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Introduction: To describe the efficacy of tocilizumab in patients with Graves' orbitopathy resistant or dependent to steroids and compare to rituximab treated patients.Patients and Methods: Graves's orbitopathy response was considered as decrease of at least 2 points of the CAS.Results: Twenty-one patients were included, 7 patients were treated with tocilizumab and 14 with rituximab. The primary was achieved in all 7 patients (100%) on tocilizumab and 9 out of 14 patients on (64%) rituximab (p = .17). Mean change in CAS was consistent with a decrease of 3.3 ± 0.5 points in patients on tocilizumab versus 2.5 ± 1.9 in patients on rituximab (p = .07). One patient on tocilizumab (14%) and 4 patients (29%) on rituximab experienced significant relapse during the follow-up. The difference in relapse-free survival was not significant in patients on tocilizumab (10.8 ± 4 months) compared with rituximab (17.88 ± 3.66).Conclusion: We showed a significant improvement in the CAS, visual acuity, diplopia, and proptosis with both tocilizumab and rituximab.

Comme suite à la réémergence du sérotype 8 de la fièvre catarrhale ovine (FCO)ovine en septembre 2015, un nouveau dispositif de surveillance entomologique des populations de Culicoides a été déployé en France continentale à l'automne-hiver 2016-2017, pour la deuxième année consécutive. Cette surveillance entomologique a permis de déterminer avec succès les périodes d'inactivité vectorielle relatives aux 24 zones de piégeage définies sur le territoire continental. Les informations issues de ce dispositif couplées à une surveillance de la circulation virale ont permis de déclarer jusqu'à seize départements de la zone réglementée en zones saisonnièrement indemnes (ZSI) sur des durées variables.

International audience; Mycobacterium bovis infection was first described in free-ranging wildlife in France in 2001, with subsequent detection in hunter-harvested ungulates and badgers in areas where outbreaks of bovine tuberculosis (TB) were also detected in cattle. Increasing concerns regarding TB in wildlife led the French General Directorate for Food (DGAL) and the main institutions involved in animal health and wildlife management, to establish a national surveillance system for TB in free-ranging wildlife. This surveillance system is known as “Sylvatub.” The system coordinates the activities of various national and local partners. The main goal of Sylvatub is to detect and monitor M. bovis infection in wildlife through a combination of passive and active surveillance protocols adapted to the estimated risk level in each area of the country. Event-base surveillance relies on M. bovis identification (molecular detection) (i) in gross lesions detected in hunter-harvested ungulates, (ii) in ungulates that are found dead or dying, and (iii) in road-killed badgers. Additional targeted surveillance in badgers, wild boars and red deer is implemented on samples from trapped or hunted animals in at-risk areas. With the exception of one unexplained case in a wild boar, M. bovis infection in free-living wildlife has always been detected in the vicinity of cattle TB outbreaks with the same genotype of the infectious M. bovis strains. Since 2012, M. bovis was actively monitored in these infected areas and detected mainly in badgers and wild boars with apparent infection rates of 4.57–5.14% and 2.37–3.04%, respectively depending of the diagnostic test used (culture or PCR), the period and according to areas. Sporadic infection has also been detected in red deer and roe deer. This surveillance has demonstrated that M. bovis infection, in different areas of France, involves a multi-host system including cattle and wildlife. However, infection rates are lower than those observed in badgers in the United Kingdom or in wild boars in Spain.

Following the re-emergence of the bluetongue virus serotype 8 (BTV8) in Septem-ber 2015 and in accordance with the European Commission's regulatory require-ments, a new entomological surveillance network has been set up throughout mainland France to monitor the activity of Culicoides, which are vectors of BTV. The new Culicoides surveillance network uses suction light traps that opera-te one night per week in one site per eco-climatic zone. Twenty-four eco-clima-tic zones were determined in mainland France by analyzing the data collected by the first surveillance network set up from 2009 to 2012 during the emergen-ce of BTV8. Each eco-climatic zone, regrouping one or more French departments, is homogeneous, taking into account the diversity of Culicoides species, the dura-tion of vector inactivity and the week of the beginning and the end of inactivity. This entomological surveillance active from November (Y0) to April (Y1) has made it possible to determine successfully periods without Culicoides vectors for the different eco-climatic zones defined on the continental territory. The informa-tion provided by this network, coupled with the surveillance of viral circulation, made it possible to report during winters 2015 to 2018 several French departmen-ts in BTV seasonally free zones, thus lifting restrictions on livestock movements. Research impact highlights: Following the re-emergence of BTV8 in September 2015, a new Culicoides surveillance network is operational throughout mainland France to determine the periods without vectors in each eco-climatic zone. The information pro-vided by this network, coupled with viral circulation monitoring, allows BTV's seasonal free zones to be declared each winter, thus lifting restrictions on livestock movements.

