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1. COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure

Author: Loris Pironi, Denise Jezerski, Jacek Sobocki, Simon Lal, Tim Vanuytsel, Miriam Theilla, Anna S. Sasdelli, Cecile Chambrier, Konrad Matysiak, Umberto Aimasso, Henrik H. Rasmussen, Amelia Jukes, Marek Kunecki, David Seguy, Stéphane M. Schneider, Joanne Daniels, Florian Poullenot, Manpreet S. Mundi, Przemysław Matras, Marcin Folwarski, Adriana Crivelli, Nicola Wyer, Lars Ellegard, Lidia Santarpia, Marianna Arvanitakis, Corrado Spaggiari, Georg Lamprecht, Francesco W. Guglielmi, Antonella Lezo, Sabrina Layec, Esther Ramos Boluda, Anat Guz-Mark, Paolo Gandullia, Cristina Cuerda, Emma Osland, Maria I. Spagnuolo, Zeljko Krznaric, Luisa Masconale, Brooke Chapman, María Maíz-Jiménez, Paolo Orlandoni, Mariana Hollanda Martins da Rocha, M. Nuria Virgili-Casas, Maryana Doitchinova-Simeonova, Laszlo Czako, Andrè Van Gossum, Lorenzo D'Antiga, Looi C. Ee, Daruneewan Warodomwichit, Marina Taus, Sanja Kolaček, Ronan Thibault, Giovanna Verlato, Aurora E. Serralde-Zúñiga, José I. Botella-Carretero, Pilar Serrano Aguayo, Gabriel Olveira, Sirinuch Chomtho, Veeradej Pisprasert, Georgijs Moisejevs, Ana Zugasti Murillo, Ma Estrella Petrina Jáuregui, Marta Bueno Díez, Mohammad Shukri Jahit, Narumon Densupsoontorn, Ali Tamer, Giorgia Brillanti, Francisca Joly, University of Bologna/Università di Bologna, Cleveland Clinic, Centre of Postgraduate Medical Education, University of Manchester [Manchester], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Tel Aviv University (TAU), Hospices Civils de Lyon (HCL), Poznan University of Life Sciences (Uniwersytet Przyrodniczy w Poznaniu) (PULS), Città della Salute e della Scienza University-Hospital, Aalborg University [Denmark] (AAU), University Hospital of Wales (UHW), University of Lódź, CHU Lille, Centre Hospitalier Universitaire de Nice (CHU Nice), Nottingham University Hospitals NHS Trust (NUH), CHU Bordeaux [Bordeaux], Mayo Clinic and Mayo College of Medicine, Rochester, Medical University of Lublin, Medical University of Gdańsk, Hospital Universitario Fundacion Favaloro, University Hospital Coventry, Sahlgrenska Academy at University of Gothenburg [Göteborg], University of Naples Federico II = Università degli studi di Napoli Federico II, Hôpital Erasme [Bruxelles], Clinique Saint-Yves [Rennes], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de Málaga [Málaga] = University of Málaga [Málaga], Mahidol University [Bangkok], University of Sakarya, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and The project of the ESPEN database for Chronic Intestinal Failure was promoted by the ESPEN Executive Committee in 2013, was approved by the ESPEN Council and was supported by an ESPEN grant.
Subjects: Home parenteral nutrition, Nutrition and Dietetics, Pandemic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, COVID-19, 03.02. Klinikai orvostan, Intestinal failure, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background and aimsTo investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN).MethodsPeriod of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.ResultsSixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.ConclusionsIn patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death. Background and aimsTo investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN).MethodsPeriod of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.ResultsSixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.ConclusionsIn patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.
Published: 2023
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2. Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

Author: Azizi, Michel, Mahfoud, Felix, Weber, Michael, Sharp, Andrew, Schmieder, Roland, Lurz, Philipp, Lobo, Melvin, Fisher, Naomi, Daemen, Joost, Bloch, Michael, Basile, Jan, Sanghvi, Kintur, Saxena, Manish, Gosse, Philippe, Jenkins, J. Stephen, Levy, Terry, Persu, Alexandre, Kably, Benjamin, Claude, Lisa, Reeve-Stoffer, Helen, Mcclure, Candace, Kirtane, Ajay, Mullin, Christopher, Thackeray, Lisa, Chertow, Glenn, Kahan, Thomas, Dauerman, Harold, Ullery, Steven, Abbott, J. Dawn, Loening, Andreas, Zagoria, Ron, Costello, John, Krathan, Courtney, Lewis, Luot, Mcelvarr, Andrew, Reilly, John, Cash, Michael, Williams, Shannon, Jarvis, Maria, Fong, Pete, Laffer, Cheryl, Gainer, James, Robbins, Mark, Crook, Sherron, Maddel, Sarita, Hsi, David, Martin, Scott, Portnay, Edward, Ducey, Maryanne, Rose, Suzanne, Delmastro, Elizabeth, Bangalore, Sripal, Williams, Stephen, Cabos, Stanley, Rodriguez Alvarez, Carolina, Todoran, Thomas, Powers, Eric, Hodskins, Emily, Paladugu, Vijay, Tecklenburg, Anna, Devireddy, Chandan, Lea, Janice, Wells, Bryan, Fiebach, Amanda, Merlin, Claudia, Rader, Florian, Dohad, Suhail, Kim, Hyun-Min, Rashid, Mohammad, Abraham, Josephine, Owan, Theophilus, Abraham, Anu, Lavasani, Iran, Neilson, Hailey, Calhoun, David, Mcelderry, Thomas, Maddox, William, Oparil, Suzanne, Kinder, Sheila, Radhakrishnan, Jai, Batres, Candido, Edwards, Suzanne, Garasic, Joseph, Drachman, Doug, Zusman, Randy, Rosenfield, Kenneth, Do, Danny, Khuddus, Matheen, Zentko, Suzanne, O'Meara, James, Barb, Ilie, Foster, Abby, Boyette, Alice, Wang, Yale, Jay, Desmond, Skeik, Nedaa, Schwartz, Robert, Peterson, Rose, Goldman, Jo Anne, Goldman, Jessie, Ledley, Gary, Katof, Nancy, Potluri, Srinivasa, Biedermann, Scott, Ward, Jacquelyn, White, Megan, Mauri, Laura, Sobieszczky, Piotr, Smith, Alex, Aseltine, Laura, Stouffer, Rick, Hinderliter, Alan, Pauley, Eric, Wade, Tyrone, Zidar, David, Shishehbor, Mehdi, Effron, Barry, Costa, Marco, Semenec, Terence, Roongsritong, Chanwit, Nelson, Priscilla, Neumann, Bridget, Cohen, Debbie, Giri, Jay, Neubauer, Robin, Vo, Thu, Chugh, Atul, Huang, Pei-Hsiu, Jose, Powell, Flack, John, Fishman, Robert, Jones, Michael, Adams, Todd, Bajzer, Christopher, Mathur, Anthony, Jain, Ajay, Balawon, Armida, Zongo, Olivier, Bent, Clare, Beckett, David, Lakeman, Nicki, Kennard, Sarah, D’souza, Richard, Statton, Sarah, Wilkes, Lindsay, Anning, Christine, Sayer, Jeremy, Iyer, Sudha Ganesh, Robinson, Nicholas, Sevillano, Annaliza, Ocampo, Madelaine, Gerber, Robert, Faris, Mohamad, Marshall, Andrew John, Sinclair, Janet, Pepper, Hayley, Davies, Justin, Chapman, Neil, Burak, Paula, Carvelli, Paula, Jadhav, Sachin, Quinn, Jane, Rump, Lars Christian, Stegbauer, Johannes, Schimmöller, Lars, Potthoff, Sebastian, Schmid, Claudia, Roeder, Sylvia, Weil, Joachim, Hafer, Lukas, Agdirlioglu, Tolga, Köllner, Tanja, Böhm, Michael, Ewen, Sebastian, Kulenthiran, Saarraaken, Wachter, Angelika, Koch, Christina, Fengler, Karl, Rommel, Karl-Philipp, Trautmann, Kai, Petzold, Martin, Ott, Christian, Schmid, Axel, Uder, Michael, Heinritz, Ulrike, Fröhlich-Endres, Kerstin, Genth-Zotz, Sabine, Kämpfner, Denise, Grawe, Armin, Höhne, Johannes, Kaesberger, Bärbel, von Zur Mühlen, Constantin, Wolf, Dennis, Welzel, Markus, Heinrichs, Gudrun, Trabitzsch, Barbara, Cremer, Antoine, Trillaud, Hervé, Papadopoulos, Panteleimon, Maire, Florent, Gaudissard, Julie, Sapoval, Marc, Livrozet, Marine, Lorthioir, Aurélien, Amar, Laurence, Paquet, Valérie, Pathak, Atul, Honton, Benjamin, Cottin, Marianne, Petit, Frédéric, Lantelme, Pierre, Berge, Constance, Courand, Pierre-Yves, Langevin, Fatou, Delsart, Pascal, Longere, Benjamin, Ledieu, Guillaume, Pontana, François, Sommeville, Coralie, Bertrand, Fabien, Feyz, Lida, Zeijen, Victor, Ruiter, Arno, Huysken, Elisabeth, Blankestijn, Peter, Voskuil, Michiel, Rittersma, Zwaantina, Dolmans, Helma, Kroon, A.A., van Zwam, W.H., Vranken, Jeannique, de Haan., Claudia, Renkin, Jean, Maes, Frédéric, Beauloye, Christophe, Lengelé, Jean-Philippe, Huyberechts, Dominique, Bouvie, Anne, Witkowski, Adam, Januszewicz, Andrzej, Kądziela, Jacek, Prejbisj, Aleksander, Hering, Dagmara, Ciecwierz, Dariusz, Jaguszewski, Milosz, Owczuk, Radoslaw, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Saarland University [Saarbrücken], Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), University Hospital of Wales (UHW), University of Exeter, Universitätsklinikum Erlangen [Erlangen], Leipzig University, Queen Mary University of London (QMUL), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Nevada [Reno], Medical University of South Carolina [Charleston] (MUSC), Hôpital Saint-André, Royal Bournemouth Hospital, Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Columbia University Medical Center (CUMC), Columbia University [New York], Danderyds sjukhus = Danderyd University Hospital, University of Vermont [Burlington], Stanford University, Argolyn Bioscience, Inc., and Argolyn Bioscience
Subjects: [SDV]Life Sciences [q-bio]
Abstract: Auteurs : RADIANCE-HTN Investigators; International audience; Importance Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. Objectives To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. Design, Setting, and Participants This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m 2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. Interventions uRDN vs sham procedure in conjunction with added medications to target BP control. Main Outcomes and Measures Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. Results A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m 2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of −2.4 [16.6] vs −7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. Conclusions and Relevance In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. Trial Registration ClinicalTrials.gov Identifier: NCT02649426
Published: 2022
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3. CT findings of COVID-19-associated pulmonary aspergillosis: a systematic review and individual patient data analysis

Author: Wonju Hong, P. Lewis White, Matthijs Backx, Jean-Pierre Gangneux, Florian Reizine, Philipp Koehler, Robbert G. Bentvelsen, María Luján Cuestas, Hamed Fakhim, Jung Im Jung, Young Kyung Lee, Nishil R. Dalsania, Ravi Karan Patti, Soon Ho Yoon, Hallym University, University Hospital of Wales (UHW), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], University of Cologne, Amphia Ziekenhuis = Amphia Hospital [Breda, The Netherlands] (AZ=AH), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Isfahan University of Medical Sciences [Iran] (MUI), Catholic University of Korea, Asan Medical Center [Seoul], University of Ulsan, Maimonides Medical Center, Seoul National University Hospital, None, and Jonchère, Laurent
Subjects: Data Analysis, Male, [SDV]Life Sciences [q-bio], COVID-19, X-ray computed, Middle Aged, [SDV] Life Sciences [q-bio], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Coronavirus 2019, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Aspergillosis, Radiology, Nuclear Medicine and imaging, Pulmonary Aspergillosis, Tomography, X-Ray Computed, Lung, Tomography, Aged
Abstract: International audience; PURPOSE: Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities. RESULTS: The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%). CONCLUSION: CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.
Published: 2022
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4. Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19 Associated Pulmonary Aspergillosis (CAPA): A multicenter study

