title: Modeling Clinical Failure in Prostate Cancer Patients Based on a Two-stage Statistical Model

acronym: PREDYC

summary:
Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure.

The two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework is particularly flexible to account for such data. Prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy can be monitored. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. The prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure based on a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. the aim of this research is to model prostate specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability can be expressed as a function of prostate-specific antigens concentration. Covariates in the survival model can include : hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process.

study_start_date_type: Actual

status: Completed

study_completion_date_type: Actual

study_type: Observational

time_perspective: Retrospective

enrollment_type: Actual

ReferenceType: result

ReferenceCitation: Bellera C, Proust-Lima C, Joseph L, Richaud P, Taylor J, Sandler H, Hanley J, Mathoulin-Pelissier S. A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication. Stat Methods Med Res. 2018 Apr;27(4):1271-1281. doi: 10.1177/0962280216660127. Epub 2016 Sep 1.

oa_host_type: closed

repositories_concat: closed

publisher_dissemination: SAGE Publications

ipd_sharing: Undecided

lead_sponsor: Institut Bergonié

collaborators: Institut National de la Santé Et de la Recherche Médicale, France

intervention_type: Radiation

lead_sponsor_type: industriel

status_simplified: Completed


title: Sample Size Determination in Heterogeneous Populations for Multivariate Time-to-event Data

summary: Most of randomized clinical trials (RCT) using time-to-event criteria as the primary endpoint are designed, powered and analyzed based on an hypothetical hazard ratio (HR) corresponding to the targeted effect size between experimental and control arms. Usually, one assumes that populations are homogeneous within each treatment arm, that is, within each arm, (i) the baseline risk is identical for all patients, and (ii) the treatment effect is identical for all patients. This assumption however may not hold in all circumstances. This project aims at providing a statistical method for the estimation of sample size in RCT, in the presence of heterogenous populations, such as assuming populations with distinct underlying baseline risks or assuming different treatment effects.

status: Active, not recruiting

study_completion_date_type: Anticipated

time_perspective: Prospective

enrollment_type: Anticipated

sponsor_collaborators: Institut National de la Santé Et de la Recherche Médicale, France

location_facility: Institut Bergonié, Comprehensive Cancer Center

intervention_type: Drug

status_simplified: Ongoing


title: Immune-checkpoint Inhibitors and Surrogate Endpoints in Cancer Trials

acronym: SURROGATE-ICI

summary: The objective of this research work is two-fold: (i) to conduct a systematic literature review to identify surrogate endpoints in this specific drug class (review registered in the PROSPERO database) and (ii) to assess the surrogate properties of candidate surrogate endpoints in the specific context of melanoma cancer.

ReferenceType: background

ReferenceCitation: Branchoux S, Bellera C, Italiano A, Rustand D, Gaudin AF, Rondeau V. Immune-checkpoint inhibitors and candidate surrogate endpoints for overall survival across tumour types: A systematic literature review. Crit Rev Oncol Hematol. 2019 May;137:35-42. doi: 10.1016/j.critrevonc.2019.02.013. Epub 2019 Mar 1.


title: Takayasu Arteritis Activity Evaluation by Ultrafast Ultrasound Imaging

acronym: TAK-UF

summary:
The general activity of Takayasu vasculitis is correlated with the perfusion rate of the carotid arterial wall. This can be quantified with ultrafast ultrasound imaging in sensitive Doppler sequence associated with the concomitant injection of microbubbles (SonoVue®).

The hypothesis is that the carotid artery wall flow parameters obtained with ultrafast ultrasound imaging make possible to discriminate an active disease from an inactive disease because of the fibrous sequential arterial thickening. Thus, to improve the evaluation of Takayasu vasculitis activity and to refine the criteria for response to the various immunomodulatory treatments used.

study_type: Interventional

design_allocation: Non-Randomized

primary_purpose: Diagnostic

lead_sponsor: French Cardiology Society

intervention_type: Diagnostic Test


type: Registry Identifier

title: Phenotypic Characterization Tumor-infiltrating Lymphocytes at Diagnosis and After Chemotherapy in Advanced High-grade Serous Ovarian Cancer in Blood, Ascites, Peritoneal Biopsy

summary: This is a monocenter, interventional, non-randomized study among women patients with an ovarian or tubal cancer who will receive a surgery or adjuvant chemotherapy treatment, or a neo-adjuvant chemotherapy then surgery +/- adjuvant chemotherapy. The planned interventions are collection of biological samples at different times. The study will aim to describe the immunological profile at diagnosis in terms of phenotypic : PBMCs (peripheral blood, mononuclear cells) in peripheral blood, TILs (tumor-infiltrating lymphocytes) in ascites and in carcinomatosis.

status: Recruiting

primary_purpose: Other

ReferenceCitation: Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, Iseli C, Michel A, Le Bitoux MA, Guillaume P, Schmidt J, Bianchi V, Dangaj D, Fenwick C, Derre L, Xenarios I, Michielin O, Romero P, Monos DS, Zoete V, Gfeller D, Kandalaft LE, Coukos G, Harari A. Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer. Nat Commun. 2018 Mar 15;9(1):1092. doi: 10.1038/s41467-018-03301-0.

ReferenceCitation: Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, LeDoux S, Cochrane DR, Lim JLP, Yang W, Roth A, Smith MA, Ho J, Tse K, Zeng T, Shlafman I, Mayo MR, Moore R, Failmezger H, Heindl A, Wang YK, Bashashati A, Grewal DS, Brown SD, Lai D, Wan ANC, Nielsen CB, Huebner C, Tessier-Cloutier B, Anglesio MS, Bouchard-Cote A, Yuan Y, Wasserman WW, Gilks CB, Karnezis AN, Aparicio S, McAlpine JN, Huntsman DG, Holt RA, Nelson BH, Shah SP. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell. 2018 Jun 14;173(7):1755-1769.e22. doi: 10.1016/j.cell.2018.03.073. Epub 2018 May 10.

ReferenceCitation: Mayor P, Starbuck K, Zsiros E. Adoptive cell transfer using autologous tumor infiltrating lymphocytes in gynecologic malignancies. Gynecol Oncol. 2018 Aug;150(2):361-369. doi: 10.1016/j.ygyno.2018.05.024. Epub 2018 May 24.

ReferenceCitation: van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, de Hingh IHJT, van der Velden J, Arts HJ, Massuger LFAG, Aalbers AGJ, Verwaal VJ, Kieffer JM, Van de Vijver KK, van Tinteren H, Aaronson NK, Sonke GS. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan 18;378(3):230-240. doi: 10.1056/NEJMoa1708618.

ReferenceCitation: Odunsi K. Immunotherapy in ovarian cancer. Ann Oncol. 2017 Nov 1;28(suppl_8):viii1-viii7. doi: 10.1093/annonc/mdx444.

ReferenceCitation: Tran E, Robbins PF, Rosenberg SA. 'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations. Nat Immunol. 2017 Feb 15;18(3):255-262. doi: 10.1038/ni.3682.

ReferenceCitation: Ovarian Tumor Tissue Analysis (OTTA) Consortium; Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, Gentry-Maharaj A, Toloczko A, Hein A, Bouligny AL, Jensen A, Osorio A, Hartkopf A, Ryan A, Chudecka-Glaz A, Magliocco AM, Hartmann A, Jung AY, Gao B, Hernandez BY, Fridley BL, McCauley BM, Kennedy CJ, Wang C, Karpinskyj C, de Sousa CB, Tiezzi DG, Wachter DL, Herpel E, Taran FA, Modugno F, Nelson G, Lubinski J, Menkiszak J, Alsop J, Lester J, Garcia-Donas J, Nation J, Hung J, Palacios J, Rothstein JH, Kelley JL, de Andrade JM, Robles-Diaz L, Intermaggio MP, Widschwendter M, Beckmann MW, Ruebner M, Jimenez-Linan M, Singh N, Oszurek O, Harnett PR, Rambau PF, Sinn P, Wagner P, Ghatage P, Sharma R, Edwards RP, Ness RB, Orsulic S, Brucker SY, Johnatty SE, Longacre TA, Ursula E, McGuire V, Sieh W, Natanzon Y, Li Z, Whittemore AS, Anna A, Staebler A, Karlan BY, Gilks B, Bowtell DD, Hogdall E, Candido dos Reis FJ, Steed H, Campbell IG, Gronwald J, Benitez J, Koziak JM, Chang-Claude J, Moysich KB, Kelemen LE, Cook LS, Goodman MT, Garcia MJ, Fasching PA, Kommoss S, Deen S, Kjaer SK, Menon U, Brenton JD, Pharoah PDP, Chenevix-Trench G, Huntsman DG, Winham SJ, Kobel M, Ramus SJ. Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol. 2017 Dec 1;3(12):e173290. doi: 10.1001/jamaoncol.2017.3290.

ReferenceCitation: Delcourt V, Franck J, Leblanc E, Narducci F, Robin YM, Gimeno JP, Quanico J, Wisztorski M, Kobeissy F, Jacques JF, Roucou X, Salzet M, Fournier I. Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer. EBioMedicine. 2017 Jul;21:55-64. doi: 10.1016/j.ebiom.2017.06.001. Epub 2017 Jun 3.

ReferenceCitation: Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I. Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. Am J Pathol. 2016 May;186(5):1103-13. doi: 10.1016/j.ajpath.2015.12.029. Epub 2016 Mar 15.

ReferenceCitation: Blank CU, Haanen JB, Ribas A, Schumacher TN. CANCER IMMUNOLOGY. The "cancer immunogram". Science. 2016 May 6;352(6286):658-60. doi: 10.1126/science.aaf2834. No abstract available.

ReferenceCitation: Santoiemma PP, Powell DJ Jr. Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol Ther. 2015;16(6):807-20. doi: 10.1080/15384047.2015.1040960. Epub 2015 Apr 20.

ReferenceCitation: Hiraoka N, Ino Y, Yamazaki-Itoh R, Kanai Y, Kosuge T, Shimada K. Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer. Br J Cancer. 2015 May 26;112(11):1782-90. doi: 10.1038/bjc.2015.145. Epub 2015 May 5.

ReferenceCitation: Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S; International TILs Working Group 2014. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015 Feb;26(2):259-71. doi: 10.1093/annonc/mdu450. Epub 2014 Sep 11.

oa_host_type: repository

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

license_normalized: no license

repository_institution: PubMed Central - Europe PMC

repository_normalized: PubMed Central

version: publishedVersion

evidence: oa repository (via pmcid lookup)

repositories_concat: PubMed Central

unpaywall_oa_status: green

publisher_dissemination: Elsevier

ReferenceCitation: Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buque A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, Apte RN, Aranda F, Ayyoub M, Beckhove P, Blay JY, Bracci L, Caignard A, Castelli C, Cavallo F, Celis E, Cerundolo V, Clayton A, Colombo MP, Coussens L, Dhodapkar MV, Eggermont AM, Fearon DT, Fridman WH, Fucikova J, Gabrilovich DI, Galon J, Garg A, Ghiringhelli F, Giaccone G, Gilboa E, Gnjatic S, Hoos A, Hosmalin A, Jager D, Kalinski P, Karre K, Kepp O, Kiessling R, Kirkwood JM, Klein E, Knuth A, Lewis CE, Liblau R, Lotze MT, Lugli E, Mach JP, Mattei F, Mavilio D, Melero I, Melief CJ, Mittendorf EA, Moretta L, Odunsi A, Okada H, Palucka AK, Peter ME, Pienta KJ, Porgador A, Prendergast GC, Rabinovich GA, Restifo NP, Rizvi N, Sautes-Fridman C, Schreiber H, Seliger B, Shiku H, Silva-Santos B, Smyth MJ, Speiser DE, Spisek R, Srivastava PK, Talmadge JE, Tartour E, Van Der Burg SH, Van Den Eynde BJ, Vile R, Wagner H, Weber JS, Whiteside TL, Wolchok JD, Zitvogel L, Zou W, Kroemer G. Classification of current anticancer immunotherapies. Oncotarget. 2014 Dec 30;5(24):12472-508. doi: 10.18632/oncotarget.2998.

