Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Funder: CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Italian Association for Cancer Research (AIRC; grant no.16933) to L. Ottini. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. Jacopo Azzollini is supported by funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5x1000’). DEMOKRITOS: European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. FPGMX: FISPI05/2275 and Mutua Madrileña Foundation (FMMA). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association “Le cancer du sein, parlons-en!” Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and “5x1000” Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MODSQUAD: MH CZ - DRO (MMCI, 00209805), MEYS - NPS I - LO1413 to LF and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, P20CA233307, American Cancer Society (MRSG-13-063-01-TBG, CRP-10-119-01-CCE), Breast Cancer Research Foundation, Susan G. Komen Foundation (SAC110026), and Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance. Mr. Qian was supported by the Alpha Omega Alpha Carolyn L. Cuckein Student Research Fellowship. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Research UK. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124.Abstract: Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

BACKGROUND : Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS : We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS : Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCUSION : Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.https://www.nature.com/bjc2020-06-19hj2020Genetic

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Echocardiographic assessment of cardiac function in horses with colic

Endotoxemia is a common complication of colic in adult horses and its outcome is mainly related to cardiovascular status. Endotoxic shock, like septic shock, involves hypovolemic, cardiogenic and distributive components leading to tissue hypoperfusion with a high risk for multiple organ failure and an elevated mortality rate in equine and human intensive care units. Via the release of pro-inflammatory mediators, endotoxins induce a fall in systemic vascular resistance (SVR) and a drop of cardiac output (CO) resulting both from reduction in venous return and myocardial depression. First, CO is preserved thanks to a compensatory vasoconstriction and an increase in heart rate (HR), myocardial contractility and venous return. However, a loss of vascular responsiveness to catecholamines and a myocardial depression finally result in a drop of CO and SVR with a progressive hypotension despite a persistent tachycardia. The time point during the course of septic shock when hemodynamic monitoring is used has been proven to influence outcome, allowing early goal-directed therapy in humans. Unfortunately, hemodynamic monitoring in conscious horses is often limited due to animal size, working conditions and lack of patient cooperation. Therefore, such as in human patients, echocardiography could provide useful non invasive information about stroke volume (SV) and CO, systolic and diastolic function as well as fluid status. In human septic shock patients, this technique has emphasised a myocardial depression with both diastolic and systolic dysfunction reversible in survivors. Previous studies in horses focused on quantitative evaluation of hemodynamic parameters after an experimental endotoxin challenge. However, LV function had not been reported in naturally-occurring endotoxemia in horses. The purpose of the first prospective study was to assess the impact of clinically-occuring endotoxic shock on echocardiographic indices of LV systolic function in horses. Fifty horses admitted in clinic on emergency for colic were submitted to an echocardiographic exam on admission. A shock score from 1 to 4 was established for each horse based on clinical evaluation, non invasive systolic blood pressure and blood tests measurements. LV echocardiographic parameters were compared between the 4 groups according to the shock score (SS) (SS1: no or discrete signs of shock, n=11; SS2 : mild, n=17; SS3: moderate, n=12; SS4: severe, n=10) using a multivariable analysis. Significance was set at p < 0.05. Stroke volume, stroke index (SI), ejection time (ET), ejection time index corrected for HR (ETI), aortic velocity time integral (AoVTI), aortic flow acceleration time (TTP) and deceleration time (DTAo) were significantly lower, whereas aortic flow acceleration rate (dv/dtAo) was significantly higher in shocked horses than in SS1. CO was not significantly different between groups. Even if those results were difficult to interpret because of the shock-induced changes in loading conditions of the heart, they suggested that alterations in some indicators of systolic function can be quantified by Doppler echocardiography in horses with colic-induced endotoxemic shock. The aim of the second study was to non invasively assess the impact of colic-related endotoxic shock on equine diastolic cardiac function. Sixty-eight horses admitted in clinic on emergency with colic were included in this study. A similar SS was established for each horse. LV echocardiographic parameters were compared between the 4 groups according to the SS (SS1 n=14; SS2 n=16; SS3 n=27; SS4 n=12) using a multivariable analysis. Significance was set at p < 0.05. Deceleration rate of peak early LV filling velocity, peak late LV filling velocity and E/Em (peak early LV filling velocity (E) to peak early myocardial velocity (Em) ratio) were significantly higher whereas time to Em onset was significantly lower in high shock score groups compared with horses with no or mild signs of shock. The results of this second study could suggest a diastolic dysfunction with a rise of LV filling pressure ocurring with endotoxic shock in horses. Since E/Em has shown to be a very reliable predictor of mortality in human with septic shock, the results of this second study warranted further investigations. To assess the prognostic value of echocardiographic parameters of LV function in horses with endotoxic shock, 41 horses admitted for colic with clinical evidence of systemic inflammatory response syndrome associated to hyperlactatemia or hypotension underwent echocardiographic examination on admission. LV echocardiographic parameters were compared between nonsurvivors (n=29) and horses that survived to discharge (n=12). With comparable heart rate and LV preload estimate, LV SV, AoVTI, DTAo, ET and ETI of aortic flow and Em were lower in the nonsurviving than in the surviving horses while pre-ejection period to ejection time ratio (PEP/ET) of Doppler aortic flow and E/Em ratio were higher (p<0.05). A cut-off value of 0.26 for PEP/ET predicted mortality with 100% sensitivity and 42% specificity (area under the receiver operating characteristic curve (AUC): 0.71), whereas a cut-off value of 2.67 for E/Em predicted mortality with 100% sensitivity and 83% specificity (AUC: 0.89). The results of this third study suggested that echocardiography may provide prognostic information in colic horses with clinical evidence of endotoxic shock. Especially, PEP/ET and E/Em could be useful markers of systolic and diastolic dysfunction, respectively, to detect horses with a high risk of death requiring more intensive cardiovascular monitoring as it has been reported in human patients with septic shock. Finally, to assess LV function after preload restoration in colic horses, 5 horses were followed echocardiographically from admission to at least 24 hours after colic surgery in a preliminary study. Systolic dysfunction was detected in 4/5 horses and diastolic dysfunction assumed in 2/5 horses and suspected in the 3 other horses during hospitalisation. Moreover, echocardiography provided useful diagnosis informations about hemodynamic and fluid status suggesting that ultrasonographic monitoring of cardiovascular function could be of interest in equine intensive care