Author: Jean-Pierre Gangneux, P. Lewis White, Juergen Prattes, Matthias Egger, Jessica S Price, Marina Machado, Maricela Valerio, Brice Autier, Martin Hoenigl, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Medical University Graz, University Hospital of Wales (UHW), Hospital General Universitario 'Gregorio Marañón' [Madrid], Karl-Franzens-Universität Graz, CHU Pontchaillou [Rennes], University of California [San Diego] (UC San Diego), University of California (UC), Provided some of the LFA test kits, IMMY Diagnostics, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), University Hospital of Wales [Cardiff, UK], Karl-Franzens-Universität [Graz, Autriche], University of California, University of Graz, Hanson, Kimberly E, and Jonchère, Laurent
Subjects: [SDV]Life Sciences [q-bio], nondirected bronchial lavage, Gastroenterology, Medical and Health Sciences, law.invention, Mannans, chemistry.chemical_compound, 0302 clinical medicine, law, Cutoff, bronchoalveolar lavage, tracheal aspirate, Lung, Invasive Pulmonary Aspergillosis, 0303 health sciences, medicine.diagnostic_test, biology, Area under the curve, Biological Sciences, Intensive care unit, 3. Good health, Aspergillus galactomannan lateral flow assay (LFA), [SDV] Life Sciences [q-bio], Infectious Diseases, Aspergillus, Bronchoalveolar Lavage Fluid, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Microbiology, Sensitivity and Specificity, 03 medical and health sciences, Galactomannan, Rare Diseases, Clinical Research, Internal medicine, medicine, Aspergillus galactomannan lateral flow assay, Humans, Retrospective Studies, Receiver operating characteristic, Agricultural and Veterinary Sciences, 030306 microbiology, business.industry, SARS-CoV-2, COVID-19, biology.organism_classification, Bronchoalveolar lavage, 030228 respiratory system, chemistry, galactomannan, Pulmonary Aspergillosis, business, serum
Abstract: International audience; This multicenter study evaluated the IMMY Aspergillus Galactomannan Lateral Flow Assay (LFA) with automated reader for diagnosis of pulmonary aspergillosis in patients with COVID-19 associated acute respiratory failure (ARF) requiring intensive care unit (ICU) admission between 03/2020 and 04/2021. A total of 196 respiratory samples and 148 serum samples (n=344) from 238 patients were retrospectively included, with a maximum of one of each sample type per patient. Cases were retrospectively classified for COVID-19 associated pulmonary aspergillosis (CAPA) status following the 2020 consensus criteria, with the exclusion of LFA results as a mycological criterion. At the 1.0 cutoff, sensitivity of LFA for CAPA (proven/probable/possible) was 52%, 80% and 81%, and specificity was 98%, 88% and 67%, for bronchoalveolar lavage fluid (BALF), non-directed bronchoalveolar lavage (NBL), and tracheal aspiration (TA), respectively. At the 0.5 manufacturer’s cutoff, sensitivity was 72%, 90% and 100%, and specificity was 79%, 83% and 44%, for BALF, NBL and TA, respectively. When combining all respiratory samples, the receiver operating characteristic (ROC) area under the curve (AUC) was 0.823, versus 0.754, 0.890 and 0.814 for BALF, NBL and TA, respectively. Sensitivity and specificity of serum LFA were 20% and 93%, respectively, at the 0.5 ODI cutoff. Overall, the Aspergillus Galactomannan LFA showed good performances for CAPA diagnosis, when used from respiratory samples at the 1.0 cutoff, while sensitivity from serum was limited, linked to weak invasiveness during CAPA. As some false positive results can occur, isolated results slightly above the recommended cutoff should lead to further mycological investigations.
Published: 2022
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5. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries

Author: Martin Hoenigl, Danila Seidel, Agostinho Carvalho, Shivaprakash M Rudramurthy, Amir Arastehfar, Jean-Pierre Gangneux, Nosheen Nasir, Alexandro Bonifaz, Javier Araiza, Nikolai Klimko, Alexandra Serris, Katrien Lagrou, Jacques F Meis, Oliver A Cornely, John R Perfect, P Lewis White, Arunaloke Chakrabarti, Jonchère, Laurent, Medical University of Graz, University of California [San Diego] (UC San Diego), University of California (UC), University of Cologne, Universidade do Minho = University of Minho [Braga], Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), Center for Discovery and Innovation - Hackensack Meridian Health (CDI), Hackensack Meridian Health, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), The Aga Khan University, Hospital General de México Dr. Eduardo Liceaga (HGM), North-Western State Medical University [St Petersburg, Russia], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Radboud University Medical Center [Nijmegen], Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Duke University Medical Center, University Hospital of Wales (UHW), National Institutes of Health, NIH: UL1TR001442, Pfizer, Astellas Pharma US, APUS: ISR005824, ISR005838, Gilead Sciences, Meso Scale Diagnostics, MSD, 'la Caixa' Foundation: 100010434, LCF/PR/HR17/52190003, Fundação para a Ciência e a Tecnologia, FCT: UIDB/50026/2020, UIDP/50026/2020, and European Regional Development Fund, ERDF: NORTE-01-0145-FEDER-000039
Subjects: Microbiology (medical), SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, Review, Microbiology, [SDV] Life Sciences [q-bio], Infectious Diseases, Risk Factors, Virology, Diabetes Mellitus, Humans, Mucormycosis, RNA, Viral, ECMM and ISHAM collaborators
Abstract: International audience; Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Published: 2022
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6. Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome:An international multicenter survey

Author: Loris Pironi, Ezra Steiger, Francisca Joly, Palle B. Jeppesen, Geert Wanten, Anna S. Sasdelli, Cecile Chambrier, Umberto Aimasso, Manpreet S. Mundi, Kinga Szczepanek, Amelia Jukes, Miriam Theilla, Marek Kunecki, Joanne Daniels, Mireille Serlie, Florian Poullenot, Sheldon C. Cooper, Henrik H. Rasmussen, Charlene Compher, David Seguy, Adriana Crivelli, Lidia Santarpia, Francesco W. Guglielmi, Nada Rotovnik Kozjek, Stéphane M. Schneider, Lars Ellegard, Ronan Thibault, Przemysław Matras, Konrad Matysiak, Andrè Van Gossum, Alastair Forbes, Nicola Wyer, Marina Taus, Nuria M. Virgili, Margie O'Callaghan, Brooke Chapman, Emma Osland, Cristina Cuerda, Gábor Udvarhelyi, Lynn Jones, Andre D. Won Lee, Luisa Masconale, Paolo Orlandoni, Corrado Spaggiari, Marta Bueno Díez, Maryana Doitchinova-Simeonova, Aurora E. Serralde-Zúñiga, Gabriel Olveira, Zeljko Krznaric, Laszlo Czako, Gintautas Kekstas, Alejandro Sanz-Paris, Mª Estrella Petrina Jáuregui, Ana Zugasti Murillo, Eszter Schafer, Jann Arends, José P. Suárez-Llanos, Nader N. Youssef, Giorgia Brillanti, Elena Nardi, Simon Lal, Adriana N. Crivelli, Hector Solar Muñiz, Brooke R. Chapman, Ruth Hodgson, Siobhan Wallin, Kay Lasenby, Andre Van Gossum, Andre Dong Won Lee, Henrik Højgaard Rasmussen, Chrisoffer Brandt, Vanessa Boehm, Julie Bataille, Lore Billiauws, Tomas Molnar, Mihaly Zsilak-Urban, Ferenc Izbéki, Peter Sahin, Anna Simona Sasdelli, Merlo F. Dario, Valentino Bertasi, Nunzia Regano, Santarpia Lidia, Lucia Alfonsi, Debora Busni, Lyn Gillanders, Anna Zmarzly, Marta Bueno, Carmen Garde, Ma Estrella Petrina Jáuregui, Cora Jonker, Simona Di Caro, Niamh Keane, Pinal Patel, Sarah-Jane Nelson Hughes, Rachel Lloyd, Arun Abraham, Gerda Garside, Michael Taylor, Jian Wu, Trevor Smith, Charlotte Pither, Michael Stroud, Reena Parmar, Nicola Burch, Sarah Zeraschi, Manpreet Mundi, Denise Jezerski, Pironi L., Steiger E., Joly F., Jeppesen P.B., Wanten G., Sasdelli A.S., Chambrier C., Aimasso U., Mundi M.M., Szczepanek K., Jukes A., Theilla M., Kunecki M., Daniels J., Serlie M., Poullenot F., Cooper S.C., Rasmussen H.H., Compher C., Seguy D., Crivelli A., Santarpia L., Guglielmi F.W., Kozjek N.R., Schneider S.M., Ellegard L., Thibault R., Matras P., Matysiak K., Van Gossum A., Forbes A., Wyer N., Taus M., Virgili N.M., O'Callaghan M., Chapman B., Osland E., Cuerda C., Udvarhelyi G., Jones L., Won Lee A.D., Masconale L., Orlandoni P., Spaggiari C., Diez M.B., Doitchinova-Simeonova M., Serralde-Zuniga A.E., Olveira G., Krznaric Z., Czako L., Kekstas G., Sanz-Paris A., Jauregui M.E.P., Murillo A.Z., Schafer E., Arends J., Suarez-Llanos J.P., Youssef N.N., Brillanti G., Nardi E., Lal S., Crivelli A.N., Muniz H.S., Chapman B.R., Hodgson R., Wallin S., Lasenby K., Brandt C., Boehm V., Bataille J., Billiauws L., Molnar T., Zsilak-Urban M., Izbeki F., Sahin P., Dario M.F., Bertasi V., Regano N., Lidia S., Alfonsi L., Busni D., Gillanders L., Zmarzly A., Bueno M., Garde C., Jonker C., Di Caro S., Keane N., Patel P., Nelson Hughes S.-J., Lloyd R., Abraham A., Garside G., Taylor M., Wu J., Smith T., Pither C., Stroud M., Parmar R., Burch N., Zeraschi S., Mundi M., Jezerski D., Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, University of Bologna, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cleveland Clinic, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], Hospices Civils de Lyon (HCL), Città della Salute e della Scienza University-Hospital, Mayo Clinic and Mayo College of Medicine, Rochester, Stanley Dudrick's Memorial Hospital, Partenaires INRAE, University Hospital of Wales, Tel Aviv University [Tel Aviv], University of Lódź, Nottingham University Hospitals NHS Trust [UK], VU University Medical Center [Amsterdam], CHU Bordeaux [Bordeaux], University Hospitals Birmingham NHS Foundation Trust, Aalborg University Hospital, Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospital Universitario Fundacion Favaloro, University of Naples Federico II, Monsignor di Miccoli Hospital, Institute of Oncology - Ljubljana, Institute of Oncology Ljubljana, Centre Hospitalier Universitaire de Nice (CHU Nice), University of Gothenburg (GU), The project of the ESPEN database for Chronic Intestinal Failure was promoted by the ESPEN Executive Committee in 2013, was approved by the ESPEN Council and was supported by an ESPEN grant., University of Bologna/Università di Bologna, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital of Wales (UHW), Tel Aviv University (TAU), Nottingham University Hospitals NHS Trust (NUH), University of Pennsylvania-University of Pennsylvania, University of Naples Federico II = Università degli studi di Napoli Federico II, and Institute of Oncology [Ljubljana]
Subjects: Parenteral Nutrition, Epidemiology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH: Intestinal Diseases, Malalties intestinals, 0302 clinical medicine, Indicadors de salut, Medicine, 030212 general & internal medicine, Intestines--Diseases, Nutrition and Dietetics, Intestinal Disease, Short bowel syndrome, Intestinal failure, Health status indicators, 3. Good health, Chronic intestinal failure, Intestine, Intestines, medicine.anatomical_structure, Cohort, 030211 gastroenterology & hepatology, Female, MESH: Intestines, Human, Adult, Short Bowel Syndrome, medicine.medical_specialty, Anastomosis, 03 medical and health sciences, Ileocecal valve, MESH: Cross-Sectional Studies, epidemiology, home parenteral nutrition, intestinal failure, intravenous supplementation, short bowel syndrome, Internal medicine, MESH: Short Bowel Syndrome, Humans, Cross-Sectional Studie, Home parenteral nutrition, MESH: Humans, business.industry, MESH: Adult, medicine.disease, Intravenous supplementation, Intestinal Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parenteral nutrition, Cross-Sectional Studies, Jejunostomy, business, MESH: Female, MESH: Parenteral Nutrition
Abstract: Contains fulltext : 244566.pdf (Publisher’s version ) (Closed access) BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as 3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.
Published: 2021
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7. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Author: Nishanthan Rajakumaraswamy, Simon Rule, Krimo Bouabdallah, John Radford, Loic Ysebaert, Christopher Fegan, Stephen E. Spurgeon, Gilles Salles, Alexey V. Danilov, Rita Humeniuk, Xi Huang, Pankaj Bhargava, Guillaume Cartron, Biao Li, Martin J. S. Dyer, Harriet S. Walter, Andrew Davies, Daniel J. Hodson, Franck Morschhauser, Juliane M. Jürgensmeier, Morschhauser, Franck [0000-0002-3714-9824], Walter, Harriet S [0000-0003-2618-711X], Hodson, Daniel James [0000-0001-6225-2033], Rule, Simon A [0000-0001-8937-6351], Rajakumaraswamy, Nishanthan [0000-0002-0226-0637], Salles, Gilles [0000-0002-9541-8666], Apollo - University of Cambridge Repository, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ernest and Helen Scott Haematological Research Institute, University of Leicester, City of Hope National Medical Center, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Cambridge [UK] (CAM), University Hospital of Wales (UHW), Plymouth University, University of Manchester [Manchester], The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], University of Southampton, Knight Cancer Institute, Oregon Health and Science University [Portland] (OHSU), Gilead Sciences, Inc. [Foster City, CA, USA], Hospices Civils de Lyon (HCL), Université de Lyon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Herrada, Anthony, CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Wales [Cardiff, UK], Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Walter, Harriet S. [0000-0003-2618-711X], and Rule, Simon A. [0000-0001-8937-6351]
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Cancer Research, Letter, Entospletinib, Indazoles, Lymphoma, B-Cell, Cancer therapy, Drug development, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, 692/699/67/1059, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, Phase (matter), hemic and lymphatic diseases, medicine, Humans, 692/308/153, B-cell lymphoma, Purine metabolism, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, Quinazolinones, 0303 health sciences, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Imidazoles, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Pyrimidines, Oncology, Purines, 030220 oncology & carcinogenesis, Pyrazines, Cancer research, Female, Idelalisib, Previously treated, business
Abstract: B-cell receptor (BCR) signaling pathway inhibitors (including Bruton’s tyrosine kinase [BTK] inhibitors, and phosphatidylinositol-3 kinase inhibitors [PI3Ki]) have shown clinical efficacy in non-Hodgkin lymphoma (NHL). However, responses to these agents have been limited in depth and duration. This may be due to resistance to PI3Kδ and BTK inhibitors as monotherapy [1,2,3,4,5]. The emergence of resistant clones may be addressed by combining these 2 classes of drugs. Furthermore, tolerability of these drug classes has been a concern. Combination therapy using lower doses of one or more classes of inhibitors may address some limitations.
Published: 2021
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8. Ethylzingerone, a Novel Compound with Antifungal Activity

