Pneumopathie induite par l'hydroxyurée. [Hydroxyurea-induced pneumonia].

International audienceIntroduction: Hydroxyurea is an antimetabolite widely used in the treatment of myeloproliferative diseases. Usual side effects are mainly hematological, gastrointestinal, neurological disorders and induced-fevers. More rarely, hydroxyurea-induced pneumonitis are reported. Case report: We report a case of a patient treated for polycythemia vera. She was admitted 20 days after introduction of hydroxyurea for a high fever, productive cough and clear sputum associated with nausea. Chest CT-scan found diffuse bilateral ground-glass opacities. The microbiological investigations were negative. Symptoms disappeared few days after discontinuation of treatment. Its reintroduction led to recurrence of symptoms. Conclusion: This additional case completes the 15 cases of hydroxyurea-induced pneumonitis described in the literature. Two forms of this disease seem to exist: an acute form with fever occurring in the month following introduction of hydroxyurea; and a chronic form without fever. Even if it is uncommon, pulmonologists should be aware of this complication

Recherche sur les types de temps associes aux brises de mer

Les circulations de brise de mer favorisent l’apparition de types de temps relativement frais et humides mais le plus souvent ensoleillés sur les espaces côtiers par rapport aux régions intérieures. Une méthode d’identification des fronts de brise par télédétection a été appliquée à l’Europe de l’Ouest et au nord-est du Brésil, afin d’en calculer la fréquence d’apparition et la distance préférentielle de pénétration dans les terres aux heures chaudes de la journée. Le suivi des fronts de brise a été effectué durant la saison chaude en Europe occidentale (mai à septembre 2000) et la moins arrosée dans le Nord-Est du Brésil (septembre à décembre 2000). La distance de pénétration des fronts de brise varie en fonction de l’exposition de la côte aux vents dominants, en Europe comme au Brésil. Cependant, la succession de situations météorologiques variées impose des configurations diverses d’un mois à l’autre en Europe de l’Ouest, tandis de la régularité des alizés fait ressortir une plus grande permanence, dans l’espace et dans le temps, de la localisation des fronts de brise au nord-est du Brésil.The sea breeze circulations involve cool and damp but sunny weather types over coastal fringes compared to inland areas. A method of identification of the sea breeze fronts was performed and applied to Western Europe and North-eastern Brazil, in order to calculate the occurrence of sea breeze fronts during the warmest period of the day and to calculate the most frequent distance of inland penetration. The sea breeze front monitoring was carried out during the warm season in Western Europe (May-September 2000) and during the less rainy season in North-eastern Brazil (September-December 2000). In Europe and Brazil, the inland penetration of sea breeze fronts varied according to the exposure of the coast to the prevailing wind. The succession of varied meteorological situations involved varied spatial organisation of the sea breeze fronts in Western Europe, while the more regular trade winds circulation allowed a less variable space and time organisation of the sea breeze fronts in the northeast of Brazil

Incidence of Pneumocystis jiroveci Pneumonia among Groups at Risk in HIV-negative Patients

International audienceBackground - Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV)-negative immunocompromised patients is associated with high mortality rates. Although trimethoprim-sulfamethoxazole provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging due to suboptimal characterization of patients most at risk, hence precluding targeted prophylaxis. Methods - We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (Program of Medicalization of the Information System [PMSI]). Results - From 1990 to 2010, 293 cases of pneumocystosis were documented, of which 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in 3 categories: 1) high risk (incidence rates >45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; 2) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and 3) low risk (<25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma. Conclusions - These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk

Analysis of a compartmental model of endogenous immunoglobulin G metabolism with application to multiple myeloma

Immunoglobulin G (IgG) metabolism has received much attention in the literature for two reasons: (i) IgG homeostasis is regulated by the neonatal Fc receptor (FcRn), by a pH-dependent and saturable recycling process, which presents an interesting biological system; (ii) the IgG-FcRn interaction may be exploitable as a means for extending the plasma half-life of therapeutic monoclonal antibodies, which are primarily IgG-based. A less-studied problem is the importance of endogenous IgG metabolism in IgG multiple myeloma. In multiple myeloma, quantification of serum monoclonal immunoglobulin plays an important role in diagnosis, monitoring and response assessment. In order to investigate the dynamics of IgG in this setting, a mathematical model characterizing the metabolism of endogenous IgG in humans is required. A number of authors have proposed a two-compartment nonlinear model of IgG metabolism in which saturable recycling is described using Michaelis-Menten kinetics; however it may be difficult to estimate the model parameters from the limited experimental data that are available. The purpose of this study is to analyse the model alongside the available data from experiments in humans and estimate the model parameters. In order to achieve this aim we linearize the model and use several methods of model and parameter validation: stability analysis, structural identifiability analysis, and sensitivity analysis based on traditional sensitivity functions and generalized sensitivity functions. We find that all model parameters are identifiable, structurally and taking into account parameter correlations, when several types of model output are used for parameter estimation. Based on these analyses we estimate parameter values from the limited available data and compare them with previously published parameter values. Finally we show how the model can be applied in future studies of treatment effectiveness in IgG multiple myeloma with simulations of serum monoclonal IgG responses during treatment

