Author: "Bruneel A" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Bruneel A"' showing total 327 results

Start Over Author "Bruneel A" Topic humans

327 results on '"Bruneel A"'

1. N-Glycosylation Deficiency Reduces the Activation of Protein C and Disrupts Endothelial Barrier Integrity

Author: Tiffany Pascreau, François Saller, Elsa P. Bianchini, Dominique Lasne, Arnaud Bruneel, Christelle Reperant, François Foulquier, Cécile V. Denis, Pascale De Lonlay, and Delphine Borgel
Subjects: Congenital Disorders of Glycosylation, Glycosylation, Phosphotransferases (Phosphomutases), Thrombin, Humans, Endothelium, Hematology, Protein C
Abstract: Phosphomannomutase 2 (PMM2) deficiency is the most prevalent congenital disorder of glycosylation. It is associated with coagulopathy, including protein C deficiency. Since all components of the anticoagulant and cytoprotective protein C system are glycosylated, we sought to investigate the impact of an N-glycosylation deficiency on this system as a whole. To this end, we developed a PMM2 knockdown model in the brain endothelial cell line hCMEC/D3. The resulting PMM2low cells were less able to generate activated protein C (APC), due to lower surface expression of thrombomodulin and endothelial protein C receptor. The low protein levels were due to downregulated transcription of the corresponding genes (THBD and PROCR, respectively), which itself was related to downregulation of transcription regulators Krüppel-like factors 2 and 4 and forkhead box C2. PMM2 knockdown was also associated with impaired integrity of the endothelial cell monolayer—partly due to an alteration in the structure of VE-cadherin in adherens junctions. The expression of protease-activated receptor 1 (involved in the cytoprotective effects of APC on the endothelium) was not affected by PMM2 knockdown. Thrombin stimulation induced hyperpermeability in PMM2low cells. However, pretreatment of cells with APC before thrombin simulation was still associated with a barrier-protecting effect. Taken as a whole, our results show that the partial loss of PMM2 in hCMEC/D3 cells is associated with impaired activation of protein C and a relative increase in barrier permeability.
Published: 2022
Full Text: View/download PDF

2. Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy

Author: Alessandra Guasto, Johanne Dubail, Sergio Aguilera-Albesa, Chiara Paganini, Catherine Vanhulle, Walid Haouari, Nerea Gorría-Redondo, Elena Aznal-Sainz, Nathalie Boddaert, Laura Planas-Serra, Agatha Schlüter, Valentina Vélez-Santamaría, Edgard Verdura, Arnaud Bruneel, Antonio Rossi, Céline Huber, Aurora Pujol, and Valérie Cormier-Daire
Subjects: Sulfate Transporters, Intellectual Disability, Homozygote, Exome Sequencing, Humans, Proteoglycans, RNA, Messenger, Neurology (clinical)
Abstract: Sulphated proteoglycans are essential in skeletal and brain development. Recently, pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis have been identified in a range of chondrodysplasia associated with intellectual disability. Nevertheless, several patients remain with unidentified molecular basis. This study aimed to contribute to the deciphering of new molecular bases in patients with chondrodysplasia and neurodevelopmental disease. Exome sequencing was performed to identify pathogenic variants in patients presenting with chondrodysplasia and intellectual disability. The pathogenic effects of the potentially causative variants were analysed by functional studies. We identified homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2 in two patients with pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy. By functional analyses, we showed that the variants affect SLC35B2 mRNA expression and protein subcellular localization leading to a functional impairment of the protein. Consistent with those results, we detected proteoglycan sulphation impairment in SLC35B2 patient fibroblasts and serum. Our data support that SLC35B2 functional impairment causes a novel syndromic chondrodysplasia with hypomyelinating leukodystrophy, most likely through a proteoglycan sulphation defect. This is the first time that SLC35B2 variants are associated with bone and brain development in human.
Published: 2022
Full Text: View/download PDF

3. Postextubation Stridor in Severe COVID-19

Author: Georges Abi, Abdallah, Alexis, Ferré, Antoine, Gros, Christelle, Simon, Fabrice, Bruneel, Stéphanie, Marque-Juillet, Stéphane, Legriel, and Marine, Paul
Subjects: Male, Pulmonary and Respiratory Medicine, SARS-CoV-2, COVID-19, General Medicine, Critical Care and Intensive Care Medicine, Respiration, Artificial, Severity of Illness Index, Risk Factors, Intubation, Intratracheal, Humans, Female, Respiratory Sounds, Retrospective Studies
Abstract: During the coronavirus disease 2019 (COVID-19) pandemic, 60-80% of patients admitted to ICU require mechanical ventilation for respiratory distress. We aimed to compare the frequency of postextubation stridor (PES) and to explore risk factors in COVID-19 subjects compared to those without COVID-19.We performed an observational retrospective study on subjects admitted for severe COVID-19 requiring mechanical ventilation48 h during the first and second waves in 2020 and compared these subjects to historical controls without COVID-19 who received mechanical ventilation48 h between 2016-2019. The primary outcome was the frequency of PES, defined as audible stridor within 2 h following extubation.Of the 134 subjects admitted with severe COVID-19 requiring mechanical ventilation, 96 were extubated and included and compared to 211 controls. The frequency of PES was 22.9% in the COVID-19 subjects and 3.8% in the controlsPES affected nearly one-quarter of subjects with COVID-19, a proportion significantly higher than that seen in controls. Independent risk factors for PES were COVID-19, female sex, and tube mobilization or re-intubation or prone positioning. PES was associated with persistent viral shedding at the time of extubation.
Published: 2022
Full Text: View/download PDF

4. Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low‐grade glioma

Author: Alicia Probst, Emilie De Carli, Isabelle Aerts, Pascal Chastagner, Natacha Entz-Werle, Caroline Solas, Anne-Isabelle Bertozzi-Salamon, Nicolas André, Anne Pagnier, Emmanuelle Tresch-Bruneel, Pierre Leblond, Jacques Grill, Didier Frappaz, Mourad Hamimed, Florence Gattacceca, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité des Virus émergents [Marseille] (UVE - Faculté de Médecine), Université de la Méditerranée - Aix-Marseille 2-Faculté de Médecine [Marseille], Université de la Méditerranée - Aix-Marseille 2, and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: medicine.medical_specialty, Adolescent, Phases of clinical research, Vinorelbine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Bayesian multivariate linear regression, Glioma, Internal medicine, Humans, Medicine, Pharmacology (medical), Child, Infusions, Intravenous, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, Body surface area, Volume of distribution, 0303 health sciences, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Low-Grade Glioma, Neoplasm Recurrence, Local, business, Half-Life, medicine.drug
Abstract: AIM There is a crucial need for pharmacokinetic (PK) data of oral vinorelbine (VNR) in pediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). METHODS A multicentric, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumors, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The Influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. RESULTS PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t1/2 ) and their between-subject variability (CV%) at 60 mg.m-2 dose level, were 472 L.h-1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (p = 0.004). Lower area under the concentration-time curve (AUC) levels were observed among children in comparison to adults. CONCLUSION Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among pediatric patients.
Published: 2021
Full Text: View/download PDF

5. Critically ill patients with severe infections related to Geotrichum species: A French retrospective multicentre study

Author: Nadia Aissaoui, Benoit Champigneulle, Muriel Picard, Michael Darmon, Andrine Valade, Anne Sophie Moreau, Julien Mayaux, Laure Calvet, Etienne de Montmollin, Fabrice Bruneel, Frédéric Pène, Martin Murgier, Florence Boissier, Laurent Argaud, Elie Azoulay, Naïke Bigé, Djamel Mokart, CarMeN, laboratoire, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier de Versailles André Mignot (CHV), AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Lille, and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)
Subjects: Adult, Antifungal, medicine.medical_specialty, multiple organ failure, medicine.drug_class, health care facilities, manpower, and services, [SDV]Life Sciences [q-bio], Critical Illness, Dermatology, Internal medicine, Intensive care, medicine, Humans, Geotrichum species, Hospital Mortality, intensive care, Retrospective Studies, invasive fungal infections, Adult patients, business.industry, Critically ill, Geotrichosis, General Medicine, Middle Aged, Geotrichum, Icu admission, [SDV] Life Sciences [q-bio], Intensive Care Units, Infectious Diseases, Respiratory failure, outcome, SOFA score, France, business
Abstract: International audience; OBJECTIVES: Geotrichum spp can be responsible for severe infections in immunocompromised patients. We aim to describe Geotrichum-related infections in the ICU and to assess risk factors of mortality. METHODS: Retrospective multicentre study, conducted in 14 French ICUs between 2002 and 2018, including critically ill adult patients with proven or probable infection related to Geotrichum species. Data were obtained from the medical charts. RESULTS: Thirty-six patients, median age 60 years IQR [53; 66] were included. Most of the patients had haematological malignancies (78%). The reason for ICU admission was shock in half of the patients (n = 19, 53%) and respiratory failure in thirteen patients (36%). Median SOFA score was 8.5 IQR [7; 15]. Time between ICU admission and fungal diagnosis was 2.5 days [-1; 4]. Infection was disseminated in 27 (75%) patients with positive blood cultures in 25 patients (69%). Thirty patients (83%) received curative antifungal treatment in the ICU, in a median time of 1 day [0;1] after ICU admission. Twenty-four patients (67%) died in the ICU and hospital mortality rate was 69%. The number and extent of organ failures, as represented by SOFA score, were associated with mortality. CONCLUSIONS: This study demonstrates poor outcome in critically ill patients with Geotrichum-related infections, which encourages a high level of suspicion.
Published: 2021
Full Text: View/download PDF

6. Is High-Intensity Speech Intervention Better? A Comparison of High-Intensity Intervention Versus Low-Intensity Intervention in Children With a Cleft Palate

Author: Kris Demuynck, Evelien D'haeseleer, Anne-Sophie De Caesemaeker, Laura Bruneel, Kristiane Van Lierde, Kim Bettens, and Cassandra Alighieri
Subjects: Linguistics and Language, medicine.medical_specialty, Cleft Lip, MEDLINE, Speech Therapy, Language and Linguistics, Speech therapy, law.invention, Speech and Hearing, Randomized controlled trial, Quality of life, law, Intervention (counseling), medicine, Humans, Speech, Prospective Studies, Child, Prospective cohort study, business.industry, High intensity, Intensity (physics), Cleft Palate, Quality of Life, Physical therapy, business
Abstract: Purpose The purpose of this study was to compare the effect of speech intervention provided with a low intensity with speech intervention provided with a high intensity on the speech and health-related quality of life (HRQoL) in Dutch-speaking children with a cleft palate with or without a cleft lip (CP ± L) between 4 and 12 years. Method A longitudinal, prospective, randomized controlled trial with a multiple baseline design was used. Twelve children with a CP ± L ( M age = 8.0 years, SD = 1.54) were divided into two groups using block randomization stratified by age and gender: One group received low-intensity speech intervention (LISI; n = 6) and one group received high-intensity speech intervention (HISI; n = 6). Children in the LISI group received intervention with a session duration of 1 hr, a dose frequency of 1 session per week, and a total intervention duration of 10 weeks. Children in the HISI group received intervention with a session duration of 1 hr, a dose frequency of 5 sessions per week, and a total intervention duration of 2 weeks. The cumulative intervention intensity was kept constant. Both groups received identical therapy programs provided by the same experienced speech therapist. Perceptual speech assessments were performed on baseline and posttreatment data points. Changes in HRQoL were assessed using the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) questionnaire. Both groups were compared over time using (generalized) linear mixed models. Results No significant Time × Group interactions were observed for the percentage of correctly produced consonants at the word and sentence levels, indicating no differences in evolution over time among the two groups. The variables speech understandability, speech acceptability, and the total VELO scores significantly improved following HISI, but not following LISI. Conclusions Children in the HISI group made equal and, for some variables, even superior progress in only 2 weeks of therapy compared to children in the LISI group who received 10 weeks of therapy. HISI is a promising strategy to improve speech outcomes and HRQoL in a shorter time period.
Published: 2021
Full Text: View/download PDF

7. Normal transferrin patterns in congenital disorders of glycosylation with Golgi homeostasis disruption: apolipoprotein C-III at the rescue!