Author: Rosemary Ann Barnes, Laurence Decourty, Sylvie Cupferman, Florence Menard-Szczebara, Christophe d'Enfert, Cosmin Saveanu, Maria Dalko-Sciba, Jean-Yves Maillard, Sadri Znaidi, Rebecca Wesgate, Murielle Chauvel, Tristan Rossignol, Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique (LR11IPT01), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Cardiff University, Génétique des Interactions macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), L’Oréal Research and Innovation, University Hospital of Wales [Cardiff, UK], Cardiff University (Cardiff University), L'Oreal Group, L'Oreal, France, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-08-JCJC-0019,GENO-GIM,Obtention d'une carte d'interactions génétiques à l'échelle génomique chez la levure(2008), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University Hospital of Wales (UHW)
Subjects: Antifungal Agents, [SDV]Life Sciences [q-bio], Saccharomyces cerevisiae, HEPB, Microbiology, ethylzingerone, 03 medical and health sciences, chemistry.chemical_compound, hydroxyethoxyphenyl butanone, Candida albicans, Aromatic amino acids, Pharmacology (medical), Mechanisms of Action: Physiological Effects, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Amino acid synthesis, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, Candida glabrata, biology, cosmetics, 030306 microbiology, Antimicrobial, biology.organism_classification, Corpus albicans, 3. Good health, Triclosan, Infectious Diseases, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, antifungal, mechanism of action
Abstract: International audience; Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of ethylzingerone (hydroxyethoxyphenyl butanone [HEPB]), an SCCS-approved new preservative for use in rinse-off, oral care, and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans, Candida giabrata, and Saccharomyces cerevisiae, acting fungicidally against C. albicans. Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae nonessential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trpl LI mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode of action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in the cosmetic industry, and exemplifies the powerful use of functional genomics to illuminate the mode of action of antimicrobial agents.
Published: 2021
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9. Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

Author: Bertrand Isidor, Ruth Armstrong, Thabo M. Yates, Susan M. White, Ruth Richardson, Solveig Heide, Katherine B. Burke, Tjitske Kleefstra, Marie Vincent, Meena Balasubramanian, Maria Irene Valenzuela Palafoll, Sébastien Küry, Rolph Pfundt, Ruth Newbury-Ecob, Sahar Mansour, Wendy K. Chung, Caroline Nava, Sofia Douzgou, Erika Leenders, Annachiara De Sandre-Giovannoli, Saba Sharif, Andrew E. Fry, Helen Stewart, Nicola K. Ragge, Alexander J. M. Dingemans, Pradeep C. Vasudevan, Alison Foster, Sahar Elouej, Shadi Albaba, François-Guillaume Debray, Boris Keren, Serwet Demirdas, Francis H. Sansbury, Thomas Scheffner, Arie van Haeringen, Alice S. Brooks, Meyke Schouten, Helen Cox, Kate Wilson, Sheffield Children's NHS Foundation Trust, University of Sheffield [Sheffield], Radboud University Medical Center [Nijmegen], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Birmingham Children’s Hospital, Manchester University NHS Foundation Trust (MFT), University of Manchester [Manchester], Addenbrooke's Hospital, Cambridge University NHS Trust, University Hospital of Wales, Oxford Brookes University, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), St. George’s Hospital University, Oxford University Hospitals NHS Foundation Trust, Partenaires INRAE, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Leiden University Medical Center (LUMC), Reutlingen University, Centre Hospitalier Universitaire de Liège (CHU-Liège), Murdoch Children's Research Institute (MCRI), University of Melbourne, Vall d'Hebron University Hospital [Barcelona], University Hospitals Bristol, Clinical Genetics, Institut Català de la Salut, [Balasubramanian M] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. Academic Unit of Child Health, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK. [Dingemans AJM] Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. [Albaba S] Sheffield Diagnostic Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Richardson R] Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Trust, Newcastle, UK. [Yates TM] Sheffield Clinical Genetics Service, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. [Cox H] West Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, UK. [Palafoll MIV] Servei de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Medicina Genètica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, University Hospital of Wales (UHW), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and Universiteit Leiden
Subjects: Male, Pediatrics, Genetic testing, Developmental Disabilities, Craniofacial Abnormalities, Intellectual disability, Missense mutation, Child, Genetics (clinical), trastornos mentales::trastornos del desarrollo neurológico::discapacidades del desarrollo [PSIQUIATRÍA Y PSICOLOGÍA], 0303 health sciences, Otros calificadores::Otros calificadores::/genética [Otros calificadores], 030305 genetics & heredity, Cognition, Syndrome, Autism spectrum disorders, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hypotonia, 3. Good health, Fenotip, Sin3 Histone Deacetylase and Corepressor Complex, Phenotype, Autism spectrum disorder, Child, Preschool, Cohort, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Trastorns del desenvolupament - Aspectes genètics, Infants, medicine.medical_specialty, Adolescent, personas::Grupos de Edad::niño [DENOMINACIONES DE GRUPOS], Article, 03 medical and health sciences, Mental Disorders::Neurodevelopmental Disorders::Developmental Disabilities [PSYCHIATRY AND PSYCHOLOGY], Intellectual Disability, Genetics, medicine, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Attention deficit hyperactivity disorder, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Infant, Persons::Age Groups::Child [NAMED GROUPS], medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Genetic Phenomena::Phenotype [PHENOMENA AND PROCESSES], Autism, business, fenómenos genéticos::fenotipo [FENÓMENOS Y PROCESOS]
Abstract: Trastornos del espectro autista; Prueba genética Trastorns de l'espectre autista; Prova genètica Autism spectrum disorders; Genetic testing Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12. Funding for the project was provided by the Wellcome Trust and by grants from the Netherlands Organization for Health Research and Development (ZonMw grant 91718310 and the Dutch Scientific Organization (NWO, grant NWA 1160.18.320). WKC is supported by grants from SFARI and the JPB Foundation
Published: 2021
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10. Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease

Author: Leticia Quintanilla-Martinez, Inga Müller, Dominik Nann, Itziar Salaverria, Julia Salmeron-Villalobos, Falko Fend, Barbara Mankel, Blanca Gonzalez-Farre, Dolors Colomer, Sven Mattern, Elaine S. Jaffe, Stefan Dojcinov, Irina Bonzheim, Christiane Copie-Bergman, Lorenzo Leoncini, Olga Balagué, Joan Enric Ramis-Zaldivar, Caoimhe Egan, Vanessa Szablewski, Elias Campo, Carmen Lome-Maldonado, Andreas Chott, Guillem Clot, Janine Schmidt, Franziska Otto, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Universitätsklinikum Tübingen - University Hospital of Tübingen, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Instituto Nacional de Cancerología, Università degli Studi di Siena = University of Siena (UNISI), University Hospital of Wales (UHW), Wilhelminenspital Vienna = Wilhelminen Hospital, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University Hospital of Wales [Cardiff, UK], Wilhelminenspital Vienna, and Herrada, Anthony
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Mutation, DNA Copy Number Variations, Follicular lymphoma, Gene mutation, Biology, Follicular lymphoma, Genetic heterogeneity, CD23 antigen, BCL6 gene, CREBBP gene, EZH2 gene, STAT6 gene, TNFRSF14 gene, CD23 antigen, STAT6 gene, medicine.disease_cause, Genetic heterogeneity, 03 medical and health sciences, MESH: Lymphoma, Follicular, 0302 clinical medicine, MAP2K1, MESH: Child, medicine, EZH2 gene, Humans, CREBBP gene, Child, MESH: Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, B cell, 030304 developmental biology, 0303 health sciences, Mutation, Lymphoid Neoplasia, MESH: Humans, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Lymphoma, B-Cell, Marginal Zone, medicine.disease, Marginal zone, BCL6, Molecular biology, 3. Good health, Lymphoma, medicine.anatomical_structure, 030220 oncology & carcinogenesis, BCL6 gene, Female, MESH: DNA Copy Number Variations, MESH: Female, TNFRSF14 gene
Abstract: Fifty-five cases of t(14;18)− follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)− FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)− FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)+ FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)− FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P < .05). STAT6 mutations showed a positive correlation with CD23 expression (P < .001). In summary, t(14;18)− FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.
Published: 2020
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11. NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly

Author: Sonal Mahida, Elliott H. Sherr, Elodie Lacaze, William B. Dobyns, Kosuke Izumi, Hilde Peeters, Marielle Alders, Catherine Nowak, Dawn L. Earl, Richard M. Gronostajski, Ryan J. Dean, Megan T. Cho, Anouck Schneider, Siren Berland, Patricia Blanchet, Laurence Faivre, Martin Zenker, Ina Schanze, Caitlin J. Bridges, Daniela T. Pilz, Sangamitra Boppudi, Ilse Wieland, Jens Bunt, Avni Santani, Jessica Douglas, Elaine H. Zackai, Muriel Holder-Espinasse, Linda J. Richards, Jean Baptiste Rivière, Tania Attié-Bitach, Timothy J. Edwards, Vincent Gatinois, Jacques Puechberty, Jonathan W. C. Lim, Ghayda Mirzaa, Sian Morgan, Phillis Lakeman, Steven Boogert, Samuel Huth, Marion Gérard, Denny Schanze, Florence Petit, Xiaonan Zhao, Eyal Reinstein, David Geneviève, Bronwyn Kerr, Dian Donnai, Constance Smith-Hicks, Brieana Fregeau, Amsterdam Reproduction & Development (AR&D), ACS - Pulmonary hypertension & thrombosis, Human Genetics, Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Queensland Brain Institute, University of Queensland [Brisbane], University of Amsterdam [Amsterdam] (UvA), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Embryology and genetics of human malformation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Haukeland University Hospital, University of Bergen (UiB), GeneDx [Gaithersburg, MD, USA], University of Washington [Seattle], Seattle Children’s Hospital, University of Manchester [Manchester], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, FHU TRANSLAD (CHU de Dijon), University of California [San Francisco] (UC San Francisco), University of California (UC), Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, Children’s Hospital of Philadelphia (CHOP ), Département de génétique (groupe hospitalier le Havre), Groupe Hospitalier du Havre, Kennedy Krieger Institute [Baltimore], University Hospital of Wales (UHW), University Hospitals Leuven [Leuven], University of Glasgow, Sackler Faculty of Medicine, Tel Aviv University (TAU), Perelman School of Medicine, University of Pennsylvania, This work was supported by grants from the National Healthand Medical Research Council Australia (GNT1100443 to L.J.R.), the French Ministry of Health (PHRC national 2008/2008-A00515-50), Regional Council of Burgundy/Dijon University hospital (PARI 2012), The Genesis Foundation for Children, the US National Institutes of Health under NINDS grants(1R01NS092772 and 234567890 to W.B.D., 1R01NS058721 toW.B.D. and E.H.S., and K08NS092898 to G.M.M.), and Jordan’s Guardian Angels (G.M.M.). J.W.C.L. was supported by an International Postgraduate Research Scholarship and UQ Centennial Scholarship. R.M.G. was supported by NYSTEM grants (C026714,C026429, and C030133). R.J.D. was supported by Brain Injured Children’s Aftercare Recovery Endeavours (BICARE) Fellowship.L.J.R. was supported by an NHMRC Principal Research Fellowship(GNT1005751). M.Z. was supported by a grant from the GermanMinistry of Education and Research (BMBF) (GeNeRARe01GM1519A). We acknowledge the Linkage Infrastructure, Equipment and Facilities (LIEF) grant (LE100100074) awarded to the Queensland Brain Institute for the Slide Scanner and the facilities of the National Imaging Facility (NIF) at the Centre for Advanced Imaging, University of Queensland, used in the animal experiments., European Project: 270259,EC:FP7:ICT,FP7-ICT-2009-6,TBICARE(2011), Institute of Human Genetics (University Hospital Magdeburg), University Hospital of the Otto von Guericke University of Magdeburg, Department of Clinical Genetics, Academic Medical Centre, Amsterdam, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), Seattle Children's Research Institute, Department of Neurology (University of California : San Francisco), University of California [San Francisco] (UCSF), University of California-University of California, Department of Medical Genetics, HMNC Brain Health, Seattle Children’s Hospital [Seattle, WA, USA], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Université de Lorraine (UL), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Pediatrics (Perelman School of Medicine), University of Pennsylvania [Philadelphia], Regional Genetic Service, St Mary's Hospital, Manchester, Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Department of Pediatrics [Seattle, WA, USA] (Division of Genetic Medicine), University of Washington [Seattle]-Seattle Children’s Hospital [Seattle, WA, USA], Institute of Medical Genetics (University Hospital of Wales), University Hospital of Wales, Center for Human Genetics, University Hospitals Leuven, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille 2 - Faculté de Médecine -Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), West of Scotland Genetics Service (Queen Elizabeth University Hospital), University Hospital Birmingham Queen Elizabeth, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Medical Genetics Institute, Meir Medical Center, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Department of Pathology and Laboratory Medicine [Philadelphia, PA, USA], University of Pennsylvania [Philadelphia]-Perelman School of Medicine, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, School of Computer Science and Technology, Northwestern Polytechnical University [Xi'an] (NPU), Department of Biochemistry and Developmental Genomics Group, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY)-State University of New York (SUNY)-Center of Excellence in Bioinformatics and Life Sciences, Institute of Human Genetics, University Hospital Magdeburg, université de Bourgogne, LNC, Evidence based Diagnostic and Treatment Planning Solution for Traumatic Brain Injuries - TBICARE - - EC:FP7:ICT2011-02-01 - 2014-07-31 - 270259 - VALID, Otto-von-Guericke University [Magdeburg] (OVGU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of California, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital of Wales [Cardiff, UK], and Tel Aviv University [Tel Aviv]
Subjects: Male, 0301 basic medicine, chromosome 9p23, Medical and Health Sciences, Corpus Callosum, Cohort Studies, Mice, 2.1 Biological and endogenous factors, Megalencephaly, Aetiology, Child, Agenesis of the corpus callosum, Genetics (clinical), Pediatric, Genetics & Heredity, Cerebral Cortex, Mice, Knockout, Genetics, Single Nucleotide, nuclear factor I, Biological Sciences, NFIB, NFIX, developmental delay, Mental Health, Codon, Nonsense, NFIA, intellectual disability, Child, Preschool, chromosome 9p22.3, Neurological, Speech delay, Female, medicine.symptom, Haploinsufficiency, Adult, Adolescent, Knockout, Intellectual and Developmental Disabilities (IDD), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, macrocephaly, Polymorphism, Single Nucleotide, Article, Young Adult, 03 medical and health sciences, Rare Diseases, Behavioral and Social Science, medicine, megalencephaly, Animals, Humans, Polymorphism, Codon, Preschool, Neurosciences, Macrocephaly, medicine.disease, Brain Disorders, haploinsufficiency, NFI Transcription Factors, 030104 developmental biology, Nonsense, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, agenesis of the corpus callosum
Abstract: The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:103 issue:5 pages:752-768 ispartof: location:United States status: published
Published: 2018
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12. Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey

Author: Pironi, Loris, Steiger, Ezra, Brandt, Chrisoffer, Joly, Francisca, Wanten, Geert, Chambrier, Cecile, Aimasso, Umberto, Sasdelli, Anna Simona, Zeraschi, Sarah, Kelly, Darlene, Szczepanek, Kinga, Jukes, Amelia, Di Caro, Simona, Theilla, Miriam, Kunecki, Marek, Daniels, Joanne, Serlie, Mireille, Poullenot, Florian, Wu, Jian, Cooper, Sheldon C, Rasmussen, Henrik H, Compher, Charlene, Seguy, David, Crivelli, Adriana, Pagano, Maria C, Hughes, Sarah-Jane, Guglielmi, Francesco W, Kozjek, Nada Rotovnik, Schneider, Stéphane M, Gillanders, Lyn, Ellegard, Lars, Thibault, Ronan, Matras, Przemysław, Zmarzly, Anna, Matysiak, Konrad, Van Gossum, Andrè, Forbes, Alastair, Wyer, Nicola, Taus, Marina, Virgili, Nuria M, O'Callaghan, Margie, Chapman, Brooke, Osland, Emma, Cuerda, Cristina, Sahin, Peter, Jones, Lynn, Won Lee, Andre Dong, Masconale, Luisa, Orlandoni, Paolo, Izbéki, Ferenc, Spaggiari, Corrado, Bueno, Marta, Doitchinova-Simeonova, Maryana, Garde, Carmen, Serralde-Zúñiga, Aurora E, Olveira, Gabriel, Krznaric, Zeljko, Czako, Laszlo, Kekstas, Gintautas, Sanz-Paris, Alejandro, Jáuregui, Estrella Petrina, Murillo, Ana Zugasti, Schafer, Eszter, Arends, Jann, Suárez-Llanos, José P, Lal, Simon, Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN, European Society for Clinical Nutrition and Metabolism, Pironi L., Steiger E., Brandt C., Joly F., Wanten G., Chambrier C., Aimasso U., Sasdelli A.S., Zeraschi S., Kelly D., Szczepanek K., Jukes A., Di Caro S., Theilla M., Kunecki M., Daniels J., Serlie M., Poullenot F., Wu J., Cooper S.C., Rasmussen H.H., Compher C., Seguy D., Crivelli A., Pagano M.C., Hughes S.-J., Guglielmi F.W., Kozjek N.R., Schneider S.M., Gillanders L., Ellegard L., Thibault R., Matras P., Zmarzly A., Matysiak K., Van Gossum A., Forbes A., Wyer N., Taus M., Virgili N.M., O'Callaghan M., Chapman B., Osland E., Cuerda C., Sahin P., Jones L., Won Lee A.D., Masconale L., Orlandoni P., Izbeki F., Spaggiari C., Bueno M., Doitchinova-Simeonova M., Garde C., Serralde-Zuniga A.E., Olveira G., Krznaric Z., Czako L., Kekstas G., Sanz-Paris A., Jauregui E.P., Murillo A.Z., Schafer E., Arends J., Suarez-Llanos J.P., Lal S., St. Orsola University Hospital, Cleveland Clinic, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], Hospices Civils de Lyon, Departement de Neurologie (HCL), Leeds Teaching Hospitals NHS Trust, University Hospital of Wales, Rabin Medical Center, Nottingham University Hospital NHS Trust, Department of Infectious Diseases [Amsterdam, Netherlands] (Academic Medical Center), University of Amsterdam [Amsterdam] (UvA)-Center for Tropical and Travel Medicine [Amsterdam, Netherlands], University Hospital Southampton NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, 'Federico II' University of Naples Medical School, Sahlgrenska University Hospital [Gothenburg], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], University Hospitals Birmingham NHS Foundation Trust Institut National de la Santé et de la Recherche Médicale University of Pennsylvania, PennRoyal Marsden NHS Foundation TrustNottingham University Hospitals NHS TrustCleveland Clinic FoundationUniversity Hospital Southampton NHS Foundation TrustChung Hua University Fondazione Città della SperanzaInstitut National de la Recherche Agronomique Hospices Civils de Lyon European Society for Clinical Nutrition and Metabolism, Endocrinology, AGEM - Endocrinology, metabolism and nutrition, University Hospital of Wales (UHW), Nottingham University Hospitals NHS Trust (NUH), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Internationality, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Pharmacy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Health care, Chronic renal failure, Medicine, Humans, Medical prescription, Cancer, Home parenteral nutrition, 030109 nutrition & dietetics, Nutrition and Dietetics, Modalities, Adult patients, Intestinal failure, Intravenous supplementation, business.industry, International survey, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, Health Surveys, 3. Good health, Chronic intestinal failure, Intestinal Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parenteral nutrition, Cross-Sectional Studies, Treatment Outcome, Alimentació parenteral, Chronic Disease, Parenteral feeding, Insuficiència renal crònica, Female, business, Parenteral Nutrition, Home, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Contains fulltext : 220087.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF). METHODS: In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions. RESULTS: HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p
Published: 2020
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13. The broad phenotypic spectrum of PPP2R1A -related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

Author: Amy McTague, Siddharth Srivastava, Tamison Jewett, Ali Al-Beshri, Constance Smith-Hicks, Shelagh Joss, Jennifer A. Sullivan, Sarju G. Mehta, Koenraad Devriendt, Pascal Joset, Laurence Faivre, Emma Kivuva, William G. Wilson, Gunnar Houge, Naama Orenstein, Yana Hoorne, Vickie L. Hannig, Malou Heijligers, Bart Loeys, Vandana Shashi, Katrina Prescott, Iris Verbinnen, Annick Toutain, Lauren M. Baldwin, Stephen P. Fulton, Katharina Steindl, Anne Marie Childs, Anna Chassevent, Shelley Towner, Cornelia Daumer-Haas, Oded Wechsberg, Alison Male, Hannah F. Johnson, Wendy K. Chung, Anita Rauch, Anna Ruiz, Isabelle Maystadt, Sara Reynhout, Sébastien Moutton, Yvette van Ierland, Veerle Janssens, Frédéric Laumonnier, Martina Baethmann, Lisa Lenaerts, Vani Jain, Vinod Varghese, Suzanne M. Koudijs, Elisabeth Gabau, Frédérique Bonnet-Brilhault, Rizwan Hamid, Susan E. Holder, Barbara Plecko, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Queen Elizabeth University Hospital (Glasgow), Kennedy Krieger Institute [Baltimore], University of Antwerp (UA), Universität Zürich [Zürich] = University of Zurich (UZH), Addenbrooke’s Hospital [Cambridge, UK], Columbia University Medical Center (CUMC), Columbia University [New York], North West Thames Regional Genetics Service [London, UK] (Harrow), North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow-Northwick Park Hospital [Harrow, UK] (NPH), Wake Forest University, University of Virginia [Charlottesville], Boston Children's Hospital, Prenatal Medicine Munich [Munich, Germany] (PMM), Klinikum Dritter Orden [Munich], Universitat Autònoma de Barcelona (UAB), University Hospital of Wales [Cardiff, UK], University of Alabama at Birmingham [ Birmingham] (UAB), Le Bonheur Children's Hospital [Memphis, TN, USA] (LBCH), Schneider Children’s Medical Center of Israel [Petah Tikva], Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Leeds Teaching Hospitals NHS Trust, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Maison de Santé Protestante de Bordeaux-Bagatelle (MSPB), Duke University Medical Center, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Royal Devon and Exeter NHS Foundation Trust [UK], Great Ormond Street Institute of Child Health [London, UK] (UCL), University College of London [London] (UCL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University Graz, Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Haukeland University Hospital, University of Bergen (UiB), Leuven Brain Institute [Leuven, Belgium] (LBI), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Clinical Genetics, University of Virginia, University Hospital of Wales (UHW), Tel Aviv University (TAU), Great Ormond Street Institute of Child Health (UCL), and Laumonnier, Frédéric
Subjects: 0301 basic medicine, Microcephaly, [SDV]Life Sciences [q-bio], Intellectual disability, 030105 genetics & heredity, Bioinformatics, Epilepsy, Neurodevelopmental disorder, CORE, Protein Phosphatase 2, SPECIFICITY, Genetics (clinical), PROTEIN PHOSPHATASE 2A, Phenotype, Hypotonia, FAMILY, 3. Good health, PP2A, [SDV] Life Sciences [q-bio], PPP2R1A, PPP2R5D, INSIGHTS, intellectual disability, Muscle Hypotonia, medicine.symptom, Language delay, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, 03 medical and health sciences, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, business.industry, Macrocephaly, DEPHOSPHORYLATION, medicine.disease, neurodevelopmental disorder, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, SUBUNIT, epilepsy, Human medicine, TAU, business, Transcription Factors
Abstract: PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. CONCLUSION: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported. ispartof: Genetics In Medicine vol:23 issue:2 ispartof: location:United States status: Published online
Published: 2020
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14. Proceedings from the 3rd European Clinical Consensus Conference for clinical trials in device-based hypertension therapies

