Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma.

BACKGROUND: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRA289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFRA289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma. PATIENTS AND METHODS: An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFRA289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFRA289mut on survival. RESULTS: One hundred twenty-eight patients were included and analyzed: 11% had EGFRA289mut glioblastoma (n = 14/128). EGFRA289mut glioblastomas had a relapse pattern that was more marginal than EGFRA289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFRA289mut group versus 1 in the EGFRA289wt group (P = 0.05). Half of the population with EGFRA289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap scoreVr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFRA289wt group, P = 0.035. EGFRA289mut did not influence survival. CONCLUSION: We highlighted a link between the EGFRA289 mutation and the relapse pattern in glioblastoma. The independent role of EGFRA289mut and its clinical implication should now be explored in further studies.

Factors associated with the risk of abortions on dairy cattle farms and their notification by farmers in Algeria. / Facteurs associés au risque de survenue d'avortements dans les élevages de bovins laitiers et à leur déclaration par les éleveurs en Algérie.

Whether or not the cause is infection, abortions result in major economic losses on Algerian cattle farms. Between September 2014 and February 2016, an epidemiological survey was carried out in the form of direct interviews with 162 dairy cattle farmers in eight wilayas (regions) in the north and centre of Algeria, in order to estimate the prevalence of notification of abortions and to identify the factors that influence notification by farmers. The prevalence of notification of abortions by the farmers interviewed was estimated using a precise binomial distribution. Influencing factors were analysed using a classification tree analysis. It seems from the responses obtained that, 82.1% (confidence interval [CI] 95%: 75.3-87.7%) of farmers call a veterinarian to report when abortions have occurred and for post-abortion follow-up. The classification tree generated from the survey data indicates that the three most predictable variables for notification of abortions are, in order of decreasing importance: the type of cow affected by the abortion (importance of the variable = 100 on a scale of 0 to 100); the wilaya of origin (importance of the variable = 72.7); and the dominant physiological stage (importance of the variable = 42.5). Recommendations were made to improve conditions for the notification of bovine abortions by farmers and their handling in Algeria. These recommendations relate to regular information and awareness campaigns aimed at farmers concerning bovine abortions and the possible repercussions of non-reporting on animal and human health; workshops for farmers, attended by veterinarians, on the appropriate handling of cows that have aborted and post-abortion products (milk, aborted foetuses, placenta and foetal membranes); and the creation of an agricultural fund to compensate farmers for losses incurred due to bovine abortions in the context of notifiable diseases. Finally, there is a reminder of the importance of the effective use of quarantine for all animals newly introduced into herds.

Qu'ils soient d'origine infectieuse ou non, les avortements occasionnent d'importantes pertes économiques dans les élevages bovins algériens. De septembre 2014 à février 2016, une enquête épidémiologique a été menée sous la forme d'entretiens directs auprès de 162 éleveurs de bovins laitiers répartis dans huit wilayas du nord et du centre de l'Algérie, en vue d'estimer la prévalence de déclaration des avortements et d'identifier les facteurs qui influencent ces déclarations par l'éleveur. La prévalence de déclaration des avortements par les éleveurs audités a été estimée en s'appuyant sur une distribution binomiale exacte. L'analyse des facteurs d'influence a été effectuée à l'aide d'une analyse par arbre de classification. Il ressort des réponses obtenues que 82,1 % (intervalle de confiance [IC] à 95 % : 75,3-87,7 %) des éleveurs appellent le vétérinaire lors de la survenue d'avortements pour les déclarer et pour réaliser un suivi post-avortement. L'arbre de classification, généré à partir des données de l'enquête, indique que les trois variables les plus prédictibles de la déclaration des avortements sont, par ordre décroissant d'importance : le type de vaches touchées par les avortements (importance de la variable = 100 sur une échelle allant de 0 à 100) ; la wilaya d'origine (importance de la variable = 72,7) ; et le stade physiologique dominant (importance de la variable = 42,5). Des recommandations sont émises pour améliorer les conditions de la déclaration des avortements bovins par les éleveurs ainsi que leur prise en charge en Algérie. Ces recommandations portent sur : la conduite régulière de campagnes d'information et de sensibilisation auprès des éleveurs sur les avortements bovins et les possibles répercussions de la non-déclaration de ceux-ci sur la santé animale et humaine ; l'organisation d'ateliers pour les éleveurs, auxquels participent les vétérinaires, afin de parvenir à une gestion adéquate des vaches avortées et des produits post-avortement (lait, avorton, placenta et membranes foetales) ainsi que la création d'un fonds agricole destiné à indemniser les éleveurs pour les pertes occasionnées imputables à la survenue d'avortements bovins dans le cadre de maladies réglementées. Enfin, l'importance particulière de l'usage effectif de la quarantaine de tous les animaux nouvellement introduits dans les troupeaux est rappelée.