ReferenceCitation: Tangye SG, Ma CS, Brink R, Deenick EK. The good, the bad and the ugly - TFH cells in human health and disease. Nat Rev Immunol. 2013 Jun;13(6):412-26. doi: 10.1038/nri3447. Epub 2013 May 17.

ReferenceCitation: Bachmayr-Heyda A, Aust S, Heinze G, Polterauer S, Grimm C, Braicu EI, Sehouli J, Lambrechts S, Vergote I, Mahner S, Pils D, Schuster E, Thalhammer T, Horvat R, Denkert C, Zeillinger R, Castillo-Tong DC. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients--a study of the OVCAD consortium. BMC Cancer. 2013 Sep 17;13:422. doi: 10.1186/1471-2407-13-422.

ReferenceCitation: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23.

ReferenceCitation: Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012 Feb;124(2):192-8. doi: 10.1016/j.ygyno.2011.09.039. Epub 2011 Oct 29.

ReferenceCitation: Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. doi: 10.1056/NEJMoa1104390.

ReferenceCitation: Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 29;474(7353):609-15. doi: 10.1038/nature10166. Erratum In: Nature. 2012 Oct 11;490(7419):298.

ReferenceCitation: Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43. doi: 10.1073/pnas.0509182102. Epub 2005 Dec 12.

ReferenceCitation: Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004 Sep;10(9):942-9. doi: 10.1038/nm1093. Epub 2004 Aug 22.

ReferenceCitation: Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003 Jan 16;348(3):203-13. doi: 10.1056/NEJMoa020177.

ReferenceCitation: Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002 Nov;3(11):991-8. doi: 10.1038/ni1102-991.

ipd_sharing: No

lead_sponsor: Centre Oscar Lambret

intervention_type: Procedure


title: Identifying New Therapeutic Targets for Lupus Treatment

acronym: ELUDIAL

summary: Lupus is an autoimmune disease affecting mainly young women (9/1). Lupus nephritis (LN) occurs in 30% of the cases of lupus and is associated with end stage renal disease (ESRD) in 17 to 25% of cases after 10 years. Overall, nearly 7% of lupus patients will develop ESRD due to LN. Historically, 5-year survival after LN was lower than 20%. Nowadays, 45% of patients suffer from multiple relapses that are associated with an intermediate risk of ESRD. When ESRD occurs, lupus activity decreases progressively to reach a stable extinct state. At this stage it is possible to stop all medications to control lupus, without any flare of lupus activity. Lupus extinction following ESRD corresponds to a state of complete remission. Obtaining such a result before ESRD would avoid damages to several organs and side effects of immunosuppressive therapy. Understanding the mechanisms responsible for lupus extinction following ESRD is an innovative approach to decipher lupus pathophysiology. The objective of the study is to identify the mechanisms responsible for lupus extinction and to propose new therapeutic options based on these new mechanisms. Mechanisms responsible for lupus extinction are unknown. Lupus extinction depends on the duration of ESRD. Accumulation of several toxins that kidneys would normally eliminate in the urine is a hallmark of ESRD. Such toxins are called "uremic toxins" since they accumulate during "uremia" (ESRD). They affect biological systems such as fertility and immunity that are both closely related to lupus pathophysiology. The investigators hypothesize that studying LN extinction after ESRD will provide novel therapeutic targets to extinct lupus before ESRD. To this end, they will investigate several non-exclusive hypotheses based on previous findings of our consortium, or issued from clinical observations: the sexual dysfunction hypothesis and the ESRD-associated immune cells dysfunction hypothesis. In parallel, they will conduct an open screening of new mechanisms underlying the lupus extinction through the characterization of the differential gene expression profile associated with lupus extinction in patients undergoing dialysis.

time_perspective: Cross-Sectional

lead_sponsor: Assistance Publique - Hôpitaux de Paris

lead_sponsor_type: academique

appel_a_projets: PRTS

region: Île-de-France

nom_etablissement: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS

type_etablissement: CHUR

acronyme: ELuDial

titre: Nouveaux traitement issus de l'extinction du lupus en dialyse

discipline_principale: autre

nom_porteur: DAUGAS

prenom_porteur: Eric


title: Biological Collection for Studying Vaccine-induced Immune Responses

acronym: BioCol-VIR

summary:
Introduction: Vaccination is a powerful weapon in the fight against infectious diseases, which has led to dramatic reduction in mortality and complications from some diseases. In this respect, vaccination is a real worldwide public health challenge (WHO). Thus, vaccine research benefits from an exponential development of knowledge in immunology and biotechnology. In particular, the advent of recent tools ("omics", new cytometric assays) and the description of new categories of immune cells (Tfh, BReg...) have revolutionized the characterization of immune responses, particularly post-vaccination. To study of the immune response following vaccination remains essential in order to define the immunological correlates to vaccine protection. This response also varies according to parameters related to the vaccine (type, adjuvant, dose, regimen…) and to the vaccinated host (genetics, age, morbidity, treatment …). Analyzing with new generation immune assays, new data on immunological responses post-vaccination from a clinical cohort is therefore essential to better define these correlates.

Objective: To develop new vaccines (HIV, emerging infectious diseases) the investigators use a "System vaccinology" method to decipher the mechanisms of immune responses set up against vaccines currently being developed or marketed, specifically in specific populations (patients with primary immune deficiency, sickle cell patients, solid organ transplanted patients, COPD).

Method: Description of the genetic, molecular and cellular mechanisms of the immune response to vaccines recommended for adults, in particular influenza and pneumococcal vaccines, but also other mandatory vaccines (MMR,...) or vaccine for travelers (yellow fever, ...) as part of routine care in different population categories (healthy subjects, HIV+ subjects, COPD patients, …), using qualitative and quantitative immunological assays: transcriptional analysis of the dynamic innate immune response, analysis of the lymphocytes B & T responses (phenotype, repertoire analysis, functional analysis including T reg and TFH populations, antibody response), genetic analysis in the context of primary immune deficiencies) Conclusion: The data generated will allow the best possible analysis of vaccine responses according to vaccines and vaccinated populations, providing important information for the research developed within the department.


type: Other Identifier

title: Involvement of the Mediodorsal Nucleus of the Thalamus in Higher Order Cognitive Processes : a Study in Patients With a Thalamic Infarct

summary: The aim is to expand evidence about the importance of the mediodorsal nucleus of the thalamus as a key node in human higher-order cognitive functions such as learning, decision-making, and adaptive behavior. Thus, the project proposes to assess global cognition along with higher-order cognition integrity via sensitive behavior tasks in patients with well localized lesions (mediodorsal thalamic infarcts) compared with healthy participants.

status: Unknown status

ReferenceCitation: Kopelman MD. What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia? Neurosci Biobehav Rev. 2015 Jul;54:46-56. doi: 10.1016/j.neubiorev.2014.08.014. Epub 2014 Sep 16.

ReferenceCitation: Pergola G, Gunturkun O, Koch B, Schwarz M, Daum I, Suchan B. Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus. Neuropsychologia. 2012 Aug;50(10):2477-91. doi: 10.1016/j.neuropsychologia.2012.06.019. Epub 2012 Jun 30.

ReferenceCitation: Cipolotti L, Husain M, Crinion J, Bird CM, Khan SS, Losseff N, Howard RS, Leff AP. The role of the thalamus in amnesia: a tractography, high-resolution MRI and neuropsychological study. Neuropsychologia. 2008 Sep;46(11):2745-58. doi: 10.1016/j.neuropsychologia.2008.05.009. Epub 2008 May 21.

ReferenceCitation: Danet L, Barbeau EJ, Eustache P, Planton M, Raposo N, Sibon I, Albucher JF, Bonneville F, Peran P, Pariente J. Thalamic amnesia after infarct: The role of the mammillothalamic tract and mediodorsal nucleus. Neurology. 2015 Dec 15;85(24):2107-15. doi: 10.1212/WNL.0000000000002226. Epub 2015 Nov 13.

lead_sponsor: University Hospital, Toulouse

intervention_type: Other

status_simplified: Unknown


title: Study of the Role of Innate Lymphoid Cells and Natural Killer Cells in Immune Activation of Vitiligo

acronym: INNATEvitiligo

summary: The cohort included only major patients with non-segmental vitiligo and no other autoimmune or inflammatory associated diseases (except thyroiditis). Control subjects should have no autoimmune or inflammatory diseases. Patients and controls should not take treatment with corticosteroids or other potentially immunomodulatory therapies. Patients and controls are recruited in the Dermatology Department of the University Hospital of Nice and the Hospital of Fréjus. The investigators have already initiated the collection of tissues and blood from patients and control subjects and we have succeeded in isolating ILCs and NKs from a blood volume of 50ml. We were able to sort the ILC subpopulations. Early data suggest an increase in Natural Killer (NK) and Innate Lymphoïdes Cells 1 (ILC1) in the blood of vitiligo patients compared to control subjects. The investigators also managed to extract the melanocytes from the skin biopsies of the first patients and control subjects.

ReferenceCitation: Spritz RA. Six decades of vitiligo genetics: genome-wide studies provide insights into autoimmune pathogenesis. J Invest Dermatol. 2012 Feb;132(2):268-73. doi: 10.1038/jid.2011.321. Epub 2011 Oct 13.

ReferenceCitation: Jin Y, Birlea SA, Fain PR, Ferrara TM, Ben S, Riccardi SL, Cole JB, Gowan K, Holland PJ, Bennett DC, Luiten RM, Wolkerstorfer A, van der Veen JP, Hartmann A, Eichner S, Schuler G, van Geel N, Lambert J, Kemp EH, Gawkrodger DJ, Weetman AP, Taieb A, Jouary T, Ezzedine K, Wallace MR, McCormack WT, Picardo M, Leone G, Overbeck A, Silverberg NB, Spritz RA. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012 May 6;44(6):676-80. doi: 10.1038/ng.2272.

ReferenceCitation: Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, Holland PJ, Birlea SA, Siebert J, Hartmann A, Lienert A, van Geel N, Lambert J, Luiten RM, Wolkerstorfer A, Wietze van der Veen JP, Bennett DC, Taieb A, Ezzedine K, Kemp EH, Gawkrodger DJ, Weetman AP, Koks S, Prans E, Kingo K, Karelson M, Wallace MR, McCormack WT, Overbeck A, Moretti S, Colucci R, Picardo M, Silverberg NB, Olsson M, Valle Y, Korobko I, Bohm M, Lim HW, Hamzavi I, Zhou L, Mi QS, Fain PR, Santorico SA, Spritz RA. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.