Author: Costas Tsioufis, Michael Böhm, David E. Kandzari, William Wijns, Faisal Sharif, Felix Mahfoud, Atul Pathak, Christian Ukena, Massimo Volpe, L. M. Ruilope, Gianfranco Parati, Sverre E. Kjeldsen, Markus P. Schlaich, Roland E. Schmieder, Atif Shahzad, Ajay J. Kirtane, Horst Sievert, Guido Grassi, Isabelle Durand Zaleski, Michael A. Weber, Michael Joner, John W. McEvoy, Michel Azizi, Gilles Chatellier, Sebastian Ewen, Peter J. Blankestijn, Andrew S.P. Sharp, Thomas F. Lüscher, Patrick Rossignol, Melvin D. Lobo, Michel Burnier, Massachusetts Institute of Technology (MIT), Universität des Saarlandes [Saarbrücken], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Princesse Grace, Utrecht Brain Center [UMC], University Medical Center [Utrecht], Université de Lausanne = University of Lausanne (UNIL), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Piedmont Heart Institute, Columbia University Irving Medical Center (CUIMC), Oslo University Hospital [Oslo], Queen Mary University of London (QMUL), Imperial College London, Universität Zürich [Zürich] = University of Zurich (UZH), National University of Ireland [Galway] (NUI Galway), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospital Universitario 12 de Octubre [Madrid], The University of Western Australia (UWA), Baker Heart and Diabetes Institute (AUSTRALIA), University Hospital Galway, University Hospital of Wales (UHW), University of Exeter, Anglia Ruskin University (ARU), University of California [San Francisco] (UC San Francisco), University of California (UC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), State University of New York (SUNY), University Hospital Erlangen = Uniklinikum Erlangen, National and Kapodistrian University of Athens (NKUA), HULOT, Jean-Sébastien, Mahfoud, F, Azizi, M, Ewen, S, Pathak, A, Ukena, C, Blankestijn, P, Böhm, M, Burnier, M, Chatellier, G, Durand Zaleski, I, Grassi, G, Joner, M, Kandzari, D, Kirtane, A, Kjeldsen, S, Lobo, M, Lüscher, T, Mcevoy, J, Parati, G, Rossignol, P, Ruilope, L, Schlaich, M, Shahzad, A, Sharif, F, Sharp, A, Sievert, H, Volpe, M, Weber, M, Schmieder, R, Tsioufis, C, and Wijns, W
Subjects: safety, medicine.medical_specialty, hypertension, [SDV]Life Sciences [q-bio], Calidad de vida, therapy, device, guidelines, Enfermedad cardiovascular, MEDLINE, 030204 cardiovascular system & hematology, medical devices, Consensus, Humans, Hypertension/drug therapy, Medical History Taking, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, Hipertensión, medicine, 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Consensus conference, Medicamentos cardiovasculares, [SDV] Life Sciences [q-bio], Clinical trial, Current Opinion, consensus, RDN, baroreceptor activation therapy, Cardiology and Cardiovascular Medicine, business
Abstract: Sin financiación 22.673 JCR (2019) Q1, 2/138 Cardiac & Cardiovascular Systems 5.883 SJR (2019) Q1, 4/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM
Published: 2020
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15. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Author: Anne H. O’Donnell-Luria, Lynn S. Pais, Víctor Faundes, Jordan C. Wood, Abigail Sveden, Victor Luria, Rami Abou Jamra, Andrea Accogli, Kimberly Amburgey, Britt Marie Anderlid, Silvia Azzarello-Burri, Alice A. Basinger, Claudia Bianchini, Lynne M. Bird, Rebecca Buchert, Wilfrid Carre, Sophia Ceulemans, Perrine Charles, Helen Cox, Lisa Culliton, Aurora Currò, Florence Demurger, James J. Dowling, Benedicte Duban-Bedu, Christèle Dubourg, Saga Elise Eiset, Luis F. Escobar, Alessandra Ferrarini, Tobias B. Haack, Mona Hashim, Solveig Heide, Katherine L. Helbig, Ingo Helbig, Raul Heredia, Delphine Héron, Bertrand Isidor, Amy R. Jonasson, Pascal Joset, Boris Keren, Fernando Kok, Hester Y. Kroes, Alinoë Lavillaureix, Xin Lu, Saskia M. Maas, Gustavo H.B. Maegawa, Carlo L.M. Marcelis, Paul R. Mark, Marcelo R. Masruha, Heather M. McLaughlin, Kirsty McWalter, Esther U. Melchinger, Saadet Mercimek-Andrews, Caroline Nava, Manuela Pendziwiat, Richard Person, Gian Paolo Ramelli, Luiza L.P. Ramos, Anita Rauch, Caitlin Reavey, Alessandra Renieri, Angelika Rieß, Amarilis Sanchez-Valle, Shifteh Sattar, Carol Saunders, Niklas Schwarz, Thomas Smol, Myriam Srour, Katharina Steindl, Steffen Syrbe, Jenny C. Taylor, Aida Telegrafi, Isabelle Thiffault, Doris A. Trauner, Helio van der Linden, Silvana van Koningsbruggen, Laurent Villard, Ida Vogel, Julie Vogt, Yvonne G. Weber, Ingrid M. Wentzensen, Elysa Widjaja, Jaroslav Zak, Samantha Baxter, Siddharth Banka, Lance H. Rodan, Jeremy F. McRae, Stephen Clayton, Tomas W. Fitzgerald, Joanna Kaplanis, Elena Prigmore, Diana Rajan, Alejandro Sifrim, Stuart Aitken, Nadia Akawi, Mohsan Alvi, Kirsty Ambridge, Daniel M. Barrett, Tanya Bayzetinova, Philip Jones, Wendy D. Jones, Daniel King, Netravathi Krishnappa, Laura E. Mason, Tarjinder Singh, Adrian R. Tivey, Munaza Ahmed, Uruj Anjum, Hayley Archer, Ruth Armstrong, Jana Awada, Meena Balasubramanian, Diana Baralle, Angela Barnicoat, Paul Batstone, David Baty, Chris Bennett, Jonathan Berg, Birgitta Bernhard, A. Paul Bevan, Maria Bitner-Glindzicz, Edward Blair, Moira Blyth, David Bohanna, Louise Bourdon, David Bourn, Lisa Bradley, Angela Brady, Simon Brent, Carole Brewer, Kate Brunstrom, David J. Bunyan, John Burn, Natalie Canham, Bruce Castle, Kate Chandler, Elena Chatzimichali, Deirdre Cilliers, Angus Clarke, Susan Clasper, Jill Clayton-Smith, Virginia Clowes, Andrea Coates, Trevor Cole, Irina Colgiu, Amanda Collins, Morag N. Collinson, Fiona Connell, Nicola Cooper, Lara Cresswell, Gareth Cross, Yanick Crow, Mariella D’Alessandro, Tabib Dabir, Rosemarie Davidson, Sally Davies, Dylan de Vries, John Dean, Charu Deshpande, Gemma Devlin, Abhijit Dixit, Angus Dobbie, Alan Donaldson, Dian Donnai, Deirdre Donnelly, Carina Donnelly, Angela Douglas, Sofia Douzgou, Alexis Duncan, Jacqueline Eason, Sian Ellard, Ian Ellis, Frances Elmslie, Karenza Evans, Sarah Everest, Tina Fendick, Richard Fisher, Frances Flinter, Nicola Foulds, Andrew Fry, Alan Fryer, Carol Gardiner, Lorraine Gaunt, Neeti Ghali, Richard Gibbons, Harinder Gill, Judith Goodship, David Goudie, Emma Gray, Andrew Green, Philip Greene, Lynn Greenhalgh, Susan Gribble, Rachel Harrison, Lucy Harrison, Victoria Harrison, Rose Hawkins, Liu He, Stephen Hellens, Alex Henderson, Sarah Hewitt, Lucy Hildyard, Emma Hobson, Simon Holden, Muriel Holder, Susan Holder, Georgina Hollingsworth, Tessa Homfray, Mervyn Humphreys, Jane Hurst, Ben Hutton, Stuart Ingram, Melita Irving, Lily Islam, Andrew Jackson, Joanna Jarvis, Lucy Jenkins, Diana Johnson, Elizabeth Jones, Dragana Josifova, Shelagh Joss, Beckie Kaemba, Sandra Kazembe, Rosemary Kelsell, Bronwyn Kerr, Helen Kingston, Usha Kini, Esther Kinning, Gail Kirby, Claire Kirk, Emma Kivuva, Alison Kraus, Dhavendra Kumar, V. K. Ajith Kumar, Katherine Lachlan, Wayne Lam, Anne Lampe, Caroline Langman, Melissa Lees, Derek Lim, Cheryl Longman, Gordon Lowther, Sally A. Lynch, Alex Magee, Eddy Maher, Alison Male, Sahar Mansour, Karen Marks, Katherine Martin, Una Maye, Emma McCann, Vivienne McConnell, Meriel McEntagart, Ruth McGowan, Kirsten McKay, Shane McKee, Dominic J. McMullan, Susan McNerlan, Catherine McWilliam, Sarju Mehta, Kay Metcalfe, Anna Middleton, Zosia Miedzybrodzka, Emma Miles, Shehla Mohammed, Tara Montgomery, David Moore, Sian Morgan, Jenny Morton, Hood Mugalaasi, Victoria Murday, Helen Murphy, Swati Naik, Andrea Nemeth, Louise Nevitt, Ruth Newbury-Ecob, Andrew Norman, Rosie O’Shea, Caroline Ogilvie, Kai-Ren Ong, Soo-Mi Park, Michael J. Parker, Chirag Patel, Joan Paterson, Stewart Payne, Daniel Perrett, Julie Phipps, Daniela T. Pilz, Martin Pollard, Caroline Pottinger, Joanna Poulton, Norman Pratt, Katrina Prescott, Sue Price, Abigail Pridham, Annie Procter, Hellen Purnell, Oliver Quarrell, Nicola Ragge, Raheleh Rahbari, Josh Randall, Julia Rankin, Lucy Raymond, Debbie Rice, Leema Robert, Eileen Roberts, Jonathan Roberts, Paul Roberts, Gillian Roberts, Alison Ross, Elisabeth Rosser, Anand Saggar, Shalaka Samant, Julian Sampson, Richard Sandford, Ajoy Sarkar, Susann Schweiger, Richard Scott, Ingrid Scurr, Ann Selby, Anneke Seller, Cheryl Sequeira, Nora Shannon, Saba Sharif, Charles Shaw-Smith, Emma Shearing, Debbie Shears, Eamonn Sheridan, Ingrid Simonic, Roldan Singzon, Zara Skitt, Audrey Smith, Kath Smith, Sarah Smithson, Linda Sneddon, Miranda Splitt, Miranda Squires, Fiona Stewart, Helen Stewart, Volker Straub, Mohnish Suri, Vivienne Sutton, Ganesh Jawahar Swaminathan, Elizabeth Sweeney, Kate Tatton-Brown, Cat Taylor, Rohan Taylor, Mark Tein, I. Karen Temple, Jenny Thomson, Marc Tischkowitz, Susan Tomkins, Audrey Torokwa, Becky Treacy, Claire Turner, Peter Turnpenny, Carolyn Tysoe, Anthony Vandersteen, Vinod Varghese, Pradeep Vasudevan, Parthiban Vijayarangakannan, Emma Wakeling, Sarah Wallwark, Jonathon Waters, Astrid Weber, Diana Wellesley, Margo Whiteford, Sara Widaa, Sarah Wilcox, Emily Wilkinson, Denise Williams, Nicola Williams, Louise Wilson, Geoff Woods, Christopher Wragg, Michael Wright, Laura Yates, Michael Yau, Chris Nellåker, Michael Parker, Helen V. Firth, Caroline F. Wright, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles, Department of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for Medical Genetics, Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC, CNR), Istituto di Scienze e Tecnologie della Cognizione, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatrics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Children’s Hospital of Philadelphia (CHOP ), Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Public Health Sciences, Karolinska Institutet [Stockholm], Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Università degli Studi di Camerino = University of Camerino (UNICAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Oxford, GeneDx [Gaithersburg, MD, USA], Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Genetics, Aarhus University Hospital, Boston Children's Hospital, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Institute of Biomedical Engineering [Oxford] (IBME), Climatic Research Unit, University of East Anglia [Norwich] (UEA), Imperial College London, St Mary's Hospital, East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital, Sheffield Children's NHS Foundation Trust, Regional Genetic Service, St Mary's Hospital, Manchester, Genetics, University of Southampton, Great Ormond Street Hospital for Children [London] (GOSH), Yorkshire Regional Clinical Genetics Service, Chapel Allerton Hospital, Molecular and Clinical Medicine [Dundee, UK] (School of Medicine), University of Dundee [UK]-Ninewells Hospital & Medical School [Dundee, UK], Department of Clinical Genetics, Oxford Regional Genetics Service, The Churchill hospital, North West Thames Regional Genetics, Northwick Park Hospital, Royal Devon & Exeter Hospital, Wessex Clinical Genetics Service, Wessex clinical genetics service, Manchester University NHS Foundation Trust (MFT), West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Guy's Hospital [London], University Hospitals Leicester, University of Edinburgh, Belfast City Hospital, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Institute of Medical Genetics, Heath Park, Cardiff, The London Clinic, Nottingham City Hospital, Clinical Genetics Department, St Michael's Hospital, Department of Genetic Medicine, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust (NUH), Royal Devon and Exeter Foundation Trust, Histopathology, St. George's Hospital, Teesside Genetics Unit, James Cook University (JCU), Kansas State University, Liverpool Women's NHS Foundation Trust, Department of Medical Genetics, HMNC Brain Health, North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, Leicester Royal Infirmary, University Hospitals Leicester-University Hospitals Leicester, Ninewells Hospital and Medical School [Dundee], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Oxford Brookes University, Institute of medicinal plant development, Chinese Academy of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Trust, Service d'explorations fonctionnelles respiratoires [Lille], Department of Computer Science - Trinity College Dublin, University of Dublin, Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Division of Medical & Molecular Genetics, NHS Greater Glasgow & Clyde [Glasgow] (NHSGGC), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Weizmann Institute of Science [Rehovot, Israël], Southampton General Hospital, Western General Hospital, Head of the Department of Medical Genetics, University of Birmingham [Birmingham], SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), All Wales Medical Genetics Services, Singleton Hospital, Central Manchester University Hospitals NHS Foundation Trust, University of North Texas (UNT), Clinical Genetics, Northern Genetics Service, Newcastle University [Newcastle], United Kingdom Met Office [Exeter], Institute of Medical Genetics (University Hospital of Wales), University Hospital of Wales (UHW), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Department of Genetics, Cell- and Immunobiology, Semmelweis University, University Hospitals Bristol, Marketing (MKT), EESC-GEM Grenoble Ecole de Management, Addenbrookes Hospital, West of Scotland Genetics Service (Queen Elizabeth University Hospital), University Hospital Birmingham Queen Elizabeth, Department of Clnical Genetics, Chapel Allerton Hospital, Department of Clinical Genetics, Northampton General Hospital, Northampton, Royal Devon and Exeter Hospital [Exeter, UK] (RDEH), Guy's and St Thomas' Hospital [London], School of Computer Science, Bangor University, University Hospital Southampton, Clinical Genetics Unit, St Georges, University of London, Medical Genetics, Cardiff University, Research and Development, Futurelab, Nottingham Regional Genetics Service [Nottingham, UK], Nottingham University Hospitals NHS Trust (NUH)-City Hospital Campus [Nottingham, UK], University of St Andrews [Scotland], Clinical Genetics Service, Nottingham University Hospitals NHS Trust - City Hospital Campus, West Midlands Regional Genetics Unit, Department of Neurology, Johns Hopkins University (JHU), Oxford University Hospitals NHS Trust, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge University NHS Trust, Institute of Human Genetics, Newcastle, Division of Biological Stress Response [Amsterdam, The Netherlands], The Netherlands Cancer Institute [Amsterdam, The Netherlands], Johns Hopkins Bloomberg School of Public Health [Baltimore], Birmingham Women’s Hospital, Department of Genetics, Portuguese Oncology Institute, Molecular Genetics, IWK Health Centre, IWK health centre, North West london hospitals NHS Trust, Department of Clinical Genetics (Queen Elizabeth University Hospital, Glasgow), Queen Elizabeth University Hospital (Glasgow), Birmingham women's hospital, Birmingham, Ethox Centre, Department of Public Health and Primary Health Care, University of Oxford, Badenoch Building, Old Road Campus, Headington, R01 HD091846, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, National Institutes of Health’s National Institute of Child Health and Human Development, Boston Children’s Hospital Faculty Development Fellowship, UM1HG008900, Broad Center for Mendelian Genomics, Chile’s National Commission for Scientific and Technological Research, DFG WE4896/3-1, German Research Society, WT 100127, Health Innovation Challenge Fund, Comprehensive Clinical Research Network, Skaggs-Oxford Scholarship, 10/H0305/83, Cambridge South REC, REC GEN/284/12, Republic of Ireland, WT098051, Wellcome Sanger Institute, 72160007, Comisión Nacional de Investigación Científica y Tecnológica, Children's Hospital of Philadelphia, Technische Universität Kaiserslautern, 1DH1813319, Dietmar Hopp Stiftung, National Institute for Health Research, Department of Health & Social Care, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Saint Vincent de Paul-GHICL, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Camerino (UNICAM), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nottingham University Hospitals NHS Trust, Nottingham University Hospitals, SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, University Hospital of Wales, Grenoble Ecole de Management, Royal Devon and Exeter Hospital, City Hospital Campus [Nottingham, UK]-Nottingham University Hospitals NHS Trust [UK], ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], GHICL-Hôpital Saint Vincent de Paul, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Friedrich-Alexander d'Erlangen-Nuremberg, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique [Vannes], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], University of Zürich [Zürich] (UZH), Università di Camerino (UNICAM), Birmingham Women's Hospital Healthcare NHS Trust, University Hospitals of Leicester, Sheffield Children’s Hospital, Weizmann Institute of Science, and Grenoble Ecole de Management (GEM)
Subjects: 0301 basic medicine, Male, Microcephaly, [SDV]Life Sciences [q-bio], Haploinsufficiency, autism, epilepsy, epileptic encephalopathy, global developmental delay, H3K4 methylation, intellectual disability, KMT2E, neurodevelopmental disorder, Adolescent, Adult, Child, Child, Preschool, DNA-Binding Proteins, Epilepsy, Female, Humans, Infant, Neurodevelopmental Disorders, Pedigree, Phenotype, Young Adult, Genetic Variation, Heterozygote, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Global developmental delay, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Hypotonia, 030220 oncology & carcinogenesis, medicine.symptom, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], 03 medical and health sciences, Report, medicine, Journal Article, Expressivity (genetics), Preschool, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Macrocephaly, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism, business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 206572.pdf (Publisher’s version ) (Open Access) We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
Published: 2019
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16. Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells

Author: Chen, Hung-Chang, Joalland, Noémie, Bridgeman, John S, Alchami, Fouad S, Jarry, Ulrich, Khan, Mohd Wajid A, Piggott, Luke, Shanneik, Yasmin, Li, Jianqiang, Herold, Marco J, Herrmann, Thomas, Price, David A, Gallimore, Awen M, Clarkson, Richard W, Scotet, Emmanuel, Moser, Bernhard, Eberl, Matthias, Division of Infection and Immunity [Cardiff, UK] (School of Medicine), Cardiff University, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Cardiff and Vale University Health Board [Cardiff, UK], University Hospital of Wales [Cardiff, UK], School of Biosciences [Cardiff], Institute for Virology and Immunobiology [Würzburg, Germany], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), The Walter and Eliza Hall Institute of Medical Research (WEHI), Systems Immunity Research Institute [Cardiff, UK], European Cancer Stem Cell Research Institute [Cardiff, UK], Bernardo, Elizabeth, University Hospital of Wales (UHW), and Julius-Maximilians-Universität Würzburg (JMU)
Subjects: Cytotoxicity, Immunologic, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, Zoledronic Acid, Antibodies, Major Histocompatibility Complex, RC0254, Epitopes, Interferon-gamma, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Animals, Humans, Breast, Diphosphonates, Imidazoles, Epithelial Cells, Receptors, Antigen, T-Cell, gamma-delta, Immunity, Innate, Phenotype, ras Proteins, Neoplastic Stem Cells, Female, Original Article
Abstract: International audience; The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8 + T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44 hi CD24 lo GD2 + phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice. The resistance of CSC-like cells to γδ T cells could be overcome by inhibition of farnesyl pyrophosphate synthase (FPPS) through pretreatment with zoledronate or with FPPS-targeting short hairpin RNA. γδ T cells induced upregulation of MHC class I and CD54/ICAM-1 on CSC-like cells and thereby increased the susceptibility to antigen-specific killing by CD8 + T cells. Alternatively, γδ T-cell responses could be specifically directed against CSC-like cells using the humanised anti-GD2 monoclonal antibody hu14.18K322A. Our findings identify a powerful synergism between MHC-restricted and non-MHC-restricted T cells in the eradication of cancer cells including breast CSCs. Our research suggests that novel immunotherapies may benefit from a two-pronged approach combining γδ T-cell and CD8 + T-cell targeting strategies that triggers effective innate-like and tumour-specific adaptive responses.
Published: 2017
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17. Should transcobalamin deficiency be treated aggressively?

Author: Stuart J. Moat, Sylvie Odent, Guy Touati, Stéphane Giraudier, Ghislaine Bard, Graham Shortland, Manuel Schiff, Hélène Ogier de Baulny, Christian P. Hamel, Vincent Barlogis, De Villemeur, Hervé, Centre de référence des Maladies Métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Réanimation et Pédiatrie Néonatales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Centre de référence Maladies Métaboliques, Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de référence des affections sensorielles d'origine génétique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui De Chaulliac, Department of Medical Biochemistry and Immunology, University Hospital of Wales (UHW), Centre de référence des anomalies du développement d'origine génétique, Department of Paediatrics, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and University Hospital of Wales
Subjects: medicine.medical_specialty, Anemia, Megaloblastic, Homocysteine, Anemia, DNA Mutational Analysis, Methylmalonic acid, [SDV.GEN] Life Sciences [q-bio]/Genetics, Polymerase Chain Reaction, Cobalamin, 03 medical and health sciences, chemistry.chemical_compound, Methionine, 0302 clinical medicine, Transcobalamin, Internal medicine, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetics, medicine, Humans, Megaloblastic anemia, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), DNA Primers, 030304 developmental biology, Transcobalamins, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, business.industry, Infant, Newborn, Infant, Biological Transport, medicine.disease, Pancytopenia, Protein Structure, Tertiary, 3. Good health, Endocrinology, chemistry, Mutation, Failure to thrive, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Methylmalonic Acid
Abstract: International audience; Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.
Published: 2010
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18. Intraductal carcinoma of prostate reporting practice: a survey of expert European uropathologists

Author: Murali Varma, Rainer Grobholz, Jonathan H Shanks, Ferran Algaba, David J. Griffiths, Glen Kristiansen, Antonio Lopez-Beltran, Andrea Haitel, Gabriella Nesi, Gerhard Seitz, Philippe Camparo, Christina A. Hulsbergen-van de Kaa, Barbara Loftus, Eva Comperat, Jon Oxley, Lars Egevad, Nick Mayer, Nathalie Rioux-Leclercq, Cord Langner, Andreas Erbersdobler, Lukas Bubendorf, Daniel M. Berney, Pedro Oliveira, Histopathology, University Hospital of Wales (UHW), Pathology Group, karolinska institute, Centre de pathologie Amiens, Centre de pathologie Amiens - Picardie, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Urology, Medical University Graz, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University Hospital of Wales, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pathology, [SDV]Life Sciences [q-bio], Pathology and Forensic Medicine, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Surveys and Questionnaires, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, Carcinoma, Humans, UROPATHOLOGY, PROSTATE, skin and connective tissue diseases, GENITOURINARY PATHOLOGY, Grading (tumors), neoplasms, Prostatic Intraepithelial Neoplasia, Neoplasm Grading, business.industry, Biopsy, Needle, Prostatic Neoplasms, General Medicine, HISTOPATHOLOGY, medicine.disease, Immunohistochemistry, 3. Good health, Europe, Pathologists, Carcinoma, Intraductal, Noninfiltrating, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cribriform, Histopathology, Radiology, business
Abstract: International audience; BACKGROUND: It is unclear whether the reported variation in the diagnosis of intraductal carcinoma of the prostate (IDC-P) is due to variable interpretation of borderline morphology, use of different diagnostic criteria or both. AIMS: We sought to determine the degree of variation in the diagnostic criteria and reporting rules for IDC-P in prostate biopsies employed by expert uropathologists. METHODS: A questionnaire survey was circulated to 23 expert uropathologists from 11 European countries. RESULTS: Criteria used for diagnosis of IDC-P included solid intraductal growth (100%), dense cribriform (96%), loose cribriform/micropapillary with nuclear size \textgreater6× normal (83%) or comedonecrosis (74%) and dilated ducts \textgreater2× normal (39%). 'Nuclear size' was interpreted as nuclear area by 74% and nuclear diameter by 21%. Pure IDC-P in needle biopsies was reported by 100% and Gleason graded by 30%. All would perform immunohistochemistry in such cases to rule out invasive cancer. An IDC-P component associated with invasive cancer would be included in the determination of tumour extent and number of cores involved by 74% and 83%, respectively. 52% would include IDC-P component when grading invasive cancer. 48% would perform immunohistochemistry in solid or cribriform nests with comedonecrosis to exclude IDC-P (17% routinely, 30% if the focus appeared to have basal cells on H&E). 48% graded such foci as Gleason pattern 5 even if immunohistochemistry demonstrated the presence of basal cells. CONCLUSIONS: There is a need for more clarity in the definition of some of the diagnostic criteria for IDC-P as well as for greater standardisation of IDC-P reporting
Published: 2016
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19. De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability

