Journées conchylicoles 1999 Ifremer Nantes les 24 et 25 mars

Ce rapport synthétise les communications présentées lors des "journées conchylicoles" sur les travaux scientifiques de l'Ifremer en soutien aux activités conchylicoles

Metal implant allergy: a diagnostic challenge illustrating the limits of the nickel spot test

International audienc

The Sodium Pump alpha1 Subunit: a Disease Progression-Related Target for Metastatic Melanoma Treatment.

Abstract Background: Melanomas remain associated with dismal prognosis because they are naturally resistant to apoptosis and they markedly metastasize. Up-regulated expression of sodium pump alpha subunits has previously been demonstrated when comparing metastatic to non-metastatic melanomas. Our previous data revealed that impairing sodium pump alpha1 activity by means of selective ligands i.e. cardenolides, markedly impairs cell migration and kills apoptosis-resistant cancer cells. Objectives: To determine the expression levels of sodium pump alpha subunits in melanoma clinical samples and cell lines, and to characterize the role of alpha1 subunits in melanoma cell biology. Methods: Quantitative RT-PCR, western blotting and immunohistochemistry were used to determine the expression levels of sodium pump alpha subunits. In vitro cytotoxicity of various cardenolides and of an anti-alpha1 siRNA were evaluated by means of MTT assay, quantitative videomicroscopy and through apoptosis assays. The in vivo activity of a novel cardenolide UNBS1450 was evaluated in a melanoma brain metastasis model. Results: Our data show that all investigated human melanoma cell lines expressed high levels of the alpha1 subunit and 33% of human melanomas displayed significant alpha1 subunit expression in correlation with the Breslow index. Furthermore, cardenolides (notably UNBS1450; currently in Phase I clinical trials) displayed marked anti-tumor effects against melanomas in vitro. This activity was closely paralleled by decreases in cMyc expression and by increases in apoptotic features. UNBS1450 also displayed marked anti-tumor activity in the aggressive human metastatic brain melanoma model in vivo. Conclusion: The alpha1 sodium pump subunit could represent a potential novel target for combating melanoma.JOURNAL ARTICLEinfo:eu-repo/semantics/publishe

The sodium pump alpha1 subunit is implicated in melanoma aggressiveness and represents a novel target to combat melanoma brain metastases.

Conférence orale (abstract 1988)info:eu-repo/semantics/publishe

Comparative effectiveness of dimethyl fumarate in multiple sclerosis

International audienceAims : To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting.Methods : A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1–3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively.Results : Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61–0.86]) and TERI (0.81 [0.68–0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts.Conclusion : DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM)

Ten-Year Trend of Opioid and Non-Opioid Analgesic Use in the French Adult Population

International audienceAim Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the Addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence. Methods A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and socio-demographic characteristics of patients treated were analyzed. Results The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253,976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those over 84 years old. Peripheral analgesics were the most used (55.3%, 234,739 users). The prevalence of weak analgesic use decreased (21.3%, 90,257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5,129 users), morphine was the most widely used with a dramatic increase in oxycodone use, especially in the elderly. Discussion The prevalence of analgesic use is high: approximately 31 million adults had at least one analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics

Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations

Intra-database validation of case-identifying algorithms using reconstituted electronic health records from healthcare claims data

BACKGROUND: Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. OBJECTIVES: To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). METHODS: Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. RESULTS: Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. CONCLUSION: The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative

Genomic epidemiology reveals multidrug resistant plasmid spread between Vibrio cholerae lineages in Yemen.

Acknowledgements: This research was funded in whole, or in part, by the Wellcome Trust (grant nos 206194 and 108413/A/15/D). This work was supported by Institut Pasteur, Santé publique France, and by the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID). F.L., M.J.D., G.A.B., A.T.-B., M.A.B., A.C. and N.R.T. were supported by Wellcome funding to the Sanger Institute (grant nos 206194 and 108413/A/15/D). E.N., J.R., M.-L.Q. and F.-X.W. were supported by French Government funding to Institute Pasteur (grant no. ANR-10-LABX-62-IBEID). We thank J. Woolfolk, S. Clare and C. Tolley for their support in sample management at Wellcome Sanger Institute, as well as the Sanger Pipelines team for support. M.J.D. is an Official Fellow of Churchill College, Cambridge, and was previously supported by a Junior Research Fellowship at the College. For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission.Funder: LABoratoire d’EXcellence IBEID (Labex IBEID); ANR-10-LABX-62-IBEIDSince 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera patients in 2018. Here, to characterize circulating genotypes, we analysed 260 isolates sampled in Yemen between 2018 and 2019. Eighty-four percent of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sub-lineage T13, whereas 16% were non-toxigenic, from divergent non-7PET lineages. Treatment of severe cholera with macrolides between 2016 and 2019 coincided with the emergence and dominance of T13 subclones carrying an incompatibility type C (IncC) plasmid harbouring an MDR pseudo-compound transposon. MDR plasmid detection also in endemic non-7PET V. cholerae lineages suggested genetic exchange with 7PET epidemic strains. Stable co-occurrence of the IncC plasmid with the SXT family of integrative and conjugative element in the 7PET background has major implications for cholera control, highlighting the importance of genomic epidemiological surveillance to limit MDR spread