ReferenceCitation: Chatterjee S, Eby JM, Al-Khami AA, Soloshchenko M, Kang HK, Kaur N, Naga OS, Murali A, Nishimura MI, Caroline Le Poole I, Mehrotra S. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol. 2014 May;134(5):1285-1294. doi: 10.1038/jid.2013.540. Epub 2013 Dec 23.

ReferenceCitation: Mosenson JA, Zloza A, Nieland JD, Garrett-Mayer E, Eby JM, Huelsmann EJ, Kumar P, Denman CJ, Lacek AT, Kohlhapp FJ, Alamiri A, Hughes T, Bines SD, Kaufman HL, Overbeck A, Mehrotra S, Hernandez C, Nishimura MI, Guevara-Patino JA, Le Poole IC. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci Transl Med. 2013 Feb 27;5(174):174ra28. doi: 10.1126/scitranslmed.3005127.

ReferenceCitation: Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin. J Invest Dermatol. 2012 Jul;132(7):1869-76. doi: 10.1038/jid.2011.463. Epub 2012 Feb 2.

ReferenceCitation: Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, Zhou Y, Deng A, Hunter CA, Luster AD, Harris JE. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014 Feb 12;6(223):223ra23. doi: 10.1126/scitranslmed.3007811.

ReferenceCitation: Boniface K, Jacquemin C, Darrigade AS, Dessarthe B, Martins C, Boukhedouni N, Vernisse C, Grasseau A, Thiolat D, Rambert J, Lucchese F, Bertolotti A, Ezzedine K, Taieb A, Seneschal J. Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3. J Invest Dermatol. 2018 Feb;138(2):355-364. doi: 10.1016/j.jid.2017.08.038. Epub 2017 Sep 18.

ReferenceCitation: Yu R, Broady R, Huang Y, Wang Y, Yu J, Gao M, Levings M, Wei S, Zhang S, Xu A, Su M, Dutz J, Zhang X, Zhou Y. Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin. PLoS One. 2012;7(12):e51040. doi: 10.1371/journal.pone.0051040. Epub 2012 Dec 10.

ReferenceCitation: Regazzetti C, Joly F, Marty C, Rivier M, Mehul B, Reiniche P, Mounier C, Rival Y, Piwnica D, Cavalie M, Chignon-Sicard B, Ballotti R, Voegel J, Passeron T. Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients. J Invest Dermatol. 2015 Dec;135(12):3105-3114. doi: 10.1038/jid.2015.335. Epub 2015 Aug 31.

ReferenceCitation: Bernardini G, Gismondi A, Santoni A. Chemokines and NK cells: regulators of development, trafficking and functions. Immunol Lett. 2012 Jul 30;145(1-2):39-46. doi: 10.1016/j.imlet.2012.04.014.

ReferenceCitation: Bruggen MC, Bauer WM, Reininger B, Clim E, Captarencu C, Steiner GE, Brunner PM, Meier B, French LE, Stingl G. In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable Differences between Normal and Inflamed Skin. J Invest Dermatol. 2016 Dec;136(12):2396-2405. doi: 10.1016/j.jid.2016.07.017. Epub 2016 Jul 22.

lead_sponsor: Centre Hospitalier Universitaire de Nice


title: iPS Cells of Patients for Models of Retinal Dystrophies

acronym: RETIPS

summary:
The investigators are focused on inherited retinal dystrophies with an aim to further understand disease pathophysiology and to elaborate novel treatments, as, to date, there is no effective treatment to prevent blindness.

The main goal of this study is to generate human cellular models of healthy and disease retinas and perform studies to evaluate the efficiency of gene therapy approaches for different diseases.

Skin biopsies of volunteers are cultured to isolate fibroblasts that are then reprogrammed into iPS cells. Healthy and disease-specific iPS cells are then differentiated into retinal models.

This study should help to elucidate disease pathways and to provide proof-of-concept for various therapeutic approaches.

lead_sponsor: University Hospital, Montpellier


title: Influence of the Surgical Technique Used for Colectomies on the Concentration of Circulating Tumor DNA and the Presence of Circulating Tumor Cells: Comparison of the "no Touch" Technic With Either First Clamping of the Mesenteric Vessels or First Mobilization of the Tumor Followed by Clamping.

acronym: ADNCHIR

summary: Colectomy is the most commonly used therapeutic approach for the treatment of non-metastatic colorectal cancer. This approach is generally very effective however the rate of recurrence and the appearance of metachronous metastasis remains a major problem in the postoperative period. One of the hypothesis that can explain this tumor progression is the dissemination of tumor cells at the time of tumor mobilization. In this work, we wish to verify this hypothesis by comparing two surgical technics used in our department for left or right colectomies: respectively either first section of the mesenteric vessels followed by the mobilization of the tumor or first mobilization of the tumor followed by the section of the mesenteric vessels. To evaluate the dissemination, we will study two disseminations markers that have shown their prognostic value: i) circulating tumor cells (which represent a direct marker of dissemination) and ii) tumor circulating DNA (which is an indirect marker) but has the advantage of being more representative of all tumor clones and therefore the tumor burden released into the blood at the time of surgery).

location_facility: Department of Digestive Surgery, Hôpital Saint-Antoine


title: Characterization of Manual Dexterity by Finger Force Manipuladum (FFM) in Patients With Writer's Cramp and in Control Subjects

summary:
Writer's cramp is a focal dystonia characterized by abnormal movements and postures during writing. Limited finger independence during writing manifests as difficulty suppressing unwanted activations of neighbouring non task-relevant fingers. Patients with Writer's cramp also have difficulty in fine control of grip force.

The investigators have recently developed the Finger Force Manipulandum which quantifies the forces applied by each fingers in different tasks. This method is sensitive for detection and quantification of small unwanted contractions in non-active ('stationary') fingers. Different tasks have been developed to assess abilities such as finger individuation but also fine finger force control, finger movement regularity and speed.

The aim of this study is to assess if developed tasks allow to precisely characterize writer's cramp condition in terms of abilities aforementioned.

To do so, performance of 20 writer's cramp patients in the developed task will be compared with performance of 20 control participants (matched in age, sex and writing hand) in the same tasks.

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild

intervention_type: Device


title: Evaluation of Individual Sensitivity to the Gonadotoxicity of Chemotherapy in Young Patients With Breast Cancer

acronym: ESIGON

summary:
Over the past decade, advances in diagnosis and treatments have dramatically increased the rates of cure for young patients with cancer. As a consequence, a new population of cancer survivors has emerged whose fertility is compromised after cancer therapy. Indeed, gonadotoxicity is a well-known long-term side effect of cancer treatment in young patients having survived malignant diseases. More than 80% of women of childbearing age, treated for breast cancer with standard protocol of neoadjuvant (4 cycles of 5-fluorouracile - epirubicin- cyclophosphamide (FEC) and 4 cycles of docetaxel) or adjuvant chemotherapy (3 FEC and 3 docetaxel), show an alteration of their ovarian reserve 2 years after completion of the treatment, as a result of chemotherapy-related follicular loss. Therefore, according to the extent of the follicular damages, the gonadal function may vary from moderate to severe diminished ovarian reserve (DOR) and possibly to the ultimate stage of premature ovarian insufficiency (POI).

Investigators propose a multicentric and prospective study of a cohort of young women with breast cancer to evaluate whether genetic polymorphisms, previously identified as being correlated with age at menopause in the healthy population, are associated with the intensity of the follicular decline following chemotherapy in young breast cancer survivors.

primary_purpose: Screening

appel_a_projets: PHRCK

acronyme: ESIGON

titre: ESIGON : Evaluation de la Sensibilité Individuelle à la GONadotoxicité de la chimiothérapie chez la femme jeune atteinte de cancer du sein

discipline_principale: cancer

nom_porteur: SONIGO

prenom_porteur: Charlotte


title: Evaluation of the Location and the Treatment by High-intensity Focused Ultrasounds (HIFU) of Posterior Deep Infiltrating Endometriosis (DIE) Lesions With Intestinal Involvement

summary:
Deep invasive endometriosis (DIE) includes lesions of the rectosigmoid. Theses lesions are associated with painful symptoms that can alter quality of life. High Intensity Focused Ultrasound (HIFU) is a non-invasive ablative procedure using a high-intensity ultrasound probe to induce tissue devitalization using acoustic cavitation and thermal ablation. Focal One® is a transrectal HIFU device, which is validated to treat prostatic cancer.

The primary objective of this clinical trial is to evaluate the ability of the Focal One® HIFU device to detect and target posterior DIE lesions with intestinal involvement. The secondary objectives are to perform a HIFU lesion, to evaluate morphological modifications of the nodule in post-therapeutic imaging scans, to assess evolution of gynecological symptoms, intestinal symptoms, and patients' quality of life after treatment by HIFU and to collect safety data.

primary_purpose: Treatment

lead_sponsor: EDAP TMS S.A.


title: Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome

acronym: FUCHSIA-FR

summary:
Ultra-high frequency ultrasound may be useful in the field of vascular research, given its ability to accurately characterize arterial wall thickness and ultrastructure.

In patients with fibromuscular dysplasia (FMD), it may help identify the "triple signal" pattern in carotid arterial wall, while in Vascular Ehlers Danlos Syndrome (V-EDS) it may help to accurately measure carotid intima-media thickness, which may be extremely small and difficult to measure with standard equipment. Furthermore, novel features might be identified in small-to-medium sized arteries by ultra-high frequency ultrasound.

The main aim of this study is to demonstrate that ultra-high frequency ultrasound has the same accuracy of standard ultrasound for the identification of "triple signal" in the carotid artery of FMD.

Secondary aims of this study are to evaluate carotid, radial and digital intima-media thickness, wall ultrastructure and distensibility in 60 patients with FMD and in 30 patients with V-EDS.


title: Monitoring of Immune Checkpoint Inhibitors Adverse Drug Reactions Through the WHO Vigilyze and French Pharmaco-vigilance Database (Base Nationale de Pharmacovigilance BNPV)

acronym: CHIMeRA

summary: Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) from rhumatologic, endocrinologic, cardiac or other system origin. This study investigates reports of drug induced irAEs with treatment including anti-PD1, Anti-PDL-1, and Anti-CTLA4 classes using the World Health Organization (WHO) database VigiBase and the french database Base Nationale de PharmacoVigilance (BNPV).

ReferenceCitation: Davis EJ, Salem JE, Young A, Green JR, Ferrell PB, Ancell KK, Lebrun-Vignes B, Moslehi JJ, Johnson DB. Hematologic Complications of Immune Checkpoint Inhibitors. Oncologist. 2019 May;24(5):584-588. doi: 10.1634/theoncologist.2018-0574. Epub 2019 Feb 28.

ReferenceCitation: Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019 Jun 13;380(24):2377-2379. doi: 10.1056/NEJMc1901677. No abstract available.

