | Mertl P.,North Hospital | And 11 more authors.
Orthopaedics and Traumatology: Surgery and Research | Year: 2012

Introduction: Valgus high tibial osteotomy is considered to be an effective treatment for unicompartmental medial osteoarthritis. It is generally admitted that tibial slope increases after open-wedge high tibial osteotomy and decreases after closing-wedge high tibial osteotomy. However, the effects on posterior tibial slope of closing- or opening-wedge osteotomies remain controversial. Hypothesis: We analyzed the modifications of tibial slope after opening- and closing-wedge high tibial osteotomies and compared the results of these two procedures. We hypothesized that there was no difference in postoperative tibial slope between opening and closing-wedge osteotomies. Patients and methods: This prospective consecutive nonrandomized multicenter study was conducted between January 2008 and March 2009 and included 321 patients: 205 men and 116 women. A total of 224 patients underwent an opening-wedge high tibial osteotomy and 97 a closing-wedge osteotomy. The mean age was 52 years±9 and the mean body mass index was 28kg/m 2±5. The main etiology was primary arthritis. Posterior tibial slope was measured preoperatively and at the last follow-up on a lateral radiograph in relation to the posterior tibial cortex. Results: In the opening-wedge group, a definite 0.6° increase in tibial slope (P= 0.016) was observed. In the closing-wedge group, a definite 0.7° decrease in tibial slope (P= 0.02) was found. Fourteen percent of the opening-wedge osteotomies increased tibial slope by 5° or more versus only 2% of the closed-wedge osteotomies (P< 0.001). Twelve percent of the closing-wedge high tibial osteotomies led to a decrease of 5° or more of the tibial slope versus 7% of the opening-wedge osteotomies (P< 0.02). Discussion and conclusion: These results confirm what is generally reported in the literature, i.e., an increase in tibial slope in opening-wedge high tibial osteotomy and a decrease in the slope in closing-wedge osteotomies. These tibial slope changes appear to be very limited in this series, less than 1° on average. However, there was a bias since the open-wedge technique was preferred in cases with substantial varus deformity. We emphasize the importance of surgical technique to avoid alteration of the tibial slope, particularly in opening-wedge high tibial osteotomy for which we recommend a release of posterior soft tissue and a complete osteotomy of the posterior cortex of the tibia. Level of evidence: III. Prospective consecutive nonrandomized multicenter study. © 2011 Elsevier Masson SAS. Source


Parisot J.,Henri Mondor Teaching Hospital | Parisot J.,University Paris Est Creteil | Yiou R.,Assistance Publique des Hopitaux de Paris | Salomon L.,Assistance Publique des Hopitaux de Paris | And 4 more authors.
Journal of Sexual Medicine | Year: 2014

Introduction: Erectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested. Aim: This study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections. Methods: This is a 1-year follow-up cohort study of 75 patients treated by RP for localized prostate cancer in a urology department setting between January 2007 and December 2008. Data were prospectively collected at 6 and 12 months post-RP. Main Outcome Measures: The EHS, the International Index of Erectile Function (IIEF) reference questionnaire, the Global Assessment Questionnaire (GAQ), and Numeric Pain Scale (NPS) were collected. Convergent validity (Spearman correlation coefficients with IIEF domains), known-groups validity (comparing EHS scores across ED severity groups), time and treatment responsiveness (effect size with/without treatment and over the follow-up period), and predictive ability (area under the receiver operating characteristics curve [AUC-ROC]) were analyzed for this study. Results: The EHS showed good convergent validity (all Spearman coefficients significant at the P<0.05 level), adequate known-groups validity (global differentiation between IIEF-EF severity groups; P<0.001), and treatment responsiveness (effect size: +1.8 [6 months], +2.1 [12 months]), but limited time responsiveness and predictive ability of the EHS for a normal EF at 12 months follow-up when compared with the IIEF-EF domain (AUC-ROC: 0.72 vs. 0.85; P<0.01). Conclusion: Our findings support the overall good psychometric properties of the EHS in patients with post-RP ED treated with alprostadil injections. However, evidence for limited predictive validity and responsiveness to change over time should be considered for its use in clinical follow-up in this population. Parisot J, Yiou R, Salomon L, de la Taille A, Lingombet O, and Audureau E. Erection hardness score for the evaluation of erectile dysfunction: Further psychometric assessment in patients treated by intracavernous prostaglandins injections after radical prostatectomy. J Sex Med 2014;11:2109-2118. © 2014 International Society for Sexual Medicine. Source

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