Author: Anne-Sophie Alaix, Arnaud Bruneel, Claude Besmond, Thierry Dupré, Alexandre Raynor, Catherine Vincent-Delorme, Sandrine Vuillaumier-Barrot, Sophie Cholet, François Fenaille, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandre [Lille], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, ANR-15-RAR3-0004,EURO-CDG-2,A European research network directed towards improving diagnosis and treatment of inborn glycosylation disorders.(2015), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse (INSERM UMR1193), and Université Paris-Saclay
Subjects: Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Glycosylation, Apolipoprotein B, Clinical Biochemistry, Biochemistry, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, Congenital Disorders of Glycosylation, 0302 clinical medicine, Homeostasis, Humans, [CHIM]Chemical Sciences, Medicine, Exome sequencing, chemistry.chemical_classification, Apolipoprotein C-III, biology, apoC-III, business.industry, Biochemistry (medical), Haptoglobin, Infant, Newborn, Transferrin, ATP6V0A2-CDG, General Medicine, Golgi apparatus, medicine.disease, 3. Good health, Two-dimensional electrophoresis, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Immunology, biology.protein, symbols, Female, CDG, [SDV.IB]Life Sciences [q-bio]/Bioengineering, lipids (amino acids, peptides, and proteins), False negative transferrin, business, COG4-CDG, Cutis laxa
Abstract: International audience; We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Targeted gene sequencing in P1 revealed pathogenic ATP6V0A2 variants, shared by her affected older brother. In P2 and P3, whole exome sequencing revealed a homozygous COG4 variant of unknown significance. In all affected individuals, transferrin analysis was normal. Mass-spectrometry based serum N-glycome analysis and two-dimensional electrophoresis (2-DE) of haptoglobin and of mucin core 1 O-glycosylated apolipoprotein C-III (apoC-III) were performed. All results of second-line N-glycosylation analyses were initially normal. However, apoC-III 2-DE revealed characteristic "apoC-III1" pattern in P1 and specific "apoC-III0" patterns in P2 and P3. In P2 and P3, this allowed reclassifying the variant as likely pathogenic according to ACMG guidelines. These cases highlight the existence of normal transferrin patterns in CDG with Golgi homeostasis disruption, putting the clinicians at risk of misdiagnosing patients. Furthermore, they show the potential of apoC-III 2-DE in diagnosing this type of CDG, with highly specific patterns in COG-CDG.
Published: 2021
Full Text: View/download PDF

8. Reliability of Outcome Measures to Assess Consonant Proficiency Following Cleft Palate Speech Intervention: The Percentage of Consonants Correct Metric and the Probe Scoring System

Author: Laura Bruneel, Kristiane Van Lierde, Evelien D'haeseleer, Ellen Van Gaever, Kim Bettens, and Cassandra Alighieri
Subjects: Consonant, Linguistics and Language, medicine.medical_specialty, Pharyngeal flap surgery, Cleft Lip, Reproducibility of Results, Intra-rater reliability, Audiology, Language and Linguistics, Cleft Palate, Speech and Hearing, Inter-rater reliability, Outcome Assessment, Health Care, medicine, Humans, Speech, Metric (unit), Psychology, Phonological Disorder, Reliability (statistics), Sentence
Abstract: Purpose This study compared the inter- and intrarater reliability of the percentage of consonants correct (PCC) metrics and the probe scoring system between an experienced and a less experienced rater and between two experienced raters. In addition, these outcome measures' ability to reflect changes following speech intervention was measured. Method During Phase 1, two raters (Rater 1 with 5 years of experience in cleft-related speech disorders and Rater 2 with limited experience in cleft-related speech disorders) independently assessed 134 speech samples at the word and sentence levels, which were collected on different data points before, during, and following a cleft palate speech intervention. During Phase 2, a third rater (with 8 years of experience) analyzed 34 speech samples. The percentage of consonants correct–revised, the percentage of correct places and manners, and probe scores at the word and sentence levels were measured. Results Poor-to-moderate interreliability between Raters 1 and 2 was found due to differences in error classification. Interrater reliability between Raters 1 and 3 was very good for both the PCC metrics and the probe scores. The interrater reliability for the amount of targets elicited was lower compared to the interrater reliability for the amount of targets correct. The probe scoring system demonstrated a greater ability to detect changes toward the correct production of the target consonant compared to the PCC metrics. Conclusions Having an experience with the assessment of cleft-related speech disorders is a crucial factor to gain reliable results. The interrater reliability for the PCC metrics and the probe scoring system between two experienced raters did not differ, suggesting that both outcome measures can be used in cleft palate speech intervention studies. Despite the ability of the probe scoring system to detect changes, further research should provide insight in the benefits of this system both for research and clinical purposes.
Published: 2021
Full Text: View/download PDF

9. Neurologic manifestations associated with COVID-19: a multicentre registry

Author: Elodie Meppiel, Nathan Peiffer-Smadja, Alexandra Maury, Imen Bekri, Cécile Delorme, Virginie Desestret, Lucas Gorza, Geoffroy Hautecloque-Raysz, Sophie Landre, Annie Lannuzel, Solène Moulin, Peggy Perrin, Paul Petitgas, François SellaI, Adrien Wang, Pierre Tattevin, Thomas de Broucker, Sophie Abgrall, Fanny Alby-Laurent, Thibault Allou, Joséphine Amevigbe, Hanifa Amarguellay, Nabil Alloussi, Guillaume Baille, Mathilde Barbaz, Lamia Bencherif, Samia Bensaadi, Guillaume Beraud, Alexandra Bizot, Laure Bottin, Fabrice Bruneel, Jean-Philippe Camdessanche, Jeanne Chauffier, Jean-Philippe Csajaghy, Chloé De Broucker, Thomas De Broucker, Luc Defebvre, Elodie Dembloque, Nathalie Derache, Olivier Dereeper, Céline Derollez, Cécile Descotes-Genon, Mathilde Devaux, Lydie Dubuc, Gilles Edan, Andréa Fickl, Thibault Fraisse, Michel Gugenheim, Karolina Hankiewicz, Yves Hansmann, Carole Henry, Stéphanie Jobard, Fanny Jouan, Arnaud Kwiatkowski, Thibault Lalu, Johan Leguilloux, Camille Lejeune, Clémence Liegeois, Sophie Mahy, Jonathan Marey, Laure Michel, Rita Mitri, Chloé Moulin, Asma Omarjee, Canan Ozsancak, Fernando Pico, Marie Poupard, Valérie Rabier, Camille Rizzato, Caroline Roos, Julien Saison, Naomi Sayre, Nicolas Sedillot, François Sellal, Jérôme Servan, Caroline Storey, Laurent Suchet, Paul Tarteret, Mathilde Thiebaut, Claudia Vaduva, David Varlan, Virginie Zarrouk, Centre Hospitalier de Saint-Denis [Ile-de-France], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre Hospitalier de Versailles André Mignot (CHV), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Hôpitaux Civils de Colmar, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]
Subjects: Male, 0301 basic medicine, Microbiology (medical), Registry, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Encephalopathy, Nervous System, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Pleocytosis, Aged, Retrospective Studies, medicine.diagnostic_test, SARS-CoV-2, business.industry, Mortality rate, Brain, COVID-19, Retrospective cohort study, Magnetic resonance imaging, General Medicine, Neurologic manifestations, Middle Aged, medicine.disease, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Neurological manifestations, Female, Original Article, France, Nervous System Diseases, business, Encephalitis
Abstract: International audience; OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.
Published: 2021
Full Text: View/download PDF

10. SLC37A4-CDG: New biochemical insights for an emerging congenital disorder of glycosylation with major coagulopathy

Author: Tiffany Pascreau, Walid Haouari, Celia Raulet-Bussian, Annie Harroche, Arnaud Bruneel, Sophie Cholet, Bobby G. Ng, Sandrine Vuillaumier-Barrot, Hudson H. Freeze, Samra Lounis-Ouaras, Alexandre Raynor, François Fenaille, and Delphine Borgel
Subjects: Gene isoform, Glycosylation, Monosaccharide Transport Proteins, Clinical Biochemistry, Golgi Apparatus, Disease, Biology, Endoplasmic Reticulum, Bioinformatics, Biochemistry, Antiporters, Article, chemistry.chemical_compound, symbols.namesake, Congenital Disorders of Glycosylation, Polysaccharides, Coagulopathy, medicine, Humans, Endoplasmic reticulum, Biochemistry (medical), General Medicine, Golgi apparatus, medicine.disease, carbohydrates (lipids), chemistry, Proteoglycan, biology.protein, symbols, Congenital disorder of glycosylation
Abstract: SLC37A4-CDG is an emerging congenital disorder of glycosylation which is characterized by a dominant inheritance and a major coagulopathy originating from the liver. Recent studies took interest in the biochemical alterations found in this CDG and showed that they consisted of multiple glycosylation abnormalities, which result from mislocalization of the endoplasmic reticulum glucose-6-phosphate transporter and associated Golgi homeostasis defects. In this work, we highlight in six affected individuals abnormal patterns for various serum N-glycoproteins and bikunin proteoglycan isoforms, together with specific alterations of the mass spectra of endoglycosidase H-released serum N-glycans. Collectively, these data complement previous findings, help to better delineate SLC37A4-CDG and could present interest in diagnosing this disease.
Published: 2021
Full Text: View/download PDF

11. Expanding the phenotype of X‐linked SSR4–CDG: Connective tissue implications

Author: Nathalie Seta, Mercedes Serrano, Claudia Castiglioni, Cristina Hernando-Davalillo, Thierry Dupré, Arnaud Wiedemann, Raquel Montero, Arnaud Bruneel, Fanny Cortés, François Feillet, Christine Barnerias, Jordi Muchart, and Sandrine Vuillaumier-Barrot
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, Connective Tissue Disorder, Glycosylation, Receptors, Peptide, Genetic counseling, Nonsense mutation, Receptors, Cytoplasmic and Nuclear, Connective tissue, Biology, 03 medical and health sciences, chemistry.chemical_compound, Congenital Disorders of Glycosylation, Genetics, medicine, Humans, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Membrane Glycoproteins, Calcium-Binding Proteins, 030305 genetics & heredity, medicine.disease, Phenotype, Hypotonia, medicine.anatomical_structure, chemistry, Connective Tissue, medicine.symptom, Congenital disorder of glycosylation
Abstract: Signal sequence receptor protein 4 (SSR4) is a subunit of the translocon-associated protein complex, which participates in the translocation of proteins across the endoplasmic reticulum membrane, enhancing the efficiency of N-linked glycosylation. Pathogenic variants in SSR4 cause a congenital disorder of glycosylation: SSR4-congenital disorders of glycosylation (CDG). We describe three SSR4-CDG boys and review the previously reported. All subjects presented with hypotonia, failure to thrive, developmental delay, and dysmorphic traits and showed a type 1 serum sialotransferrin profile, facilitating the diagnosis. Genetic confirmation of this X-linked CDG revealed one de novo hemizygous deletion, one maternally inherited deletion, and one de novo nonsense mutation of SSR4. The present subjects highlight the similarities with a connective tissue disorder (redundant skin, joint laxity, blue sclerae, and vascular tortuosity). The connective tissue problems are relevant, and require preventive rehabilitation measures. As an X-linked disorder, genetic counseling is essential.
Published: 2020
Full Text: View/download PDF

12. Rapid screening of COVID‐19 patients using white blood cell scattergrams, a study on 381 patients

Author: Victoria Raggueneau, François Mignon, Ernesto Diaz-Flores, Claire Flaujac, Mehrsa Koukabi, Marie Temple, Philippe Rousselot, Benjamin Manéglier, Jennifer Osman, Fabrice Bruneel, Floriane Devaux, Alix Greder-Belan, Stéphanie Marque-Juillet, Rémy Favre, Jérôme Lambert, Reza Azarian, Véronique Hentgen, Delphine Bridoux, Centre Hospitalier de Versailles André Mignot (CHV), Institute of Medical Biometry and Statistics [Fribourg] (IMBI), Faculty of Medicine and Medical Center, University of Fribourg-University of Fribourg, UCSF Benioff Children's Hospital Oakland, University of California [San Francisco] (UCSF), University of California-University of California, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and None reported.
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Pneumonia, Viral, Short Report, coronavirus, Chest ct, white blood cells scattergram, Computed tomography, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Short Reports, COVID‐19, Plasmacytoid Lymphocytes, White blood cell, Humans, Mass Screening, Medicine, Lymphocyte Count, Lymphocytes, Pandemics, Mass screening, Aged, Aged, 80 and over, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, business.industry, COVID-19, Hematology, Middle Aged, Predictive value, SARS‐Cov‐2, Reverse transcriptase, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, plasmacytoid lymphocytes, Female, Radiology, Coronavirus Infections, Tomography, X-Ray Computed, business, 030215 immunology
Abstract: International audience; Complementary tools are warranted to increase the sensitivity of the initial testing for COVID-19. We identified a specific ‘sandglass’ aspect on the white blood cell scattergram of COVID-19 patients reflecting the presence of circulating plasmacytoid lymphocytes. Patients were dichotomized as COVID-19-positive or -negative based on reverse transcriptase polymerase chain reaction (RT-PCR) and chest computed tomography (CT) scan results. Sensitivity and specificity of the ‘sandglass’ aspect were 85·9% and 83·5% respectively. The positive predictive value was 94·3%. Our findings provide a non-invasive and simple tool to quickly categorize symptomatic patients as either COVID-19-probable or -improbable especially when RT-PCR and/or chest CT are not rapidly available.
Published: 2020
Full Text: View/download PDF

13. Systemic Modelling in Bioethics

Author: Henri-Corto Stoeklé, Christian Hervé, Guillaume Vogt, Philippe Charlier, and Marie-France Mamzer-Bruneel
Subjects: Systems Analysis, Organisms, Genetically Modified, Ethical issues, Computer science, business.industry, Management science, Genetic Therapy, Bioethics, Models, Theoretical, Issues, ethics and legal aspects, Humans, Identification (biology), Genetic Testing, Personalized medicine, Precision Medicine, business, Ethical Analysis
Abstract: We present here a new method for bioethics: systemic modelling. In this method, the complex phenomenon being studied (e.g. personalized medicine, genetic testing, gene therapy, genetically modified organisms) is modelled as a whole, to shed light on its organization and functioning, and major (bio)ethical issues and solutions for their resolution are then identified. This systemic modelling method is ideal for use in the identification of solutions, rather than their validation, with other methods then used to test the solutions found. We provide a description and reproducible instructions for the application of systemic modelling in bioethics, together with a brief example of the application of this method to the study of the impact of personalized medicine on French society.
Published: 2020
Full Text: View/download PDF

14. Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study*

Author: Stéphanie Pons, Jean-Jacques Tudesq, Adrien Mirouse, Martine Nyunga, Fabrice Bruneel, Magali Bisbal, Achille Kouatchet, Yannick Hourmant, Dominique Benoit, Elie Azoulay, Matthieu Legrand, Virginie Lemiale, Anne-Pascale Meert, Frédéric Pène, Michael Darmon, Djamel Mokart, Lara Zafrani, Julien Mayaux, and Edith Borcoman
Subjects: Male, medicine.medical_specialty, Time Factors, Critical Illness, medicine.medical_treatment, Population, Hematopoietic stem cell transplantation, Neutropenia, Critical Care and Intensive Care Medicine, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, law, Neoplasms, Internal medicine, medicine, Humans, Hospital Mortality, education, Aged, education.field_of_study, business.industry, Septic shock, 030208 emergency & critical care medicine, Odds ratio, Middle Aged, medicine.disease, Respiration, Artificial, Shock, Septic, Intensive care unit, Europe, Survival Rate, Intensive Care Units, 030228 respiratory system, Hematologic Neoplasms, Female, business
Abstract: Objectives: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. Data Source: Seven European ICUs. Study Selection: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. Data Extraction: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique database (1994-2015). Data Synthesis: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. Conclusions: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.
Published: 2020
Full Text: View/download PDF

15. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

Author: David Hajage, Alain Combes, Christophe Guervilly, Guillaume Lebreton, Alain Mercat, Arthur Pavot, Saad Nseir, Armand Mekontso-Dessap, Nicolas Mongardon, Jean Paul Mira, Jean-Damien Ricard, Alexandra Beurton, Guillaume Tachon, Loay Kontar, Christophe Le Terrier, Jean Christophe Richard, Bruno Mégarbane, Ruth H. Keogh, Aurélien Belot, Camille Maringe, Clémence Leyrat, Matthieu Schmidt, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W. Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, Sébastian Voicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Meriam Lamraoui, Claire Alessandri, Quentin de Roux, Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien Pili Floury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris-Saclay, CHU Lille, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS [Créteil] (UPEC/Faculté de Médecine de Créteil), 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), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Foch [Suresnes], CHU Amiens-Picardie, Geneva University Hospital (HUG), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], London School of Hygiene and Tropical Medicine (LSHTM), RICHARD, Jean-Christophe, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, Adult, Respiratory Distress Syndrome, SARS-CoV-2, [SDV]Life Sciences [q-bio], acute respiratory distress syndrome (ARDS), COVID-19, extracorporeal membrane oxygenation, Critical Care and Intensive Care Medicine, Cohort Studies, [SDV] Life Sciences [q-bio], emulated target trial, acute respiratory distress syndrome, Treatment Outcome, surgical procedures, operative, Humans, Retrospective Studies
Abstract: International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2
Published: 2022
Full Text: View/download PDF

16. Lab-in-droplet: From glycan sample treatment toward diagnostic screening of congenital disorders of glycosylation

Author: Théo Liénard--Mayor, Camille Bricteux, Amel Bendali, Nguyet-Thuy Tran, Arnaud Bruneel, Myriam Taverna, and Thanh Duc Mai
Subjects: Congenital Disorders of Glycosylation, Glycosylation, Polysaccharides, Environmental Chemistry, Electrophoresis, Capillary, Humans, Biochemistry, Spectroscopy, Analytical Chemistry, Glycoproteins
Abstract: We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. Several operations are required for the sample treatment of a given glycoprotein to profile its N-glycans. In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation.
Published: 2022

17. Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis

Author: Mourad Hamimed, Pierre Leblond, Aurélie Dumont, Florence Gattacceca, Emmanuelle Tresch-Bruneel, Alicia Probst, Pascal Chastagner, Anne Pagnier, Emilie De Carli, Natacha Entz-Werlé, Jacques Grill, Isabelle Aerts, Didier Frappaz, Anne-Isabelle Bertozzi-Salamon, Caroline Solas, Nicolas André, Joseph Ciccolini, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), and Centre de Recherche en Cancérologie de Marseille (CRCM)
Subjects: Pharmacology, Cancer Research, MESH: Humans, MESH: Polymorphism, Single Nucleotide, [SDV]Life Sciences [q-bio], MESH: Models, Biological, MESH: Pharmacogenetics, ABCB1, Vinorelbine, P-glycoprotein, Toxicology, Models, Biological, Polymorphism, Single Nucleotide, Population pharmacokinetic analysis, Oncology, Pediatric drug development, Pharmacogenetics, MESH: Child, Humans, Pharmacology (medical), MESH: Vinorelbine, Neoplasm Recurrence, Local, Child, MESH: Neoplasm Recurrence, Local
Abstract: Better understanding of pharmacokinetics of oral vinorelbine (VNR) in children would help predicting drug exposure and, beyond, clinical outcome. Here, we have characterized the population pharmacokinetics of oral VNR and studied the factors likely to explain the variability observed in VNR exposure among young patients.We collected blood samples from 36 patients (mean age 11.6 years) of the OVIMA multicentric phase II study in children with recurrent/progressive low-grade glioma. Patients received 60 mg/mA three-compartment model, with a delayed double zero-order absorption and a first-order elimination, best described VNR pharmacokinetics in children. Typical population estimates for the apparent central volume of distribution (VBeyond canonical BSA and leukocytes, ABCB1-rs2032582 polymorphism showed a meaningful impact on VNR systemic exposure. Simulations showed that the identified covariates could have an impact on both efficacy and toxicity outcomes. Thus, a personalized dosing strategy, using those covariates, could help to optimize the efficacy/toxicity balance of VNR in children.
Published: 2022
Full Text: View/download PDF

18. One Size Doesn't Fit All: A Pilot Study Toward Performance-Specific Speech Intervention in Children With a Cleft (Lip and) Palate

Author: Cassandra Alighieri, Kim Bettens, Laura Bruneel, Jamie Perry, Greet Hens, and Kristiane Van Lierde
Subjects: Cleft Palate, Speech and Hearing, Linguistics and Language, Cleft Lip, Quality of Life, Humans, Speech, Pilot Projects, Child, Language and Linguistics
Abstract: Purpose:Speech-language pathologists usually apply a “one size fits all” approach to eliminate compensatory cleft speech characteristics (CSCs). It is necessary to investigate what intervention works best for a particular patient. This pilot study compared the effectiveness of two therapy approaches (a motor-phonetic approach and a linguistic-phonological approach) on different subtypes of compensatory CSCs in Dutch-speaking children with a cleft (lip and) palate (CP ± L).Method:Fourteen children with a CP ± L (Mage= 7.71 years) were divided into two groups using block randomization stratified by age, gender, and type of compensatory CSC. Six children received intervention to eliminate anterior oral CSCs (n= 3 motor-phonetic intervention,n= 3 linguistic-phonological intervention). Eight children received intervention to eliminate non-oral CSCs (n= 4 motor-phonetic intervention,n= 4 linguistic-phonological intervention). Each child received 10 hr of speech intervention divided over 2 weeks. Perceptual and psychosocial outcome measures were used to determine intervention effects.Results:Children who received linguistic-phonological intervention to eliminate anterior oral CSCs had significantly higher correctly produced consonant scores and health-related quality of life (HRQoL) scores compared to children who received motor-phonetic intervention to eliminate anterior oral CSCs. In the group of children who received intervention to eliminate non-oral CSCs, no significant differences were found in the correctly produced consonant scores nor in the HRQoL scores between the two intervention approaches.Conclusions:Linguistic-phonological intervention seems to be more appropriate to eliminate anterior oral CSCs. The beneficial effects of linguistic-phonological intervention were less pronounced in children with non-oral CSCs. Perhaps, children with non-oral CSCs benefit more from a hybrid phonetic-phonological approach. This study is a step forward in the provision of performance-specific intervention in children with a CP ± L. Replication in larger samples is needed and will aid to tailor treatment plans to the needs of our patients.
Published: 2022

19. Training speech pathology students in the perceptual evaluation of speech in patients with cleft palate: Reliability results and the students' perspective

Author: Laura Bruneel, Astrid Danhieux, and Kristiane Van Lierde
Subjects: Cleft Palate, Speech-Language Pathology, Velopharyngeal Insufficiency, Voice Disorders, Otorhinolaryngology, Speech Production Measurement, Pediatrics, Perinatology and Child Health, Nose Diseases, Humans, Reproducibility of Results, Speech, General Medicine, Students
Abstract: Listener training is necessary to achieve agreement between perceptual ratings. However, evidence is limited regarding the effect of a training in the perceptual evaluation of cleft palate speech on the reliability of students in speech pathology. The aim of this study was to evaluate the short-term and longer-term effect of a training using the Belgian Dutch outcome tool for cleft palate speech on reliability and the students' experiences.A 2-h training was provided during a specialist course for 31 first year master students in speech pathology. Information regarding listener characteristics, speech documentation and speech analysis (speech parameters and rating scales) was discussed. This last part focused on the Belgian Dutch outcome tool for speech in patients with cleft palate, including reference samples and consensus listening exercises. Pre training (T1) and post-training reliability (immediately following the training (T2) and one month later (T3)) were collected for the speech variables speech understandability, speech acceptability, hypernasality, hyponasality, nasal emission and nasal turbulence that were rated by means of ordinal scales. Inter-rater reliability was determined with interclass correlation coefficients whereas percentages of agreement were calculated for the intra-rater reliability.Qualitative inter-rater ICC categories improved for hyponasality and speech acceptability at T2 and T3, whereas the inter-rater reliability of the other variables remained stable regarding their interpreted categories. All ICC values quantitatively improved at T2, except hypernasality and nasal emission. At T3, three of those variables showed a small drop one month later. Regarding intra-rater reliability, a significant decrease for hypernasality and nasal turbulence was found at T2, whereas a significant increase was observed for nasal turbulence and speech acceptability at T3. All variables, except hypernasality, had improved intra-rater reliability at T3 in comparison with T1. Students experienced fewer difficulties with most variables after training. Evaluation of nasal emission and nasal turbulence remained however difficult and required, in the students' opinion, more attention.Overall a positive training effect was noted, especially regarding the inter-rater reliability and the students' confidence in perceptual ratings. However, it remains a challenge to achieve a positive training effect for all target variables that is maintained over-time.
Published: 2021

20. [SORD-related hereditary neuropathies]

Author: Gorka, Fernández-Eulate, Arnaud, Bruneel, and Tanya, Stojkovic
Subjects: Charcot-Marie-Tooth Disease, Mutation, Humans
Abstract: Mutations in the SORD gene have recently been identified as a cause of autosomal Charcot-Marie-Tooth disease as well as the underlying defect in some cases of hereditary distal motoneuronopathies. Patients may be amenable to therapies in a near future.
Published: 2021

21. Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

Author: Schmidt, Matthieu, Demoule, Alexandre, Hajage, David, Pham, Tài, Combes, Alain, Dres, Martin, Lebbah, Said, Kimmoun, Antoine, Mercat, Alain, Beduneau, Gaëtan, Palmyre, Jessica, Prevost, Margot, Ricard, Jean-Damien, Ferré, Alexis, Fayolle, Pierre-Marie, Girault, Christophe, Pradel, Gael, Asfar, Pierre, Beloncle, François, Demiselle, Julien, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Mayaux, Julien, Beurton, Alexandra, Daubin, Cédric, Descamps, Richard, Joret, Aurélie, Du Cheyron, Damien, Pene, Frédéric, Chiche, Jean-Daniel, Jozwiak, Mathieu, Jaubert, Paul, Voiriot, Guillaume, Fartoukh, Muriel, Teulier, Marion, Blayau, Clarisse, L’her, Erwen, Aubron, Cécile, Bodenes, Laetitia, Ferriere, Nicolas, Auchabie, Johann, Le Meur, Anthony, Pignal, Sylvain, Mazzoni, Thierry, Quenot, Jean-Pierre, Andreu, Pascal, Roudau, Jean-Baptiste, Labruyère, Marie, Nseir, Saad, Preau, Sébastien, Poissy, Julien, Mathieu, Daniel, Benhamida, Sarah, Paulet, Rémi, Roucaud, Nicolas, Thyrault, Martial, Daviet, Florence, Hraiech, Sami, Parzy, Gabriel, Sylvestre, Aude, Jochmans, Sébastien, Bouilland, Anne-Laure, Monchi, Mehran, Des Déserts, Marc Danguy, Mathais, Quentin, Rager, Gwendoline, Pasquier, Pierre, Jean, Reignier, Amélie, Seguin, Charlotte, Garret, Emmanuel, Canet, Dellamonica, Jean, Saccheri, Clément, Lombardi, Romain, Kouchit, Yanis, Jacquier, Sophie, Mathonnet, Armelle, Nay, Mai-Ahn, Runge, Isabelle, Martino, Frédéric, Flurin, Laure, Rolle, Amélie, Carles, Michel, Coudroy, Rémi, Thille, Arnaud, Frat, Jean-Pierre, Rodriguez, Maeva, Beuret, Pascal, Tientcheu, Audrey, Vincent, Arthur, Michelin, Florian, Tamion, Fabienne, Carpentier, Dorothée, Boyer, Déborah, Gissot, Valérie, Ehrmann, Stéphan, Gandonniere, Charlotte Salmon, Elaroussi, Djlali, Delbove, Agathe, Fedun, Yannick, Huntzinger, Julien, Lebas, Eddy, Kisoka, Grâce, Grégoire, Céline, Marchetta, Stella, Lambermont, Bernard, Argaud, Laurent, Baudry, Thomas, Bertrand, Pierre-Jean, Dargent, Auguste, Guitton, Christophe, Chudeau, Nicolas, Landais, Mickaël, Darreau, Cédric, Ferre, Alexis, Gros, Antoine, Lacave, Guillaume, Bruneel, Fabrice, Neuville, Mathilde, Devaquet, Jérôme, Tachon, Guillaume, Gallot, Richard, Chelha, Riad, Galbois, Arnaud, Jallot, Anne, Lemoine, Ludivine Chalumeau, Kuteifan, Khaldoun, Pointurier, Valentin, Jandeaux, Louise-Marie, Mootien, Joy, Damoisel, Charles, Sztrymf, Benjamin, Chommeloux, Juliette, Luyt, Charles Edouard, Schortgen, Frédérique, Rusel, Leon, Jung, Camille, Gobert, Florent, Vimpere, Damien, Lamhaut, Lionel, Sauneuf, Bertrand, Charrrier, Liliane, Calus, Julien, Desmeules, Isabelle, Painvin, Benoît, Tadie, Jean-Marc, Castelain, Vincent, Michard, Baptiste, Herbrecht, Jean-Etienne, Baldacini, Mathieu, Weiss, Nicolas, Demeret, Sophie, Marois, Clémence, Rohaut, Benjamin, Moury, Pierre-Henri, Savida, Anne-Charlotte, Couadau, Emmanuel, Série, Mathieu, Alexandru, Nica, Bruel, Cédric, Fontaine, Candice, Garrigou, Sonia, Mahler, Juliette Courtiade, Leclerc, Maxime, Ramakers, Michel, Garçon, Pierre, Massou, Nicole, van Vong, Ly, Sen, Juliane, Lucas, Nolwenn, Chemouni, Franck, Stoclin, Annabelle, Avenel, Alexandre, Faure, Henri, Gentilhomme, Angélie, Ricome, Sylvie, Abraham, Paul, Monard, Céline, Textoris, Julien, Rimmele, Thomas, Montini, Florent, Lejour, Gabriel, Lazard, Thierry, Etienney, Isabelle, Kerroumi, Younes, Dupuis, Claire, Bereiziat, Marine, Coupez, Elisabeth, Thouy, François, Hoffmann, Clément, Donat, Nicolas, Chrisment, Anne, Blot, Rose-Marie, Jacquot, Audrey, Mattei, Matthieu, Levy, Bruno, Ravan, Ramin, Dopeux, Loïc, Liteaudon, Jean-Mathias, Roux, Delphine, Rey, Brice, Anghel, Radu, Schenesse, Deborah, Gevrey, Vincent, Castanera, Jermy, Petua, Philippe, Madeux, Benjamin, Hartman, Otto, Piagnerelli, Michael, Joosten, Anne, Noel, Cinderella, Biston, Patrick, Noel, Thibaut, Bouar, Gurvan, Boukhanza, Messabi, Demarest, Elsa, Bajolet, Marie-France, Charrier, Nathanaël, Quenet, Audrey, Zylberfajn, Cécile, Dufour, Nicolas, Mégarbane, Buno, Voicu, Sqébastian, Deye, Nicolas, Malissin, Isabelle, Legay, François, Debarre, Matthieu, Barbarot, Nicolas, Fillatre, Pierre, Delord, Bertrand, Laterrade, Thomas, Saghi, Tahar, Pujol, Wilfried, Cungi, Pierre Julien, Esnault, Pierre, Cardinale, Mickael, Ha, Vivien Hong Tuan, Fleury, Grégory, Brou, Marie-Ange, Zafimahazo, Daniel, Tran-Van, David, Avargues, Patrick, Carenco, Lisa, Robin, Nicolas, Ouali, Alexandre, Houdou, Lucie, Le Terrier, Christophe, Suh, Noémie, Primmaz, Steve, Pugin, Jérome, Weiss, Emmanuel, Gauss, Tobias, Moyer, Jean-Denis, Burtz, Catherine Paugam, La Combe, Béatrice, Smonig, Rolland, Violleau, Jade, Cailliez, Pauline, Chelly, Jonathan, Marchalot, Antoine, Saladin, Cécile, Bigot, Christelle, Fatséas, Jules, Ibrahim, Amr, Resiere, Dabor, Hage, Rabih, Cholet, Clémentine, Cantier, Marie, Trouiler, Pierre, Montravers, Philippe, Lortat-Jacob, Brice, Tanaka, Sebastien, Dinh, Alexy Tran, Duranteau, Jacques, Harrois, Anatole, Dubreuil, Guillaume, Werner, Marie, Godier, Anne, Hamada, Sophie, Zlotnik, Diane, Nougue, Hélène, Mekontso-Dessap, Armand, Carteaux, Guillaume, Razazi, Keyvan, de Prost, Nicolas, Mongardon, Nicolas, Langeron, Olivier, Levesque, Eric, Attias, Arié, de Roquetaillade, Charles, Chousterman, Benjamin, Mebazaa, Alexandre, Gayat, Etienne, Garnier, Marc, Pardo, Emmanuel, Satre-Buisson, Lea, Gutton, Christophe, Yvin, Elise, Marcault, Clémence, Azoulay, Elie, Darmon, Michael, Oufella, Hafid Ait, Hariri, Geoffroy, Urbina, Tomas, Mazerand, Sandie, Heming, Nicholas, Santi, Francesca, Moine, Pierre, Annane, Djillali, Bouglé, Adrien, Omar, Edris, Lancelot, Aymeric, Begot, Emmanuelle, Plantefeve, Gaétan, Contou, Damien, Mentec, Hervé, Pajot, Olivier, Faguer, Stanislas, Cointault, Olivier, Lavayssiere, Laurence, Nogier, Marie-Béatrice, Jamme, Matthieu, Pichereau, Claire, Hayon, Jan, Outin, Hervé, Dépret, François, Coutrot, Maxime, Chaussard, Maité, Guillemet, Lucie, Goffin, Pierre, Thouny, Romain, Guntz, Julien, Jadot, Laurent, Persichini, Romain, Jean-Michel, Vanessa, Georges, Hugues, Caulier, Thomas, Pradel, Gaël, Hausermann, Marie-Hélène, Nguyen-Valat, Thi My Hue, Boudinaud, Michel, Vivier, Emmanuel, Rosseli, Sylvène, Bourdin, Gaël, Pommier, Christian, Vinclair, Marc, Poignant, Simon, Mons, Sandrine, Bougouin, Wulfran, Bruna, Franklin, Maestraggi, Quentin, Roth, Christian, Bitker, Laurent, Dhelft, François, Bonnet-Chateau, Justine, Filippelli, Mathilde, Morichau-Beauchant, Tristan, Thierry, Stéphane, Le Roy, Charlotte, Jouan, Mélanie Saint, Goncalves, Bruno, Mazeraud, Aurélien, Daniel, Matthieu, Sharshar, Tarek, Cadoz, Cyril, Gaci, Rostane, Gette, Sébastien, Louis, Guillaune, Sacleux, Sophe-Caroline, Ordan, Marie-Amélie, Cravoisy, Aurélie, Conrad, Marie, Courte, Guilhem, Gibot, Sébastien, Benzidi, Younès, Casella, Claudia, Serpin, Laurent, Setti, Jean-Lou, Besse, Marie-Catherine, Bourreau, Anna, Pillot, Jérôme, Rivera, Caroline, Vinclair, Camille, Robaux, Marie-Aline, Achino, Chloé, Delignette, Marie-Charlotte, Mazard, Tessa, Aubrun, Frédéric, Bouchet, Bruno, Frérou, Aurélien, Muller, Laura, Quentin, Charlotte, Degoul, Samuel, Stihle, Xavier, Sumian, Claude, Bergero, Nicoletta, Lanaspre, Bernard, Quintard, Hervé, Maiziere, Eve Marie, Egreteau, Pierre-Yves, Leloup, Guillaume, Berteau, Florin, Cottrel, Marjolaine, Bouteloup, Marie, Jeannot, Matthieu, Blanc, Quentin, Saison, Julien, Geneau, Isabelle, Grenot, Romaric, Ouchike, Abdel, Hazera, Pascal, Masse, Anne-Lyse, Demiri, Suela, Vezinet, Corinne, Baron, Elodie, Benchetrit, Deborah, Monsel, Antoine, Trebbia, Grégoire, Schaack, Emmanuelle, Lepecq, Raphaël, Bobet, Mathieu, Vinsonneau, Christophe, Dekeyser, Thibault, Delforge, Quentin, Rahmani, Imen, Vivet, Bérengère, Paillot, Jonathan, Hierle, Lucie, Chaignat, Claire, Valette, Sarah, Her, Benoït, Brunet, Jennifier, Page, Mathieu, Boiste, Fabienne, Collin, Anthony, Bavozet, Florent, Garin, Aude, Dlala, Mohamed, Mhamdi, Kais, Beilouny, Bassem, Lavalard, Alexandra, Perez, Severine, Veber, Benoit, Guitard, Pierre-Gildas, Gouin, Philippe, Lamacz, Anna, Plouvier, Fabienne, Delaborde, Bertrand, Kherchache, Aïssa, Chaalal, Amina, Amouretti, Marc, Freita-Ramos, Santiago, Roux, Damien, Constantin, Jean-Michel, Assefi, Mona, Lecore, Marine, Selves, Agathe, Prevost, Florian, Lamer, Christian, Shi, Ruiying, Knani, Lyes, Floury, Sébastien Pili, Vettoretti, Lucie, Levy, Michael, Marsac, Lucile, Dauger, Stéphane, Guilmin-Crépon, Sophie, Winiszewski, Hadrien, Piton, Gael, Soumagne, Thibaud, Capellier, Gilles, Putegnat, Jean-Baptiste, Bayle, Frédérique, Perrou, Maya, Thao, Ghyslaine, Géri, Guillaume, Charron, Cyril, Repessé, Xavier, Vieillard-Baron, Antoine, Guilbart, Mathieu, Roger, Pierre-Alexandre, Hinard, Sébastien, Macq, Pierre-Yves, Chaulier, Kevin, Goutte, Sylvie, Chillet, Patrick, Pitta, Anaïs, Darjent, Barbara, Bruneau, Amandine, Lasocki, Sigismond, Leger, Maxime, Gergaud, Soizic, Lemarie, Pierre, Terzi, Nicolas, Schwebel, Carole, Dartevel, Anaïs, Galerneau, Louis-Marie, Diehl, Jean-Luc, Hauw-Berlemont, Caroline, Péron, Nicolas, Guérot, Emmanuel, Amoli, Abolfazl Mohebbi, Benhamou, Michel, Deyme, Jean-Pierre, Andremont, Olivier, Lena, Diane, Cady, Julien, Causeret, Arnaud, de la Chapelle, Arnaud, Cracco, Christophe, Rouleau, Stéphane, Schnell, David, Foucault, Camille, Lory, Cécile, Chapelle, Thibault, Bruckert, Vincent, Garcia, Julie, Sahraoui, Abdlazize, Abbosh, Nathalie, Bornstain, Caroline, Pernet, Pierre, Poirson, Florent, Pasem, Ahmed, Karoubi, Philippe, Poupinel, Virginie, Gauthier, Caroline, Bouniol, François, Feuchere, Philippe, Heron, Anne, Carreira, Serge, Emery, Malo, Le Floch, Anne Sophie, Giovannangeli, Luana, Herzog, Nicolas, Giacardi, Christophe, Baudic, Thibaut, Thill, Chloé, Tubach, Florence, Bonnet, Nicolas, Ebstein, Nathan, Gaudry, Stéphane, Cohen, Yves, Noublanche, Julie, Lesieur, Olivier, Sément, Arnaud, Roca-Cerezo, Isabel, Pascal, Michel, Sma, Nesrine, Colin, Gwenhaël, Lacherade, Jean-Claude, Bionz, Gauthier, Maquigneau, Natacha, Bouzat, Pierre, Durand, Michel, Hérault, Marie-Christine, Payen, Jean-Francois, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), COVID-ICU group, for the REVA network, COVID-ICU investigators, and Mégarbane, Bruno
Subjects: Critical Care and Intensive Care Medicine, Acute respiratory failure, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Risk Assessment, Mechanical ventilation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Prospective Studies, Mortality, Outcome, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Noninvasive Ventilation, Acute respiratory distress syndrome, RC86-88.9, Research, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, [SDV.TOX]Life Sciences [q-bio]/Toxicology, High-flow nasal cannula, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Intubation
Abstract: Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) (P P P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed.
Published: 2021
Full Text: View/download PDF

22. Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients

Author: Paul Gabarre, Vincent Bonny, Tomas Urbina, Geoffroy Hariri, Thierry Dupré, Lisa Raia, Eric Maury, Naïke Bigé, Bertrand Guidet, Hafid Ait Oufella, Arnaud Bruneel, Jean-Luc Baudel, Jean-Rémi Lavillegrand, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies métaboliques, diabète et co-morbidités = Metabolic Diseases, Diabetes and co-morbidities [CRC], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Gestionnaire, HAL Sorbonne Université 5
Subjects: Pathology, medicine.medical_specialty, Resuscitation, Tissue perfusion, Mottling, Ascorbic Acid, Critical Care and Intensive Care Medicine, Microvascular function, Peripheral perfusion, Sepsis, medicine, Humans, Reactivity (chemistry), Vitamin C, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RC86-88.9, Septic shock, business.industry, Microcirculation, Research, Medical emergencies. Critical care. Intensive care. First aid, medicine.disease, Shock, Septic, Perfusion, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients. Methods Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period. Results We included 30 patients with septic shock. SOFA score was 11 [8–14], SAPS II was 66 [54–79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430–4246] vs 5362 [1744–10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), finger-tip (p = 0.0003) and knee capillary refill time (3.7 [2.6–5.5] vs 2.9 [1.9–4.7] s, p p Conclusion In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C. ClinicalTrials.gov Identifier: NCT04778605 registered 26 January 2021.
Published: 2021
Full Text: View/download PDF

23. The EMT Transcription Factor ZEB2 Promotes Proliferation of Primary and Metastatic Melanoma While Suppressing an Invasive, Mesenchymal-Like Phenotype

Author: William M. Gallagher, Nicolas Skrypek, Mairin Rafferty, Jean-Christophe Marine, Niels Vandamme, Joost van den Oord, Joachim Taminau, Marieke I.G. Raaijmakers, Corinna Köhler, Lieve Brochez, Gillian Blancke, Florian Rambow, Geertrui Denecker, Eva De Smedt, Pieter Van Vlierberghe, Vanessa Andries, David Nittner, Kenneth Bruneel, Douglas S. Darling, Jody J. Haigh, Steven Goossens, Jasper Wouters, Geert Berx, Wouter Van Loocke, Phil F. Cheng, Balázs Bálint, Özden Akay, Udupi Girish Mallya, Jordy De Coninck, Danny Huylebroeck, Mitchell P. Levesque, Ophthalmology, and Cell biology
Subjects: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Fate mapping, medicine, Tumor Cells, Cultured, Animals, Humans, Neoplasm Invasiveness, Gene, Transcription factor, Melanoma, Cell Proliferation, Zinc Finger E-box Binding Homeobox 2, Mesenchymal stem cell, medicine.disease, Phenotype, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Ectopic expression, Transcription Factors
Abstract: Epithelial-to-mesenchymal transition (EMT)-inducing transcription factors (TF) are well known for their ability to induce mesenchymal states associated with increased migratory and invasive properties. Unexpectedly, nuclear expression of the EMT-TF ZEB2 in human primary melanoma has been shown to correlate with reduced invasion. We report here that ZEB2 is required for outgrowth for primary melanomas and metastases at secondary sites. Ablation of Zeb2 hampered outgrowth of primary melanomas in vivo, whereas ectopic expression enhanced proliferation and growth at both primary and secondary sites. Gain of Zeb2 expression in pulmonary-residing melanoma cells promoted the development of macroscopic lesions. In vivo fate mapping made clear that melanoma cells undergo a conversion in state where ZEB2 expression is replaced by ZEB1 expression associated with gain of an invasive phenotype. These findings suggest that reversible switching of the ZEB2/ZEB1 ratio enhances melanoma metastatic dissemination. Significance: ZEB2 function exerts opposing behaviors in melanoma by promoting proliferation and expansion and conversely inhibiting invasiveness, which could be of future clinical relevance.
Published: 2020

24. Elevated thrombin generation in patients with congenital disorder of glycosylation and combined coagulation factor deficiencies

Author: Arnaud Bruneel, Mercedes Serrano, Dominique Lasne, Nathalie Seta, Nathalie Boddaert, Elsa P. Bianchini, María Eugenia de la Morena-Barrio, Tiffany Pascreau, Delphine Borgel, Javier Corral, Vicente Vicente, Pascale de Lonlay, and Manoelle Kossorotoff
Subjects: Male, Paris, medicine.medical_specialty, Adolescent, Coagulation Protein Disorders, 030204 cardiovascular system & hematology, Thrombomodulin, Protein S, 03 medical and health sciences, Blood Coagulation Disorders, Inherited, Congenital Disorders of Glycosylation, 0302 clinical medicine, Thrombin, Internal medicine, Humans, Medicine, Genetic Predisposition to Disease, Child, Blood Coagulation, Retrospective Studies, Factor IX, biology, business.industry, Antithrombin, Hematology, medicine.disease, Phenotype, Endocrinology, Coagulation, Spain, Child, Preschool, biology.protein, Female, business, Congenital disorder of glycosylation, Protein C, medicine.drug
Abstract: Background Congenital disorders of glycosylation are rare inherited diseases affecting many different proteins. The lack of glycosylation notably affects the hemostatic system and leads to deficiencies of both procoagulant and anticoagulant factors. Objective To assess the hemostatic balance in patients with multiple coagulation disorders by using a thrombin generation assay. Method We performed conventional coagulation assays and a thrombin generation assay on samples from patients with congenital disorder of glycosylation. The thrombin generation assay was performed before and after activation of the protein C system by the addition of soluble thrombomodulin. Results A total of 35 patients were included: 71% and 57% had low antithrombin and factor XI levels, respectively. Protein C and protein S levels were abnormally low in 29% and 26% of the patients, respectively, whereas only 11% displayed low factor IX levels. Under baseline conditions, the thrombin generation assay revealed a significantly higher endogenous thrombin potential and thrombin peak in patients, relative to controls. After spiking with thrombomodulin, we observed impaired involvement of the protein C system. Hence, 54% of patients displayed a hypercoagulant phenotype in vitro. All the patients with a history of stroke-like episodes or thrombosis displayed this hypercoagulant phenotype. Conclusion A thrombin generation assay revealed a hypercoagulant in vitro phenotype under baseline condition; this was accentuated by impaired involvement of the protein C system. This procoagulant phenotype may thus reflect the risk of severe vascular complications. Further research will have to determine whether the thrombin generation assay is predictive of vascular events.
Published: 2019
Full Text: View/download PDF

25. The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents

Author: Ann De Guchtenaere, Sarah Dejonckheere, Kim Pauwaert, Johan Vande Walle, Jolien Van der Jeugt, Laura Keersmaekers, Saskia Roggeman, Elke Bruneel, and Karel Everaert
Subjects: Male, medicine.medical_specialty, Ambulatory blood pressure, Adolescent, Diuresis, Renal function, Kidney, Kidney Function Tests, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Weight loss, 030225 pediatrics, Internal medicine, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Circadian rhythm, Child, Creatinine, Hormone activity, business.industry, Circadian Rhythm, Weight Reduction Programs, Free water clearance, Endocrinology, chemistry, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Biomarkers
Abstract: Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss.In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59-0.77) and nighttime clearance was 0.46 mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85-1.17) and nighttime clearance increased to 0.78 mL/min (0.64-0.93).Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:• Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:• In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.• Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss.
Published: 2019
Full Text: View/download PDF

26. Health-related quality of life in patients with cleft palate: Reproducibility, responsiveness and construct validity of the Dutch version of the VELO questionnaire

Author: Kristiane Van Lierde, Cassandra Alighieri, Kim Bettens, Laura Bruneel, Sofie de Smet, and Marc De Bodt
Subjects: Male, Parents, Velopharyngeal Insufficiency, Adolescent, Wilcoxon signed-rank test, Speech Therapy, Velopharyngeal insufficiency, Quality of life, Cronbach's alpha, Surveys and Questionnaires, Humans, Speech, Medicine, In patient, Child, Netherlands, Reproducibility, Descriptive statistics, business.industry, Reproducibility of Results, Construct validity, General Medicine, Translating, Cleft Palate, Otorhinolaryngology, Pediatrics, Perinatology and Child Health, Quality of Life, Female, Human medicine, business, Clinical psychology
Abstract: Objectives Recently, the Velopharyngeal Insufficiency (VPI) Effects on Life Outcomes (VELO) questionnaire, which evaluates the impact of speech and swallowing difficulties on health-related quality of life (HRQoL) in patients with VPI (Skirko et al., 2012), was translated to Dutch (Bruneel et al., 2017). The purpose of this study was to evaluate the reproducibility, responsiveness and construct validity of this Dutch version of the questionnaire. Methods To evaluate the reproducibility, 50 parents and 14 children with cleft palate re-completed the questionnaire after two weeks. Thirty-five parents and 8 children with cleft palate completed the VELO questionnaire after one year for the evaluation of the responsiveness. The correlation between age and the VELO questionnaire (construct validity), and the internal consistency (Cronbach's α) were re-determined based on the responses of 73 parents and 24 children. Results Based on descriptive statistics, results of the Wilcoxon signed rank-test, and the absolute (SEM) and relative (ICC) consistency, the questionnaire showed good reproducibility. VELO scores did not significantly differ after one year, neither when performing separate analyses for the intervention (speech therapy) and the non-intervention group. Correlations indicated higher HRQoL, as perceived by the parents, with increasing age. The reverse was the case for the youth report. Cronbach's α showed excellent internal consistency for both reports. Conclusions The VELO questionnaire showed good reproducibility and internal consistency. Moreover, results reconfirmed the age effect on VELO scores. To understand the implications of the results regarding the questionnaire's responsiveness, future research should focus on the identification of factors influencing the patient's evolution in HRQoL.
Published: 2019
Full Text: View/download PDF

27. Massed Versus Spaced Practice in Vocology: Effect of a Short-Term Intensive Voice Therapy Versus a Long-Term Traditional Voice Therapy

Author: Kristiane Van Lierde, Sofie Claeys, Laura Bruneel, Iris Meerschman, Kim Bettens, and Evelien D'haeseleer
Subjects: Adult, Male, Linguistics and Language, medicine.medical_specialty, Time Factors, Adolescent, Voice Quality, Voice therapy, medicine.medical_treatment, MEDLINE, Language and Linguistics, Group psychotherapy, Young Adult, 030507 speech-language pathology & audiology, 03 medical and health sciences, Speech and Hearing, 0302 clinical medicine, medicine, Humans, Young adult, 030223 otorhinolaryngology, business.industry, Attendance, Middle Aged, Dysphonia, Term (time), Clinical trial, Voice Training, Physical therapy, Female, 0305 other medical science, business
Abstract: Purpose The aim of this study was to compare the effect of a short-term intensive voice therapy (IVT) with a long-term traditional voice therapy (TVT) on the vocal quality, vocal capacities, psychosocial impact, vocal tract discomfort, laryngological anatomy/physiology, and session attendance of patients with dysphonia. An additional comparison was made between an individual IVT (IVT-I) and a group IVT (IVT-G). Method A longitudinal, prospective controlled trial was used. Forty-six adults diagnosed with dysphonia were assigned to 1 of the 3 treatment groups. The IVT groups practiced with a frequency of 1 hr 20 min a day and a duration of 2 weeks. The TVT group practiced with a frequency of two 30-min sessions a week and a duration of 6 months. Both therapy programs were content-identical and guided by the same voice therapist. A multidimensional voice assessment consisting of both objective (maximum performance task, aerodynamic measurements, voice range profile, acoustic analysis, multiparametric voice quality indices) and subjective (subject's self-report, auditory-perceptual evaluation, flexible videolaryngostroboscopy) outcomes was used to evaluate the participants' voice. Results IVT made an equal progress in only 2 weeks and 12 hr of therapy compared with TVT that needed 6 months and 24 hr of therapy. IVT-I and IVT-G showed comparable results. Session attendance was clearly higher in IVT compared with TVT. Long-term follow-up results (1 year) were positive for the 3 groups, except for the self-reported psychosocial impact that increased in the IVT-I group. Conclusions Short-term IVT is at least equally effective in treating patients with dysphonia as long-term TVT. Group treatment seemed as effective as individual treatment. Attendance and cost-effectiveness are important advantages of IVT. A potential drawback might be an insufficient psychosocial progress. The golden mean between intensive and traditional treatment might therefore be an achievable, effective, and efficient solution for everyday clinical practice. Supplemental Material https://doi.org/10.23641/asha.7761872
Published: 2019
Full Text: View/download PDF

