21 research outputs found

    Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults

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    International audienceEssentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 109 L-1 and < 10 × 109 L-1 . Exposure to anticoagulants was a major risk factor of severe bleeding.Summary: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the CytopĂ©nies Auto-immunes Registre Midi-PyrĂ©nĂ©EN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L-1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L-1 versus ≄ 20 × 109 L-1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 109 L-1 and 19 × 109 L-1 versus ≄ 20 × 109 L-1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 109 L-1 and < 10 × 109 L-1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding

    Evaluation of peak power flux densities based on full ion orbit calculation: Application to WEST ITER-like target

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    International audienceThe peak power flux densities from plasma ion bombardment on tokamak armor surfaces can deviate from geometric-optical projection when the ion thermal Larmor radius becomes comparable to the characteristic size of the surface relief (gaps, misalignments, shaping). We present a fast and reliable tool to estimate the effect of finite ion Larmor radius on heat load deposition for complex 3D elements. The two possible geometrical design options foreseen for WEST tungsten monoblocks are asymmetric chamfer shaping and no shaping on top of monoblocks. This paper presents an evaluation of peak power flux densities for a WEST ITER-like tungsten monoblock plasma facing component which is vertically misaligned with respect to the other components of a maximum expected value of +0.3 mm, for steady state convected plasma power with ion temperature ranging from 10 to 500 eV. With the +0.5 mm asymmetric chamfer, leading edges between plasma facing components are shadowed and there is no significant difference between the optical calculations and the full ion orbit model. For an unshaped and +0.3 mm misaligned monoblock, when considering the full ion orbit model, the heat load on the exposed edge is reduced by a factor of 3-5 compared to the geometric-optical projection. Energy is found to be deposited over several millimetres on top of the monoblock just after the leading edge which prevents the tungsten armor from melting. (C) 2016 Elsevier B.V. All rights reserved

    Validity and limitations of simple reaction kinetics to calculate concentrations of organic compounds from ion counts in PTR-MS

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    In September 2017, we conducted a proton-transfer-reaction mass-spectrometry (PTR-MS) intercomparison campaign at the CESAR observatory, a rural site in the central Netherlands near the village of Cabauw. Nine research groups deployed a total of 11 instruments covering a wide range of instrument types and performance. We applied a new calibration method based on fast injection of a gas standard through a sample loop. This approach allows calibrations on timescales of seconds, and within a few minutes an automated sequence can be run allowing one to retrieve diagnostic parameters that indicate the performance status. We developed a method to retrieve the mass-dependent transmission from the fast calibrations, which is an essential characteristic of PTR-MS instruments, limiting the potential to calculate concentrations based on counting statistics and simple reaction kinetics in the reactor/drift tube. Our measurements show that PTR-MS instruments follow the simple reaction kinetics if operated in the standard range for pressures and temperature of the reaction chamber (i.e. 1–4 mbar, 30–120∘, respectively), as well as a reduced field strength E∕N in the range of 100–160 Td. If artefacts can be ruled out, it becomes possible to quantify the signals of uncalibrated organics with accuracies better than ±30 %. The simple reaction kinetics approach produces less accurate results at E∕N levels below 100 Td, because significant fractions of primary ions form water hydronium clusters. Deprotonation through reactive collisions of protonated organics with water molecules needs to be considered when the collision energy is a substantial fraction of the exoergicity of the proton transfer reaction and/or if protonated organics undergo many collisions with water molecules

    Taux de rĂ©missions prolongĂ©es Ă  l’arrĂȘt d’un traitement par agoniste du rĂ©cepteur de la thrombopoĂŻĂ©tine au cours de la thrombopĂ©nie immunologique : suivi Ă  long-terme de l’étude STOPAGO, cohorte prospective multicentrique