ReferenceCitation: Johnson DB, Manouchehri A, Haugh AM, Quach HT, Balko JM, Lebrun-Vignes B, Mammen A, Moslehi JJ, Salem JE. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer. 2019 May 22;7(1):134. doi: 10.1186/s40425-019-0617-x.

ReferenceCitation: Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC, Salem JE, Wang DY, Sanchez V, Wang Y, Chastain CA, Barker K, Liang Y, Warren S, Beechem JM, Menzies AM, Tio M, Long GV, Cohen JV, Guidon AC, O'Hare M, Chandra S, Chowdhary A, Lebrun-Vignes B, Goldinger SM, Rushing EJ, Buchbinder EI, Mallal SA, Shi C, Xu Y, Moslehi JJ, Sanders ME, Sosman JA, Balko JM. A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat Med. 2019 Aug;25(8):1243-1250. doi: 10.1038/s41591-019-0523-2. Epub 2019 Jul 22.

ReferenceCitation: Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Stewart GC, Choueiri TK, Di Carli M, Allenbach Y, Kumbhani DJ, Heinzerling L, Amiri-Kordestani L, Lyon AR, Thavendiranathan P, Padera R, Lichtman A, Liu PP, Johnson DB, Moslehi J. Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology. Circulation. 2019 Jul 2;140(2):80-91. doi: 10.1161/CIRCULATIONAHA.118.034497.

ReferenceCitation: Arnaud L, Lebrun-Vignes B, Salem JE. Checkpoint inhibitor-associated immune arthritis. Ann Rheum Dis. 2019 Jul;78(7):e68. doi: 10.1136/annrheumdis-2018-213470. Epub 2018 May 3. No abstract available.

oa_host_type: publisher

evidence: open (via free pdf)

host_type: publisher

unpaywall_oa_status: bronze

publisher_dissemination: British Medical Journal

ReferenceCitation: Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, Rathmell WK, Ancell KK, Balko JM, Bowman C, Davis EJ, Chism DD, Horn L, Long GV, Carlino MS, Lebrun-Vignes B, Eroglu Z, Hassel JC, Menzies AM, Sosman JA, Sullivan RJ, Moslehi JJ, Johnson DB. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 Dec 1;4(12):1721-1728. doi: 10.1001/jamaoncol.2018.3923. Erratum In: JAMA Oncol. 2018 Dec 1;4(12):1792.

oa_colors: green other

oa_host_type: publisher;repository

publisher_dissemination: American Medical Association

ReferenceCitation: Alexandre J, Moslehi JJ, Bersell KR, Funck-Brentano C, Roden DM, Salem JE. Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms. Pharmacol Ther. 2018 Sep;189:89-103. doi: 10.1016/j.pharmthera.2018.04.009. Epub 2018 Apr 24.

ReferenceCitation: Wright JJ, Salem JE, Johnson DB, Lebrun-Vignes B, Stamatouli A, Thomas JW, Herold KC, Moslehi J, Powers AC. Increased Reporting of Immune Checkpoint Inhibitor-Associated Diabetes. Diabetes Care. 2018 Dec;41(12):e150-e151. doi: 10.2337/dc18-1465. Epub 2018 Oct 10. No abstract available.

license: unspecified-oa

license_normalized: unspecified-oa

publisher_dissemination: American Diabetes Association

ReferenceCitation: Anquetil C, Salem JE, Lebrun-Vignes B, Johnson DB, Mammen AL, Stenzel W, Leonard-Louis S, Benveniste O, Moslehi JJ, Allenbach Y. Immune Checkpoint Inhibitor-Associated Myositis: Expanding the Spectrum of Cardiac Complications of the Immunotherapy Revolution. Circulation. 2018 Aug 14;138(7):743-745. doi: 10.1161/CIRCULATIONAHA.118.035898. No abstract available.

publisher_dissemination: Wolters Kluwer Health

ReferenceType: derived

ReferenceCitation: Nguyen LS, Raia L, Lebrun-Vignes B, Salem JE. Graft Versus Host Disease Associated with Immune Checkpoint Inhibitors: A Pharmacovigilance Study and Systematic Literature Review. Front Pharmacol. 2021 Feb 5;11:619649. doi: 10.3389/fphar.2020.619649. eCollection 2020.

oa_colors: green gold

evidence: oa journal (via doaj)

license: cc-by

license_normalized: cc-by

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inria

repository_normalized: HAL

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

ReferenceCitation: Vozy A, De Martin E, Johnson DB, Lebrun-Vignes B, Moslehi JJ, Salem JE. Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors. Eur J Cancer. 2019 Dec;123:112-115. doi: 10.1016/j.ejca.2019.09.022. Epub 2019 Nov 1. No abstract available.

evidence: open (via crossref license, author manuscript)

location_facility: AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.


title: Aberrant Splicings Due to Microsatellite Instability in Colorectal Cancer : Physiopathological and Clinical Impact (MICROSPLICOTHER)

summary:
MSI (Microsatellite Instability) colorectal cancer (CRC) show improved survival, are less prone to metastasis and show poor response to chemotherapy (compared to MSS tumors). The underlying reasons for these characteristics are still not understood and no specific therapeutic approach for MSI colon tumours (15% of CRC overall) has yet been developed.

The MSI process is oncogenic when it affects DNA repeat sequences that have a functional role, e.g. Small Coding Repeats (SCR). MSI also frequently affects Long Non-Coding Repeats (LNCR) in tumour DNA. In contrast to SCR, only a few LNCR are endowed with biological activity. Consequently, this area has received very little attention. Our group recently identified HSP110 mutant chaperone protein in MSI CRC that was generated by somatic deletion of a LNCR. Of interest, HSP110 mutant (due to exon skipping) have anti-oncogenic properties and the survival of MSI CRC patients receiving chemotherapy is positively associated with HSP110 mutations in tumour DNA.

The aim of the current project is to identify additional clinically relevant MSI-associated splicing aberrations due to mutations in LNCR located in splice acceptor sites. The four main steps are as follows:

To identify exon/intron sites affected by aberrant splicing events due to MSI in CRC . All RNASeq data will be exploited to identify recurrent splicing aberrations (mostly exon skipping) that occur specifically in MSI colon tumours;
To investigate for possible functional links between MSI and any detected aberrant splicing events . All specific aberrant splicing events detected by RNAseq in MSI CRC samples will be first confirmed (quantitative RT-PCR) in order to eliminate false positive cases. For validated exon candidates, the allelic profiles of adjacent intronic LNCR will be analysed (PCR and fluorescence genotyping) in CRC cell lines and primary tumours (MSI and MSS), as well as in matching normal mucosa samples in order to assess their polymorphic status;
To identify splicing events and LNCR mutations with clinical relevance in MSI CRC patients . All LNCR with a confirmed role in gene splicing in MSI CRC will be analysed. The clinical relevance of candidate genes will be assessed using multivariate survival regression models for Relapse- Free Survival, with interaction terms (response to chemotherapy);
To initiate functional studies on a limited number of clinically relevant, cancer-related genes whose splicing is perturbed in MSI cancer cells, and to develop biological tools to simplify screening in future clinical assays Similar to HSP110, we will focus on 4 or 5 mutant proteins that are promising drug therapeutic targets. Functional assays will be developed to further elucidate their role in the pathophysiology of MSI tumours. We also aim to develop biological tools for these candidate genes, such as the detection of wild-type or mutant proteins by immunohistochemistry.

location_facility: Service d'Anatomie et de Cytologie Pathologique

appel_a_projets: PRTK

acronyme: MICROSPLICOTHER

titre: Epissages Aberrants Générés par Instabilité des Microsatellites dans les Cancers Colorectaux : Impact Physiopathologique et Relevance Clinique

nom_porteur: FLEJOUX

prenom_porteur: Jean-François


title: Rhythm and the Multisensoriality's Effects on the Motor Development in Children With Cerebral Palsy

acronym: APP-PaC

summary:
Cerebral palsy (CP) affects the motor function but also the cognitive function of the child. Physical activity brings motor and cognitive benefits and appears as an important aspect of the therapy that is offered to them.

The child is seating in front of a computer, seating comfortably on a chair during 1 hour. The experimental task consists in learning a sequence of taps on "Serial reaction time task" type buzzers (SRTT) in which the child must press a buzzer corresponding to one of the 4 squares that on the screen. The sequence corresponds to 10 steps in a particular order.

primary_purpose: Supportive Care


title: Methyl-qPCR : a New Predictive Marker for Epstein-Barr Virus-associated Lymphoproliferations During Allogeneic Hematopoietic Stem Cell Transplantation

acronym: EBVALLO

summary:
Scientific context

Epstein-Barr virus has a causal role in the pathogenesis of multiple distinct lymphomas. Post-transplant lymphoproliferative diseases (PTLD) are the most frequent EBV-induced proliferations. PTLD after allogeneic stem cell transplantation has an incidence lower than 5% but may increase up to 10-20% in patients with established risk factors. EBV-DNAemia is predictive of EBV-PTLD and is routinely performed using qPCR on whole blood. Preemptive therapeutic strategies with anti-CD20 antibody are used when patients are above a defined EBV-DNAemia threshold. This approach remains limited since it does not discriminate between an EBV-induced lymphoproliferation (latent cycle) and/or a replicating virus (replicative cycle).

Epigenetic modifications plays a central role in regulating the switch from latent to lytic gene expression. Specific DNA modifications can be regarded as molecular signatures for EBV genomes associated with the status of the viral infection (latent vs lytic). Accordingly, these signatures may be envisioned as a potent tool to characterize the state of the viral infection in vivo.

Description of the project Our primary objective is to estimate the respective percentages of EBV-lytic and EBV-latent genomes (proliferating cells) in patients presenting with a high EBV-DNAemia after allogeneic stem cell transplantation HSCT by analysing the epigenetic modifications of EBV genome on specific sites. Our secondary objectives are i) to determine risk factors associated with each "latent versus lytic EBV" profiles and ii) to correlate the "latent versus lytic EBV" profiles with response to rituximab infusion and patient outcomes.

For this purpose, a retrospective study (n=80) and a prospective study (estimation n=58) will be established. The different steps of this project are:

To study epigenetic modifications. The laboratory is developing a new approach to distinguish between latent and lytic genomes.
To realize quantitative analysis by RT-PCR of different EBV transcripts specific of the latent or of the lytic phase of the virus This method will be applied on RNA extracted from patient blood samples with elevated EBV viral load, under condition preserving RNA integrity. The results will be validated on a prospective cohort of HSCT patients (n=58) (Saint-Antoine Hospital and La Pitié-Salpêtrière Hospital).
To perform quantitative analysis of EBV genomes in plasma, saliva and total blood samples by current routine procedures In addition to total blood samples, plasma and saliva will be collected since free viral particles are known to accumulate in these biological fluids upon EBV reactivation. These samples will be treated by normalized procedures that are routinely used in the medical virology laboratory to quantify EBV in human samples.