Author: Sébastien Schmitt, Amélie Piton, Christian P. Schaaf, Xenia Latypova, Brigitte Gilbert-Dussardier, Jill A. Rosenfeld, Kozo Tanaka, Robert Roger Lebel, Sylvie Odent, Haley Streff, Bertrand Isidor, Philippe Parent, Audrey Donnart, Sébastien Küry, Pierre Lindenbaum, Estelle Colin, Nodoka Chida, Masanori Ikeda, Marie Vincent, Alex Henderson, Thomas Besnard, Christian Dina, Dominique Bonneau, Eric Charpentier, Sally J. Davies, Yaping Yang, Anne Sophie Denommé, Benjamin Cogné, Stéphane Bézieau, Vani Jain, Richard Redon, Cédric Le Caignec, Sandra Mercier, Shelagh Joss, Annick Toutain, Kenji Iemura, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Baylor College of Medicine (BCM), Baylor University, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), NHS Greater Glasgow & Clyde [Glasgow] (NHSGGC), University Hospital of Wales, SUNY Upstate Medical University, State University of New York (SUNY), Newcastle Upon Tyne Hospitals NHS Trust, Tohoku University [Sendai], Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pédiatrie et de Génétique Médicale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique Médicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre de Référence Anomalies du Développement Ouest, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Contract grant sponsors: French Ministry of Health and Health Regional Agency from Poitou-Charentes (HUGODIMS, 2013, RC14_0107), Japanese Society of Promotion of Science, Ministry of Education Culture, Sports, Science and Technology of Japan, Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), The Japan Agency for Medical Research and Development, Takeda Science Foundation., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), University Hospital of Wales (UHW), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and Jonchère, Laurent
Subjects: 0301 basic medicine, Male, Microcephaly, Chromosomal Proteins, Non-Histone, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, POGZ, Microtubules, 03 medical and health sciences, Intellectual Disability, Intellectual disability, Genetics, medicine, Humans, Exome, microcephaly, Allele, Child, Gene, Genetics (clinical), Alleles, Sequence Deletion, Kinetochore, HP1, Chromosome, kinetochores, Facies, High-Throughput Nucleotide Sequencing, Syndrome, medicine.disease, Phosphoproteins, Chromatin, 030104 developmental biology, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Female, CHAMP1
Abstract: International audience; A rare syndromic form of intellectual disability with impaired speech was recently found associated with mutations in CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), the protein product of which is directly involved in microtubule-kinetochore attachment. Through whole-exome sequencing in six unrelated non-consanguineous families having a sporadic case of intellectual disability, we identified six novel de novo truncating mutations in CHAMP1: c.1880C\textgreaterG p.(Ser627*), c.1489C\textgreaterT; p.(Arg497*), c.1876\₁877delAG; p.(Ser626Leufs*4), c.1043G\textgreaterA; p.(Trp348*), c.1002G\textgreaterA; p.(Trp334*) and c.958\₉59delCC; p.(Pro320*). Our clinical observations confirm the phenotypic homogeneity of the syndrome, which represents therefore a distinct clinical entity. Besides, our functional studies show that CHAMP1 protein variants are delocalized from chromatin and are unable to bind to two of its direct partners, POGZ and HP1. These data suggest a pathogenic mechanism of the CHAMP1-associated intellectual disability syndrome mediated by direct interacting partners of CHAMP1, several of which are involved in chromo/kinetochore-related disorders.
Published: 2015
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20. BMI in relation to sperm count:an updated systematic review and collaborative meta-analysis

Author: Cecilia Høst Ramlau-Hansen, Tina Kold Jensen, Kelton Tremellen, Jan Tan Cao, I Fejes, M Eskandar, Jens Peter Bonde, M. van Wely, John M. Twigt, Brenda Eskenazi, Jorge E. Chavarro, S. La Vignera, Alex J. Polotsky, Céline Faure, Léopold Fezeu, A G Shayeb, Edson Borges, Rachel Levy, Francesco Lotti, Régine P.M. Steegers-Theunissen, Sébastien Czernichow, A. C. Martini, S Koloszar, Nathalie Sermondade, B Zorn, Serge Hercberg, E V Magnusdottir, ProdInra, Migration, U1125, Institut National de la Recherche Agronomique (INRA), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), CRNH IdF, University Hospital of Wales (UHW), University of Copenhagen = Københavns Universitet (UCPH), National Institute of Diabetes and Digestive and Kidney Diseases [5P30DK046200-19], National Institutes of Health [P42ES04705], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), University Hospital of Wales, University of Copenhagen = Københavns Universitet (KU), Sermondade, N, Faure, C, Fezeu, L, Shayeb, AG, Tremellen, K, Czernichow, S, Hematology, and Obstetrics & Gynecology
Subjects: Male, obesity, [SDV]Life Sciences [q-bio], Medicina Clínica, Overweight, urologic and male genital diseases, Body Mass Index, 0302 clinical medicine, Odds Ratio, REPRODUCTIVE HORMONES, media_common, Azoospermia, education.field_of_study, 030219 obstetrics & reproductive medicine, obstetrics, medicine.diagnostic_test, Sperm Count, Total sperm count, reproductive biology, Obstetrics and Gynecology, SUBFERTILE COUPLES, Spermatozoa, 3. Good health, [SDV] Life Sciences [q-bio], Meta-analysis, France, medicine.symptom, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, media_common.quotation_subject, Population, Reviews, total sperm count, 030209 endocrinology & metabolism, Fertility, Semen analysis, HEALTHY-MEN, PARAMETERS, INTERINDIVIDUAL VARIABILITY, 03 medical and health sciences, BMI, Internal medicine, medicine, Humans, Obesity, education, Gynecology, business.industry, INHIBIN-B, sperm concentration, Body Weight, gynecology, Odds ratio, Oligospermia, medicine.disease, Semen Analysis, meta-analysis, BODY-MASS INDEX, Sperm concentration, Reproductive Medicine, SEMEN QUALITY, Andrología, OBESE MEN, business, DNA INTEGRITY
Abstract: Background: The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. Methods: A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n ¼ 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. Results: A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93–1.43) for underweight, 1.11 (1.01–1.21) for overweight, 1.28 (1.06– 1.55) for obese and 2.04 (1.59–2.62) for morbidly obese men. Conclusions: Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further. Fil: Sermondade, N.. Hôpital Jean Verdier; Francia. Universite de Paris 13-nord; Francia Fil: Faure, C.. Hôpital Jean Verdier; Francia. Universite de Paris 13-nord; Francia Fil: Fezeu, L.. Universite de Paris 13-nord; Francia Fil: Shayeb, A. G.. University Hospital of Wales; Reino Unido Fil: Bonde, J. P.. Bispebjerg Hospital of Copenhagen University; Dinamarca Fil: Jensen, J. K.. University Department of Growth and Reproduction; Dinamarca Fil: Van Wely, M.. Academic Medical Centre; Países Bajos Fil: Cao, J.. Third Military Medical University; China Fil: Martini, Ana Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Eskandar, M.. King Khalid University; Arabia Saudita Fil: Chavarro, J. E.. Harvard University. Harvard School Of Public Health; Estados Unidos. Harvard Medical School; Estados Unidos Fil: Koloszar, S.. University of Szeged; Hungría Fil: Twigt, J. M.. University Medical Center; Países Bajos Fil: Ramlau Hansen, C. H.. Aarhus University; Dinamarca Fil: Borges Jr, E.. Fertility-Assisted Fertilization Center; Brasil Fil: Lotti, F.. Universita Degli Studi Di Firenze; Italia Fil: Steegers Theunissen, R. P. M.. University Medical Center; Países Bajos Fil: Zorn, B.. University Medical Center Ljubljana; Eslovenia Fil: Polotsky, A. J.. University of Colorado Denver; Estados Unidos Fil: La Vignera, S.. University of Catania; Italia Fil: Eskenazi, B.. University Of California Berkeley; Estados Unidos Fil: Tremellen, K.. University of South Australia; Australia Fil: Magnusdottir, E. V.. University of Iceland; Islandia Fil: Fejes, I.. University of Szeged; Hungría Fil: Hercberg, S.. Universite de Paris 13-nord; Francia. Hôpital Avicenne; Francia Fil: Lévy, R.. Hôpital Jean Verdier; Francia. Universite de Paris 13-nord; Francia Fil: Czernichow, S.. University of Versailles Saint Quentin en Yvelines; Francia. Centre for Research in Epidemiology and Population Health; Francia
Published: 2013
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21. European Porphyria Network (EPNET) for information, epidemiological data, quality and equity of service

Author: Jean-Charles Deybach, Samantha Parker, Mike Badmiton, Sverre Sandberg, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), EPNET Programme Manager, EPNET Programme, Cardiff and Vale NHS Trust, University Hospital of Wales, Department of Public Health and Primary Health Care, University of Bergen (UiB), University Hospital of Wales (UHW), and BMC, Ed.
Subjects: medicine.medical_specialty, media_common.quotation_subject, Population, lcsh:Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Genetics(clinical), Pharmacology (medical), education, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Acute intermittent porphyria, Medicine(all), 0303 health sciences, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Public health, lcsh:R, General Medicine, Consumer protection, medicine.disease, 3. Good health, Porphyria, 030220 oncology & carcinogenesis, Data quality, Family medicine, Service (economics), Poster Presentation, business
Abstract: Porphyrias are metabolic diseases that affect about 1 in 20,000 of the EU population. Most healthcare professionals rarely encounter these disorders and there is disparity between countries in the levels of support provided for patients and their carers. EPNET is a DG Sanco funded project (1/4/2007-31/3/2010) with 15 participating countries that aims to establish a network of specialist porphyria centres, each working to agreed quality criteria. Work achieved: 1. Information on porphyria for patients in 10 languages, and for healthcare professionals in English, is available at http://www.porphyria-europe.org with easily downloadable pdf files. 2. Data on the safety of drugs in acute porphyria has been collected from participating countries (2901 drug reports on 616 drugs). Information is disseminated on http://www.drugs-porphyria.org 3. European Quality Assessment (EQA) schemes have been established for specialist laboratories (24 participants in 17 countries) and data on laboratory performance collected annually. Variations between centres are being addressed and diagnostic protocols developed. 4. The EPNET registry now contains data on 371 patients (320 new cases; 51 with long term complications) that is being used to calculate the incidence of each porphyria in participating countries and the prevalence of long term complications, The incidence of new cases of acute intermittent porphyria is around 0.15/million/year in most countries. The initial purposes of the EPNET project have been achieved; we have established a rich data resource, a network for improving quality of care and a European platform for expert exchange. EPNET has been funded by the European Commission through its Public Health and Consumer Protection Directorate (DG SANCO), PHEA programme.
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22. Multi-center evaluation of the highly sensitive Abbott ARCHITECT and Alinity thyroglobulin chemiluminescent microparticle immunoassay.

