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Sainte-Foy-lès-Lyon, France

Jardin F.,University of Rouen | Jais J.-P.,Service de Biostatistique | Molina T.-J.,AP HP | Parmentier F.,University of Rouen | And 13 more authors.
Blood | Year: 2010

Genomic alterations play a crucial role in the development and progression of diffuse large B-cell lymphomas (DLBCLs). We determined gene copy number alterations (GCNAs) of TP53, CDKN2A, CDKN1B, BCL2, MYC, REL, and RB1 with a single polymerase chain reaction (PCR) assay (quantitative multiplex PCR of short fragments [QMPSF]) in a cohort of 114 patients with DLBCL to assess their prognostic value and relationship with the gene expression profile. Losses of TP53 and CDKN2A, observed in 8% and 35% of patients, respectively, were significantly associated with a shorter survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, independently of the International Prognostic Index and of the cell of origin. Analysis of the 9p21 genomic region indicated that transcripts encoding p14ARF and p16INK4A were both disrupted in most patients with CDKN2A deletion. These patients predominantly had an activated B-cell profile and showed a specific gene expression signature, characterized by dysregulation of the RB/E2F pathway, activation of cellular metabolism, and decreased immune and inflammatory responses. These features may constitute the molecular basis sustaining the unfavorable outcome and chemoresistance of this DLBCL subgroup. Detection of TP53 and CDKN2A loss by QMPSF is a powerful tool that could be used for patient stratification in future clinical trials. © 2010 by The American Society of Hematology. Source

Boutitie F.,Service de Biostatistique | Boutitie F.,French National Center for Scientific Research | Buffin R.,Service de Reanimation Neonatale | Huissoud C.,Service dObstetrique | And 2 more authors.
Placenta | Year: 2014

Objective: to test the hypothesis that placental fetal thrombotic vasculopathy (FTV) is associated with obstetric complications and predisposes the child to unfavorable outcomes. Methods: 54 placentas with FTV lesions and 100 placentas without FTV lesions were collected over a 5- year period at the Croix-Rousse Pathology Department. Clinical findings including maternal, fetal, neonatal condition and pediatric outcome up to three years were collected for each case and control observation. The statistical analyses were assessed with Wald's chi-square derived from conditional logistic regression modeling. Results: FTV was associated with a significantly higher frequency of obstetric complications: (pregnancyinduced hypertension (OR 3.620, CI 1.563-8.385), preeclampsia (OR 3.674, CI 1.500-8.998), emergency delivery procedures (OR 3.727, CI 1.477-9.403), cesarean sections (OR 2.684, CI 1.016-7.088)), poor fetal condition (intrauterine growth restriction (IUGR) (OR 5.440, CI 2.007-14.748), nonreassuring fetal heart tracing (OR 6.062, CI 2.280-16.115), difficulties in immediate ex utero adaptation (OR 3.416, CI 1.087 e10.732)) and perinatal or early childhood demise (OR 3.043, CI 1.327-6.978). On pathological examination, FTV was associated with marginal cord insertion (OR 3.492, CI 1.350-9.035), cord stricture and hypercoiled cord (OR 3.936, CI 1.209-12.813). Thromboembolic events were significantly more frequent in cases with FTV (OR 2.154, CI 1.032-5.622). Neurological complications within the first 3 years of life were also more frequent in the FTV group compared to the control group, but this association was not statistically significant. Conclusions: FTV is associated with maternal complications, pathological findings in the placenta, especially gross cord abnormalities, IUGR, and poor perinatal or early childhood outcome. It may also predispose children to somatic thromboembolic events. © 2014 Elsevier Ltd. All rights reserved. Source

Crouzet S.,Edouard Herriot Hospital | Crouzet S.,French Institute of Health and Medical Research | Murat F.-J.,Edouard Herriot Hospital | Pommier P.,Center Leon Berard | And 11 more authors.
Radiotherapy and Oncology | Year: 2012