Expected results By establishing a simple method for studying epigenetic modifications of EBV genomes, we expect to understand the significance of high EBV viral load and the pathophysiology of post-HSCT PTLD. We aim to distinguish between the latent / lytic profiles of HSCT patients and to correlate their respective risks for developing PTLD. Establishing the epigenetic EBV profile in the post-HSCT setting when facing increase viral load and PTLD will improve our understanding of the biological mechanisms determining EBV-status in post-HSCT. This should improve major medical and economical issues. These results could have a major therapeutic

primary_purpose: Basic Science

intervention_type: Biological

acronyme: EBVmethqPCR

titre: La méthyl-qPCR : un nouveau marqueur prédictif  des lymphoproliférations associées au virus Epstein-Barr  en allogreffe de cellules souches hématopoïétiques

nom_porteur: BRISSOT

prenom_porteur: Eolia


title: Memorial Anxiety Scale for Patients With Prostate Cancer: French Validation, Links With Quality Of Life and Future Temporal Perspective.

summary: A specific scale allowing the measure of anxiety of patients with protate cancer has been designed and validated but the French version needs to be validated. This study aims at validating the French translation of this scale.

lead_sponsor: Institut Paoli-Calmettes

intervention_type: Behavioral


title: Study of the Predictive Impact of MMP2 and MMP9 Levels for Patients With Metastatic Kidney Cancer Treated With Anti-angiogenic Agents Compared to Patients Not Treated With Antiangiogenic (Localized Kidney Cancer and Oligometastatic)

summary: Prospective research of Matrix Metalloproteinases (MMP) 2 and 9 as predictive biomarkers in metastatic kidney cancer patients treated with 2 anti angiogenic agents (Sunitinib or Pazopanib).

ReferenceCitation: Jubb AM, Harris AL. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol. 2010 Dec;11(12):1172-83. doi: 10.1016/S1470-2045(10)70232-1.

ReferenceCitation: Tabouret E, Boudouresque F, Barrie M, Matta M, Boucard C, Loundou A, Carpentier A, Sanson M, Metellus P, Figarella-Branger D, Ouafik L, Chinot O. Association of matrix metalloproteinase 2 plasma level with response and survival in patients treated with bevacizumab for recurrent high-grade glioma. Neuro Oncol. 2014 Mar;16(3):392-9. doi: 10.1093/neuonc/not226. Epub 2013 Dec 9.

publisher_dissemination: Oxford University Press

ReferenceCitation: Tabouret E, Boudouresque F, Farina P, Barrie M, Bequet C, Sanson M, Chinot O. MMP2 and MMP9 as candidate biomarkers to monitor bevacizumab therapy in high-grade glioma. Neuro Oncol. 2015 Aug;17(8):1174-6. doi: 10.1093/neuonc/nov094. No abstract available.

ReferenceCitation: Tabouret E, Bertucci F, Pierga JY, Petit T, Levy C, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roche H, Bachelot T, van Laere S, Ueno NT, Toiron Y, Finetti P, Birnbaum D, Borg JP, Viens P, Chinot O, Goncalves A. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study. Oncotarget. 2016 Apr 5;7(14):18531-40. doi: 10.18632/oncotarget.7612.

evidence: open (via page says license)

repository_institution: University of Antwerp - Institutional Repository University of Antwerp

repository_normalized: irua

version: submittedVersion

evidence: oa repository (semantic scholar lookup)

repositories:
PubMed Central
irua
pdfs.semanticscholar.org

unpaywall_oa_status: gold

publisher_dissemination: Impact Journals, LLC


title: Relation Between Pregnenolone Endocannabinoids in Normal-weight and Obese Men

acronym: CannaPREG

summary: Measured plasmatic concentration of pregnenolone and endocannabinoid in fasting conditions and over a meal in obese and normal-weight men subjects, to research a dysfunction in the negative feed-back between pregnenolone and CB1 ligand in obese subjects. This dysfunction could participate to the hyperactivity of endocannabinoid system saw in obesity.

lead_sponsor: University Hospital, Bordeaux


title: ELR+CXCL Cytokines in Metastatic Kidney Cancers: Predictive Markers of Resistance to Sunitinib and New Relevant Therapeutic Targets in Refractory Patients

acronym: SUNITRES

summary: Metastatic renal cell carcinomas (mRCC) are highly angiogenic tumors because of mutation of the pVHL gene leading to over-expression of VEGF. Therefore, mRCC represent a paradigm for the use of anti-angiogenic treatments targeting the VEGF/VEGFR pathway. Despite an increase of the time to progression these treatments, taken alone, are not curative with ineluctable progression especially for the reference treatment sunitinib a multi kinase inhibitors of VEGF, PDGF, CSF1 receptors and c-kit, FLT3 and RET. At progression on sunitinib, patients received mTOR inhibitors which is responsible, at least, of HIF1A mRNA translation, then on a third line sorafenib that inhibits VEGFR2, 3 PDGFR, c-KIT and B-RAF. The access to these different lines of treatment has finally prolonged survival but this situation is not satisfactory. Unexpected aspect associated with the use of anti-angiogenesis treatments was the diversity of the patients' response. Some patients are right away refractory and die rapidly, but the majority of patient has a transient response then progress and a few percentages of them are responder for a very long period of time. By only targeting normal endothelial cells and tumor neo-vascularization, the response should have been more homogenous, thus highlighting that the treatment induced a "Darwinian" adaptation of tumor cells and cells of the microenvironment. Two conclusions follow from these observations: 1- The need to identify predictive markers of efficacy; 2-The identification of druggable targets participating in progression on anti-angiogenic treatments. Our results have highlighted the ELR+CXCL cytokines, pro-inflammatory and pro-angiogenic cytokines as prognosis markers of survival of mRCC patients and relevant therapeutic targets on experimental tumors in mice. As VEGF/VEGFR, these cytokines are produced by tumor, endothelial and inflammatory cells. Their receptors (CXCR1, 2) are expressed physiologically by immune and endothelial cells and aberrantly by tumor cells generating at the same time autocrine proliferation loops, chronic angiogenesis and inflammation. Therefore, the CXCL/CXCR1,2 axis constitutes an independent axis of cancer development and propagation. However, the current standard of care is to administer anti-angiogenic therapies as the first line treatment. The objective of this project is linked to the identification of potent predictive markers of efficacy, easily measured in plasma samples. Deciphering the molecular mechanisms associated with the production of such cytokines by tumor cells and by cells of the microenvironment represents an interesting intellectual challenge and a relevant way to improve the current treatments by targeting, at progression on the current standard of care, other pathways than the VEGF/VEGFR axis.

lead_sponsor: Centre Antoine Lacassagne


type: EudraCT Number

title: A Pilot Study of the Feasibility of Intraoperative Photodynamic Therapy of Glioblastoma.

acronym: INDYGO

summary: The study pilot evaluate the feasibility of a "5-ALA- PpIX (protoporhyrin IX) mediated per-PDT protocol" in patients with glioblastoma accessible for complete surgical removal of contrast. This treatment will be carried out in addition to the current reference treatment of glioblastoma: maximum resection surgery followed by radiochemotherapy according to the protocol Stupp

ReferenceCitation: Vermandel M, Dupont C, Lecomte F, Leroy HA, Tuleasca C, Mordon S, Hadjipanayis CG, Reyns N. Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. J Neurooncol. 2021 May;152(3):501-514. doi: 10.1007/s11060-021-03718-6. Epub 2021 Mar 20.

repository_institution: Université de Lausanne - SERVAL

publisher_dissemination: Springer-Nature

lead_sponsor: University Hospital, Lille


title: Phase III Multicenter Randomized Trial Evaluating in Patients at the Time of the Primary HIV-1 Infection, the Impact on the Viral Reservoir of a Combination Including Tenofovir/Emtricitabine and Dolutegravir or Tenofovir/Emtricitabine and Darunavir/Cobicistat

summary: The purpose of this study is to compare the impact of two combination of two tablets once daily: dolutegravir associated with emtricitabine / tenofovir versus darunavir / cobicistat associated with emtricitabine / tenofovir on DNA HIV measured in PBMC at 48 weeks in patients with primary HIV-1 infection.

design_allocation: Randomized

lead_sponsor: ANRS, Emerging Infectious Diseases


title: Physiological Characteristics of High Altitude Climbers

acronym: ALTIPERF

summary: Climbing at high altitude and tolerating hypoxic environment require specific physiological adaptations. Large intersubjects differences exist regarding the ability to adapt to high altitude and hypoxia. The present study aims to characterise the physiological responses to hypoxia in a group of elite climbers by comparison to sea level athletes. We hypothesised that elite climbers would show better physiological responses to hypoxia and more preserved performances compared to sea level.

primary_purpose: Health Services Research

ReferenceCitation: Verges S, Rupp T, Jubeau M, Wuyam B, Esteve F, Levy P, Perrey S, Millet GY. Cerebral perturbations during exercise in hypoxia. Am J Physiol Regul Integr Comp Physiol. 2012 Apr 15;302(8):R903-16. doi: 10.1152/ajpregu.00555.2011. Epub 2012 Feb 8.

lead_sponsor: University Hospital, Grenoble


title: High-flow Nasal Oxygen Therapy (Optiflow) in Hospitalized Infant With Moderate-to-severe Bronchiolitis: Multicentric Randomized Controlled Trial

acronym: BRONCHOPTI

summary:
Over the last decade, high-flow nasal oxygen therapy (HFN) has emerged as a new method to provide respiratory support in children with moderate to severe bronchiolitis.

However, any randomized clinical trial (RCT) have demonstrated that earlier support with HFN is superior to standard care including low -flow nasal oxygen therapy to reduce the risk of acute respiratory failure requiring non invasive (or tracheal) ventilation and subsequently the need of PICU transfer.

appel_a_projets: PHRCI

acronyme: BRONCHOPTI

titre: Oxygénothérapie à haut débit nasal dans la prise en charge précoce des bronchoalvéolites modérées et sévères du nourrisson

nom_porteur: DURAND

prenom_porteur: Philippe


title: Melanoma Cells Dissemination Study in Healthy Patients' Tissues

acronym: DISSEMELA

summary: The objective of this project is to evaluate the presence of melanoma quiescent or initiating clonal cells in peritumoral healthy tissue displaying the same molecular signature than those of the tumor/metastasis and to correlate this presence to the prognostic value.

ReferenceCitation: Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005 Nov 17;353(20):2135-47. doi: 10.1056/NEJMoa050092.

ReferenceCitation: Faries MB, Steen S, Ye X, Sim M, Morton DL. Late recurrence in melanoma: clinical implications of lost dormancy. J Am Coll Surg. 2013 Jul;217(1):27-34; discussion 34-6. doi: 10.1016/j.jamcollsurg.2013.03.007. Epub 2013 May 3.

ReferenceCitation: Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008 Dec 4;456(7222):593-8. doi: 10.1038/nature07567.

