The 8-9 September 2002 extreme flash-flood : Meteorological description and mesoscale simulations

International audienceThe Southeastern France is prone to heavy precipitating events. A major event has occurred the 8-9th September 2002, with maxima of accumulated rainfall totals having reached locally 600-700 mm; there were more than 20 deaths. The high resolution non-hydrostatic model MESO-NH (2.4 km grid-mesh) has been run a posteriori on this case. It has been found that the high resolution simulation may significantly improves the quantitative precipitation forecast of the event. A sensitivity study to initial conditions has been conducted and shows clearly that mesoscale data assimilation is the most efficient to improve the short range forecast : assimilation of mesonet surface observations, radar and satellite data helps to improve significantly the location of the precipitation maximum. The high resolution model has been also used to study the event, and in particular to understand the relative unusual location of the largest precipitation over the upwind lower mountainous area of the Gard department rather than over the Massif Central crests. The location of the most active convection is explained by a cold pool beneath the simulated storm that faced the low-level moist and unstable southeastern flow from Mediterranean sea. This density current, produced by the evaporation, sublimation and melting of precipitation, forced the unstable air to lift, generating therefore continuously new convective cells at the leading edge of the cold pool

LeDéfaut en Rab 27a (Etude rétrospective de 9 patients)

Le syndrome de Griscelli de type II est une maladie génétique autosomique récessive rare associant un albinisme oculo-cutané partiel à une déficit immunitaire d'aspect variable se compliquant d'épisodes d'activation lymphohistiocytaire. Il est du à des mutations portant sur un gène codant pour une petite GTPase, la protéine Rab 27a, impliquée dans le transport des mélanosomes des mélanocytes vers les kératinocytes et dans la cytotoxicité T et NK. Nous rapportons avec ces 9 observations l'opportunité de discuter le phénotype clinique et biologique de cette affection rare de l'homéostasie lymphocytaire, mais aussi d'insister sur l'importance du diagnostic précoce avant la survenue d'une phase accélérée réfractaire permettant ainsi de réaliser rapidement une transplantation médullaire, seul traitement curable.ST ETIENNE-BU Médecine (422182102) / SudocSudocFranceF

L’événement des 8-9 septembre 2002 : situation météorologique et simulation a mésoéchelle

La situation extrême des pluies diluviennes du 8-9 septembre 2002 fait l’objet d’une étude a posteriori avec le modèle de recherche MESO-NH utilisé à une résolution de quelques kilomètres. Après une brève description du contexte et de l’événement météorologique qui ont conduit aux pluies exceptionnelles, le potentiel de la modélisation à haute résolution pour la prévision quantitative des précipitations est examiné à l’aide de différentes expériences de sensibilité aux conditions initiales et de surface. Dans un second temps, la modélisation à haute résolution est utilisée comme outil de retour d’expérience pour mieux comprendre les phénomènes météorologiques à l’origine des fortes précipitations

The 8-9 September 2002 extreme flash-flood : Meteorological description and mesoscale simulations

International audienceThe Southeastern France is prone to heavy precipitating events. A major event has occurred the 8-9th September 2002, with maxima of accumulated rainfall totals having reached locally 600-700 mm; there were more than 20 deaths. The high resolution non-hydrostatic model MESO-NH (2.4 km grid-mesh) has been run a posteriori on this case. It has been found that the high resolution simulation may significantly improves the quantitative precipitation forecast of the event. A sensitivity study to initial conditions has been conducted and shows clearly that mesoscale data assimilation is the most efficient to improve the short range forecast : assimilation of mesonet surface observations, radar and satellite data helps to improve significantly the location of the precipitation maximum. The high resolution model has been also used to study the event, and in particular to understand the relative unusual location of the largest precipitation over the upwind lower mountainous area of the Gard department rather than over the Massif Central crests. The location of the most active convection is explained by a cold pool beneath the simulated storm that faced the low-level moist and unstable southeastern flow from Mediterranean sea. This density current, produced by the evaporation, sublimation and melting of precipitation, forced the unstable air to lift, generating therefore continuously new convective cells at the leading edge of the cold pool

Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test

International audienceSevere hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI

Efficacy and tolerance of Lidocaine 5% patches in neuropathic pain and pain related to vaso-occlusive sickle-cell crises in children

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Late cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the LEA program