Sean o no de origen infeccioso, los abortos causan importantes pérdidas económicas en las explotaciones bovinas de Argelia. De septiembre de 2014 a febrero de 2016, se llevó a cabo un estudio epidemiológico en forma de entrevistas directas con 162 criadores de bovinos lecheros repartidos en ocho wilayas del norte y el centro de Argelia, con objeto de calcular la prevalencia de la notificación de abortos y determinar los factores que influyen en el ganadero a la hora de notificarlos. Para calcular la prevalencia de la notificación de abortos por parte de los ganaderos estudiados se partió de la hipótesis de una distribución binomial exacta. Para ayudar a analizar los factores de influencia se recurrió un árbol de clasificación. Las respuestas obtenidas ponen de manifiesto que un 82,1% de los ganaderos (intervalo de confianza [IC] del 95%: 75,3-87,7%) llaman al veterinario cuando se producen abortos para notificarlos y para que después haya un seguimiento de la situación. El árbol de clasificación generado a partir de los datos del estudio indica que las tres variables más predecibles de la notificación de abortos son, por orden de importancia decreciente: el tipo de vaca afectada por el aborto (importancia de la variable = 100, en una escala de 0 a 100); la wilaya de origen (importancia de la variable = 72,7); y el estadio fisiológico dominante (importancia de la variable = 42,5). Para la situación de Argelia, los autores formulan recomendaciones destinadas a mejorar las condiciones de la notificación de abortos bovinos por los ganaderos, así como la adopción de medidas subsiguientes. Las recomendaciones consisten en: llevar a cabo campañas periódicas de información y sensibilización dirigidas a los ganaderos en relación con los abortos bovinos y las posibles consecuencias sanitarias y zoosanitarias del hecho de no notificarlos; impartir talleres para los ganaderos, en presencia de veterinarios, sobre la gestión adecuada de la vaca que ha sufrido un aborto y de los productos resultantes (leche, feto abortado, placenta y membranas fetales); y establecer un fondo agrícola destinado a indemnizar a los productores por las pérdidas que les hayan causado los abortos bovinos en el marco de enfermedades reglamentadas. Por último, los autores recuerdan la particular importancia que reviste el uso efectivo de la cuarentena de todos los animales al ser introducidos en un rebaño.

Survey of the prevalence of bovine abortions and notification and management practices by veterinary practitioners in Algeria. / Enquête sur la prévalence des avortements bovins et les pratiques de déclaration et de prise en charge par les vétérinaires praticiens en Algérie.

Whether the cause is infection or not, abortions result in major economic losses on Algerian cattle farms. However, little is known about their prevalence and the factors influencing their notification by Algerian veterinarians. In order to bridge this knowledge gap, an epidemiological survey was conducted between September 2014 and February 2016, in the form of direct interviews with 331 veterinarians randomly distributed in ten wilayas (regions) in northern and central Algeria. Influencing factors were analysed using a univariate, then multivariate, logistic regression model and a classification tree analysis. The statistical significance was set to 5% (p value of 0.05). According to 48.7% of the veterinarians interviewed, the average prevalence of abortions on the dairy farms monitored by each veterinarian during the past 12 months was greater than 5%. The results of the multivariate logistic regression model confirmed that abortion notification is far more systematic if accompanied by sampling for laboratory diagnosis (odds ratio [OR] = 467; confidence interval [CI] 95%: 56-3,897; p < 0.001). Conversely, notification is less frequent if the abortion occurred during the summer (OR = 0.14; CI 95%: 0.03-0.58; p = 0.007). The classification tree generated from the survey data indicates that the three variables most predictive of abortion notification are (in decreasing order of importance): sampling for laboratory analysis to identify the cause of abortions; the wilaya of origin; and the season during which the abortions occurred. Finally, an overall weighted score (on a scale of 0 to 100) was assigned to allow evaluation of the notification and management of bovine abortions by veterinarians. Evidently there is plenty of scope for improvement because two-thirds of veterinarians achieved scores between 0 and 25. Recommendations were made to improve notification and the management of bovine abortions in Algeria, including publishing an agreed standard procedure for abortions, conducting information and awareness-raising campaigns aimed at farmers and veterinarians and allocating additional resources to laboratory analysis of the causes of abortion and incentives to encourage notification of abortions. Another proposal was the creation of an agricultural fund to compensate cattle farmers for losses resulting from bovine abortions caused by notifiable diseases.