ReferenceCitation: How-Kit A, Tost J. Pyrosequencing(R)-Based Identification of Low-Frequency Mutations Enriched Through Enhanced-ice-COLD-PCR. Methods Mol Biol. 2015;1315:83-101. doi: 10.1007/978-1-4939-2715-9_7.

location_facility: Name:: INSERM - UMRS 938, UPMC Saint-Antoinen Hospital, Team "Stem cells and transition from pre-invasive tumors"

acronyme: DisseMela

titre: Etude de la dissémination du mélanome dans les tissus sains de malades

nom_porteur: ARACTINGI

prenom_porteur: Selim


title: SEPAGES : Following of Atmospheric Pollution Exposure During Pregnancy and Effects on Health

summary:
The SEPAGES couple-child cohort is coordinated by an Inserm (French National Institute of Health and Medical Research) team of environmental epidemiology. SEPAGES cohort is based on the general population and aims to cover several areas of environmental health research, including endocrine disruptors and air pollutants.

The main objectives is to quantify the impact of pollution during pregnancy and the first years of life on three main health outcomes : growth, respiratory health and neuro-development ; and to better understand the biological mechanism (such as genetic analysis to study the role of environmental factors on genes expression as well as the role of genetic factors on health). The objective is to include 500 families.

ReferenceCitation: Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989 Mar 4;298(6673):564-7. doi: 10.1136/bmj.298.6673.564.

ReferenceCitation: Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989 Sep 9;2(8663):577-80. doi: 10.1016/s0140-6736(89)90710-1.

ReferenceCitation: Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004 Dec;23(6 Suppl):588S-595S. doi: 10.1080/07315724.2004.10719428.

ReferenceCitation: Lawlor DA, Ebrahim S, Davey Smith G. Association of birth weight with adult lung function: findings from the British Women's Heart and Health Study and a meta-analysis. Thorax. 2005 Oct;60(10):851-8. doi: 10.1136/thx.2005.042408. Epub 2005 Jul 29.

ReferenceCitation: Rona RJ, Gulliford MC, Chinn S. Effects of prematurity and intrauterine growth on respiratory health and lung function in childhood. BMJ. 1993 Mar 27;306(6881):817-20. doi: 10.1136/bmj.306.6881.817.

ReferenceCitation: Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8. doi: 10.1056/NEJM199501193320301.

ReferenceCitation: Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, Carlsen KH; ORAACLE. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006 Oct 19;355(16):1682-9. doi: 10.1056/NEJMoa052885.

ReferenceCitation: Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007 Sep 1;370(9589):758-64. doi: 10.1016/S0140-6736(07)61379-8.

ReferenceCitation: Jensen TK, Jorgensen N, Punab M, Haugen TB, Suominen J, Zilaitiene B, Horte A, Andersen AG, Carlsen E, Magnus O, Matulevicius V, Nermoen I, Vierula M, Keiding N, Toppari J, Skakkebaek NE. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am J Epidemiol. 2004 Jan 1;159(1):49-58. doi: 10.1093/aje/kwh002.

ReferenceCitation: Moshammer H, Hoek G, Luttmann-Gibson H, Neuberger MA, Antova T, Gehring U, Hruba F, Pattenden S, Rudnai P, Slachtova H, Zlotkowska R, Fletcher T. Parental smoking and lung function in children: an international study. Am J Respir Crit Care Med. 2006 Jun 1;173(11):1255-63. doi: 10.1164/rccm.200510-1552OC. Epub 2006 Feb 16.

ReferenceCitation: McKeever TM, Lewis SA, Smith C, Collins J, Heatlie H, Frischer M, Hubbard R. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol. 2002 Jan;109(1):43-50. doi: 10.1067/mai.2002.121016.

ReferenceCitation: Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41. doi: 10.1378/chest.127.4.1232.

ReferenceCitation: Shaheen SO, Sterne JA, Montgomery SM, Azima H. Birth weight, body mass index and asthma in young adults. Thorax. 1999 May;54(5):396-402. doi: 10.1136/thx.54.5.396.

ReferenceCitation: Miller RL, Ho SM. Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med. 2008 Mar 15;177(6):567-73. doi: 10.1164/rccm.200710-1511PP. Epub 2008 Jan 10.

ReferenceCitation: Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009 Sep 1;180(5):462-7. doi: 10.1164/rccm.200901-0135OC. Epub 2009 Jun 4.

ReferenceCitation: Shaheen SO, Adcock IM. The developmental origins of asthma: does epigenetics hold the key? Am J Respir Crit Care Med. 2009 Oct 15;180(8):690-1. doi: 10.1164/rccm.200906-0893ED. No abstract available.

ReferenceCitation: Foley DL, Craig JM, Morley R, Olsson CA, Dwyer T, Smith K, Saffery R. Prospects for epigenetic epidemiology. Am J Epidemiol. 2009 Feb 15;169(4):389-400. doi: 10.1093/aje/kwn380. Epub 2009 Jan 12. Erratum In: Am J Epidemiol. 2009 Jun 1;169(11):1409. Olsson, Craig J [corrected to Olsson, Craig A].

ReferenceCitation: Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009 Apr 1;179(7):572-8. doi: 10.1164/rccm.200807-1097OC. Epub 2009 Jan 8.

ReferenceCitation: Braback L, Forsberg B. Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies. Environ Health. 2009 Apr 16;8:17. doi: 10.1186/1476-069X-8-17.

ReferenceCitation: Brauer M, Hoek G, Smit HA, de Jongste JC, Gerritsen J, Postma DS, Kerkhof M, Brunekreef B. Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J. 2007 May;29(5):879-88. doi: 10.1183/09031936.00083406. Epub 2007 Jan 24.

ReferenceCitation: Mortimer K, Neugebauer R, Lurmann F, Alcorn S, Balmes J, Tager I. Air pollution and pulmonary function in asthmatic children: effects of prenatal and lifetime exposures. Epidemiology. 2008 Jul;19(4):550-7; discussion 561-2. doi: 10.1097/EDE.0b013e31816a9dcb.

ReferenceCitation: Pinkerton KE, Joad JP. Influence of air pollution on respiratory health during perinatal development. Clin Exp Pharmacol Physiol. 2006 Mar;33(3):269-72. doi: 10.1111/j.1440-1681.2006.04357.x.

ReferenceCitation: Ritz B, Yu F. The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993. Environ Health Perspect. 1999 Jan;107(1):17-25. doi: 10.1289/ehp.9910717.

ReferenceCitation: Slama R, Darrow L, Parker J, Woodruff TJ, Strickland M, Nieuwenhuijsen M, Glinianaia S, Hoggatt KJ, Kannan S, Hurley F, Kalinka J, Sram R, Brauer M, Wilhelm M, Heinrich J, Ritz B. Meeting report: atmospheric pollution and human reproduction. Environ Health Perspect. 2008 Jun;116(6):791-8. doi: 10.1289/ehp.11074.

ReferenceCitation: Jedrychowski W, Bendkowska I, Flak E, Penar A, Jacek R, Kaim I, Spengler JD, Camann D, Perera FP. Estimated risk for altered fetal growth resulting from exposure to fine particles during pregnancy: an epidemiologic prospective cohort study in Poland. Environ Health Perspect. 2004 Oct;112(14):1398-402. doi: 10.1289/ehp.7065.

ReferenceCitation: Slama R, Thiebaugeorges O, Goua V, Aussel L, Sacco P, Bohet A, Forhan A, Ducot B, Annesi-Maesano I, Heinrich J, Magnin G, Schweitzer M, Kaminski M, Charles MA; EDEN Mother-Child Cohort Study Group. Maternal personal exposure to airborne benzene and intrauterine growth. Environ Health Perspect. 2009 Aug;117(8):1313-21. doi: 10.1289/ehp.0800465. Epub 2009 Apr 1.

ReferenceCitation: Slama R, Morgenstern V, Cyrys J, Zutavern A, Herbarth O, Wichmann HE, Heinrich J; LISA Study Group. Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: a study relying on a land-use regression exposure model. Environ Health Perspect. 2007 Sep;115(9):1283-92. doi: 10.1289/ehp.10047.

ReferenceCitation: Lepeule J, Caini F, Bottagisi S, Galineau J, Hulin A, Marquis N, Bohet A, Siroux V, Kaminski M, Charles MA, Slama R; EDEN Mother-Child Cohort Study Group. Maternal exposure to nitrogen dioxide during pregnancy and offspring birth weight: comparison of two exposure models. Environ Health Perspect. 2010 Oct;118(10):1483-9. doi: 10.1289/ehp.0901509. Epub 2010 May 14.

ReferenceCitation: Wu J, Ren C, Delfino RJ, Chung J, Wilhelm M, Ritz B. Association between local traffic-generated air pollution and preeclampsia and preterm delivery in the south coast air basin of California. Environ Health Perspect. 2009 Nov;117(11):1773-9. doi: 10.1289/ehp.0800334. Epub 2009 Jun 23.

ReferenceCitation: Gulliver J, Briggs DJ. Time-space modeling of journey-time exposure to traffic-related air pollution using GIS. Environ Res. 2005 Jan;97(1):10-25. doi: 10.1016/j.envres.2004.05.002.

ReferenceCitation: Cooper AR, Page AS, Wheeler BW, Hillsdon M, Griew P, Jago R. Patterns of GPS measured time outdoors after school and objective physical activity in English children: the PEACH project. Int J Behav Nutr Phys Act. 2010 Apr 22;7:31. doi: 10.1186/1479-5868-7-31.

ReferenceCitation: Colquhoun DR, Goldman LR, Cole RN, Gucek M, Mansharamani M, Witter FR, Apelberg BJ, Halden RU. Global screening of human cord blood proteomes for biomarkers of toxic exposure and effect. Environ Health Perspect. 2009 May;117(5):832-8. doi: 10.1289/ehp.11816. Epub 2008 Dec 2.

ReferenceCitation: Hauser R, Meeker JD, Park S, Silva MJ, Calafat AM. Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect. 2004 Dec;112(17):1734-40. doi: 10.1289/ehp.7212. Erratum In: Environ Health Perspect. 2004 Dec;112(17):1740.

ReferenceCitation: de Klerk NH, English DR, Armstrong BK. A review of the effects of random measurement error on relative risk estimates in epidemiological studies. Int J Epidemiol. 1989 Sep;18(3):705-12. doi: 10.1093/ije/18.3.705.

ReferenceCitation: Zanobetti A, Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation. 2004 Oct 12;110(15):2184-9. doi: 10.1161/01.CIR.0000143831.33243.D8. Epub 2004 Oct 4.

ReferenceCitation: Amsallem F, Gauthier R, Ramonatxo M, Counil F, Voisin M, Denjean A, Matecki S; Groupe des EFR pediatriques, Societe Francais de Physiologie. [Respiratory function testing in infants: recommendations on normal values]. Rev Mal Respir. 2008 Apr;25(4):405-32. doi: 10.1016/s0761-8425(08)71583-3. French.

ReferenceCitation: Horsley A. Lung clearance index in the assessment of airways disease. Respir Med. 2009 Jun;103(6):793-9. doi: 10.1016/j.rmed.2009.01.025. Epub 2009 Feb 25.


title: Transcranial Direct Current Stimulation (tDCS) in Acute Stroke Patients

acronym: tDCS

summary:
Very early after the onset of the focal perfusion deficit, excitotoxic mechanisms can lethally damage neurons and glia. Excitotoxicity triggers a number of events that can further contribute to tissue death. Such events include peri-infarct depolarizations (PID) and cortical spreading depolarization (CSD) within the peri-infarct zone or ischaemic penumbra. Noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) are emerging as promising tools, owing to their effects on modulating cortical activity. Experimental studies have indicated that cathodic polarization of the cortical surface blocks initiation of CSD. Moreover, it has been recently demonstrated in murine stroke models that cathodal tDCS exerts a measurable neuroprotective effect in the acute phase of stroke, decreasing the number of spreading depolarizations and reducing the infarct volume by 20 to 30%.