28. A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis

Author: Daniel Da Silva, Vincent Roubeau, Patricia Pavese, Jean-Paul Mira, Rafael Mahieu, Heidi Wille, Lydie Khatchatourian, Charlotte Biron, Geneviève Blanchet-Fourcade, Romain Lefaucheur, Laurent Argaud, Arnaud Seigneurin, Guillaume Baille, Eugénie Mutez, Hélène Brasme, Morgan Matt, Amandine Gagneux-Brunon, Alexandra Mailles, Thibaut Fraisse, Morgane Le Bras, Céline Cazorla, Isabelle Pierre, Anne Bonnetain, Hélène Savini, Nathalie Marin, Isabelle Runge, Pierre Fillatre, Mathilde Reveillon-Istin, Mathieu Godement, Cédric Bruel, Martin Martinot, Xavier Argemi, Saber Touati, Emmanuel Forestier, M. Hentzien, Jérome Honnorat, Capucine Diard-Detoeuf, Nathalie Pansu, Yvon Ruch, Thècle Degroote, Alexandre Mas, Guillaume Louis, Bernard Castan, Thomas Guimard, Aurélien Dinh, Marc-Olivier Vareil, Pierre Jaquet, Aurélie Richard-Mornas, Thibault Challan-Belval, Paul Le Turnier, Aurélie Martin, Frédéric Bourdain, Catherine Chirouze, Pascal Chavanet, Carole Henry, François Goehringer, Alain Makinson, Fabrice Bruneel, Anne Pachart, Manuela Le Cam, Johan Courjon, Elisabeth Botelho-Nevers, Pierre Tattevin, Emilie Piet, Eric Denes, Jean-Louis Herrmann, Philippe Casenave, Rodolphe Buzele, Marion Le Maréchal, Laurence Maulin, Thomas De Broucker, Agnès Riché, Sylvain Rheims, Olivier Epaulard, Solene Patrat-Delon, Aurélie Baldolli, Valentin Greigert, Isabelle Gueit, Anne-Sophie Lecompte, Nicolas Gaillard, Marie Froidure, Guillaune Marc, Dimitri Psimaras, Nathalie Asseray, Charles Cazanave, Etienne Canouï, Jean-Etienne Herbrecht, Alexandre Thibault Jacques Maria, Romain Sonneville, Patrice Morand, Jessica Krause, Jean-Marie Turmel, Tomasz Tchroboczek, Kelly Tiercelet, Gwenael Le Moal, Arnaud de la Blanchardiere, Thomas Baudry, Jean-Paul Stahl, Simon Gravier, Frédéric Méchaï, Diane Ponscarme, Christelle Lucas, Laurent Almoyna-Martinez, Colin Deschanvres, Olivier Lesieur, Véronique Pelonde-Erimée, Raphaël Lecomte, David Boutoille, Sophie Abgrall, Jérémie Orain, Philippe Lesprit, François Raffi, Magalie Vidal-Roux, Mathieu Blot, Michael Bonnan, Arnaud Galbois, V. Vitrat, Olivier Bouchaud, Guillaume Martin-Blondel, Mathieu Zuber, Stéphanie Lejeune, Solen Kernéis, Hélène Pellerin, Isabelle Tyvaert, Mathilde Puges, Xavier Lescure, Philippe Mateu, Marine Delaroche, Fanny Jomier, Julien Biberon, Pascale Goubin, Benjamin Gaborit, Etienne De Montmollin, Centre Hospitalier Universitaire [Grenoble] (CHU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), French Infectious Diseases Society, and Université de Rennes (UR)-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 )
Subjects: Infectious Encephalitis, 0301 basic medicine, Microbiology (medical), Herpesvirus 3, Human, Pediatrics, medicine.medical_specialty, Lymphocytosis, diagnosis, viruses, encephalitis, etiology, [SDV]Life Sciences [q-bio], 030106 microbiology, factor analysis, Context (language use), medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, medicine, Infectious encephalitis, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, business.industry, medicine.disease, herpes simplex virus, 3. Good health, Infectious Diseases, Herpes simplex virus, Etiology, Encephalitis, Herpes Simplex, France, medicine.symptom, business, Encephalitis
Abstract: Background New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. Results As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. Conclusions No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.
Published: 2021
Full Text: View/download PDF

29. A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction

Author: Michael Kulik, Deepti M. Warad, Nathalie Seta, Mathieu Fiore, Anne Dell, Sandrine Vuillaumier-Barrot, Zhi-Jie Xia, Tadahiro Kumagai, Hudson H. Freeze, François Fenaille, Katherine Mcgoogan, Kimiyo Raymond, Mindy Porterfield, Thierry Dupré, Marie-Christine Vergnes-Boiteux, Deborah A. Nickerson, Michael Tiemeyer, Sophie Cholet, Michael J. Bamshad, Caroline Michot, Arnaud Bruneel, Tiffany Pascreau, Heather Flanagan-Steet, Shannon M. Wagner, Stuart M. Haslam, Bobby G. Ng, Delphine Borgel, Paulina Sosicka, Stephen Dalton, Richard Steet, Yohann Huguenin, Annie Harroche, Sanford Burnham Prebys Medical Discovery Institute, Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Georgia [USA], University of Washington [Seattle], CHU Bordeaux [Bordeaux], Imperial College London, Nemours Children's Specialty Care, Jacksonville, FL., Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Mayo Clinic [Rochester], The Greenwood Genetic Center, INSERM UMR S1193, Fondation Maladies Rares (FMR) WES-20160717, Commissariat à l'Energie Atomique et aux Energies Alternatives, R01DK99551, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, Adult, Male, Glycosylation, Monosaccharide Transport Proteins, glycosylation, Phosphatase, Biology, medicine.disease_cause, Endoplasmic Reticulum, Antiporters, Article, coagulopathy, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, 0302 clinical medicine, Congenital Disorders of Glycosylation, Mutant protein, Genetics, medicine, Humans, Child, Genetics (clinical), Genes, Dominant, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, Glycogen, Golgi pH, Endoplasmic reticulum, Liver Diseases, congenital disordes of glycosylation, Infant, Newborn, Infant, Golgi apparatus, Fibroblasts, medicine.disease, Molecular biology, Pedigree, 030104 developmental biology, chemistry, Child, Preschool, symbols, Female, Congenital disorder of glycosylation, exome sequencing, 030217 neurology & neurosurgery
Abstract: International audience; SLC37A4 encodes an endoplasmic reticulum (ER)-localized multitransmembrane protein required for transporting glucose-6-phosphate (Glc-6P) into the ER. Once transported into the ER, Glc-6P is subsequently hydrolyzed by tissue-specific phosphatases to glucose and inorganic phosphate during times of glucose depletion. Pathogenic variants in SLC37A4 cause an established recessive disorder known as glycogen storage disorder 1b characterized by liver and kidney dysfunction with neutropenia. We report seven individuals who presented with liver dysfunction multifactorial coagulation deficiency and cardiac issues and were heterozygous for the same variant, c.1267C>T (p.Arg423*), in SLC37A4; the affected individuals were from four unrelated families. Serum samples from affected individuals showed profound accumulation of both high mannose and hybrid type N-glycans, while N-glycans in fibroblasts and undifferentiated iPSC were normal. Due to the liver-specific nature of this disorder, we generated a CRISPR base-edited hepatoma cell line harboring the c.1267C>T (p.Arg423*) variant. These cells replicated the secreted abnormalities seen in serum N-glycosylation, and a portion of the mutant protein appears to relocate to a distinct, non-Golgi compartment, possibly ER exit sites. These cells also show a gene dosage-dependent alteration in the Golgi morphology and reduced intraluminal pH that may account for the altered glycosylation. In summary, we identify a recurrent mutation in SLC37A4 that causes a dominantly inherited congenital disorder of glycosylation characterized by coagulopathy and liver dysfunction with abnormal serum N-glycans.
Published: 2021
Full Text: View/download PDF

30. Capillary zone electrophoresis of transferrin and EDTA samples in congenital disorders of glycosylation screening: CaNOt do, really?

Author: Celia Raulet-Bussian, Alexandre Raynor, Grégory Plouviez, Léa Verel, and Arnaud Bruneel
Subjects: chemistry.chemical_classification, Glycosylation, Chemistry, Biochemistry (medical), Clinical Biochemistry, Carbohydrate deficient transferrin, Transferrin, Electrophoresis, Capillary, General Medicine, Biochemistry, chemistry.chemical_compound, Capillary electrophoresis, Congenital Disorders of Glycosylation, Humans, Isoelectric Focusing, Edetic Acid
Published: 2021

31. Cerebrospinal fluid features in comatose survivors of cardiac arrest: A pilot study

Author: Marine Paul, Sarah Benghanem, Sybille Merceron, Hugo Bellut, Florence Dumas, Amandine Henry, Fabrice Bruneel, Jean-Pierre Bedos, Alain Cariou, Stéphane Legriel, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and HAL UVSQ, Équipe
Subjects: Multidisciplinary, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Pilot Projects, Spinal Puncture, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Arrest, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Survivors, Coma, Cerebrospinal Fluid, Retrospective Studies
Abstract: Introduction Lumbar puncture is among the investigations used to identify various neurological conditions, including some that can cause cardiac arrest (CA). However, CA per se may alter cerebrospinal fluid (CSF) characteristics. Few studies have investigated CSF findings after CA. In this descriptive work, we assessed the frequency and risk factors of abnormal CSF findings after CA and the contribution of CSF analysis to the etiological diagnosis. Materials and methods We retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007–2016 with sustained return of spontaneous circulation (ROSC) after CA and who underwent lumbar puncture as an etiological investigation. Results Of 1984 patients with sustained ROSC, 55 (2.7%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of CA in 2/55 (3.6%) patients. Nonspecific CSF abnormalities were noted in 37/53 (69.8%) patients. By multivariate analysis, postresuscitation shock was positively associated with CSF abnormalities (OR, 6.92; 95% confidence interval [95%CI], 1.62–37.26; P = 0.013). A no-flow time above 6 minutes (OR, 0.19; 95%CI, 0.03–1.11; P = 0.076) and a respiratory cause of CA (OR, 2.91; 95%CI, 0.53–23.15; P = 0.24) were not statistically associated with CSF abnormalities. Nonspecific CSF abnormalities were not significantly associated with poor outcomes (Cerebral Performance Category ≥3; P = 0.06). Conclusions Lumbar puncture, although infrequently performed, may contribute to the etiological diagnosis of CA, albeit rarely. Nonspecific CSF abnormalities seem common after CA, notably with postresuscitation shock, and may be related to blood-brain barrier disruption. These findings may help to interpret CSF findings after CA. Further studies are warranted to assess our results.
Published: 2022
Full Text: View/download PDF

32. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Author: Götz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce C V Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens, Christopher R Levi, Didier Leys, Kaori Miwa, Carlos A Molina, Keith W Muir, Norbert Nighoghossian, Mark W Parsons, Salvador Pedraza, Peter D Schellinger, Stefan Schwab, Claus Z Simonsen, Shlee S Song, Vincent Thijs, Danilo Toni, Chung Y Hsu, Nils Wahlgren, Haruko Yamamoto, Nawaf Yassi, Sohei Yoshimura, Steven Warach, Werner Hacke, Kazunori Toyoda, Geoffrey A Donnan, Stephen M Davis, Christian Gerloff, Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L. Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bharath Cheripelli, Tae-Hee Cho, Chi-un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B. Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M. Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K. Mueller, Keith W. Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H. Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H. Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z. Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Keizo Yasui, Toshiro Yonehara, Shinichi Yoshimura, K. Aarnio, F. Alemseged, C. Anderson, T. Ang, M.L. Archer, J. Attia, P. Bailey, A. Balabanski, A. Barber, P.A. Barber, J. Bernhardt, A. Bivard, D. Blacker, C.F. Bladin, A. Brodtmann, D. Cadilhac, B.C.V. Campbell, L. Carey, S. Celestino, L. Chan, W.H. Chang, A. ChangI, C.H. Chen, C.-I. Chen, H.F. Chen, T.C. Chen, W.H. Chen, Y.Y. Chen, C.A. Cheng, E. Cheong, Y.W. Chiou, P.M. Choi, H.J. Chu, C.S. Chuang, T.C. Chung, L. Churilov, B. Clissold, A. Connelly, S. Coote, B. Coulton, E. Cowley, J. Cranefield, S. Curtze, C. D'Este, S.M. Davis, S. Day, P.M. Desmond, H.M. Dewey, C. Ding, G.A. Donnan, R. Drew, S. Eirola, D. Field, T. Frost, C. Garcia-Esperon, K. George, R. Gerraty, R. Grimley, Y.C. Guo, G. Hankey, J. Harvey, S.C. Ho, K. Hogan, D. Howells, P.M. Hsiao, C.H. Hsu, C.T. Hsu, C.-S. Hsu, J.P. Hsu, Y.D. Hsu, Y.T. Hsu, C.J. Hu, C.C. Huang, H.Y. Huang, M.Y. Huang, S.C. Huang, W.S. Huang, D. Jackson, J.S. Jeng, S.K. Jiang, L. Kaauwai, O. Kasari, J. King, T.J. Kleinig, M. Koivu, J. Kolbe, M. Krause, C.W. Kuan, W.L. Kung, C. Kyndt, C.L. Lau, A. Lee, C.Y. Lee, J.T. Lee, Y. Lee, Y.C. Lee, C. Levi, C.R. Levi, L.M. Lien, J.C. Lim, C.C. Lin, C.H. Lin, C.M. Lin, D. Lin, C.H. Liu, J. Liu, Y.C. Lo, P.S. Loh, E. Low, C.H. Lu, C.J. Lu, M.K. Lu, J. Ly, H. Ma, L. Macaulay, R. Macdonnell, E. Mackey, M. Macleod, J. Mahadevan, V. Maxwell, R. McCoy, A. McDonald, S. McModie, A. Meretoja, S. Mishra, P.J. Mitchell, F. Miteff, A. Moore, C. Muller, F. Ng, F.C. Ng, J-L. Ng, W. O'Brian, V. O'Collins, T.J. Oxley, M.W. Parsons, S. Patel, G.S. Peng, L. Pesavento, T. Phan, E. Rodrigues, Z. Ross, A. Sabet, M. Sallaberger, P. Salvaris, D. Shah, G. Sharma, G. Sibolt, M. Simpson, S. Singhal, B. Snow, N. Spratt, R. Stark, J. Sturm, M.C. Sun, Y. Sun, P.S. Sung, Y.F. Sung, M. Suzuki, M. Tan, S.C. Tang, T. Tatlisumak, V. Thijs, M. Tiainen, C.H. Tsai, C.K. Tsai, C.L. Tsai, H.T. Tsai, L.K. Tsai, C.H. Tseng, L.T. Tseng, J. Tsoleridis, H. Tu, H.T-H. Tu, W. Vallat, J. Virta, W.C. Wang, Y.T. Wang, M. Waters, L. Weir, T. Wijeratne, C. Williams, W. Wilson, A.A. Wong, K. Wong, T.Y. Wu, Y.H. Wu, B. Yan, F.C. Yang, Y.W. Yang, N. Yassi, H.L. Yeh, J.H. Yeh, S.J. Yeh, C.H. Yen, D. Young, C.L. Ysai, W.W. Zhang, H. Zhao, L. Zhao, Katharina Althaus-Knaurer, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A. Dixit, Geoffrey Donnan, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R. Lees, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Peter Schellinger, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Rüdiger von Kummer, Joanna Wardlaw, Rebecca A. Betensky, Gregoire Boulouis, Raphael A. Carandang, William A. Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L. Ford, John Hallenbeck, Gordon J. Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Michael H. Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H. Schwamm, Eric Searls, Shlee S. Song, Sidney Starkman, Albert J. Yoo, Ramin Zand, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Monash University [Melbourne], National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], University of Heidelberg, Medical Faculty, Massachusetts General Hospital [Boston], University of Melbourne, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Royal Adelaide Hospital [Adelaide Australia], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Flanders Make [Leuven], Flanders Make, University of Newcastle [Australia] (UoN), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vall d'Hebron University Hospital [Barcelona], University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Ruhr-Universität Bochum [Bochum], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Aarhus University Hospital, Cedars-Sinai Medical Center, Florey Institute of Neuroscience and Mental Health [Melbourne, Victoria, Australia], Austin Health, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], China Medical University Hospital [Taichung], Karolinska Institutet [Stockholm], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Texas at Austin [Austin], Collaborators Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators: Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Florent Boutitie, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bastian Cheng, Bharath Cheripelli, Tae-Hee Cho, Chi-Un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria Del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Martin Ebinger, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Matthias Endres, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Christian Gerloff, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Robin Lemmens, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-Cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K Mueller, Keith W Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Norbert Nighoghossian, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Peter Ringleb, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Vincent Thijs, Götz Thomalla, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Mayumi Fukuda-Doi, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Manabu Inoue, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Masatoshi Koga, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Kaori Miwa, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Kazunori Toyoda, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Haruko Yamamoto, Keizo Yasui, Toshiro Yonehara, Sohei Yoshimura, Shinichi Yoshimura, K Aarnio, F Alemseged, C Anderson, T Ang, M L Archer, J Attia, P Bailey, A Balabanski, A Barber, P A Barber, J Bernhardt, A Bivard, D Blacker, C F Bladin, A Brodtmann, D Cadilhac, B C V Campbell, L Carey, S Celestino, L Chan, W H Chang, A ChangI, C H Chen, C-I Chen, H F Chen, T C Chen, W H Chen, Y Y Chen, C A Cheng, E Cheong, Y W Chiou, P M Choi, H J Chu, C S Chuang, T C Chung, L Churilov, B Clissold, A Connelly, S Coote, B Coulton, E Cowley, J Cranefield, S Curtze, C D'Este, S M Davis, S Day, P M Desmond, H M Dewey, C Ding, G A Donnan, R Drew, S Eirola, D Field, T Frost, C Garcia-Esperon, K George, R Gerraty, R Grimley, Y C Guo, G Hankey, J Harvey, S C Ho, K Hogan, D Howells, P M Hsiao, C H Hsu, C T Hsu, C-S Hsu, J P Hsu, Y D Hsu, Y T Hsu, C J Hu, C C Huang, H Y Huang, M Y Huang, S C Huang, W S Huang, D Jackson, J S Jeng, S K Jiang, L Kaauwai, O Kasari, J King, T J Kleinig, M Koivu, J Kolbe, M Krause, C W Kuan, W L Kung, C Kyndt, C L Lau, A Lee, C Y Lee, J T Lee, Y Lee, Y C Lee, C Levi, C R Levi, L M Lien, J C Lim, C C Lin, C H Lin, C M Lin, D Lin, C H Liu, J Liu, Y C Lo, P S Loh, E Low, C H Lu, C J Lu, M K Lu, J Ly, H Ma, L Macaulay, R Macdonnell, E Mackey, M Macleod, J Mahadevan, V Maxwell, R McCoy, A McDonald, S McModie, A Meretoja, S Mishra, P J Mitchell, F Miteff, A Moore, C Muller, F Ng, F C Ng, J-L Ng, W O'Brian, V O'Collins, T J Oxley, M W Parsons, S Patel, G S Peng, L Pesavento, T Phan, E Rodrigues, Z Ross, A Sabet, M Sallaberger, P Salvaris, D Shah, G Sharma, G Sibolt, M Simpson, S Singhal, B Snow, N Spratt, R Stark, J Sturm, M C Sun, Y Sun, P S Sung, Y F Sung, M Suzuki, M Tan, S C Tang, T Tatlisumak, V Thijs, M Tiainen, C H Tsai, C K Tsai, C L Tsai, H T Tsai, L K Tsai, C H Tseng, L T Tseng, J Tsoleridis, H Tu, H T-H Tu, W Vallat, J Virta, W C Wang, Y T Wang, M Waters, L Weir, T Wijeratne, C Williams, W Wilson, A A Wong, K Wong, T Y Wu, Y H Wu, B Yan, F C Yang, Y W Yang, N Yassi, H L Yeh, J H Yeh, S J Yeh, C H Yen, D Young, C L Ysai, W W Zhang, H Zhao, L Zhao, Katharina Althaus-Knaurer, Martin Bendszus, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A Dixit, Geoffrey Donnan, Rainer Dziewas, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Werner Hacke, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R Lees, Didier Leys, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Catherine Oppenheim, Sven Poli, Peter Ringleb, Peter Schellinger, Stefan Schwab, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Danilo Toni, Roland Veltkamp, Rüdiger von Kummer, Nils Wahlgren, Joanna Wardlaw, Rebecca A Betensky, Gregoire Boulouis, Raphael A Carandang, William A Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L Ford, John Hallenbeck, Gordon J Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Arne Lauer, Michael H Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H Schwamm, Eric Searls, Shlee S Song, Sidney Starkman, Steven Warach, Ona Wu, Albert J Yoo, Ramin Zand, University of Newcastle [Callaghan, Australia] (UoN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CarMeN, laboratoire, Yperzeele, Laetitia, Evaluation of Unknown Onset Stroke Thrombolysis trials (EOS) investigators, UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Supporting clinical sciences, UZB Other, Physical Medicine and Rehabilitation, Clinical sciences, Neuroprotection & Neuromodulation, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, Neurology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, Center of Experimental and Molecular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ischemic Stroke/*diagnostic imaging/*drug therapy, Tomography, X-Ray Computed/methods, Fibrinolytic Agents/adverse effects/*therapeutic use, 030204 cardiovascular system & hematology, Ischemic Stroke/diagnostic imaging, surgery, 0302 clinical medicine, Modified Rankin Scale, 030212 general & internal medicine, 10. No inequality, Infusions, Intravenous, Stroke, Tomography, Time-to-Treatment, General Medicine, Thrombolysis, X-Ray Computed/methods, Tissue Plasminogen Activator/adverse effects, 3. Good health, [SDV] Life Sciences [q-bio], Diffusion Magnetic Resonance Imaging/methods, Treatment Outcome, Meta-analysis, Tissue Plasminogen Activator, Intravenous, medicine.medical_specialty, Infusions, Intravenous thrombolysis, Neuroimaging, Neuroscience(all), Placebo, Tissue Plasminogen Activator/adverse effects/*therapeutic use, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, ddc:610, Ischemic Stroke, business.industry, neurology, Fibrinolytic Agents/adverse effects, Odds ratio, Recovery of Function, medicine.disease, Clinical research, Diffusion Magnetic Resonance Imaging, Human medicine, business, Tomography, X-Ray Computed, Fibrinolytic agent
Abstract: International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.
Published: 2020
Full Text: View/download PDF

33. Symptoms of Mental Health Disorders in Critical Care Physicians Facing the Second COVID-19 Wave: A Cross-Sectional Study

Author: Azoulay, Elie, Pochard, Frédéric, Reignier, Jean, Argaud, Laurent, Bruneel, Fabrice, Courbon, Pascale, Cariou, Alain, Klouche, Kada, Labbé, Vincent, Barbier, François, Guitton, Christophe, Demoule, Alexandre, Kouatchet, Achille, Guisset, Olivier, Jourdain, Mercé, Papazian, Laurent, van Der Meersch, Guillaume, Reuter, Danielle, Souppart, Virginie, Resche-Rigon, Matthieu, Darmont, Michaël, Kentish-Barnes, Nancy, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Cochin [AP-HP], Université de Paris (UP), Hôpital Lapeyronie [Montpellier] (CHU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Le Mans (CH Le Mans), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Saint-André, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Roger Salengro [Lille], Hôpital Nord [CHU - APHM], Hôpital Avicenne [AP-HP], Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and MORNET, Dominique
Subjects: Adult, Male, Critical Care, [SDV]Life Sciences [q-bio], Health Personnel, education, Anxiety, Psychological Distress, nurses, Physicians, Prevalence, Humans, Burnout, Professional, Pandemics, ComputingMilieux_MISCELLANEOUS, Original Research, SARS-CoV-2, Depression, pandemic, COVID-19, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Mental Health, Editorial, post-traumatic stress disorder, Female, France, surge
Abstract: Background Working in the ICU during the first COVID-19 wave was associated with high levels of mental health disorders. Research question What are the mental health symptoms in healthcare providers (HCPs) facing the second wave? Study design and methods Cross-sectional study (October 30-December 1, 2020) in sixteen ICUs during the second wave in France. HCPs completed the Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale-Revised (IES-R, for posttraumatic stress disorder), and the Maslach Burnout Inventory (MBI). Results There were 845/1203 (70%) respondents (66% nursing staff, 32% medical staff, 2% other professionals); 487 (57.6%) had managed more than ten new COVID-19 patients in the previous week. Insomnia affected 320 (37.9%) and 7.7% were taking a psychotropic drug daily. Symptoms of anxiety, depression, post-traumatic stress disorder, and burnout were reported in 60.0% [95%CI, 56.6-63.3%], 36.1% [32.9-39.5%], 28.4% [25.4-31.6%], and 45.1% [41.7-48.5%] of respondents, respectively. Independent predictors of such symptoms included respondent characteristics (sex, profession, experience, personality traits), work organization (ability to rest and to care for family), and self-perceptions (fear of getting infected or infecting family and friends, feeling pressure related to the surge, intention to leave the ICU, lassitude, working conditions, feeling they had a high risk profession, and missing the clapping). The number of COVID-19 patients managed in the first wave or over the last week was not associated with symptoms of mental health disorders. Interpretation The prevalence of symptoms of mental health disorders is high in ICU HCPs managing the second COVID-19 surge. The highest tiers of hospital management urgently need to provide psychological support, peer-support groups, and a communication structure that ensure the well-being of HCPs.
Published: 2021
Full Text: View/download PDF

34. Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients

Author: Papa Alioune Ndour, Bénédicte Lebrun-Vignes, Oussama Mouri, Olivier Bouchaud, Charlotte Chambrion, Jean-Yves Siriez, Stéphane Jauréguiberry, Sébastien Larréché, Pierre Buffet, Fabrice Bruneel, Marc Thellier, Sandrine Houzé, Nicolas Argy, Martin Danis, Benoît Henry, Renaud Piarroux, Hervé Delacour, Adela Angoulvant, Aida Taieb, Eric Kendjo, Eric Caumes, Camille Roussel, and D. Courtin
Subjects: Microbiology (medical), Pediatrics, medicine.medical_specialty, Anemia, 030231 tropical medicine, Population, Artesunate, Context (language use), Hemolysis, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, 0302 clinical medicine, Pregnancy, Epidemiology, medicine, Humans, 030212 general & internal medicine, Malaria, Falciparum, Adverse effect, education, education.field_of_study, business.industry, Incidence (epidemiology), medicine.disease, Artemisinins, Malaria, Infectious Diseases, chemistry, Female, business
Abstract: Background Intravenous artesunate is the World Health Organization–recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. Methods We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011–2017) of a national program implemented by the French Drug Agency. Results Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate–delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. Conclusions Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.
Published: 2021
Full Text: View/download PDF

