Eric Fontas

Centre Hospitalier Universitaire de Nice, Nice, Provence-Alpes-Côte d'Azur, France

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Publications (45)310.52 Total impact

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    ABSTRACT: Objectives: Whilst several antiretroviral drugs (ARVs), including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. Design: Prospective cohort study METHODS:: D:A:D participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or alpha-fetoprotein plus imaging), death, 6 months after last visit or 1/2/2014. Associations between ESLD/HCC and cumulative use of individual ARVs were investigated using Poisson regression adjusting for potential confounders. Results: During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred (incidence 1.01/1000 person-years [95%CI 0.90-1.12]) with a 62.6% one-year mortality rate. After adjustment, cumulative (per 5 years) exposure to d4T (relative rate 1.46 [95%CI 1.20-1.77]), ddI (1.32 [1.07-1.63]), tenofovir (TDF, 1.46 [1.11-1.93]) and (fos)amprenavir (APV, 1.47 [1.01-2.15]) was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine (0.51 [0.32-0.83]) and nevirapine (0.76 [0.58-0.98]) were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation. Conclusion: Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered amongst all individuals exposed for longer time-periods. The use of d-drugs should furthermore be avoided, where there are alternatives available and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis independent, TDF association calls for further investigations.
    No preview · Article · Jan 2016 · AIDS (London, England)
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    ABSTRACT: Background: Left cardiac chambers dilation, interstitial lung changes and pleural effusions are the characteristics of cardiogenic pulmonary oedema on computed tomography (CT) of the chest but mensuration of the left atrial size is not routinely performed. Cardiac chambers normal dimensions are known to be proportional to the patient's build and anthropomorphic data but adjustment of chambers dimensions to available elements seen on the axial CT images has never been evaluated before. Objectives: Our objective was to use data easily available on axial images to directly scale the left atrium. We chose to divide the left atrial diameter by the thoracic vertebral diameter, using the latter as a body-mass indicator. As a preliminary study, we aimed to evaluate the range of values of this left atrio-vertebral ratio (LAVR) by comparing patients suffering from cardiogenic pulmonary oedema with patients free of cardiac disease. We hypothesized that if the difference of values in these two populations of patients was significant enough, this ratio would be relevant and could be used as a quick criterion in different clinical situations. Method: Two radiologists reviewed CT scans of 32 of patients free of cardiac disease and 40 patients in acute cardiac failure. The maximum diameter of the left atrium at the level of the right inferior pulmonary vein was divided by the vertebral transverse diameter to generate a left atrio-vertebral ratio. Receiver operating characteristic curves identified the threshold associated with pulmonary oedema. Measurements and main results: The mean LAVR was 1.85±0.27 in asymptomatic patients and 2.48±0.35 in patients with pulmonary oedema. A LAVR of 2.1 yielded 85% sensitivity and 88% specificity for the diagnosis of cardiogenic pulmonary oedema. Conclusions: LAVR is a simple new measure directly scaling the left atrial diameter to the anthropomorphic characteristics of the patient. In our series, a ratio above 2.1 is strongly associated with cardiogenic pulmonary oedema indirectly suggesting left atrial dilation. The results were significantly different between the two populations of patients (no heart condition versus cardiogenic pulmonary oedema) suggesting a high potential for clinical application.
    No preview · Article · Nov 2015 · European journal of radiology
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    ABSTRACT: Background: As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. Methods: We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. Results: 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54-23.2)]. Conclusions: Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents".
    Preview · Article · Oct 2015 · PLoS ONE