The investigators propose here a pilot study, in acute middle cerebral artery stroke patients, with a double blind randomization: cathodal tDCS versus sham tDCS. The duration of this study will be two years. Fifty acute middle cerebral artery stroke patients will be included. The tDCS will begin within 4.5 hours of symptom onset. The main criteria of evaluation will be the extent of diffusion-weighted imaging (DWI) infarct volume between imaging on admission and 24 hours later. The investigators propose the hypothesis that in acute stroke patients, cathodal tDCS could be an adjuvant approach to recanalizing therapies.

lead_sponsor: Centre Hospitalier St Anne


title: Intestinal Microbiota and Colorectal Cancer in Inflammatory Bowel Disease - DYSCOLIC

acronym: DYSCOLIC

summary: Build a collection of fecal microbiota in order to determine the characteristics of gut microbiota associated with colorectal cancer in Inflammatory bowel disease (IBD).

location_facility: Gastroenterology Department of Saint Antoine Hospital

acronyme: DYSCOLIC

titre: Caractérisation de la dysbiose au cours du cancer colique associé à l'inflammation

nom_porteur: SOKOL

prenom_porteur: Harry


type: Other Grant/Funding Number

title: Structural-functional Brain Changes in Severely Depressed Patients Before and After Treatment With Electroconvulsive Therapy: an Exploratory Study

acronym: ECT-IM

summary: Electroconvulsive therapy (ECT) is a non-pharmacological treatment used in resistant depression whose effectiveness has been demonstrated. However, the brain mechanisms underlying this therapeutic effect remain unclear. Many animal studies show a neurotrophic action of ECT on the hippocampus: increased neurogenesis, synaptogenesis, proliferation of glial cells. In addition, functional imaging of "resting state" type have shown, among depressed patients after ECT, increased functional connectivity . These results were reinforced by the recent work of Perrin (2012). In view of this a priori contradictory, it seems appropriate to continue research neuroanatomical correlates subtending neurofunctional processes responsible at the same time improving the clinical depressive. The investigators suggest using an original technique never used in this type of population: Functional magnetic resonance imaging (fMRI) or multimodal structural-functional. This method will allow us to study the impact of ECT on brain structures involved in major depressive disorder: hippocampus.

ReferenceCitation: Abbott CC, Lemke NT, Gopal S, Thoma RJ, Bustillo J, Calhoun VD, Turner JA. Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation. Front Psychiatry. 2013 Mar 1;4:10. doi: 10.3389/fpsyt.2013.00010. eCollection 2013.

ReferenceCitation: Moreaud O, Belliard S, Snowden J, Auriacombe S, Basaglia-Pappas S, Bernard F, Bon L, Boutantin J, Boutoleau-Bretonniere C, Charnallet A, Coutant E, David D, Deramecourt V, Gaestel Y, Garnier S, Guichart E, Hahn-Barma V, Lebail B, Lebrun-Givois C, Lamy E, Le Carret N, Lemesle B, Memin A, Pariente J, Pasquier F, Renou P, Rouaud O, Sarazin M, Thomas-Anterion C, Vercelletto M, Virat-Brassaud ME. [Semantic dementia: reflexions of a French working group for diagnostic criteria and constitution of a patient cohort]. Rev Neurol (Paris). 2008 Apr;164(4):343-53. doi: 10.1016/j.neurol.2008.02.031. Epub 2008 Apr 3. French.

ReferenceCitation: Berman RM, Prudic J, Brakemeier EL, Olfson M, Sackeim HA. Subjective evaluation of the therapeutic and cognitive effects of electroconvulsive therapy. Brain Stimul. 2008 Jan;1(1):16-26. doi: 10.1016/j.brs.2007.08.005. Epub 2007 Dec 3.

ReferenceCitation: Bertolino A, Arciero G, Rubino V, Latorre V, De Candia M, Mazzola V, Blasi G, Caforio G, Hariri A, Kolachana B, Nardini M, Weinberger DR, Scarabino T. Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style. Biol Psychiatry. 2005 Jun 15;57(12):1517-25. doi: 10.1016/j.biopsych.2005.02.031.

ReferenceCitation: Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003 Dec;60(12):1201-8. doi: 10.1001/archpsyc.60.12.1201.

ReferenceCitation: Yrondi A, Nemmi F, Billoux S, Giron A, Sporer M, Taib S, Salles J, Pierre D, Thalamas C, Schmitt L, Peran P, Arbus C. Significant Decrease in Hippocampus and Amygdala Mean Diffusivity in Treatment-Resistant Depression Patients Who Respond to Electroconvulsive Therapy. Front Psychiatry. 2019 Sep 19;10:694. doi: 10.3389/fpsyt.2019.00694. eCollection 2019.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - memSIC

repositories:
HAL
PubMed Central

repositories_concat: HAL;PubMed Central

publisher_dissemination: Frontiers

ReferenceCitation: Yrondi A, Nemmi F, Billoux S, Giron A, Sporer M, Taib S, Salles J, Pierre D, Thalamas C, Rigal E, Danet L, Pariente J, Schmitt L, Arbus C, Peran P. Grey Matter changes in treatment-resistant depression during electroconvulsive therapy. J Affect Disord. 2019 Nov 1;258:42-49. doi: 10.1016/j.jad.2019.07.075. Epub 2019 Jul 31.

license: publisher-specific-oa

license_normalized: publisher-specific

version: acceptedVersion

evidence: open (author manuscript)

license: cc-by-nc

license_normalized: cc-by-nc

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inserm

repositories_concat: HAL

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

unpaywall_oa_status: hybrid


title: Description of the Endothelial Phenotypes From the Subcutaneous Abdominal and Gluteo-femoral Adipose Tissues in Women

acronym: ADIPENDO

summary: The endothelium is a key barrier between blood and tissue compartments. It is a major target of factors involved in metabolic and cardiovascular pathologies. However, the study of native human adult endothelial cells is difficult due to the lack of appropriate models and thereafter the endothelium is actually not easily accessible for clinical investigation. However, our results recently showed that the endothelium from human adipose tissue exhibit distinct phenotypes, including endothelial cell number and inflammatory, angiogenic and senescent state, according to adipose tissue location, i.e. subcutaneous and visceral. It is well recognized that estrogens favour gluteo-femoral adipose tissue deposit and their deficit after menopause is associated with increased abdominal and visceral fat mass as well as metabolic dysfunctions. These perturbations might be prevented with hormonal therapy. However, no data are available concerning the endothelial cells from gluteo-femoral and abdominal adipose tissues in women.

ReferenceCitation: Aupetit A, Decaunes P, Belles C, Riant E, Galitzky J, Chapouly C, Laisne M, Flores-Flores R, Chaput B, Vie K, Arnal JF, Bouloumie A, Briot A. Endothelial DLL4 Is an Adipose Depot-Specific Fasting Sensor Regulating Fatty Acid Fluxes. Arterioscler Thromb Vasc Biol. 2023 May;43(5):684-696. doi: 10.1161/ATVBAHA.122.318876. Epub 2023 Mar 16.

location_facility: Explorations fonctionnelles Physiologiques - Toulouse Hospital


title: Study of Platelet Activation in Septic Shock Patients

acronym: PASS

summary: Some studies have shown that antiplatelets agents could reduce organ dysfunction in septic shock in mice and human models. Platelets are actors in immunity and their activation can be complicated by tissue damage with vascular occlusions which can lead to organ dysfunction. Investigators can hypothesize an increase in platelet activation and in leukocyte-platelet aggregates in septic shock.

ReferenceCitation: Valerio-Rojas JC, Jaffer IJ, Kor DJ, Gajic O, Cartin-Ceba R. Outcomes of severe sepsis and septic shock patients on chronic antiplatelet treatment: a historical cohort study. Crit Care Res Pract. 2013;2013:782573. doi: 10.1155/2013/782573. Epub 2013 Feb 20.

ReferenceCitation: Rahman M, Gustafsson D, Wang Y, Thorlacius H, Braun OO. Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis. Platelets. 2014;25(4):257-63. doi: 10.3109/09537104.2013.809520. Epub 2013 Jul 15.

ReferenceCitation: Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: their role in host defense responses and sepsis. Thromb Res. 2011 Mar;127(3):184-8. doi: 10.1016/j.thromres.2010.10.010. Epub 2010 Nov 13.


title: Assessing the Value of Red Grapes Polyphenol Supplementation on Metabolic Parameters in Obese Insulinoresistant Subjects : Study Randomized Versus Placebo

acronym: POLYGIR

summary:
Obesity, chronic disease, is a real public health problem because of its high prevalence but also because of the high risk of complications, including insulin resistance (IR) and type 2 diabetes (T2D). The mechanisms involved in the development of IR are not well known. Oxidative stress and inflammation induced by food overload could be the initiators IR mechanisms in skeletal muscle, responsible for the use of nearly 80% glucose in response to insulin and therefore plays a major role in the regulation of glucose metabolism. Thus, an increase in ROS (Reactive Oxygen Species), markers of oxidative stress and chronic low-grade inflammation have been demonstrated in subjects with obesity, the latter decreasing in weight loss. Therapeutically, loosing weight is still very difficult these days, because of the complexity of this chronic disease. Thus, it is well established that restrictive diets to expose weight rebound, dramatic medically as in human terms for these patients. Support for physical activity is also difficult because of reduced mobility in patients, refer to the lack of motivation among some. Finally, investigators have no treatment "against-obesity" who have demonstrated a benefit / risk enough to be used routinely. It is therefore essential to seek other means of struggle against the IR, see help in weight loss.

In parallel, it is well established that the consumption of certain antioxidants, including polyphenols (PP) grape as extracts and whole foods, modulates favorably several pathways responsible for the development of IR in cell models animals. The results of antioxidants supplementation in humans are few and controversial. However, most supplementation studies in human used a PP, Resveratrol at supra nutritional doses (ie not compatible with a balanced diet of fruits and vegetables). In a previous study, investigators tested the interest of a supplementation with red grape PP nutritional doses in healthy subjects with metabolic risk (overweight subjects and related to the first degree of T2DM patients) on IR hyperinsulinemic euglycemic clamp measured. During this study, the PP have prevented the central mechanisms of muscle IR that are oxidative stress and mitochondrial dysfunction induced by a load fructose.

For this project, investigators propose to test the effect of a red grape PP supplementation at nutritional doses for 8 weeks on IR and weight loss in 30 obese insulin resistant. This is a double-blind randomized placebo-controlled. This supplementation will be associated with a standard support for their obesity performed routinely in the Nutrition and Diabetes unit.

Specific inclusion criteria: Female or male nondiabetic 50-65 years, BMI> 30 kg / m2 and with a HOMA> 3.

The main objective is to test whether supplementation PP improves systemic insulin sensitivity (GIR: rate glucose infusion) measured by hyperinsulinemic-euglycemic clamp (gold standard for measuring insulin sensitivity) in insulin-resistant obese subjects.