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    International audienceIntroductionLes agonistes du rĂ©cepteur de la thrombopoĂŻĂ©tine (ARTPO) sont des traitements efficaces dans la thrombopĂ©nie immunologique (PTI), mais du fait de leur mĂ©canisme d’action, ceux-ci ont Ă©tĂ© initialement considĂ©rĂ©s comme uniquement suspensifs. Ce dogme a Ă©tĂ© remis en question par plusieurs Ă©tudes rĂ©centes mais la plupart ont inclus des PTI nouvellement diagnostiquĂ©s pour lesquels une rĂ©mission spontanĂ©e peut se produire indĂ©pendamment des traitements. Dans ce contexte, l’étude prospective multicentrique française STOPAGO a montrĂ© que chez des patients atteints de PTI chronique en rĂ©ponse complĂšte stable depuis un an, les ARTPO pouvaient ĂȘtre interrompus sans rechute dans 50 % des cas aprĂšs un an de suivi [1]. Les rechutes survenaient principalement dans les 4 semaines suivant l’arrĂȘt des ARTPO, sans Ă©vĂ©nement hĂ©morragique sĂ©vĂšre observĂ©. En cas de rechute, la reprise de l’ARTPO permettait d’obtenir une nouvelle rĂ©ponse complĂšte chez 90 % des patients. L’objectif de ce travail est d’actualiser ces donnĂ©es avec un suivi Ă  long terme.Patients et mĂ©thodesL’étude STOPAGO (#NCT03119974) Ă©tait prospective interventionnelle ouverte multicentrique, conduite dans 20 centres en France appartenant au rĂ©seau du CERECAI. Les patients inclus Ă©taient des adultes avec un PTI persistant ou chronique en rĂ©ponse complĂšte prolongĂ©e (plaquettes > 100 G/L > 2 mois) grĂące Ă  un traitement par ARTPO (eltrombopag ou romiplostim) commencĂ© depuis au moins 3 mois. AprĂšs inclusion, la dĂ©croissance de l’ARTPO Ă©tait initiĂ©e selon un protocole standardisĂ© permettant une interruption du traitement en moins de 10 semaines. La rĂ©mission prolongĂ©e Ă©tait dĂ©finie par un taux de plaquettes > 30 G/L et l’absence de saignement, et la rĂ©mission complĂšte prolongĂ©e par un taux de plaquettes > 100 G/L et l’absence de saignement. Les donnĂ©es actualisĂ©es de suivi Ă  long terme aprĂšs la derniĂšre inclusion ont Ă©tĂ© collectĂ©es par les investigateurs des centres participants.RĂ©sultatsQuarante-huit patients, dont 61 % de femmes, ont Ă©tĂ© inclus dans l’étude STOPAGO entre septembre 2017 et fĂ©vrier 2020. Une rĂ©mission prolongĂ©e et une rĂ©mission complĂšte prolongĂ©e Ă©taient obtenues chez respectivement 27/48 (56 %) et 15/48 (31 %) patients Ă  6 mois, et 25/48 (52 %) et 14/48 (29 %) patients Ă  12 mois. Les 25 patients en rĂ©mission prolongĂ©e Ă  12 mois ont pu ĂȘtre suivis pour une durĂ©e mĂ©diane supplĂ©mentaire de 5 ans (de 3,3 Ă  6,3 ans). Parmi ces derniers, tous sauf 2 avaient reçu de l’eltrombopag, pendant en mĂ©diane 2,1 [1,1–4,1] ans avant l’arrĂȘt. À 4 ans aprĂšs l’arrĂȘt de l’ARTPO, la rĂ©mission prolongĂ©e et la rĂ©mission complĂšte prolongĂ©e Ă©taient obtenues chez respectivement 22/46 (48 %) et 17/46 (37 %) patients (2 patients perdus de vue aprĂšs 3 ans). Seulement 2 (8 %) des patients en rĂ©mission Ă  12 mois ont rechutĂ© au cours de l’extension du suivi. Aucun n’a prĂ©sentĂ© de syndrome hĂ©morragique au moment de la rechute. Le premier a rechutĂ© 5 ans aprĂšs l’arrĂȘt de l’eltrombopag et Ă©tait de nouveau en rĂ©ponse complĂšte 5 semaines aprĂšs la reprise de celui-ci. Le second a rechutĂ© 2 ans aprĂšs l’arrĂȘt de l’eltrombopag dans un contexte de grippe. La reprise de l’eltrombopag et de 3 autres lignes thĂ©rapeutiques a Ă©tĂ© inefficace motivant rĂ©cemment l’initiation d’un traitement par fostamatinib. Au cours du suivi, sont survenus une grossesse (sans rechute ni thrombopĂ©nie nĂ©onatale), une infection Ă  SARS-CoV-2, un lymphome B Ă  petites cellules et une sclĂ©rodermie sans rechute du PTI.ConclusionNos rĂ©sultats montrent le maintien d’un taux de rĂ©ponse prolongĂ© Ă  distance de l’arrĂȘt des ARTPO chez prĂšs de 50 % des patients avec un PTI chronique en rĂ©ponse complĂšte initiale sous traitement. Ces donnĂ©es actualisĂ©es confirment que les rechutes surviennent en majoritĂ© de maniĂšre prĂ©coce les premiĂšres semaines aprĂšs l’arrĂȘt, tandis que les rechutes tardives sont rares (2/25 patients). Ces rĂ©sultats plaident en faveur d’une stratĂ©gie d’arrĂȘt des ARTPO chez les patients avec un PTI chronique en rĂ©mission complĂšte stable
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