International audience; Several new highly pathogenic (HP) H5 avian influenza virus (AIV) have been detected in poultry farms from south-western France since November 2015, among which an HP H5N1. The zoonotic potential and origin of these AIVs immediately became matters of concern. One virus of each subtype H5N1 (150169a), H5N2 (150233) and H5N9 (150236) was characterised. All proved highly pathogenic for poultry as demonstrated molecularly by the presence of a polybasic cleavage site in their HA protein – with a sequence (HQRRKR/GLF) previously unknown among avian H5 HPAI viruses – or experimentally by the in vivo demonstration of an intravenous pathogenicity index of 2.9 for the H5N1 HP isolate. Phylogenetic analyses based on the full genomes obtained by NGS confirmed that the eight viral segments of the three isolates were all part of avian Eurasian phylogenetic lineage but differed from the Gs/Gd/1/96-like lineage. The study of the genetic characteristics at specific amino acid positions relevant for modulating the adaptation to and the virulence for mammals showed that presently, these viruses possess most molecular features characteristic of AIV and lack some major characteristics required for efficient respiratory transmission to or between humans. The three isolates are therefore predicted to have no significant pandemic potential.

Biosecurity : invesments for the future of french livestock. Biosecurity measures accompanied the development of above-ground livestock farming in France during the second half of the 20th century. These dispositions were progressively developed in the State health strategies in the early 2000s, following the identification of contaminations by wildlife : state compensation was then conditional to the implementation of these measures. Following the 2015-2016 influenza avian crisis, these biosecurity measures became mandatory for bird owners. In the future, all sectors, whether extensive or intensive, will have to integrate appropriate biosecurity measures to ensure their sustainability : they will have to integrate these principles into the design of the livestock organization., Les mesures de biosécurité ont accompagné le développement de l’élevage hors sol en France dans la seconde moitié du XXème siècle. Elles ont discrètement fait leur entrée dans les stratégies sanitaires de l’État au début des années 2000 avec l’identification de contaminations par la faune sauvage : l’indemnisation d’État était alors subordonnée à la mise en oeuvre de ces mesures. Avec la crise influenza aviaire de 2015–2016, les mesures de biosécurité sont devenues obligatoires pour les détenteurs d’oiseaux. A l’avenir, toutes les filières, qu’elles soient extensives ou intensives devront intégrer des mesures de biosécurité adaptées pour assurer leur pérennité, en intégrant pleinement ces principes dans la conception de l’organisation des élevages., Guériaux Didier, Fediaevsky Alexandre, Ferreira Bruno. La biosécurité : investissement d’avenir pour les élevages français. In: Bulletin de l'Académie Vétérinaire de France tome 170 n°2, 2017. pp. 112-117.

ContextPapillary thyroid microcarcinomas (PMC) defined as tumors ≤10 mm in diameter (including pT1a and pT3 according to the latest pTNM classification) have good prognosis, although recurrence is possible. Clinicians are interested in using a scoring system for predicting recurrences.ObjectiveTo identify the prognostic factors for recurrence in patients with PMC and to develop a scoring system based on lymph node involvement, multifocality, and sex. To determine the impact of extrathyroidal invasion (ETI) and a threshold value for analyzing multifocality.MethodsSingle-center retrospective study of a cohort of 1669 patients with PMC managed from 1960 to 2007. The Kaplan–Meier survival rate and prognostic factors of events were analyzed using log-rank tests and uni- and multivariate Cox model-based analyses. A scoring system was proposed.ResultsSixty-eight recurrences were observed. Initial lymph node metastases (P=0.0001), multifocality (P=0.05), and male sex (P=0.01) were significantly associated with recurrence, although there was a period effect (after 1990). PMC size was not a significant variable. Our scoring system allows us to separate patients into three risk groups according to their recurrence-free probability. For PMC Nx patients, total foci size of multifocal tumors >20 mm was significantly associated with recurrence (PConclusionOur scoring system classifies recurrence risk. In PMC Nx patients, multifocality is important in planning therapeutic strategies. Recurrence probability of pT3 PMC appears lower if RAI ablation is performed.