Qu'ils soient d'origine infectieuse ou non, les avortements engendrent d'importantes pertes économiques dans les élevages bovins algériens. Toutefois, leur prévalence et les facteurs qui influencent leur déclaration par les vétérinaires algériens sont peu connus. En vue de combler ce déficit de connaissance, une enquête épidémiologique a été menée de septembre 2014 à février 2016, sous la forme d'entretiens directs auprès de 331 vétérinaires praticiens répartis aléatoirement dans dix wilayas du nord et du centre de l'Algérie. Une analyse des facteurs d'influence a été effectuée à l'aide d'un modèle de régression logistique univariée puis multivariée ainsi qu'une analyse par arbre de classification. La significativité statistique des résultats a été fixée à 5 % (valeur de p de 0,05). Selon 48,7 % des vétérinaires interrogés, la prévalence moyenne d'avortements constatés dans les élevages laitiers surveillés au cours des 12 derniers mois par chaque vétérinaire était supérieure à 5 %. Les résultats du modèle de régression logistique multivariée ont confirmé que la déclaration d'un avortement est beaucoup plus systématique si elle s'accompagne de la réalisation d'un prélèvement en vue d'un diagnostic de laboratoire (rapport des cotes [odds ratio : OR] = 467 ; intervalle de confiance [IC] à 95 % : 56-3 897 ; p < 0,001). À l'inverse, elle est moins fréquente si l'avortement s'observe en été (OR = 0,14 ; IC à 95 % : 0,03-0,58 ; p = 0,007). L'arbre de classification, généré à partir des données de l'enquête, indique que les trois variables les plus prédictives de la déclaration des avortements sont, par ordre décroissant d'importance : la réalisation d'un prélèvement en vue d'obtenir un diagnostic de laboratoire permettant d'établir la cause des avortements ; la wilaya d'origine ; et la saison où les avortements sont constatés. Enfin, une note globale pondérée (sur une échelle de valeurs allant de 0 à 100) a été attribuée et a permis d'évaluer la déclaration et la prise en charge des avortements bovins par le vétérinaire. Il ressort que la marge de progrès est importante puisque dans deux tiers des cas, le vétérinaire obtient une note comprise entre 0 et 25. Des recommandations sont émises pour améliorer la déclaration et la prise en charge des avortements bovins en Algérie, parmi lesquelles : la rédaction d'une procédure standardisée et concertée relative aux avortements ; la réalisation de campagnes d'information et de sensibilisation à destination des éleveurs et des vétérinaires ; et l'affectation de moyens supplémentaires pour assurer un diagnostic de laboratoire des causes d'avortement et pour encourager la déclaration des avortements par des mesures incitatives. La création d'un fonds agricole destiné à indemniser les éleveurs pour les pertes engendrées par la survenue d'avortements bovins dans le cadre de maladies infectieuses réglementées est également proposée.

Sean o no de origen infeccioso, los abortos infligen importantes pérdidas económicas a las explotaciones bovinas argelinas, pese a lo cual se sabe poco de su prevalencia y de los factores que influyen en los veterinarios a la hora de notificar o no los casos de aborto. Con el fin de conocer más a fondo la cuestión, de septiembre de 2014 a febrero de 2016 se llevó a cabo una investigación epidemiológica en forma de entrevistas directas con 331 veterinarios clínicos distribuidos aleatoriamente en diez wilayas (provincias) del norte y el centro del país. Con el empleo de un modelo de regresión logística con una variable, y después con múltiples variables, aunado a un análisis por árbol de clasificación, se analizaron los factores de influencia, fijando en un 5% (p = 0,05) la significación estadística de los resultados. Según un 48,7 % de los veterinarios encuestados, la prevalencia media de abortos constatados por cada veterinario en las explotaciones lecheras vigiladas en el curso de los 12 meses anteriores era superior al 5%. Los resultados del modelo de regresión logística con múltiples variables confirmaron que la notificación de un aborto es mucho más sistemática cuando se acompaña de la obtención de una muestra con vistas al diagnóstico de laboratorio (razón de probabilidades [OR] = 467; intervalo de confianza [IC] del 95%: 56-3 897; p < 0,001). En cambio, la notificación es menos frecuente si el aborto se observa en verano (OR = 0,14; IC del 95%: 0,03-0,58; p = 0,007). El árbol de clasificación generado a partir de los datos de la investigación pone de manifiesto que las tres variables con mayor poder predictivo de la notificación de abortos son, por orden de importancia decreciente: el hecho de obtener una muestra para someterla a diagnóstico de laboratorio y poder así determinar la causa de los abortos; la wilaya de origen; y la estación en que se constatan los abortos. Por último, la atribución de una nota global ponderada (según una escala de valores que iba de 0 a 100) sirvió para evaluar la notificación de los abortos bovinos por parte del veterinario y las medidas de atención adoptadas por este. De ahí se infiere que existe un importante margen de mejora, pues en dos tercios de los casos el veterinario obtiene una nota comprendida entre 0 y 25. Los autores formulan recomendaciones encaminadas a mejorar la notificación y atención de los casos de aborto bovino en Argelia, entre ellas la confección de un procedimiento normalizado y concertado para los casos de aborto, la realización de campañas informativas y de sensibilización dirigidas a los productores y los veterinarios y la asignación de más medios para garantizar un diagnóstico de laboratorio de las causas de aborto y alentar la notificación de los casos con medidas incitativas. Los autores proponen también la creación de un fondo agrícola destinado a indemnizar a los productores por las pérdidas que les supongan los abortos bovinos causados por enfermedades infecciosas que estén reglamentadas.