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Evaluation de l'apport de l'IRM corps entier avec séquences de diffusion pour le suivi du myélome multiple

Introduction. L'IRM de diffusion est en cours d'évaluation dans le myélome multiple. L'objectif de notre étude était d'évaluer l'apport de l'IRM de diffusion corps entier pour le suivi de myélome. Méthodes. Chez 54 patients ayant eu 2 IRM corps entier avec séquences de diffusion pour le suivi d'un myélome, nous avons comparé évolution en IRM et évolution biologique. Nous avons aussi évalué l'apport des séquences de diffusion par rapport aux séquences classiques, et la concordance inter-observateurs pour l'interprétation des IRM. Résultats. L'évolution en IRM avec séquences de diffusion concordait avec l'évolution biologique dans 66,7% des cas. Cela équivalait à une concordance modérée (kappa pondéré 0,53), meilleure qu'en n'interprétant que les séquences T1 et STIR (kappa pondéré 0,50). La concordance inter-observateurs était modérée à bonne. Conclusion. L'IRM de diffusion corps entier évolue avec l'activité du myélome et semble un examen prometteur pour le suivi de cette pathologie.Introduction. Diffusion-weighted MRI (DWI) is currently evaluated in multiple myeloma. The aim of our study was to assess the interest of whole-body DWI (WB-DWI) for the follow-up of MM. Methods. 54 patients with myeloma underwent 2 WB-DWI at Rennes university hospital. We compared MRI changes to clinical evolution based on the international uniform response criteria. We also evaluated the impact of diffusion-weighted images compared to conventional MRI images, and the inter-observeur agreement. Results. We found an agreement between MRI changes and clinical evolution in 66,7% of cases. The weighted kappa coefficient was 0,53 (95% CI, 0,34 to 0,72), indicating moderate agreement, slightly higher than when taking into account only T1 and STIR weighted images (weighted kappa 0,50, 95% CI 0,31 to 0,69). Inter-observer agreement was moderate to good. Conclusion. WB-DWI correlates with clinical evolution and seems a promising technique for the follow-up of patients with MM.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Modes de révélation des cancers solides (expérience d'un service de médecine interne à propos de 174 cas)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'unité d'assistance diagnostique et thérapeutique rapide (UADTR) du service de médecine interne du CHU de Rennes (bilan d'activité et impact sur les relations entre la médecine générale et la médecine hospitalière)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Étude de l'apport d'un nouveau test (Hevylite ), permettant le calcul d'un rapport IgG /IgG et IgA /IgA , pour l'évaluation de la réponse au traitement du myélome multiple

Dans le myélome multiple (MM), la concentration de l'immunoglobuline monoclonale quantifiée par le pic à l'électrophorèse des protéines (EPS) est considérée comme le meilleur biomarqueur pour le suivi et l'évaluation de la réponse au traitement. Un nouveau test néphélémétrique (Hevylite - Binding Site Group Ltd) permet la mesure des concentrations des IgG , IgG , IgA et IgA ainsi que le calcul des rapports IgG /IgG and IgA /IgA (HLC ratio). Notre objectif était d'évaluer l'intérêt d'Hevylite dans la réponse au traitement. Nous avons analysé 114 prélèvements issus de 15 patients porteurs de MM. Dans tous les sérums initiaux, le rapport HLC était normal. Pour 3 patients, la rechute a été détectée par une majoration du rapport HLC 2 mois avant l'EPS. Le rapport HLC s'est normalisé chez 5 patients alors que l'immunofixation restait positive. Ces résultats préliminaires indiquent qu'il est possible de suivre la réponse au traitement du MM en utilisant le rapport HLC.In multiple myeloma, concentration of monoclonal immunoglobulin by quantification of protein bands in serum protein electrophoresis (SPE) is considered the best biomarker for monitoring and evaluation of response to treatment. A new nephelometric immunoassay (Hevylite - Binding Site Group Ltd) allows specific measurement of serum IgG , IgG , IgA and IgA concentrations and makes possible calculation of IgG /IgG and IgA /IgA ratios (heavy/light chain or HLC ratio). Our aim was to evaluate contribution of Hevylite to assess response to treatment. We analysed 114 samples from 15 multiple myeloma patients. In all sera taken at diagnosis, HLC ratio was abnormal . In 3 patients, relapse from partial response was indicated by an increase in HLC ratio 2 months before SPE. HLC ratio became normal in 5 patients wheras immunofixation was still positive. These preliminary results indicate that is possible to monitor response to treatment using HLC ratio.RENNES1-BU Santé (352382103) / SudocSudocFranceF