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    ABSTRACT: The goal of this study was to evaluate, in the hands of an inexperienced surgeon, the cochleostomy location of an endaural approach (MINV) compared to the conventional posterior tympanotomy (MPT) approach. Since 2010, we use in the ENT department of Nice a new surgical endaural approach to perform cochlear implantation. In the hands of an inexperienced surgeon, the position of the cochleostomy has not yet been studied in detail for this technique. This is a prospective study of 24 human heads. Straight electrode arrays were implanted by an inexperienced surgeon: on one side using MPT and on the other side using MINV. The cochleostomies were all antero-inferior, but they were performed through an endaural approach with the MINV or a posterior tympanotomy approach with the MPT. The positioning of the cochleostomies into the scala tympani was evaluated by microdissection. Cochleostomies performed through the endaural approach were well placed into the scala tympani more frequently than those performed through the posterior tympanotomy approach (87.5 and 16.7 %, respectively, p ≤ 0.001). This study highlights the biggest challenge for an inexperienced surgeon to achieve a reliable cochleostomy through a posterior tympanotomy, which requires years of experience. In case of an uncomfortable view through a posterior tympanotomy, an inexperienced surgeon might be able to successfully perform a cochleostomy through an endaural (combined approach) or an extended round window approach in order to avoid opening the scala vestibuli.
    Preview · Article · Oct 2015 · Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde
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    ABSTRACT: With the aging of the population living with HIV, the absolute risk of cardiovascular disease (CVD) is increasing. There is a need to further facilitate the identification of persons at elevated risk in routine practice. Prospective information was collected on 32,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance of the D:A:D models were compared with a recent CVD prediction model from the Framingham study, which was assessed recalibrated to the D:A:D dataset. A total of 1010 CVD events occurred during 186,364.5 person-years. The full D:A:D CVD prediction model included age, gender, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, high-density lipoprotein, CD4 lymphocyte count, cumulative exposure to protease- and nucleoside reverse transcriptase-inhibitors, and current use of abacavir. A reduced model omitted antiretroviral therapies. The D:A:D models statistically significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p < 0.001). The D:A:D models also more accurately predicted five-year CVD-risk for key prognostic subgroups. An updated, easily recalibrated, global CVD-risk equation tailored to HIV-positive persons was developed using routinely collected CVD risk parameters and incorporating markers on immune function (CD4 lymphocyte count), and exposure to antiretroviral therapies. The estimated CVD risk can be used to quantify risk and to guide preventive care. © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    No preview · Article · Apr 2015
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    ABSTRACT: Regular surveys of pneumococcal nasopharyngeal carriage have been conducted among children attending daycare centers in Southeastern France from 1999 to 2012. We compared carriage rate, susceptibility patterns and serotype distribution in 2012, following implementation of the 13-valent pneumococcal conjugate vaccine, with findings from 5 previous surveys. Carriage rate was stable, antibiotic susceptibility improved and only serotype 19A persisted among vaccine-types.
    No preview · Article · Mar 2015 · The Pediatric Infectious Disease Journal
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    ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
    Full-text · Article · Mar 2015 · PLoS Medicine
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    ABSTRACT: La généralisation du recours à l’échographie en mode B pour surveiller des lésions testiculaires suspectes a favorisé l’émergence de nodules limites de nature controversée. L’élastographie en temps réel (ETR) pourrait améliorer la précision diagnostique. Nous en avons évalué sa faisabilité et sa valeur diagnostique en pratique clinique courante.
    No preview · Article · Dec 2014 · Progrès en Urologie