Prevalence and factors associated with a higher or lower risk of exposure to Coxiella burnetii, Chlamydia abortus and Toxoplasma gondii in dairy cows that have aborted in Algeria. / Prévalences et facteurs associés à un risque augmenté ou diminué d'exposition à Coxiella burnetii, Chlamydia abortus et Toxoplasma gondii chez la vache laitière ayant avorté en Algérie.

In Algeria, the prevalence of causes of abortion on dairy cattle farms (whether infectious causes or not) has been little studied. The current study involved a serological analysis conducted between October 2014 and June 2016 in northern Algeria using an enzyme-linked immunosorbent assay test on blood samples taken from 368 cows that had aborted on 124 farms. It was complemented by a survey to identify the factors associated with a higher or lower risk of exposure to Coxiella burnetii, Chlamydia abortus and Toxoplasma gondii, using univariate logistic regression and then multivariate logistic regression. The individual serological prevalences obtained were 8.4% (31/368) for C. burnetii and 12.2% (45/368) for C. abortus. For T. gondii, the individual seroprevalence was 13.8% (51/368); the factors associated with a higher risk of individual exposure were the fourth month of gestation (odds ratio [OR] = 22.68; 95% confidence interval [CI]: 1.38-392.97) and the fifth month of gestation (OR = 25.51; 95% CI: 1.47-442.11). All the other factors identified by the multivariate logistic regression were associated with a lower risk of exposure. They are the inspection visits in 2015 (OR = 0.0006; 95% CI: 0.000004-0.12) and in 2016 (OR = 0.0005; 95% CI: 0.000002-0.13) and artificial insemination (OR = 0.15; 95% CI: 0.05-0.44) for C. burnetii ; winter (OR = 0.39; 95% CI: 0.15-1.00), spring (OR = 0.45; 95% CI: 0.20-0.97), and artificial insemination (OR = 0.27; 95% CI: 0.13-0.56) for C. abortus; and the number of gestations (OR = 0.38; 95% CI: 0.16-0.92) for T. gondii. The seroprevalence at herd level was 16.1% (20/124) for C. burnetii and 29.8% (37/124) for both C. abortus and T. gondii. At herd level, the risk factors associated with a higher risk of exposure to C. abortus and T. gondii were the practice of deworming (OR = 3.89; 95% CI: 1.53-9.89) and drilling individual wells as a source of drinking water (OR = 7.50; 95% CI: 2.11-26.69). For C. burnetii, the inspection visit in 2015 (OR = 0.02; 95% CI: 0.0008-0.65) and in 2016 (OR = 0.01; 95% CI: 0.0003-0.36), artificial insemination (OR = 0.21; 95% CI: 0.06-0.69) and rodent eradication (OR = 0.19; 95% CI: 0.06-0.57) were factors that reduced the risk of exposure.

