Assessment of bleeding risk in cancer patients treated with anticoagulants for venous thromboembolic events

IntroductionAnticoagulant is the cornerstone of the management of VTE at the cost of a non-negligible risk of bleeding. Reliable and validated clinical tools to predict thromboembolic and hemorrhagic events are crucial for individualized decision-making for the type and duration of anticoagulant treatment. We evaluate the available risk models in real life cancer patients with VTE. The objectives of the study were to describe the bleeding of cancer patients with VTE and to evaluate the performance of the different bleeding models to predict the risk of bleeding during a 6-month follow-up.Materials and MethodsVTE-diagnosed patient's demographic and clinical characteristics, treatment regimens and outcomes for up to 6 months were collected. The primary endpoint was the occurrence of a major bleeding (MB) or a clinically relevant non major bleeding (CRNMB) event, categorized according to the ISTH criteria.ResultsDuring the 6-months follow-up period, 26 out of 110 included patients (26.7%) experienced a bleeding event, with 3 recurrences of bleeding. Out of the 29 bleeding events, 19 events were CRNMB and 10 MB. One patient died because of a MB. Bleeding occurred in 27 % of the patients treated with DOACs and 22% of the patients treated with LMWH. Most of the bleedings were gastrointestinal (9 events, 31%); 26.9% of the bleedings occurred in patient with colorectal cancer and 19.6% in patients with lung cancer. In our cohort, none of the 10 RAMs used in our study were able to distinguish cancer patients with a low risk of bleeding, from all bleeding or non-bleeding patients. The Nieto et al. RAM had the best overall performance (C-statistic = 0.730, 95% CI (0.619–0.840)). However, it classified 1 out of 5 patients with major bleeding in the low risk of bleeding group. The rest of the RAMs showed a suboptimal result, with a range of C-statistic between 0.489, 95%CI (0.360–0.617)) and 0.532, 95%CI (0.406–0.658)).ConclusionsThe management of CAT patients is challenging due to a higher risk of both recurrent VTE and bleeding events, as compared with non-cancer patients with VTE. None of the existing RAMs was able to consistently identify patients with risk of anticoagulant associated bleeding events

The Click Test: A Novel Tool to Quantify the Age-Related Decline of Fast Motor Sequencing of the Thumb

International audienceAbstract : Background: The thumb plays a critical role for manual tasks during the activities of daily life and the incidence of neurological or musculoskeletal disorders affecting the voluntary movements of the thumb is high in the elderly. There is currently no tool to assess repetitive motor sequencing of the thumb during ageing.Objectives: To report a novel procedure (the Click Test) assessing the effects of ageing on fast motor sequencing of the thumb.Methods : Healthy subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years; F/M: 151/101) were asked to perform fast repeated flexion/extension movements of the thumb using a mechanical counter.Results: Motor performances (assessed by the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly decreased as a function of age for both the dominant (age effect; p< 0.0001 for 15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec). The number of clicks was significantly higher in males (gender effect; p<0.001) and was higher on the dominant side as compared to the non-dominant side (handedness effect: p<0.001). The Click Test is characterized by high repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra-rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high inter-rater reproducibility (Pearson’s product correlation ranging from 0.85 to 0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly correlated in terms of relative performances with the box and block test and the 9-hole peg test (positive linear correlation with the results of the box and block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand; negative linear correlation with the results of the 9-hole peg test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand).Conclusion : The Click Test is an entirely novel and very low cost tool to reliably discriminate the ageing effects upon the performances during fast repetitive motor sequencing of the thumb. The potential clinical and research applications for motor functions are multiple, especially in acute and chronic neurological disorders affecting the thumb as well as in the field of rheumatology and orthopedics

Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan

AbstractBackground and purposesEarly biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy.Materials and methodsPlasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC–ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan.ResultsPretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan–Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume.ConclusionsTotal plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape

Séminaire e-DIADEM sur le thème TICE (Technologies de l\u27Information et de la Communication pour l\u27Enseignement) : usages en contexte