International audienceLate cardiomyopathy in childhood acute myeloid leukemia survivors: a study from the L.E.A. program Prognosis of pediatric acute myeloid leukemia (AML) has improved significantly over the past two decades with survival rates now approaching 70%. 1 Therapy consists of a limited number of intensive chemotherapy courses mainly based on cytarabine and anthracycline. 2,3 Many pediatric late anthracycline cardiotoxicity studies have concerned heterogeneous diagnostic groups. Moreover, single childhood cancer studies were mainly conducted in acute lym-phoblastic leukemia, whereas the highest doses of anthra-cycline are given in children with AML. 4-6 We report here a prospective multi-centric study of late cardiotoxicity in 185 patients surviving childhood AML. All were treated after 1989 in French clinical trials using intensive chemotherapy alone or chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). L.E.A. (Leucémie Enfant & Adolescent) is a French prospective long-term follow-up program involving all childhood acute leukemia survivors treated in the participating centers since 1980. Details of the programm are provided elsewhere. 7 As of 31 December 2011, 282 childhood AML survivors fulfilled the L.E.A. inclusion criteria and 218 (77.3%) of them agreed to participate. Among these 218, 185 were treated according to one of the 6 multicenter trial protocols ongoing in France after January 1989. All 185 had serial echocardiographic examination as part of their L.E.A. program, and all were included in the present study. All provided written informed consent. Cardiotoxicity was defined by either clinical symptoms of congestive heart failure or by an abnormal echocardiographic left ventricular function. Left ventricular function was considered abnormal when the shortening fraction (SF) was less than 28% or when the left ventricular ejection fraction (LVEF) was less than 55% on 2D echocardiography. 8-10 Cardiotoxicity was classified as late when it started or persisted beyond one year after the completion of first-line treatment. 9 Cumulative anthracycline doses used in each trial are described in the Online Supplementary Table S1, as well as the doxorubicin-equivalent doses using conversion factors of 0.83, 4.0 and 5.0 for daunorubicin, mitoxantrone and idarubicin, respectively. 10,11 Assessment of health status, long-term late effects on health-related quality of life (QoL), and statistical analysis are described in the Online Supplementary Appendix. Characteristics of the study cohort are summarized in Table 1. Median age at the time of AML diagnosis and median follow-up duration to last cardiac evaluation were 6.53 and 9.5 years, respectively. Thirty-seven patients had a history of relapse. Median cumulative anthracycline dose was 372 mg/m² (Online Supplementary Figure S1). Ninety-nine patients were treated by chemotherapy alone, whereas the other 86 patients also received HSCT (57 in first remission, 25 in second remission, and 4 in more advanced disease). Thirty children received total body irradiation (TBI), but only 10 among the 57 transplanted in first remission did so. Median number of echographic evaluations was 3 per patient. Subclinical cardiotoxicity (SCC) was observed in 23 of 185 patients (12.4%) at least once during their follow-up program. Median time from AML diagnosis to SCC detection was 4.40 years. In these 23 patients, the median value of the worst SF was 27% and the median value of the worst LVEF was 52. Only 3 of 23 patients had a worse SF value of less than 25% (2 had 20%; 1 had 24%). Six of 23 received anti-congestive therapy and none had cardiac transplantation. Five of those receiving anti-congestive therapy were still being treated at time of last evaluation, and 4 had more than 28% SF and more than 55% LVEF. Seventeen patients never received treatment: 11 had spontaneous improvement with more than 28% SF and more than 55% LVEF at last evaluation. Finally, at last cardiac evaluation, only 8 patients had an abnormal left ventricular function. Cumulative incidence (CI) of cardiotoxicity, estimated by the Kaplan-Meier method was 16% and 27% at 10 and 15 years, respectively (Figure 1A). CI of anti-conges-tive treatment at the same follow-up times was 5% and 7%. The risk of developing cardiotoxicity depended on a previous history of relapse and on the cumulative anthracy-cline dose. At ten years from diagnosis, CI was 35% versus 11% in patients with or without history of relapse (P=0.02) (Figure 1B). Among 148 patients without any history of relapse, 10-year CI of cardiotoxicity was 14% in 97 patients treated with chemotherapy alone versus 8% in 51 patients who underwent HSCT in first remission (NS, Figure 1C). In transplanted children, the risk was not modified by either a grade 2-4 acute or an extensive chronic graft-versus-host disease. The CI of anti-congestive treatment in these 148 patients who never experienced relapse was 3% at ten an

Adolescence and Socioeconomic Factors: Key Factors in the Long-Term Impact of Leukemia on Scholastic Performance—A LEA Study

International audienceOBJECTIVE:To evaluate the association between medical and social environmental factors and the risk of repeating a grade in childhood leukemia survivors.STUDY DESIGN:A cross-sectional study of childhood leukemia survivors, recruited through the LEA cohort (Leucémie de l'Enfant et de l'Adolescent [French Childhood Cancer Survivor Study for Leukemia]) in 2014. An adjusted logistic regression model was used to identify variables linked to repeating a grade after the diagnosis among the survivors, and the rates of repeating a grade were compared between the survivors and their siblings using a multilevel logistic regression model.RESULTS:The mean age at inclusion of the 855 participants was 16.2 ± 7.0 years, and the mean duration of follow-up from diagnosis to evaluation was 10.2 ± 6.2 years. After disease onset, 244 patients (28.5%) repeated a grade, with a median interval of 4 years (IQR, 2-8 years). Independent factors associated with repeating a grade were male sex (OR, 1.78; 95% CI, 1.21-2.60), adolescence (OR, 2.70; 95% CI, 1.63-4.48), educational support during the treatment period (OR, 3.79; 95% CI, 2.45-5.88), low parental education level (OR, 2.493; 95% CI, 1.657-3.750), and household financial difficulties (OR, 2.62; 95% CI, 1.607-4.28). Compared with siblings, survivors were at greater risk of repeating a grade (OR, 1.87; 95% CI, 1.48-2.35).CONCLUSIONS:The most vulnerable patients seemed to be adolescents and those with parents of low socioeconomic status. Improving the schooling career of leukemia survivors will require that the medical community more carefully consider the social status of patients