En Algérie, la prévalence des causes d'avortement dans les élevages bovins laitiers (que ces causes soient d'origine infectieuse ou non infectieuse) a été peu étudiée. Cette étude concerne une analyse sérologique conduite d'octobre 2014 à juin 2016 dans le nord de l'Algérie à l'aide d'un test ELISA (méthode immuno-enzymatique) sur des prélèvements sanguins issus de 368 vaches ayant avorté provenant de 124 élevages et complétée par un formulaire d'enquête visant à identifier, par une régression logistique uni puis multivariée, les facteurs associés à un risque augmenté ou diminué d'exposition à Coxiella burnetii, Chlamydia abortus et Toxoplasma gondii. Les prévalences sérologiques individuelles obtenues ont été respectivement de 8,4 % (31/368) pour C. burnetii et de 12,2 % (45/368) pour C. abortus. Pour T. gondii, la séroprévalence individuelle était de 13,8 % (51/368), avec comme facteurs associés à un risque accru d'exposition individuelle, le quatrième mois de gestation (rapport des cotes [odds ratio : OR] = 22,68 ; intervalle de confiance [IC] à 95 % : 1,38-392,97) et le cinquième mois de gestation (OR = 25,51 ; IC à 95 % : 1,47-442,11). Les autres facteurs identifiés par la régression logistique multivariée étaient tous des facteurs associés à un risque diminué d'exposition. Ils concernaient l'année de visite en 2015 (OR = 0,0006 ; IC à 95 % : 0,000004-0,12) et en 2016 (OR = 0,0005 ; IC à 95 % : 0,000002-0,13) et l'insémination artificielle (OR = 0,15 ; IC à 95 % : 0,05-0,44) pour C. burnetii ; l'hiver (OR = 0,39 ; IC à 95 % : 0,15-1,00), le printemps (OR = 0,45 ; IC à 95 % : 0,20-0,97) et l'insémination artificielle (OR = 0,27 ; IC à 95 % : 0,13-0,56) pour C. abortus ; et le nombre de gestations (OR = 0,38 ; IC à 95 % : 0,16-0,92) pour T. gondii. La séroprévalence obtenue à l'échelle du troupeau a été respectivement de 16,1 % (20/124) pour C. burnetii et de 29,8 % (37/124) pour C. abortus et T. gondii. À l'échelle des troupeaux, les facteurs associés à un risque accru d'exposition à C. abortus et T. gondii concernent respectivement la pratique du déparasitage (OR = 3,89 ; IC à 95 % : 1,53-9,89) et le forage personnel comme source d'abreuvement (OR = 7,50 ; IC À 95 % : 2,11-26,69). Pour C. burnetii, l'année de visite en 2015 (OR = 0,02 ; IC à 95 % : 0,0008-0,65) et en 2016 (OR = 0,01 ; IC à 95 % : 0,0003-0,36), l'insémination artificielle (OR = 0,21 ; IC à 95 % : 0,06-0,69) et l'éradication des rongeurs (OR = 0,19 ; IC à 95 % : 0,06-0,57) sont des facteurs de diminution du risque d'exposition.

En Argelia está poco estudiada la prevalencia de las causas de aborto en las explotaciones bovinas de producción láctea (ya sean causas de tipo infeccioso o no infeccioso). Los autores exponen aquí un análisis serológico realizado entre octubre de 2014 y junio de 2016 en el norte de Argelia. Empleando una técnica de ensayo inmunoenzimático (ELISA), se examinaron muestras sanguíneas de 368 vacas que habían sufrido un aborto procedentes de 124 explotaciones, análisis que se complementó con un formulario de investigación destinado a determinar, por regresión logística de una sola variable y después multifactorial, los factores ligados a un aumento y a un decremento del riesgo de exposición a Coxiella burnetii, Chlamydia abortus y Toxoplasma gondii. Las prevalencias serológicas individuales obtenidas fueron, respectivamente, de un 8,4% (31/368) para C. burnetii y un 12,2% (45/368) para C. abortus. Por lo que respecta a T. gondii, se obtuvo una seroprevalencia individual del 13,8% (51/368). Los factores ligados a un mayor riesgo de exposición individual eran el cuarto mes de gestación (razón de probabilidades [odds ratio: OR] = 22,68; intervalo de confianza [IC] al 95%: 1,38-392,97) y el quinto mes de gestación (OR = 25,51; IC al 95%: 1,47-442,11). Todos los otros factores determinados por regresión logística multifactorial venían asociados a una reducción del riesgo de exposición. Se trataba concretamente de: el hecho de que la visita se hubiera efectuado en 2015 (OR = 0,0006; IC al 95%: 0,000004-0,12) o en 2016 (OR = 0,0005; IC al 95%: 0,000002-0,13) y la inseminación artificial (OR = 0,15; IC al 95%: 0,05-0,44), en el caso de C. burnetii; el hecho de que fuera invierno (OR = 0,39; IC al 95%: 0,15-1,00) o primavera (OR = 0,45; IC al 95%: 0,20-0,97) y la inseminación artificial (OR = 0,27; IC al 95%: 0,13-0,56), en el caso de C. abortus; y el número de gestaciones (OR = 0,38; IC al 95%: 0,16-0,92), en el caso de T. gondii. La seroprevalencia de rebaño obtenida fue respectivamente de un 16,1% (20/124) para C. burnetii y de un 29,8% (37/124) para C. abortus y T. gondii. A la escala de los rebaños, los factores vinculados a un mayor riesgo de exposición a C. abortus y T. gondii eran, respectivamente, la práctica de desparasitaciones (OR = 3,89; IC al 95%: 1,53-9,89) y el uso de un pozo propio como abrevadero (OR = 7,50; IC al 95%: 2,11-26,69). En cuanto a C. burnetii, los factores que reducían el riesgo de exposición del rebaño eran el hecho de que el año de visita fuera 2015 (OR = 0,02; IC al 95%: 0,0008-0,65) o 2016 (OR = 0,01; IC al 95%: 0,0003-0,36), la inseminación artificial (OR = 0,21; IC al 95%: 0,06-0,69) y la erradicación de los roedores (OR = 0,19; IC al 95%: 0,06-0,57).

Mediation analysis to estimate direct and indirect milk losses associated with bacterial load in bovine subclinical mammary infections.

Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e. direct losses) or to effects of the immune response triggered by the presence of mammary pathogens (i.e. indirect losses). Test-day milk somatic cell counts (SCC) and number of bacterial colony forming units (CFU) found in milk samples are putative measures of the level of immune response and of the bacterial load, respectively. Mediation models, in which one independent variable affects a second variable which, in turn, affects a third one, are conceivable models to estimate direct and indirect losses. Here, we evaluated the feasibility of a mediation model in which test-day SCC and milk were regressed toward bacterial CFU measured at three selected sampling dates, 1 week apart. We applied this method on cows free of clinical signs and with records on up to 3 test-days before and after the date of the first bacteriological samples. Most bacteriological cultures were negative (52.38%), others contained either staphylococci (23.08%), streptococci (9.16%), mixed bacteria (8.79%) or were contaminated (6.59%). Only losses mediated by an increase in SCC were significantly different from null. In cows with three consecutive bacteriological positive results, we estimated a decreased milk yield of 0.28 kg per day for each unit increase in log2-transformed CFU that elicited one unit increase in log2-transformed SCC. In cows with one or two bacteriological positive results, indirect milk loss was not significantly different from null although test-day milk decreased by 0.74 kg per day for each unit increase of log2-transformed SCC. These results highlight the importance of milk losses that are mediated by an increase in SCC during mammary infection and the feasibility of decomposing total milk loss into its direct and indirect components.

[Radiotherapy of a glioma in a pregnant woman: evaluation of the foetal dose in conformational 3D or intensity-modulated]. / Radiothérapie d'une tumeur gliale chez une femme enceinte : évaluation de la dose fœtale en irradiation conformationelle tridimensionnelle ou avec modulation d'intensité

The purpose was to assess three treatments planning techniques including one in intensity-modulated radiation therapy (IMRT) for cerebral irradiation of pregnant woman, in order to limit the dose delivered to the foetus. The treatment provided was 60 Gy to the planning target volume. Estimated foetal dose was measured using an anthropomorphic phantom, on the upper and middle part of the uterus. The first plan consisted in four beams in conformational technique delivered from a Varian accelerator with a 120 leaves collimator, the second one used non-coplanar fields and the third one assessed IMRT. With the conformational technique, the dose at the upper part of the uterus was 8.3 mGy and 6.3 mGy at the middle part. The dose delivered to the foetus was higher with the non-coplanar fields. In IMRT, the dose at the upper part of the uterus was 23.8 mGy and 14.3 mGy at the middle part. The three plans used 6 MV X-rays. Because of the use of leaves and non-coplanar fields, IMRT does not seem to be the optimal technique for the treatment of pregnant woman. However, the dose delivered to the foetus remains low and below the dose of 100 mGy recommended by the International Commission of Radiological Protection. It seems possible to consider the use of this technique for a better sparing of organs at risk for the mother.

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours.

BACKGROUND: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. PATIENTS AND METHODS: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. RESULTS: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. CONCLUSION: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.

Evaluating somatic cell scores with a Bayesian Gaussian linear state-space model.

Because accurate characterization of health state is important for managing dairy herds, we propose to validate the use of a linear state-space model (LSSM) for evaluating monthly somatic cell scores (SCSs). To do so, we retrieved SCS from a dairy database and collected reports on clinical mastitis collected in 20 farms, during the period from January 2008 to December 2011 in the Walloon region of Belgium. The dependent variable was the SCS, and the independent variables were the number of days from calving, year of calving and parity. The LSSM also incorporated an error-free underlying variable that described the trend across time as a function of previous clinical and subclinical status. We computed the mean sum of squared differences between observed SCS and median values of the posterior SCS distribution and constructed the receiver operating characteristic (ROC) curve for SCS thresholds going from 0 to 6. Our results show SCS estimates are close to observed SCS and area under the ROC curve is higher than 90%. We discuss the meaning of the parameters in light of our current knowledge of the disease and propose methods to incorporate, in LSSM, this knowledge often expressed in the form of ordinary differential equations.

A structural equation model to evaluate direct and indirect factors associated with a latent measure of mastitis in Belgian dairy herds.