Le laboratoire Elico a organisé le 3 décembre 2007 le séminaire e-DIADEM sur le thème "TICE (Technologies de l\u27Information et de la Communication pour l\u27Enseignement) : usages en contexte". Organisé par les chercheurs du groupe e-DIADEM. Trois chercheurs externes au laboratoire Elico sont intervenus au cours du séminaire : Christine DEVELOTTE (INRP), Viviane GLIKMAN (CNAM), Hélène GODINET (INRP)

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Littoraux et paysages insulaires

International audienc

Comportement des populations de cellules souches adultes dans les tissus musculaires et adipeux chez l'animal en croissance et modèle mathématique

National audienceDepuis peu, la manipulation des cellules souches adultes est considérée comme une nouvelle solution pour contrôler le nombre et les types de cellules différenciées dans un tissu. L’implication de ces cellules chez l’animal en croissance reste largement à caractériser. L’objectif de notre étude est d’analyser le comportement de cellules souches adultes, lors de la prolifération et la différenciation de ces dernières, dans différents tissus du porc en croissance ; les tissus étudiés étant le tissu musculaire et adipeux. Ce projet est porté à la fois par l'INRA (Institut National de la Recherche Agronomique) situé à Saint-Gilles, et par l'IRMAR (Institut de Recherche Mathématiques de Rennes). Les enjeux de cette étude étaient d'obtenir des informations supplémentaires sur le comportement des cellules souches pour pouvoir avoir une meilleure compréhension de la variabilité de la composition corporelle chez les porcs en croissance. Cette étude a permis de modéliser le comportement des populations de cellules souches adultes lors de la prolifération et la différenciation. Une analyse du modèle complet a également permis d'avoir un aperçu du comportement des populations de cellules lorsque la prolifération et la différenciation se font au même moment. En effet, une telle analyse était impossible in vitro car on ne peut observer les deux phénomènes en même temps. Cette étude a également permis d'obtenir des données supplémentaires à partir d'articles déjà parus ou d'expérimentations faites sur ces modèles cellulaires. On connait par exemple le temps de division cellulaire global des cellules souches adultes dans le muscle et le tissu adipeux. L'étude menée ici a permis aux chercheurs d'appréhender différemment les méthodes d'analyse et de regarder une dynamique pour observer l'état des cellules au cours de leur prolifération puis de leur différenciation

Mathematical model of the behavior of stem cell populations in skeletal muscle and adipose tissue in growing pigs

Mathematical model of the behavior of stem cell populations in skeletal muscle and adipose tissue in growing pigs. 70. Annual Meeting of the European Federation of Animal Science (EAAP

Heterogeneity of otolith chemical composition from 2D mapping: relationship with biomineralization mechanisms and implications for microchemistry analyses

Although otoliths are widely used as archives to infer life history traits and habitat use in fishes, their biomineralization process remains poorly understood. This lack of knowledge is problematic as it can lead to misinterpretation of the different types of signals (e.g. optical or chemical) that provide basic data for research in fish ecology, fisheries management and species conservation. Otolith calcification relies on a complex system involving a pericrystalline fluid, the endolymph, which organic and inorganic compositions are spatially heterogeneous for some constituents. This property stems from the particular structure of the calcifying saccular epithelium. In this study, we explored the spatial heterogeneity of elemental incorporation in otoliths for two species of high economic interest, European hake Merluccius merluccius (L. 1758) and European sea bass Dicentrarchus labrax (L. 1758). Two-dimensional mappings of chemical elements were obtained by UV-fs LA-HR-ICPMS analyses on transverse sections of sagittae. Results highlighted a clear asymmetry between proximal (sulcus) and distal (antisulcus) concentrations for elements such as magnesium Mg, phosphorus P, manganese Mn and potassium K with concentration gradient directions that varied depending on the element. Strontium Sr and barium Ba did not show a proximo-distal gradient. These results are discussed in the light of current knowledge on the endolymph composition and the mechanisms that lead to its compartmentalization, highlighting the need for further research on otolith biomineralization. Operational implications for studies based on otolith chemical composition are also discussed with emphasis on advice for sampling strategies in order to avoid analytical biases, and the need for in-depth analyses of analytical settings before comparing otolith signatures between species or geographical areas. This article is protected by copyright. All rights reserved