Objective: Germline mutations of the aryl hydrocarbon receptor-interacting protein gene (AIP) have recently been described in three families with GH or prolactin-secreting tumors, as well as in a few patients with apparently sporadic somatotropinomas. The aim of the study was to determine the prevalence of AIP mutations in a large cohort of patients with apparently sporadic GH-secreting tumors. Design: One hundred and fifty-four patients were included in a prospective cohort designed to study the genetic predisposition to GH-secreting tumors together with 270 controls. Methods: In all these subjects, the entire coding sequence of the AIP gene was screened for germline mutations. Results: AIP mutations were detected in 5 out of 154 patients (3%): nonsense mutations in exon 4 (p.Lys201X; n = 2) and in exon 6 (p.Arg304X), one deletion in exon 3 (c.404delA; pHis135LeufsX21), and one mutation affecting the splice acceptor site of exon 4 (c.469-2 A > G). The five patients with an AIP mutation were significantly younger (mean age ± S.D.: 25 ± 10 vs 43 ± 14 years, P = 0.005) and three of them presented with gigantism. One missense mutation (p.Arg304Gln) was found in a single patient that was absent in all controls. Conclusions: Germline mutations of the AIP gene were found in a small proportion of patients with sporadic pituitary somatotropinomas. This study shows that age and gigantism are simple clinical features which can help to select patients for mutation screening. It also supports the role of AIP in pituitary tumorigenesis.

Aim To analyse the change in adherence to diabetes treatment and its association with metabolic control from childhood to adolescence. The Tanner pubertal staging model was selected as a marker of developmental maturity. Methods In a multicentre, longitudinal cohort study, 142 children with Type 1 diabetes completed a scale that assessed adherence to treatment and a test of diabetes knowledge at the beginning of the study (T0) and four years later (T4). HbA1c and clinical data were collected at T0 and at T4. Results From T0 to T4, the mean HbA1c increased from 8.2 ± 1.6 to 9.1 ± 1.4% (P

Background Since 2002, active surveillance programmes have detected numerous atypical scrapie (AS) and classical scrapie cases (CS) in French sheep with almost all the PrP genotypes. The aim of this study was 1) to quantify the genetic risk of AS in French sheep and to compare it with the risk of CS, 2) to quantify the risk of AS associated with the increase of the ARR allele frequency as a result of the current genetic breeding programme against CS. Methods We obtained genotypes at codons 136, 141, 154 and 171 of the PRNP gene for representative samples of 248 AS and 245 CS cases. We used a random sample of 3,317 scrapie negative animals genotyped at codons 136, 154 and 171 and we made inferences on the position 141 by multiple imputations, using external data. To estimate the risk associated with PrP genotypes, we fitted multivariate logistic regression models and we estimated the prevalence of AS for the different genotypes. Then, we used the risk of AS estimated for the ALRR-ALRR genotype to analyse the risk of detecting an AS case in a flock homogenous for this genotype. Results Genotypes most at risk for AS were those including an AFRQ or ALHQ allele while genotypes including a VLRQ allele were less commonly associated with AS. Compared to ALRQ-ALRQ, the ALRR-ALRR genotype was significantly at risk for AS and was very significantly protective for CS. The prevalence of AS among ALRR-ALRR animals was 0.6‰ and was not different from the prevalence in the general population. Conclusion In conclusion, further selection of ALRR-ALRR animals will not result in an overall increase of AS prevalence in the French sheep population although this genotype is clearly susceptible to AS. However the probability of detecting AS cases in flocks participating in genetic breeding programme against CS should be considered.

The Schmallenberg virus (SBV) emerged in Europe in 2011 and caused a widespread epidemic in ruminants. In France, SBV emergence was monitored through a national multi-stakeholder surveillance and investigation system. Based on the monitoring data collected from January 2012 to August 2013, we describe the spread of SBV in France during two seasons of dissemination (vector seasons 2011 and 2012) and we provide a large-scale assessment of the impact of this new disease in ruminants. SBV impact in infected herds was primarily due to the birth of stillborns or deformed foetuses and neonates. Congenital SBV morbidity level was on average moderate, although higher in sheep than in other ruminant species. On average, 8% of lambs, 3% of calves and 2% of kids born in SBV-infected herds showed typical congenital SBV deformities. In addition, in infected herds, farmers reported retrospectively a lower prolificacy during the vector season, suggesting a potential impact of acute SBV infection during mating and early stages of gestation. Due to the lack of available control and prevention measures, SBV spread quickly in the naive ruminant population. France continues to monitor for SBV, and updated information is made available online on a regular basis [ http://www.plateforme-esa.fr/ ]. Outbreaks of congenital SBV are expected to occur sporadically from now on, but further epidemics may also occur if immunity at population level declines.