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  • No preview · Article · Jun 2014
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    ABSTRACT: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004--2010, and described subsequent mortality and predictors of these. Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression. Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004--2010 in this large observational cohort. The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.
    Full-text · Article · Oct 2013 · BMC Infectious Diseases
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    ABSTRACT: Background The differential diagnosis between infiltrative glioma (IG) and benign or curable glial lesions, such as gliosis, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, ganglioglioma, or demyelinating disease, may be challenging for the pathologist because specific markers are lacking. Recently, we described a strong EGFR immunolabelling pattern in cells with a high nuclear to cytoplasmic ratio that enables the discrimination of low-grade IG from gliosis. The aim of this study was to extend our observation to high-grade glioma to assess whether EGFR expression pattern is of value in the discrimination of all IG from noninfiltrative glial lesions (NIG), including gliosis, benign tumors, and demyelinating disease.Methods One hundred one IG and 58 NIG were compared for immunohistochemical expression of EGFR with use of an antibody that recognizes an epitope in the extracellular domain of both EGFRwt and EGFRvIII. Highly EGFR-positive cells with a high nuclear to cytoplasmic ratio were isolated and further characterized.ResultsCells with intense EGFR staining and a high nuclear to cytoplasmic ratio were significantly associated with the diagnosis of IG (P < .0001). The sensitivity and specificity of this staining pattern for the diagnosis of IG were 95% and 100%, respectively. EGFR expression was independent of IDH1 mutations and EGFR amplification. Finally, we showed that these particular cells displayed the phenotype and properties of glial progenitors and coexpressed CXCR4, a marker of invasiveness.Conclusions We demonstrate that cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific criteria for the diagnosis of IG, irrespective of grade, histological subtype, and progression pathway, and their identification represents a tool to discriminate IG from benign or curable glial lesions.
    Full-text · Article · Aug 2013 · Neuro-Oncology
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    ABSTRACT: Elastography is a novel imaging technology that shows promise in the identification of anatomic structures. The widespread use of ultrasound for screening testicular tumors in patients with cancer risk factors highlights unclassified testicular micronodules. We investigated the ability of elastography to accurately diagnose testicular nodules. Patients with clinical testicular nodules were assigned to undergo elastography in a prospective study. The imaging was carried out by a single radiologist using a static elastography unit with a 9-14MHz frequency linear transducer, to identify hardness score, loss of architecture of testicular parenchyma, and surrounding effect. When orchidectomy was required, the corresponding specimens were subjected to hematoxylin and eosin staining for histologic correlation. We imaged 34 testicular lesions: 26/34 (76%) malignant tumors and 8/34 (24%) non-tumor lesion including 4 hematomas, 3 orchitis and 1 ischemia. Se, Sp, PPV and NPV of hardness in elastography in differentiating between malignant and benign tissue was found to be 96.2%, 37.5%, 83%, and 75%, respectively. Further, for recognizing cancer, the loss of architecture of the testicular parenchyma detecting in elastography was 92.3%, 75%, 92.3%, and 75%, respectively, and the surrounding effect was 84.6%, 87.5%, 95.6% and 63.6%, respectively. Elastography may be a promising tool at diagnosing testicular tumor when the loss of architecture and the surrounding effect were present. Further studies are needed to evaluate whether the utility of elastography is worth pursuing to identify of unclassified testicular micronodules. 3. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Mar 2013 · European Urology Supplements
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    ABSTRACT: Background: To investigate the learning curve of "ro-botic surgery" versus "conventional laparoscopy" in two trials of the FLS program in a population of med-ical students with no experience in laparoscopy. Me-thods: A prospective trial. Students, all novices in training and surgical practice, were randomized into 2 groups: the "traditional laparoscopy" group and the "robotic assistance" group. Students were evalu-ated during two tests from the FLS: peg transfer and intracorporeal knot tying. Results: The median lapa-roscopic knot completion time was significantly lower in the "robotic surgery" group (p = 0.038). Conclu-sions: Robotic assistance training in neophytes is ef-fective in improving the completion time of laparo-scopic knots.
    Full-text · Article · Jan 2013 · Open Journal of Obstetrics and Gynecology
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    ABSTRACT: Background. Liver diseases are leading causes of death in HIV-positive persons since the widespread use of combination antiretroviral treatment (ART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus co-infections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality.Methods. All patients of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study without HCV or HBV co-infection were prospectively followed from date of entry until death, or last follow-up. In patients with liver-related death, clinical charts were reviewed using a structured questionnaire.Results. We followed 22,910 participants without hepatitis virus co-infection for 114,478 person-years. There were 12 liver-related deaths (incidence, 0.10/1000 person-years); 7 because of severe alcohol use and 5 due to established ART-related toxicity. The rate of ART-related deaths in treatment-experienced persons was 0.04 (95% CI 0.01, 0.10) per 1000 person-years.Conclusions. We found a low incidence of liver-related deaths in HIV-infected persons without HCV or HBV co-infection. Liver-related mortality because of ART-related toxicity was rare.
    Full-text · Article · Jan 2013