Author: Evans C, Lotz J, Bhandari M, Hellier RT, Wang XY, Lott R, Lackner KJ, Müller R, and Kulasingam V
Subjects: Biological Assay, Humans, Immunoassay, Immunoenzyme Techniques, Thyroidectomy, Thyroglobulin, Thyroid Neoplasms diagnosis, Thyroid Neoplasms pathology
Abstract: Background: Thyroglobulin (Tg) is an essential part for the management of patients with differentiated thyroid carcinoma (DTC) after thyroidectomy. Highly sensitive Tg assays are now established in clinical practice as they facilitate follow-up of DTC patients. In this study, we evaluated the recently launched highly sensitive Abbott Tg assay for Alinity and ARCHITECT., Methods: In this three-center study, Tg values of 447 routine patient samples, characterized for the presence of anti-Tg, were measured with the ARCHITECT Tg assay and compared with the Roche Elecsys TgII assay. In addition, a subset of 154 samples was compared also with the Beckman Tg Access assay and another subset (n = 122) with Abbott Tg on the Alinity i analyzer., Results: LoQ was verified to be less than or equal to 0.1 ng/ml confirming that the Tg assay on ARCHITECT and Alinity is highly sensitive. Correlation of ARCHITECT, Alinity, and Roche was excellent with a slope between 0.9 and 1.1 and a correlation coefficient >0.98. Correlation to Beckmann Tg was also very good, but the differences in absolute values were significant (slope: 1.477)., Conclusions: The Abbott Thyroglobulin assay, which is standardized to CRM-457, demonstrated a high correlation to the Roche and Beckman Tg assays, though good agreement of absolute values was only observed between Abbott and Roche. Strength of correlation and slope were not affected by the presence of anti-Tg indicating that all assays included in the study have a similar susceptibility to anti-Tg., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)
Published: 2022
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23. Incorporating the Detection of Single Nucleotide Polymorphisms Associated With Invasive Aspergillosis Into the Clinic.

Author: White PL and Price JS
Subjects: Genetic Predisposition to Disease etiology, Humans, Polymorphism, Single Nucleotide, Aspergillosis diagnosis, Aspergillosis genetics, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections diagnosis, Invasive Fungal Infections genetics
Abstract: Exposure to fungi is inevitable, yet only a small number of patients with significant clinical risk develop invasive aspergillosis (IA). While timing of exposure in relation to immune status, environmental and occupational factors will influence the probability of developing IA, factors specific to the individual will likely play a role and variation in the host's genetic code associated with the immunological response to fungi have been linked to increased risk of developing IA. Screening for SNPs in genes significantly associated with IA (e.g. Pentraxin-3, Toll-like receptor 4, Dectin-1, DC-SIGN) could form part of the clinical work-up on admission or post allogeneic stem cell transplantation, to complement fungal biomarker screening. Through the combination of clinical and genetic risk with mycological evidence, we are approaching a time when we should be able to accurately predict the risk of IA in the haematology patient, using predictive modelling to stratifying each individual's management. Understanding the host and their immune responses to infection through genomics, transcriptomics and metabolomics/proteomics is critical to achieving how we manage the individual's risk of IA, underpinning personalized medicine. This review will investigate what is known about the genetic risk associated with developing IA, primarily in haematology patients and whether these strategies are ready to be incorporated into routine clinical practice, and if not what are the remaining hurdles to implementation., Competing Interests: PW: performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; received speaker fees, expert advice fees, and meeting sponsorship from Gilead; received speaker and expert advice fees from F2G and speaker fees MSD and Pfizer; and is a founding member of the European Aspergillus PCR Initiative. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 White and Price.)
Published: 2022
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24. A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis.

Author: Griffiths JS, White PL, Thompson A, da Fonseca DM, Pickering RJ, Ingram W, Wilson K, Barnes R, Taylor PR, and Orr SJ
Subjects: Adult, Aged, Aspergillosis diagnosis, Aspergillosis immunology, Aspergillosis microbiology, Aspergillus fumigatus isolation & purification, Biomarkers, Tumor blood, Biomarkers, Tumor immunology, Biomarkers, Tumor metabolism, Female, Gene Expression Profiling, Graft vs Host Disease immunology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Invasive Fungal Infections diagnosis, Invasive Fungal Infections immunology, Invasive Fungal Infections microbiology, Lectins, C-Type immunology, Lectins, C-Type metabolism, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Polymerase Chain Reaction, Risk Assessment methods, Transplantation, Homologous adverse effects, Young Adult, Aspergillosis epidemiology, Aspergillus fumigatus immunology, Invasive Fungal Infections epidemiology, Lectins, C-Type blood, Leukemia, Myeloid, Acute complications
Abstract: Invasive Aspergillosis (IA), typically caused by the fungus Aspergillus fumigatus , is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of Aspergillus infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient's anti- Aspergillus immune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Griffiths, White, Thompson, da Fonseca, Pickering, Ingram, Wilson, Barnes, Taylor and Orr.)
Published: 2021
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25. Reply to Rodriguez et al and Mastrangelo et al.

Author: White PL, Dhillon R, Healy B, Wise MP, and Backs M
Published: 2021
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26. Detecting microstructural deviations in individuals with deep diffusion MRI tractometry.

Author: Chamberland M, Genc S, Tax CMW, Shastin D, Koller K, Raven EP, Cunningham A, Doherty J, van den Bree MBM, Parker GD, Hamandi K, Gray WP, and Jones DK
Abstract: Most diffusion magnetic resonance imaging studies of disease rely on statistical comparisons between large groups of patients and healthy participants to infer altered tissue states in the brain; however, clinical heterogeneity can greatly challenge their discriminative power. There is currently an unmet need to move away from the current approach of group-wise comparisons to methods with the sensitivity to detect altered tissue states at the individual level. This would ultimately enable the early detection and interpretation of microstructural abnormalities in individual patients, an important step towards personalized medicine in translational imaging. To this end, Detect was developed to advance diffusion magnetic resonance imaging tractometry towards single-patient analysis. By operating on the manifold of white-matter pathways and learning normative microstructural features, our framework captures idiosyncrasies in patterns along white-matter pathways. Our approach paves the way from traditional group-based comparisons to true personalized radiology, taking microstructural imaging from the bench to the bedside., Competing Interests: Competing interests The authors declare no competing interests.
Published: 2021
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27. C-reactive protein kinetics post elective cranial surgery. A prospective observational study.

Author: Sharouf F, Hussain RN, Hettipathirannahelage S, Martin J, Gray W, and Zaben M
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Body Temperature, Female, Humans, Kinetics, Leukocyte Count, Male, Middle Aged, Postoperative Complications blood, Predictive Value of Tests, Prospective Studies, ROC Curve, Sensitivity and Specificity, Surgical Wound Infection blood, Young Adult, C-Reactive Protein analysis, Craniotomy methods, Neurosurgical Procedures methods, Skull surgery, Surgical Wound Infection diagnosis
Abstract: Introduction: Post cranial surgery readmission, largely caused by surgical site infection (SSI), is a marker of patient-care quality requiring comprehensive discharge planning. Currently, discharge assessment is based on clinical recovery and basic laboratory tests, including C-reactive protein (CRP). Although CRP kinetics have been examined postoperatively in a handful of papers, the validity of CRP as a standalone test to predict SSI is yet to be explored. Methods: A prospective observational study was performed on adult patients undergoing elective cranial surgery over a 3-month period. Laboratory data; CRP, white cell count (WCC), neutrophil cell count (NCC), and clinical data were assessed pre and post-operatively and were evaluated as predictors for safe discharge. Readmission rates within 1 month were recorded. Results: In this study, 68 patients were included. About 8.6% were readmitted due to SSI. A postoperativepeak in CRP was seen on day 2 with a value of 57 in the non-readmitted group, and 115 in the readmitted group. CRP dropped gradually to normal levels by day 5 in the non-readmitted group. A secondary CRP rise at day 5 was noted in the readmitted group with a sensitivity, specificity, and negative predictive value of 71%, 90%, and 96%, respectively. Interestingly, our ROC analysis indicates that a CRP value of less than 65 predicts safe discharge with a sensitivity of 86%, specificity of 89% and negative predictive value of 98% of safe discharge (area under the curve, AUC: 0.782). No significant difference in other inflammatory markers was found between both groups. Conclusions: CRP increases postoperatively for 4-5 d which could be a physiological response to surgery, however, prolonged elevation or a secondary increase in CRP may indicate an ongoing infection. Our data validate the potential use of CRP levels to predict SSI. A multicentre study is warranted to investigate the role of CRP in predicting SSI.
Published: 2020
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28. Quantification of Pneumocystis jirovecii : Cross-Platform Comparison of One qPCR Assay with Leading Platforms and Six Master Mixes.

Author: Dellière S, Gits-Muselli M, White PL, Mengoli C, Bretagne S, and Alanio A
Abstract: Diagnosis of Pneumocystis jirovecii pneumonia relies on nucleic acid quantification in respiratory samples. Lack of standardization among molecular assays results in significant differences among assays/centers. To further promote standardization, we compared four thermocyclers and six master mixes for the detection of P. jirovecii . Whole nucleic acid (WNA) was extracted from broncho-alveolar lavages. Positive and negative sample extracts were pooled to get enough homogeneous materials. Three master mixes were tested to detect DNA by qPCR (D1, D2, and D3), and three to detect WNA by reverse transcriptase qPCR (W1, W2, and W3) manufactured by Roche, Eurogentec, Applied Biosystem, Invitrogen and Thermofischer Scientific. Experiments were performed on four thermocyclers (Roche LightCycler 480, Qiagen Rotor-Gene Q, Applied Biosystem ABI7500, and QuantStudio). Comparison of quantitative cycle ( Cq ) values between the methods targeting WNA versus DNA showed lower Cq values for WNA, independently of thermocycler and master mix. For high and low fungal loads, ∆ Cq values between DNA and WNA amplification were 6.97 (±2.95) and 5.81 (±3.30), respectively ( p < 0.0001). Regarding DNA detection, lower Cq s were obtained with D1 compared to D2 and D3, with median ∆ Cq values of 2.6 ( p = 0.015) and 2.9 ( p = 0.039) respectively. Regarding WNA detection, no mix was superior to the others. PCR efficiency was not significantly different according to the qPCR platform ( p = 0.14). This study confirmed the superiority of WNA over DNA detection. A calibration method (e.g., an international standard) for accurate comparative assessment of fungal load seems necessary.
Published: 2019
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29. Comparison of galactomannan enzyme immunoassay performance levels when testing serum and plasma samples.

Author: White PL, Jones T, Whittle K, Watkins J, and Barnes RA
Subjects: Galactose analogs & derivatives, Humans, Immunoenzyme Techniques methods, Sensitivity and Specificity, Antigens, Fungal blood, Aspergillosis diagnosis, Clinical Laboratory Techniques methods, Mannans blood, Plasma chemistry, Serum chemistry
Abstract: Diagnostic galactomannan (GM) enzyme immunoassay (EIA) testing is formally validated only for serum, though in practice, plasma is occasionally tested. It is assumed, but not confirmed, that results will be comparable to those for serum. GM EIA when testing plasma was evaluated, providing sensitivity (85.7%) and specificity (85.4%) comparable to those for serum. Plasma index values were higher than those for serum; if plasma GM EIA were used to define probable cases, four additional cases would have been diagnosed.
Published: 2013
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29 results on '"University Hospital of Wales (UHW)"'

1. COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure

2. Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

3. CT findings of COVID-19-associated pulmonary aspergillosis: a systematic review and individual patient data analysis

4. Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19 Associated Pulmonary Aspergillosis (CAPA): A multicenter study

5. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries

6. Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome:An international multicenter survey

7. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

8. Ethylzingerone, a Novel Compound with Antifungal Activity

9. Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

10. Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease

11. NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly

12. Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey

13. The broad phenotypic spectrum of PPP2R1A -related neurodevelopmental disorders correlates with the degree of biochemical dysfunction

14. Proceedings from the 3rd European Clinical Consensus Conference for clinical trials in device-based hypertension therapies

15. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

16. Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8+ T cells

17. Should transcobalamin deficiency be treated aggressively?

18. Intraductal carcinoma of prostate reporting practice: a survey of expert European uropathologists

19. De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability

20. BMI in relation to sperm count:an updated systematic review and collaborative meta-analysis

21. European Porphyria Network (EPNET) for information, epidemiological data, quality and equity of service

22. Multi-center evaluation of the highly sensitive Abbott ARCHITECT and Alinity thyroglobulin chemiluminescent microparticle immunoassay.

23. Incorporating the Detection of Single Nucleotide Polymorphisms Associated With Invasive Aspergillosis Into the Clinic.

24. A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis.

25. Reply to Rodriguez et al and Mastrangelo et al.

26. Detecting microstructural deviations in individuals with deep diffusion MRI tractometry.

27. C-reactive protein kinetics post elective cranial surgery. A prospective observational study.

28. Quantification of Pneumocystis jirovecii : Cross-Platform Comparison of One qPCR Assay with Leading Platforms and Six Master Mixes.

29. Comparison of galactomannan enzyme immunoassay performance levels when testing serum and plasma samples.

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