Introduction L’orbitopathie basedowienne (OB) est une complication pouvant mettre en jeu le pronostic visuel des patients. Le traitement de premiere intention est la corticotherapie intraveineuse, mais les rechutes sont frequentes. Certains patients necessitent le maintien d’une corticotherapie orale posant le probleme des effets indesirables associes. Le rituximab a fait l’objet de plusieurs etudes, avec des resultats parfois contradictoires. Nous avons etudie l’interet de faibles doses de rituximab chez des patients presentant une orbitopathie refractaire. Patients et methodes Les patients atteints d’OB corticodependante, apres un echec ou une contre-indication a une radiotherapie orbitaire, ont ete traites par des perfusions de rituximab a la dose de 100 mg. L’evaluation initiale et le suivi etaient assures par les memes investigateurs, une endocrinologue et un ophtalmologiste. Le critere principal de jugement etait le score d’activite clinique (SAC), une OB active etant definie par un SAC ≥ 3. Les criteres secondaires etaient la mesure de la fente palpebrale, de l’exophtalmie, et l’arret definitif de la corticotherapie. Resultats Quatorze patients de 48 ans d’âge median ont ete inclus entre avril 2012 et decembre 2014. La dose mediane de methylprednisolone precedemment recue etait de 4,7 ± 0,2 gramme. Tous avaient recu une corticotherapie orale, et la moitie des patients avaient beneficie d’une radiotherapie orbitaire. Le score d’activite clinique median a l’inclusion etait de 4 ± 0,85. Les patients ont recu 1 ( n = 1), 2 ( n = 9), 3 ( n = 1) et 4 ( n = 3) injections de 100 mg rituximab. Douze patients sur les 14 (86 %) ont eu une baisse d’au moins 2 points du SAC, et avaient un score d’activite final inferieur a 3. La corticotherapie a ete definitivement interrompue chez 86 % des patients. Il n’a pas ete observe de difference significative dans les mesures d’exophtalmie et de fente palpebrale. Aucun patient n’a presente d’effet indesirable modere ni severe attribuable au rituximab. Discussion La place du rituximab dans le traitement des OB est encore mal definie. Les donnees actuelles de la litterature ne permettent notamment pas d’affirmer son interet comme traitement initial. Notre etude montre des resultats encourageants pour des patients chez qui les traitements de premiere intention ont echoue. Pour les doses faibles utilisees chez ces patients, le profil de tolerance est bon. Des etudes de plus grande ampleur et comprenant un groupe temoin, seront necessaires pour confirmer ces resultats. Conclusion Dans cette etude ouverte sur cohorte, nous montrons que le traitement par rituximab a faibles doses peut representer une alternative therapeutique pour des patients atteints d’OB refractaire.

Purpose: To compare sexual behavior in adolescents with a physical handicap or a chronic illness (HCI, n = 604) to a healthy group (HG, n = 7,332). Methods: Data drawn from a French national health survey carried out among 7,936 adolescents (mean age=16.2 years) were used. A self-report questionnaire concerning health behavior, sexual behavior, and chronic illness was used in 186 public secondary schools. HCI and HG groups were compared on reported sexual behavior as well as on information (on sexuality, AIDS, and pregnancy) given by the parents. Logistic regression was performed for boys and girls to explore the relationship of health status (HCI or HG) to sexual intercourse, adjusted for sociodemographic variables. Results: Fifty-two percent of HCI boys and 38% of HCI girls reported sexual intercourse (vs. 42% of HG boys and 28% of HG girls). The HCI girls reported more often than HG girls changing partners, pregnancy, and use of oral contraceptives. The HCI boys reported more often than HG boys receiving information on sexuality from their parents. Conclusion: French HCI adolescents were found to be at high risk for pregnancy and sexually transmitted diseases (STD).