  • No preview · Article · Nov 2012 · Progrès en Urologie
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    ABSTRACT: Background: Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)-positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality. Methods: All patients in the Data Collection on Adverse Events of Anti-HIV Drugs study without HCV or HBV coinfection were prospectively followed from date of entry until death or last follow-up. In patients with liver-related death, clinical charts were reviewed using a structured questionnaire. Results: We followed 22 910 participants without hepatitis virus coinfection for 114 478 person-years. There were 12 liver-related deaths (incidence, 0.10/1000 person-years); 7 due to severe alcohol use and 5 due to established ART-related toxicity. The rate of ART-related deaths in treatment-experienced persons was 0.04/1000 person-years (95% confidence interval, .01, .10). Conclusions: We found a low incidence of liver-related deaths in HIV-infected persons without HCV or HBV coinfection. Liver-related mortality because of ART-related toxicity was rare.
    Preview · Article · Oct 2012 · Clinical Infectious Diseases
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    ABSTRACT: INTRODUCTION: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. METHODS: All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. RESULTS: Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of <200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m(2). CONCLUSIONS: The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham.
    Full-text · Article · Oct 2012 · Journal of the International AIDS Society
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    ABSTRACT: Concerns have arisen about possible effects of protease inhibitors (PIs) on cardiac conductivity. We found no significant association between current or recent PI exposure and sudden death or nonhemorrhagic stroke (adjusted rate ratio, 1.22; 95% confidence interval, .95–1.57), whereas cumulative exposure to PIs was associated with an increased risk (adjusted rate ratio, 1.06 per year of exposure; 95% confidence interval, 1.01–1.11).
    Full-text · Article · Feb 2012 · The Journal of Infectious Diseases
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    ABSTRACT: Since many years, caesarean section rate has increased in France. The purpose of the study was to compare the different French obstetrical attitudes after a prior caesarean section. This retrospective study was performed between March 2008 and February 2010. We collected the answers of a majority of maternity centres contacted with an anonymous questionnaire sent by postal, electronic, fax mails. Of the 194 maternity centres which have responded, there were 37 university hospitals and 312 obstetricians: 75.6% of them worked in public sector and 19.2% in private one. The use of a protocol is registered for 29.6% of questioned obstetricians (only 14% in private sector, P=0.002). Pelvimetry is consistently proposed by 44.4% of them. A trial of labour in case of breech presentation is proposed by 20% of questioned obstetricians, with twin pregnancies by 23.7%, with two prior low-transverse caesarean delivery by 12%, most in university hospitals, level III, with more than 1500 births per year. Induction of labour is allowed by 73.9% of questioned obstetricians, by ocytocics as a majority. Induction by Prostine(®) is underwent by 14.5% of them (24.6% in academic centres, P=0.01), by Propess(®) by 19.2% of them (30% in university hospitals, P=0.008). These findings showed that the management of delivery after caesarean section is associated with statistically significant differences in France. These informations are relevant for counselling French obstetrical practices.
    No preview · Article · Nov 2011 · Journal de Gynécologie Obstétrique et Biologie de la Reproduction

Publication Stats

2k Citations
310.52 Total Impact Points

Institutions

  • 2008-2015
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Inselspital, Universitätsspital Bern
      Berna, Bern, Switzerland
  • 2012
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 2010
    • University of Zurich
      • Internal Medicine Unit
      Zürich, Zurich, Switzerland