Purpose: To evaluate pre-operative prognostic risk factors to predict oncologic outcome of Salvage High-Intensity Focused Ultrasound (S-HIFU) for radiorecurrent prostate cancer (PCa). Methods and materials: A total of 290 men with biopsy-confirmed locally radiorecurrent PCa, underwent S-HIFU. D'Amico risk group before external beam radiotherapy (EBRT), Prostate Specific Antigen (PSA), estimated Gleason score prior HIFU and post HIFU biopsies were analyzed for predictive utility of local cancer control, cancer-specific, metastasis free, and progression free survival rates (PFSR). Results: Local cancer control with negative biopsy results was obtained in 81% of the 208 patients who underwent post-S-HIFU biopsies. Median PSA nadir was 0.14 ng/ml and 127 patients did not require androgen deprivation therapy (ADT). The mean follow up was 48 months for cancer-specific survival rates. The cancer-specific and metastasis-free survival rates at 7 years were 80% and 79.6% respectively. The PFSR was significantly influenced by: the pre-HIFU PSA level (hazard ratio (HR): 1.09, 95% CI 1.04-1.13), a Gleason score ≥8 versus ≤6 (HR: 1.17, 95% CI 1.03-1.3), and a previous ADT (HR: 1.28, 95% CI 1.09-1.46). The rates of recto-urethral fistula (0.4%) and grade II/III incontinence (19.5%) indicate significant reduction in serious side effects with use of dedicated post-radiation acoustic parameters compared with standard parameters. Conclusion: S-HIFU is an effective curative option for radiorecurrent PCa with acceptable morbidity for localized radiorecurrent PCa, but should be initiated early following EBRT failure. Use of prognostic risk factors can optimize patient selection. © 2012 Elsevier Ireland Ltd. All rights reserved. Source

Maman D.,Epicentre | Zeh C.,Centers for Disease Control and Prevention | Mukui I.,National AIDS and STI Control Programme | Kirubi B.,Medecins Sans Frontieres | And 6 more authors.
AIDS | Year: 2015

Introduction: Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation especially HIV incidence, population viral load, and ART eligibility is rare in sub-Saharan Africa. Design/methods: To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 1559 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4 cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections. Results: Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.025.2] and 1.9 new cases/100 person-years (95% CI 1.12.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.861.9) were previously diagnosed, 53.1% (95% CI 50.555.7) were receiving care, and 39.7% (95% CI 37.142.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3 62.7) to 82.0% (95% CI 79.584.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4 cell count (500749 vs. ≤750 cells/ml, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.200.60, P<0.01). Conclusion: This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Guglielminotti J.,APHP | Guglielminotti J.,French Institute of Health and Medical Research | Dechartres A.,Center dEpidemiologie Clinique | Dechartres A.,University of Paris Descartes | And 6 more authors.
Anesthesia and Analgesia | Year: 2015

BACKGROUND: Prognostic research studies in anesthesiology aim to identify risk factors for an outcome (explanatory studies) or calculate the risk of this outcome on the basis of patients' risk factors (predictive studies). Multivariable models express the relationship between predictors and an outcome and are used in both explanatory and predictive studies. Model development demands a strict methodology and a clear reporting to assess its reliability. In this methodological descriptive review, we critically assessed the reporting and methodology of multivariable analysis used in observational prognostic studies published in anesthesiology journals. METHODS: A systematic search was conducted on Medline through Web of Knowledge, PubMed, and journal websites to identify observational prognostic studies with multivariable analysis published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and Anaesthesia in 2010 and 2011. Data were extracted by 2 independent readers. First, studies were analyzed with respect to reporting of outcomes, design, size, methods of analysis, model performance (discrimination and calibration), model validation, clinical usefulness, and STROBE (i.e., Strengthening the Reporting of Observational Studies in Epidemiology) checklist. A reporting rate was calculated on the basis of 21 items of the aforementioned points. Second, they were analyzed with respect to some predefined methodological points. RESULTS: Eighty-six studies were included: 87.2% were explanatory and 80.2% investigated a postoperative event. The reporting was fairly good, with a median reporting rate of 79% (75% in explanatory studies and 100% in predictive studies). Six items had a reporting rate <36% (i.e., the 25th percentile), with some of them not identified in the STROBE checklist: blinded evaluation of the outcome (11.9%), reason for sample size (15.1%), handling of missing data (36.0%), assessment of colinearity (17.4%), assessment of interactions (13.9%), and calibration (34.9%). When reported, a few methodological shortcomings were observed, both in explanatory and predictive studies, such as an insufficient number of events of the outcome (44.6%), exclusion of cases with missing data (93.6%), or categorization of continuous variables (65.1%.). CONCLUSIONS: The reporting of multivariable analysis was fairly good and could be further improved by checking reporting guidelines and EQUATOR Network website. Limiting the number of candidate variables, including cases with missing data, and not arbitrarily categorizing continuous variables should be encouraged. Copyright © 2014 International Anesthesia Research Society. Source

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