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., The Eurasian wild boar (Sus scrofa) is increasingly considered as a relevant actor in the epidemiology of animal tuberculosis (TB). Therefore, monitoring TB in wild boar becomes a key tool for establishing comprehensive control schemes for this disease. To estimate the exposure of free living wild boar to Mycobacterium tuberculosis complex (MTC) in France, a bovine-purified protein derivative based ELISA was used to test 2,080 archived serum samples of hunter-harvested animals in 58 French “départements”. Two cut-off values were used for diagnostic interpretation: 0.2, recommended by the manufacturer (specificity: 96.43%; sensitivity: 72.6%), and 0.5 (specificity: 100%; sensitivity: 64%). During the same period, at the 0.2 cut-off, global true seroprevalence was 5.9% (IC95%: 4.3%-7.7%) and 76% of the sampled “départements” had seropositive wild boar, including seven cattle TB-free “départements. At the 0.5 cut-off, global true seroprevalence was 2.2% (IC95%: 1.5-3.2) and positive wild boar belonged to 21% of the “départements”. All but one of these positive “départements” had reported at least one cattle TB outbreak since 2000. A good consistence between seropositive wild boar and TB outbreaks in cattle was found, especially at the 0.5 cut-off value (the mean distance to the nearest cattle TB outbreak was 13km and 27km for seropositive and seronegative wild boar, respectively; P, This study was funded by our own institutional resources (Anses).

Riedel's thyroiditis (RT) is a rare disease characterized by a chronic inflammatory lesion of the thyroid gland with invasion by a dense fibrosis. Publications of the imaging features of RT are scarce. To our knowledge, ultrasound elastography (USE) findings have not been previously reported. Therefore, we describe two patients with RT who were imaged with ultrasonography (US), USE, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).Two women were referred for a large, hard goiter with compressive symptoms (dyspnea and dysphagia); in one patient, the goiter was associated with retroperitoneal fibrosis. In both cases, RT was confirmed by surgical biopsy with pathological examination. Thyroid US imaging was performed with a US scan and a 10-13 MHz linear transducer. The hardness of the tissues was analyzed using transient USE (ShearWave, Aixplorer-SuperSonic Imagine). PET/CT scanning was performed with a Philips Gemini GXL camera (GE Medical Systems). In the first patient, US examination revealed a compressive multinodular goiter with large solid hypoechoic and poorly vascularized areas adjacent to the nodules. The predominant right nodule was hypoechoic with irregular margins. The second patient had a hypoechoic goiter with large bilateral hypoechoic areas. In both cases, an unusual feature was observed: the presence of tissue surrounding the primitive carotid artery, associated with thrombi of the internal jugular vein. Further, USE showed heterogeneity in the stiffness values of the thyroid parenchyma varying between 21 kPa and 281 kPa. FDG-PET/CT imaging showed uptake foci in the thyroid gland. In both cases, US showed a decrease in the thyroid gland volume and the disappearance of encasement of the neck vasculature in response to corticosteroid treatment. In contrast, the FDG-PET/CT features remained unchanged.US features, such as vascular encasement and improvement under corticosteroid treatment, seem to be specific to this rare disease. For the first time, USE documents the hardness of RT tissues. Apart from the FDG-PET/CT findings that merit further investigation, US and USE prove useful tools in the assessment of such a rare disease.

National audience; Atypical scrapie (AS) is a recently discovered form of transmissible spongiform encephalopathy of sheep and goats. It exhibits phenotypic and epidemiological differences from the classical form of scrapie (CS). Whether AS is contagious or not remains an open issue, whereas some arguments favour the hypothesis that it could occur spontaneously, without infectious exposure. To address this issue the spatial distribution of the two diseases was studied, applying two different methods to the French active surveillance data from 2003 to 2007. First, the Kulldorff scan statistic was applied to detect low and high risk clusters. Second, smoothed relative risks of each disease were mapped according to Bayesian conditional autoregressive hierarchical models. The two diseases differed by their spatial distribution patterns. The relative risk of AS was diffuse across the whole country except in one area with moderately increased risk. In contrast, several areas with high or low relative risk of CS were identified. The results do not indicate that the two diseases are spatially associated. Moreover, the relatively homogenous distribution of AS is not characteristic of a contagious disease.

La visite sanitaire bovine (VSB) mise en place en 2005 correspond de facto à un réseau de surveillance épidémiologique des élevages de bovins reposant sur les vétérinaires sanitaires.

La tremblante atypique des petits ruminants a été découverte de façon fortuite. Les caractéristiques épidémiologiques et physiopathologiques de cette maladie sporadique la séparent clairement de la tremblante classique. La tremblante atypique semble peu ou pas contagieuse et se développe chez des animaux âgés, sous l’influence de facteurs de risque génétiques et/ou environnementaux. Les mesures de contrôle ont été adaptées aux connaissances actuelles mais aussi à leurs limites, certaines questions restant en suspens.