In dairy cattle, many farming practices have been associated with occurrence of mastitis but it is often difficult to disentangle the causal threads. Structural equation models may reduce the complexity of such situations. Here, we applied the method to examine the links between mastitis (subclinical and clinical) and risk factors such as herd demographics, housing conditions, feeding procedures, milking practices, and strategies of mastitis prevention and treatment in 345 dairy herds from the Walloon region of Belgium. During the period January 2006 to October 2007, up to 110 different herd management variables were recorded by two surveyors using a questionnaire for the farm managers and during a farm visit. Monthly somatic cell counts of all lactating cows were collected by the local dairy herd improvement association. Structural equation models were created to obtain a latent measure of mastitis and to reduce the complexity of the relationships between farming practices, between indicators of herd mastitis and between both. Robust maximum likelihood estimates were obtained for the effects of the herd management variables on the latent measure of herd mastitis. Variables associated directly (p<0.05) with the latent measure of herd mastitis were the addition of urea in the rations; the practices of machine stripping, of pre-and post-milking teat disinfection; the presence of cows with hyperkeratotic teats, of cubicles for housing and of dirty liners before milking; the treatment of subclinical cases of mastitis; and the age of the herd (latent variable for average age and parity of cows, and percentage of heifers in the herd). Treatment of subclinical mastitis was also an intermediate in the association between herd mastitis and post-milking teat disinfection. The study illustrates how structural equation model provides information regarding the linear relationships between risk factors and a latent measure of mastitis, distinguishes between direct relationships and relationships mediated through intermediate risk factors, allows the construction of latent variables and tests the directional hypotheses proposed in the model.

[Assessing the contribution of a standardized method in defining the tumor bed using surgical clips in breast cancer]. / Évaluation de l'apport d'une méthode standardisée dans la définition du lit tumoral à l'aide de clips chirurgicaux dans le cancer du sein.

PURPOSE OF THE STUDY: The objective of this study was to compare prospectively the delineations of tumour bed after breast conserving surgery from two techniques for defining the target volume. PATIENTS AND METHODS: Sixteen patients treated by lumpectomy with development of surgical clips were included. For each patient, four radiation oncologists delineated the clinical target volume (CTV boost) following its own method (technique 1) or using a predefined methodology (technique 2), the diameter to be applied around each clip relative to the risk of local recurrence. Factors taken into account to adjust the volume were tumour size, age, surgical margins and the presence of extensive ductal carcinoma. We then analyzed the factors varying the volume and variation of delineation for each method by calculating the concordance index: Kappa index and overlap. RESULTS: For all 16 patients, the volume delineated was nearly identical: 29.65 cm(3) with technique 1 and 33.54 cm(3) with technique 2 (P=0.6). The correlation was higher with technique 2 over technique 1, with KI from 0.146 to 0.285 (P=0.0001) and an OV of 0.302 to 0.458 (P=0.0002). CONCLUSION: Our study shows that within the same institute, there is a great variability in CTV delineation boost, even in the presence of surgical clips. A standardized approach to adjusting the volume of relapse risk factors has improved the consistency.

[Conservative treatment for breast cancer: optimization of the tumor bed localization]. / Traitement conservateur du cancer du sein: optimisation du repérage du lit tumoral.

PURPOSE: The main objective was to assess contributions and limits of surgical clips combined with computed tomography to define the tumor bed after conservative treatment of breast cancer. This retrospective observational study enrolled 16 patients treated by lumpectomy with surgical clips placed in the tumor bed. PATIENTS AND METHODS: We assessed the difficulties in localizing the tumour bed based on collected data (i.e. clinical description, mammography, ultrasound examination, surgical procedure and pathology data). The clip's number and localization, and the volumes of the boost were also analyzed. RESULTS: There was no preoperative occurrence of localization in 57 % of cases for palpable tumours, and in 13 % of cases where the lesion was subclinical. The collected data did not allow establishing a precise localization. The mean number of surgical clips per patient was 4 (range 1-9), and the delineation of the target volumes by radiation oncologists was not standardized. Oncoplastic techniques may produce difficulties in the localization of tumour bed. CONCLUSION: The placement of surgical clips by the surgeon is helpful, primarily when oncoplastic techniques are used. In many situations, these clips may cause problems of interpretation. In order to optimize the delineation of the boost, we propose a multidisciplinary approach and methodology to be used at the Henri Becquerel Cancer Centre.

[Surgical and radiotherapeutic approaches according to postoperative margins analysis in breast cancer: survey realized in 20 French cancer centers]. / Attitudes chirurgicales et radiothérapiques en fonction de l'analyse des berges-marges dans les tumeurs mammaires: enquête réalisée auprès de 20 centres de lutte contre le cancer.

Margin status is regarded as a major prognostic factor for local recurrence after breast conservative treatment. Margin definition in the literature is not always clear and precise. The impact on the therapeutic management may be quite different. This paper presents the radiotherapeutic attitude according to a survey realized in the twenty French cancer centers. The surgical practice in terms of margins status is appraised. The radiotherapist attitude in terms of boost's modulation is specified.

Relative accuracy of the identification of ovarian structures in the cow by ultrasonography and palpation per rectum.