Secondary objectives are to:

Test whether supplementation PP improves insulin sensitivity to tissue (fat and muscle) and compare the response to supplementation in these two tissues.
Determining the cellular and molecular mechanisms involved in improving IR: regulation of inflammation, oxidative stress.
Determine whether supplementation PP optimizes weight reduction compared to a standard single support.

NSN: The number of subjects required was evaluated from our previous work (2013 Hokayem et al.) Whose main objective was to assess the impact of PD versus placebo in first degree relatives of patients with diabetes type 2. Under a bilateral alternative hypothesis of a nonparametric test (Mann-Whitney), 1: 1 ratio, a power of 80% and an alpha risk of 0.05, the number of subjects was estimated at 15 per group.

Methodology: Anthropometric measurements, assessment of body composition (DEXA) system application characterization (metabolism, inflammation, oxidative stress, adipokines and insulin sensitivity: clamp hyperinsulinemic-euglycemic, lipopolysaccharides: LPS) / tissue characterization (biopsies of skeletal muscle and tissue adipose): insulin sensitivity, inflammation, oxidative stress, gene regulation (sirt1), mitochondrial activity / cell characterization (adipocyte precursor and muscle) insulin sensitivity, inflammation, oxidative stress, sirt1.

Investigators hope to demonstrate that a non-pharmacological treatment based on nutritional doses of PP supplementation can improve insulin sensitivity in insulin-resistant obese patients, refer to optimize weight loss compared to a standardized management of obesity and determine the mechanisms involved.


acronym: EPIDEX

summary: The combined administration of high dose of oral betamethasone and nebulization of adrenaline seems to be an attractive therapeutic alternative for reducing the rate of hospitalization for acute bronchiolitis treated in the emergency department. However, it is essential to confirm the trend previously observed with this treatment before using it in current practice.

status: Terminated

title: Nebulized Adrenalin and Oral Betamethasone in Children With Bronchiolitis Attending Pediatric Emergencies : a Multicentre Randomized Controlled Trial

source: euctr

appel_a_projets: PHRCN

acronyme: EPIDEX

titre: Efficacité de l'association Nébulisation d'adrénaline - Dexamethasone orale dans la prise en charge des bronchiolites aiguës du nourrisson aux urgences pédiatriques : essai multicentrique en double insu

discipline_principale: médecine d'urgence

nom_porteur: JOFFRE

prenom_porteur: Christelle


acronym: BRADYVASC

lead_sponsor: University Hospital, Rouen

summary:
The conduit arteries exhibit a viscoelastic behavior. Visco-elasticity is partially regulated by endothelium and contributes to the optimization of the heart-vessel coupling. Aging or high resting heart rate (HR) could alter visco-elastic properties leading to increase stiffness of the conduit arteries, an independent cardiovascular risk factor, and degradation of heart-vessel coupling. Lowering HR with ivabradine could reduce these effects.

The objective of this study is to assess the effect of HR reduction by repeated administration of ivabradine on visco-elastic properties, vascular geometry and function of common carotid artery, and on cardiovascular hemodynamic in healthy subject. The influence of aging on ivabradine effects are studied too.

30 healthy volunteers aged between 25 and 65 years old, with a HR ≥ 70 bpm, will receive ivabradine or placebo during 8 days in a single center, randomized, cross-group, double blinded, placebo-controlled study. Each period of treatment will be separate by 12 to 16 days of wash-out. Each subject will participate in an exploration visit, including evaluation of visco-elastic properties, vascular geometry and function of common carotid artery, and cardiovascular hemodynamic, before and after ivabradine or placebo taking.

ReferenceCitation: Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation. 1999 Jul 27;100(4):354-60. doi: 10.1161/01.cir.100.4.354.

ReferenceCitation: Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25.

ReferenceCitation: Benetos A, Rudnichi A, Thomas F, Safar M, Guize L. Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. Hypertension. 1999 Jan;33(1):44-52. doi: 10.1161/01.hyp.33.1.44.

ReferenceCitation: Lantelme P, Mestre C, Lievre M, Gressard A, Milon H. Heart rate: an important confounder of pulse wave velocity assessment. Hypertension. 2002 Jun;39(6):1083-7. doi: 10.1161/01.hyp.0000019132.41066.95.

ReferenceCitation: Bellien J, Iacob M, Remy-Jouet I, Lucas D, Monteil C, Gutierrez L, Vendeville C, Dreano Y, Mercier A, Thuillez C, Joannides R. Epoxyeicosatrienoic acids contribute with altered nitric oxide and endothelin-1 pathways to conduit artery endothelial dysfunction in essential hypertension. Circulation. 2012 Mar 13;125(10):1266-75. doi: 10.1161/CIRCULATIONAHA.111.070680.

ReferenceCitation: Fox K, Ford I, Steg PG, Tendera M, Ferrari R; BEAUTIFUL Investigators. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Sep 6;372(9641):807-16. doi: 10.1016/S0140-6736(08)61170-8. Epub 2008 Aug 29.

ReferenceCitation: Bellien J, Remy-Jouet I, Iacob M, Blot E, Mercier A, Lucas D, Dreano Y, Gutierrez L, Donnadieu N, Thuillez C, Joannides R. Impaired role of epoxyeicosatrienoic acids in the regulation of basal conduit artery diameter during essential hypertension. Hypertension. 2012 Dec;60(6):1415-21. doi: 10.1161/HYPERTENSIONAHA.112.201087. Epub 2012 Oct 22.

ReferenceCitation: Reil JC, Tardif JC, Ford I, Lloyd SM, O'Meara E, Komajda M, Borer JS, Tavazzi L, Swedberg K, Bohm M. Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients. J Am Coll Cardiol. 2013 Nov 19;62(21):1977-1985. doi: 10.1016/j.jacc.2013.07.027. Epub 2013 Aug 7.

ReferenceCitation: Joannides R, Moore N, Iacob M, Compagnon P, Lerebours G, Menard JF, Thuillez C. Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise. Br J Clin Pharmacol. 2006 Feb;61(2):127-37. doi: 10.1111/j.1365-2125.2005.02544.x.

ReferenceCitation: Boutouyrie P, Beaussier H, Achouba A, Laurent S; EXPLOR trialists. Destiffening effect of valsartan and atenolol: influence of heart rate and blood pressure. J Hypertens. 2014 Jan;32(1):108-14. doi: 10.1097/HJH.0000000000000014.

ReferenceCitation: Tropeano AI, Boutouyrie P, Pannier B, Joannides R, Balkestein E, Katsahian S, Laloux B, Thuillez C, Struijker-Boudier H, Laurent S. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006 Jul;48(1):80-6. doi: 10.1161/01.HYP.0000224283.76347.8c. Epub 2006 May 15.

ReferenceCitation: Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9. doi: 10.1056/NEJMoa1406430. Epub 2014 Aug 31.

ReferenceCitation: Drouin A, Gendron ME, Thorin E, Gillis MA, Mahlberg-Gaudin F, Tardif JC. Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br J Pharmacol. 2008 Jun;154(4):749-57. doi: 10.1038/bjp.2008.116. Epub 2008 Apr 14.

ReferenceCitation: Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O'Rourke M; CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006 Mar 7;113(9):1213-25. doi: 10.1161/CIRCULATIONAHA.105.595496. Epub 2006 Feb 13.

ReferenceCitation: Bolduc V, Drouin A, Gillis MA, Duquette N, Thorin-Trescases N, Frayne-Robillard I, Des Rosiers C, Tardif JC, Thorin E. Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2081-92. doi: 10.1152/ajpheart.00706.2011. Epub 2011 Sep 16.

ReferenceCitation: Maltete D, Bellien J, Cabrejo L, Iacob M, Proust F, Mihout B, Thuillez C, Guegan-Massardier E, Joannides R. Hypertrophic remodeling and increased arterial stiffness in patients with intracranial aneurysms. Atherosclerosis. 2010 Aug;211(2):486-91. doi: 10.1016/j.atherosclerosis.2010.04.002. Epub 2010 Apr 13.

location_facility: Department of Pharmacology, Rouen university Hospital

title: Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall (BRADYVASC)


title: Prospective Population Based Cohort Study on Cognitive and Cardiovascular Aging

acronym: MLP

summary: Aging is a long term process, starting early in life, and progressively affecting various functions and organs. Cardiovascular diseases and cognitive impairment are two conditions related to advancing age and sharing common risk factors. The Mona Lisa- PREDOR study is a population-based prospective cohort study carried out to develop risk prediction algorithms aimed at identifying people who are the most likely to develop impaired psychometric and cognitive functioning and impaired cardiovascular risk, in the coming years.


title: Non-invasive Evaluation of Myocardial Stiffness by Elastography in the Elderly Suffering From Isolated Diastolic Heart Failure: New Diagnostic Tool?

acronym: Elasto-Cardio

summary:
SITUATION ON RESEARCH Diastolic heart failure (HF) or heart failure with preserved systolic function (SF) is the primary cause of heart failure in the elderly (over 2/3 of heart failure in patients over 60 years). Its main cause is hypertension. The diagnosis of diastolic heart failure is still controversial in clinical practice. It is based on ultrasound and biological criteria (or MRI). Basically, it is concerned patients making acute pulmonary edema with preserved SF and high BNP. It is now recognized that the "primum movens" of this type of HF is increased myocardial stiffness secondary to LVH. Noninvasive assessment of this parameter would allow a more accurate and reliable diagnosis because not dependent on load conditions unlike the ejection fraction (EF) and trans-mitral Doppler. However, the absence of non-invasive tool for the direct evaluation of the diastolic stiffness (so-called passive) prevents to date to use this diagnostic parameter.

The investigators propose here to evaluate noninvasively myocardial stiffness in elderly patients with diastolic heart failure using a new imaging tool that uses an innovative ultrasonic technology, the ultrafast echo associated with its elastography function "ShearWave Imaging" (SWI). The investigators work for several years in collaboration with the Langevin Institute on this technology which was recently validated in experimental models. Its principle is based on the creation of a shear wave from a standard ultrasound and calculating the velocity of this wave with the high time resolution of the ultrasound probe, this being correlated with the speed myocardial stiffness.

The human study was recently made possible by the development of a phased array probe having the opportunity to work with elastography mode (SWI).

PURPOSE OF RESEARCH The goal will be to demonstrate the interest of the non-invasive evaluation by ultrafast echo (SWI) of myocardial stiffness in the diagnosis of diastolic heart failure in the elderly.

ReferenceCitation: Villemain O, Correia M, Mousseaux E, Baranger J, Zarka S, Podetti I, Soulat G, Damy T, Hagege A, Tanter M, Pernot M, Messas E. Myocardial Stiffness Evaluation Using Noninvasive Shear Wave Imaging in Healthy and Hypertrophic Cardiomyopathic Adults. JACC Cardiovasc Imaging. 2019 Jul;12(7 Pt 1):1135-1145. doi: 10.1016/j.jcmg.2018.02.002. Epub 2018 Mar 14.

oa_colors: green hybrid

evidence: open (via crossref license)

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Paris Descartes

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - memSIC