Pascal Staccini

Preventive Cancer Stem Cell‐Based Vaccination Reduces Liver Metastasis Development in a Rat Colon Carcinoma Syngeneic Model

Cancer stem cells (CSCs) represent a minor population of self‐renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC‐based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC‐enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase‐1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDHhigh cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27‐kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb‐vaccinated groups, 50% of the CSC‐based vaccinated animals became resistant to tumor development. In addition, CSC‐based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC‐based vaccination to prevent liver metastasis development. Our data demonstrate that a CSC‐based vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model. STEM CELLS2013;31:423–432

hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization

MSH5 is a MutS-homologous protein required for meiotic DNA recombination. In addition, recent studies suggest that the human MSH5 protein (hMSH5) participates to mitotic recombination and to the cellular response to DNA damage and thus raise the possibility that a tight control of hMSH5 function(s) may be important for genomic stability. With the aim to characterize mechanisms potentially involved in the regulation of hMSH5 activity, we investigated its intracellular trafficking properties. We demonstrate that hMSH5 possesses a CRM1-dependent nuclear export signal (NES) and a nuclear localization signal that participates to its nuclear targeting. Localization analysis of various mutated forms of hMSH5 by confocal microscopy indicates that hMSH5 shuttles between the nucleus and the cytoplasm. We also provide evidence suggesting that hMSH5 stability depends on its subcellular compartmentalization, hMSH5 being much less stable in the nucleus than in the cytoplasm. Together, these data suggest that hMSH5 activity may be regulated by nucleocytoplasmic shuttling and nuclear proteasomal degradation, both of these mechanisms contributing to the control of nuclear hMSH5 content. Moreover, data herein also support that in tissues where both hMSH5 and hMSH4 proteins are expressed, hMSH5 might be retained in the nucleus through masking of its NES by binding of hMSH4.

ARIANE: integration of information databases within a hospital intranet

Large information systems handle massive volume of data stored in heterogeneous sources. Each server has its own model of representation of concepts with regard to its aims. One of the main problems end-users encounter when accessing different servers is to match their own viewpoint on biomedical concepts with the various representations that are made in the databases servers. The aim of the project ARIANE is to provide end-users with easy-to-use and natural means to access and query heterogeneous information databases. The objectives of this research work consist in building a conceptual interface by means of the Internet technology inside an enterprise Intranet and to propose a method to realize it. This method is based on the knowledge sources provided by the Unified Medical Language System (UMLS) project of the US National Library of Medicine. Experiments concern queries to three different information servers: PubMed, a Medline server of the NLM; Thériaque, a French database on drugs implemented in the Hospital Intranet; and a Web site dedicated to Internet resources in gastroenterology and nutrition, located at the Faculty of Medicine of Nice (France). Accessing to each of these servers is different according to the kind of information delivered and according to the technology used to query it. Dealing with health care professional workstation, the authors introduced in the ARIANE project quality criteria in order to attempt a homogeneous and efficient way to build a query system able to be integrated in existing information systems and to integrate existing and new information sources.

Mortality and morbidity of urban road traffic crashes in Africa: capture-recapture estimates in Bamako, Mali, 2012

Background Low- and middle-income countries are currently facing the massive public health challenge of road traffic injuries. The lack of effective surveillance systems hinders proper assessment of epidemiologic status and intervention priorities. The objective of our study was to estimate the mortality and morbidity attributable to road crashes in Bamako, Mali using the capture-recapture method. Methods During the 1 January, 2012–31 April, 2012 period, we collected data on road traffic crashes from the road accident registers of the police forces of Bamako, Mali on the one hand, and from a register kept by health facilities in the same area. An automatic, then manual matching procedure was performed to find pairs of records related to the same crash victims. The number of victims and the number of fatalities were estimated by the capture-recapture method using the Chapman estimator. Results The health facility and the police registries included 3587 and 1432 records, respectively. The matching procedure identified 603 common records, 31 of which were fatalities. The annual incidence estimate for road victims was 1038 in 100 000 and the annual incidence estimate for road fatalities was 12 in 100 000. Victims from both sources were more likely to be male, in the 15–34 age group, and almost half of all injured road users and two in three fatalities were using motorized two-wheelers. One victim out of five was a pedestrian. Conclusion Our estimates are in line with available literature data from low-income countries. While more cases were reported by health facilities than by police forces, we believe that an effective surveillance system should not be based solely on medical reports as much would be missing as regards the crash circumstances and characteristics.

Evaluation of Professional Practices in Transfusion Medicine: Design and Implementation of a Web-Based and Tutored ePortfolio

In order to manage a nationwide assessment program for certifying professional competence in blood transfusion throughout France, the National Institute of Blood Transfusion and the University of Nice-Sophia Antipolis developed a Web-based and tutored portfolio. The structure of this e-portfolio is based on a matrix of actions defined according to standards of practice. For each action, elements of proof are uploaded by the physician and peer reviewed by an expert before being validated. The electronic portfolio stores all the history of the actions done by users. This tracking feature generates alerts emailed to users according to a list of monitored events. After one year of design and development, the application is used in routine. Based on open-source components, we forecast integration with the CME system in blood transfusion handled by INTS.