Manual palpation or ultrasonographic examination of the cow's genital tract are currently used by veterinarians involved in reproductive management, but knowledge of the potential and the limitations of both methods is important to obtain an optimal accuracy in the diagnosis of physiological and pathological ovarian structures. This review presents the main features of manual and ultrasonographic characteristics of follicles, corpora lutea (with or without a cavity), follicular and lutenized cysts and the reliability of the two methods is compared. Manual diagnosis of follicles <10 mm is rather inaccurate, but ultrasound offers the possibility to diagnose follicles <5 mm and to measure their inner diameter. The predictive values of the presence or absence of a corpus luteum as determined by palpation are similar (78 vs. 75%). Manual or ultrasonographic diagnosis of the growing or regressing corpus luteum is rather difficult. The positive predictive value of a mature corpus luteum diagnosed by ultrasonography is lower (87%) than the negative predictive value (92%). Compared to manual palpation, ultrasonography permits a better estimation of the number and to determine more precisely the size of the mature corpus luteum. The positive values for follicular cysts diagnosed by palpation or by ultrasonography are 66 and 74% respectively, and for luteal cysts, the values are 66 and 85%, respectively.Manual palpation or ultrasonography are useful tools to diagnose ovarian structures in the cow. The accuracy of such methods can be enhanced by securing information on the reproductive history of the animal, palpation of uterine horns, vaginal examination or progesterone determinations.

Bronchial stenosis and sclerosing mediastinitis: an uncommon complication of external thoracic radiotherapy.

The side-effects of radiation therapy on the bronchial tree or on the mediastinum are seldom reported. In this setting, we report a case of sclerosing mediastinitis with bronchial stenosis discovered 1 yr after external radiotherapy for lung cancer. The patient was treated with a Dumont stent and has so far had an uneventful further course for up to 42 months. Bronchial stenosis related to mediastinal fibrosis after radiotherapy has not been reported previously.

Evaluation of false ultrasonographic diagnoses in cows by measuring plasma levels of bovine pregnancy-associated glycoprotein 1.

Between days 27 and 59 after artificial insemination (AI), 189 ultrasonographic pregnancy diagnoses were made in 56 dairy cows using a 7.5 MHz linear-array rectal transducer. Blood samples were withdrawn from a jugular vein on the day of AI, on day 21, and after each ultrasonographic examination between days 27 and 31, days 34 and 38, days 41 and 45 and days 55 and 59 after AI. Plasma concentrations of bovine pregnancy-associated glycoprotein 1 (bPAG-1) were measured by radioimmunoassay. The results showed that before day 31, ultrasonographic scanning was not very sensitive because six of the 30 calving cows were incorrectly diagnosed as non-pregnant. In five of these animals, the uterus was located far cranial to the pelvic inlet. Five of the cows examined between days 27 and 31 were pregnant on the basis of plasma bPAG-1 levels on the same day, using 0.5 ng/ml as the cut-off point. Plasma levels of bPAG-1 and progesterone proved that four of the cows which had early positive ultrasonographic diagnoses but did not produce a calf, were pregnant when they were examined.

Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer.

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

Comparison of reproductive performance in Belgian dairy and beef cattle.

A computerized program was written to collect, evaluate and compare reproductive performance data of 2004 beef (Belgian Blue breed) and 1649 dairy (Friesian Holstein and German Red) cattle in 35 Belgian herds (6 suckler beef herds, 9 milked beef herds and 20 dairy herds). Reproduction data were collected at monthly herd health visits. No difference in age at first calving was observed. Significant differences were observed among the 3 kinds of herds, and the best results were obtained in dairy herds for the calving interval, interval from calving to the first estrus, interval from calving to the first service and average number of days open. Concerning these parameters, first calvers had lower results than multiparous cows, mainly in suckler and milked beef herds. Significant differences were noted in the number of services per pregnancy. Heifers that had never calved presented the highest fertility. Primiparous beef cows had higher fertility than pluriparous cows. In dairy herds, pluriparous cows had higher fertility than primiparous cows. Estrus detection was better in milked beef herds than in suckled beef and dairy herds. Suckled beef herds had the lowest incidence of metritis and ovarian cysts of the three types of herds. Rates of abortion, overall culling and retained fetal membranes were similar in all the herds. The percentage of animals removed for infertility was highest in milked beef herds and lowest in dairy herds. Because 90% of the 1159 calvings recorded in the beef herds required a caesarean section, the reproductive performance of beef cattle represent results after caesarean section.

Postoperative irradiation for thyroid cancer.

The place of external irradiation for thyroid cancers remains controversial. Between 1974 and 1989, 94 patients with a differentiated thyroid cancer were seen in our department for additional treatment (radioiodine with or without external radiation) after a surgical resection. 56 patients were treated with radioiodine alone and 38 patients had an additional course of external radiation. Survival was identical for the two groups but the local relapse rates were 21% and 3% respectively. So, in this retrospective study, the addition of external radiation appears to improve the local control especially in the case of an incomplete surgical resection or extracapsular tumor extension. This benefit was achieved without severe radiation-induced late effects.