L électrochimiothérapie des tumeurs cutanées des équidés

L électrochimiothérapie (ECT) est un traitement antitumoral récent qui associe l administration d un agent chimiothérapeutique à la délivrance locale d impulsions électriques qui potentialisent son action cytotoxique en favorisant sa pénétration et son accumulation dans les cellules cibles grâce à une électroperméabilisation membranaire transitoire. Après un rappel des diverses tumeurs cutanées équines et des traitements disponibles, le principe de l ECT est énoncé avant d aborder l étude expérimentale. A travers les résultats obtenus par ECT avec le cisplatine sur 88 tumeurs cutanées et 18 cas, ce premier essai clinique montre que la technique est bien tolérée chez les équidés sous réserve de l induction d une anesthésie générale et très efficace comme traitement local tant qu elle est combinée à la chirurgie sur les lésions volumineuses. Les résultats thérapeutiques, esthétiques et fonctionnels sont excellents notamment sur les sarcoïdes (94,8% de réponses complètes après 12 mois).TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF

Retrospective study of ventricular septal defects in 12 horses

peer reviewedIntroduction Le défaut du septum interventriculaire ou communication interventriculaire (CIV) est l’anomalie congénitale la plus fréquente chez le cheval. Le diagnostic et le pronostic de cette pathologie sont réalisés au moyen de l’échocardiographie Doppler pulsé. Cette étude a pour but de décrire les cas observés entre 1998 et 2008 à la clinique équine de l’Université de Liège, mais aussi de déterminer leur devenir à long terme. Matériel et méthodes Sept chevaux présentant une CIV ont été présentés en clinique. Leur race, âge, sexe, symptômes, et le motif de la consultation ont été notés puis une échocardiographie Doppler pulsé a été effectuée. Un suivi téléphonique a aussi été mis en place en 2011 pour connaître leur évolution à long terme. Résultats Les 7 chevaux présentés avaient entre 1 mois et 11 ans. Six chevaux étaient des demi-sang et le septième était un poney islandais. Tous les chevaux présentaient un souffle bilatéral holo- ou pan-systolique de grade égale ou supérieur à 5/6, plus intense à droite en région tricuspide. Cinq chevaux étaient référés pour souffle sans symptôme associé tandis que les 2 autres présentaient des œdèmes, de l’intolérance à l’effort et de la dyspnée. A l’échocardiographie, toutes les CIV étaient localisées à la base du septum dans sa partie membraneuse. Cependant, pour le premier cheval, examiné en 1998, une communication atypique entre le ventricule gauche (VG) et l’oreillette droite (OD) fut observée. La taille des CIV variait entre 0,5 et 6,6cm et la vitesse du shunt, toujours dirigé de gauche à droite, était comprise entre 2,5 et 5,5 m/s. Le premier cheval, référé en clinique en 1998, était en insuffisance cardiaque très sévère et présentait une dilatation des 2 ventricules et des 2 oreillettes, une fibrillation auriculaire et une insuffisance mitrale et tricuspide sévères. Le 2ème cheval avec des signes d’insuffisance cardiaque était un poulain d’1 mois avec une CIV de grande taille (2,6 cm) associé à un début de dilatation du ventricule droit sans autre anomalie cardiaque. Enfin, 3 des 5 chevaux asymptomatiques présentaient différentes insuffisances valvulaires mais seulement légères à modérées et une sténose pulmonaire a été observé chez l’un d’entre eux. Discussion et conclusions Les résultats de cette étude sont en accord avec la littérature. Les CIV sont associées à un souffle bilatéral holo- ou pan-systolique important et sont majoritairement localisés dans la partie membraneuse du septum. Une vitesse élevée du shunt est associée à une CIV de petite taille et à un pronostic vital et sportif bon. Par contre, en cas de CIV associé à d’autres anomalies graves comme des insuffisances valvulaires sévères, le pronostic est sombre