Impact on medical practice of accessing pharmaceutical records

INTRODUCTION The pharmaceutical record system (PRS) is a French nationwide centralized electronic database shared among all community pharmacists listing all drugs dispensed by community pharmacists in the last four months. The objective of this study, the Medication Assessment Through Real time Information eXchange - Distributed Pharmaceutical Record System (MATRIX - DPRS) study, was to assess the clinical impact of the PRS upon granting access to physicians in three hospital specialties: anesthesiology, emergency medicine and geriatrics. MATERIAL AND METHODS A multicenter prospective study was conducted in six hospital departments, two per specialty. Participating physicians noted medication information found exclusively in the pharmaceutical record (PR) of each patient unavailable elsewhere and any diagnostic or therapeutic management changes resulting from the PR information. The primary objective was to assess the proportion of diagnostic or therapeutic management changes attributable to the PR among patients who had an accessible PR. RESULTS The inclusion level ranged from 1.1 to 30% in the six departments. The rate of diagnostic or therapeutic management changes was highest in geriatrics (n = 31/67; 46.3% 95% Confidence IntervaI (CI): 34.0-58.9%) and lowest in anesthesiology (n = 36/227; 15.9% 95% CI: 11.4-21.3%). Emergency medicine was intermediate (n = 5/22; 22.7% 95% CI: 7.8-45.4%). CONCLUSION Although the inclusion rate and statistical precision were low, these findings suggest that the information contained in the PRS is useful and may result in modifying patient management in a sizeable proportion of patients. This opens the prospect of evaluating other hospital specialties, as well as primary and secondary care settings.

InterSTIS: Interopérabilité sémantique de terminologies de santé francophones

Background: the proliferation of health-related documents raises issues of indexing and search in large databases. Various terminologies are then used to index documents of all types: SNOMED Int. for clinical information coding, ICD-10 and the French CCAM for medico-economic coding, ICPC used by general practitioners, the MeSH for scientific literature, etc. Objective: the goal of the project InterSTIS was to unify these terminologies and to make them interoperable within a “multisource terminology server”. Material and method: the design and developments are based on standards and norms recognized for modeling and implementation. Results: results are a meta-model for healthcare terminologies, the integration of some of them in a unique system, the mapping of terminologies by means of the UMLS Metathesaurus, and the demonstration made by the integration of a new terminology dedicated to drugs documentation, and services applied to indexing and retrieving information. Discussion: further developments may involve both the National Cancer Institute Metathesaurus and the Semantic Network of the UMLS which complete the UMLS Metathesaurus by means of explicit semantic relationships.

Évaluation du portfolio électronique et de son système d’accompagnement dédié à l’évaluation des pratiques professionnelles en technique et médecin e transfusionnelles

In order 10 help physicians to meet the compulsory evaluation of professional practices as regards blood transfusion, the French National Blood Transfusion Institute and the University of Nice imagined a structured and accompanied eportfolio available on the Internet, This innovative system, faced up problem of the approval of an implement of new technology intended for a specific professional environment. This article offers to analyze conditions of approval of system and actions to implement so as to increase its performance and to optimize its use. The chosen methodology is that of questionary of contentment based on the evaluation of the performance of an information system offered by DeLone and McLean. The main results show that the eportfolio and its organizational system meet the physician’s expectations. Indeed, the technological device and the provided information make the implementation of their EPP easier. Besides the notion of accompaniment by tutor has been shown as indispensable to the appropriation of this step.

Proposition de modélisation de la performance par le biais du management des risques : application au circuit du médicament

Sous les diverses contraintes actuelles, l’organisation des établissements de santé connaît une évolution irréversible. Elle s’inspire pour cela et cherche effectivement à se rapprocher de l’approche industrielle maintenant maîtrisée et reconnue, recentrée autour du client, de la notion de processus organisationnel et d’une cartographie des compétences. Si cela est possible, il faut cependant repenser cette approche pour tenir compte des contraintes propres des systèmes de santé et d’un certain nombre de risques propres auxmétiers mis en jeu. Enfin, le pilotage de cette organisation émergente doit lui aussi s’adapter. Il nécessite plus que jamais des indicateurs adaptés, fiables et pertinents vis-à-vis de l’autorité de tutelle. Cet article décrit et formalise un modèle de pilotage de la performance d’un système de santé crucial, le circuit du médicament hospitalier au travers du management des risques iatrogènes. Ce circuit, processus de soins transversal par excellence, mal maîtrisé aujourd’hui, sera décrit à travers une cartographie dynamique des processus selon une approche d’ingénierie des systèmes aboutissant à une cartographie des risques a priori.