35. Articulation, oral function, and quality of life in patients treated with implant overdentures in the mandible: A prospective study

Author: Laura Bruneel, Carine Matthys, Hugo De Bruyn, Laurence Becue, Kristiane Van Lierde, and Ester Fonteyne
Subjects: 0206 medical engineering, Dentistry, Mandible, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, McNemar's test, Quality of life, Humans, Jaw, Edentulous, Medicine, Prospective Studies, Stage (cooking), Prospective cohort study, General Dentistry, Dental Implants, business.industry, 030206 dentistry, Denture, Overlay, Denture Retention, 020601 biomedical engineering, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Patient Satisfaction, Quality of Life, Dental Prosthesis, Implant-Supported, Implant, Oral Surgery, Articulation (phonetics), business
Abstract: Contains fulltext : 238870.pdf (Publisher’s version ) (Closed access) BACKGROUND: Modifications of facial and oral structures affect aesthetic appearance, orofacial functions, and have impact on quality of life. PURPOSE: This study determined alterations of articulation, oromyofunctional behavior, and Oral Health Related Quality of Life (OHRQoL) in patients replacing complete removable dentures by implant retained overdentures in the mandible. MATERIALS AND METHODS: Twenty-one fully edentulous patients received mandibular overdenture retained on a bar connecting two titanium dental implants. Patients were evaluated after receiving a new set of fully removable dentures (stage 1), after surgery during provisionalization on healing abutments (stage 2), and after final connection to the bar (stage 3). Assessments were taken by speech therapists and included evaluation of: articulation (picture naming and reading); oromyofunctional behavior; OHRQoL (OHIP-14 questionnaire), and overall satisfaction and speech (VAS). To measure changes over time, Wilcoxon matched-pairs signed-rank-test and McNemar test was used. RESULTS: There was no significant impact of the treatment on speech nor on the results of oromyofunction. In stage 1, patients had different kinds of articulation errors (mean:1.21) which evolved to 0.71 and 0.67. In stage 3, especially problems with the /s/ sound are seen in 37% (7/19) of the participants. Results of OHRQoL and satisfaction reveal that the average of satisfaction with oral health evolved from 67% to 63% and finally 78%. OHIP-14 total score was 17.4/56 in stage 1, remained unchanged in stage 2 and evolved in stage 3 to 9.8/56 (P: .010). This indicates improvement. Satisfaction with speech evolved significantly from 68% pretreatment to 82% in stage 3 (P: .013). CONCLUSION: Despite existing articulation and oromyofunctional disorders after treatment, people are very satisfied with their OHRQoL and their speech. Impact of mandibular denture wearing on OHRQoL declines once connected. It's important to inform patients that speech and oromyofunctional disorders may occur during treatment where especially the /s/ sound is vulnerable.
Published: 2021
Full Text: View/download PDF

36. Hepatic dysfunction impairs prognosis in critically ill patients with hematological malignancies: A post-hoc analysis of a prospective multicenter multinational dataset

Author: Colombe Saillard, Michael Darmon, Vincent Mallet, Dominique Benoit, Achille Kouatchet, Djamel Mokart, Elie Azoulay, Christine Lebert, François Vincent, Alexandre Demoule, Anne Renault, Magali Bisbal, Martine Nyunga, Anne-Pascale Meert, Virginie Lemiale, Rebecca Hamidfar, Mercé Jourdain, Fabrice Bruneel, Frédéric Pène, Charlotte Mouliade, Département d'hépatologie [CHU Cochin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Hepatic dysfunction, medicine.medical_specialty, Soins intensifs réanimation, Critical Illness, [SDV]Life Sciences [q-bio], Context (language use), Neutropenia, Critical Care and Intensive Care Medicine, law.invention, Hematological malignancies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, law, Internal medicine, Post-hoc analysis, medicine, Humans, Hospital Mortality, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Hyperbilirubinemia, Outcome, Hematology, business.industry, Liver Diseases, 030208 emergency & critical care medicine, medicine.disease, Prognosis, Intensive care unit, 3. Good health, Intensive Care Units, 030228 respiratory system, Hematologic Neoplasms, Cohort, Etiology, Critically ill patient, business
Abstract: Purpose: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce. Methods: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 μmol/L at ICU admission) and patients without HD. Results: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49–2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69–5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22–2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21–2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04–1.14, p < 0.0001). Conclusions: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
Full Text: View/download PDF

37. Perceptual Speech Outcomes After Early Primary Palatal Repair in Ugandan Patients With Cleft Palate

Author: Laura Bruneel, Isaac Ojok, Kristiane Van Lierde, Duncan Musasizib, Anke Adriaansen, George Galiwango, Daniel Sseremba, Cassandra Alighieri, Kim Bettens, Hubert Vermeersch, Evelien D'haeseleer, and Andrew Hodges
Subjects: Male, medicine.medical_specialty, Velopharyngeal Insufficiency, Referral, media_common.quotation_subject, Cleft Lip, Audiology, 03 medical and health sciences, 0302 clinical medicine, Perception, medicine, Humans, Speech, Uganda, Prospective Studies, 030223 otorhinolaryngology, Child, media_common, Nasality, business.industry, 030206 dentistry, Cleft Palate, Treatment Outcome, Otorhinolaryngology, Case-Control Studies, Female, Oral Surgery, Articulation (phonetics), business
Abstract: Objective: To provide speech outcomes of English-speaking Ugandan patients with a cleft palate with or without cleft lip (CP±L). Design: Prospective case–control study. Setting: Referral hospital for patients with cleft lip and palate in Uganda. Participants: Twenty-four English-speaking Ugandan children with a CP±L (15 boys, 9 girls, mean 8.4 years) who received palatal closure prior to 6 months of age and an age- and gender-matched control group of Ugandan children without cleft palate. Interventions: Comparison of speech outcomes of the patient and control group. Main Outcome Measures: Perceptual speech outcomes including articulation, resonance, speech understandability and acceptability, and velopharyngeal composite score (VPC-sum). Information regarding speech therapy, fistula rate, and secondary surgery. Results: Normal speech understandability was observed in 42% of the patients, and 38% were judged with normal speech acceptability. Only 16% showed compensatory articulation. Acceptable resonance was found in 71%, and 75% of the patients were judged perceptually to present with competent velopharyngeal function based on the VPC-sum. Additional speech intervention was recommended in 25% of the patients. Statistically significant differences for all these variables were still observed with the control children ( P < .05). Conclusions: Overall, acceptable speech outcomes were found after early primary palatal closure. Comparable or even better results were found in comparison with international benchmarks, especially regarding the presence of compensatory articulation. Whether this approach is transferable to Western countries is the subject for further research.
Published: 2021

38. Effectiveness of Speech Intervention in Patients With a Cleft Palate: Comparison of Motor-Phonetic Versus Linguistic-Phonological Speech Approaches

Author: Laura Bruneel, Kristiane Van Lierde, Evelien D'haeseleer, Kim Bettens, Cassandra Alighieri, and Ellen Van Gaever
Subjects: Linguistics and Language, Reading disability, medicine.medical_specialty, Cleft Lip, MEDLINE, Phonetics, Audiology, Language and Linguistics, Speech therapy, Cleft Palate, Speech and Hearing, Quality of life (healthcare), Intervention (counseling), Child, Preschool, medicine, Quality of Life, Humans, Speech, In patient, Psychology, Child
Abstract: Purpose The purpose of this study was to compare the effect of two different speech therapy approaches, a traditional motor-phonetic approach and a linguistic-phonological approach, on the speech and health-related quality of life in Dutch-speaking children with a cleft palate with or without a cleft lip (CP ± L) between 4 and 12 years old. Method A block-randomized, sham-controlled design was used. Fourteen children with a CP ± L ( M age = 7.71 years) were divided into two groups using block randomization stratified by age and gender: one receiving motor-phonetic intervention ( n = 7) and one receiving linguistic-phonological intervention ( n = 7). Each group received 10 hr of speech therapy divided over 2 weeks. Perceptual speech assessments were performed on several baseline and posttreatment data points. The psychosocial effects of the intervention were assessed using the patient-reported Velopharyngeal Insufficiency Effects on Life Outcomes questionnaire. Both groups were compared over time using (generalized) linear mixed models. Within-group effects of time were determined using pairwise comparisons with post hoc Bonferroni correction. Results Significant Time × Group interactions with large effect sizes were revealed in terms of consonant proficiency, indicating significant differences in evolution over time among the two groups. Only in the group receiving linguistic-phonological intervention, percentage of correctly produced consonants and places significantly improved after the treatment. Total Velopharyngeal Insufficiency Effects on Life Outcomes scores of the parents significantly improved in both groups after the intervention. Conclusions Both motor-phonetic and linguistic-phonological speech interventions can have a positive impact on the occurrence of cleft speech characteristics and consonant proficiency in children with a CP ± L. A linguistic-phonological approach, however, was observed to be more effective in terms of improving these speech outcomes compared with a motor-phonetic approach. Speech intervention, irrespective of the used approach, significantly improved the participant's health-related quality of life.
Published: 2020

39. Symptoms of Anxiety, Depression, and Peritraumatic Dissociation in Critical Care Clinicians Managing Patients with COVID-19. A Cross-Sectional Study

Author: Michael Darmon, Jean Reignier, Frédéric Pochard, Virginie Souppart, Alain Combes, Guillaume Geri, François Barbier, Alain Cariou, Danielle Reuter, Fabrice Bruneel, Alexandre Demoule, Bertrand Guidet, Kada Klouche, Matthieu Resche-Rigon, Bruno Mégarbane, Mercé Jourdain, Christophe Guitton, Olivier Guisset, Laurent Papazian, Elie Azoulay, Guillaume Van Der Meersch, Vincent Labbé, Diane Friedman, Achille Kouatchet, Laurent Argaud, Nancy Kentish-Barnes, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de Corbeil, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine chirurgicale intensive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital La Source (Orléans), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Ambroise Paré [AP-HP], Groupe hospitalier Saint-André, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Hôpital Raymond Poincaré [AP-HP], HAL-SU, Gestionnaire, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Sud Francilien, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Pitié-Salpétrière], Hôpital La Source [Orléans] (HLSO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], CHU Saint-Antoine [AP-HP], and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Stress Disorders, Traumatic, Cross-sectional study, coronavirus, Poison control, Critical Care and Intensive Care Medicine, Hospital Anxiety and Depression Scale, Suicide prevention, 0302 clinical medicine, Surveys and Questionnaires, Prevalence, 030212 general & internal medicine, Depression (differential diagnoses), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, anxiety, 3. Good health, depression, Anxiety, Female, France, medicine.symptom, Coronavirus Infections, COVID-19/Critical Care, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Health Personnel, Pneumonia, Viral, Betacoronavirus, 03 medical and health sciences, medicine, Humans, pneumonia, Psychiatry, Pandemics, SARS-CoV-2, business.industry, Editorials, COVID-19, Original Articles, Mental illness, medicine.disease, Mental health, Cross-Sectional Studies, 030228 respiratory system, ICU, business, Stress, Psychological, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Rationale: Frontline healthcare providers (HCPs) during the coronavirus disease (COVID-19) pandemic are at high risk of mental morbidity.Objectives: To assess the prevalence of symptoms of anxiety, depression, and peritraumatic dissociation in HCPs.Methods: This was a cross-sectional study in 21 ICUs in France between April 20, 2020, and May 21, 2020. The Hospital Anxiety and Depression Scale and the Peritraumatic Dissociative Experience Questionnaire were used. Factors independently associated with reported symptoms of mental health disorders were identified.Measurements and Main Results: The response rate was 67%, with 1,058 respondents (median age 33 yr; 71% women; 68% nursing staff). The prevalence of symptoms of anxiety, depression, and peritraumatic dissociation was 50.4%, 30.4%, and 32%, respectively, with the highest rates in nurses. By multivariable analysis, male sex was independently associated with lower prevalence of symptoms of anxiety, depression, and peritraumatic dissociation (odds ratio of 0.58 [95% confidence interval, 0.42–0.79], 0.57 [95% confidence interval, 0.39–0.82], and 0.49 [95% confidence interval, 0.34–0.72], respectively). HCPs working in non–university-affiliated hospitals and nursing assistants were at high risk of symptoms of anxiety and peritraumatic dissociation. Importantly, we identified the following six modifiable determinants of symptoms of mental health disorders: fear of being infected, inability to rest, inability to care for family, struggling with difficult emotions, regret about the restrictions in visitation policies, and witnessing hasty end-of-life decisions.Conclusions: HCPs experience high levels of psychological burden during the COVID-19 pandemic. Hospitals, ICU directors, and ICU staff must devise strategies to overcome the modifiable determinants of adverse mental illness symptoms.
Published: 2020
Full Text: View/download PDF

40. Long term outcome of MPI‐CDG patients on D‐mannose therapy

Author: Muriel Girard, Pascale de Lonlay, Arnaud Bruneel, Thierry Dupré, Lena Damaj, Dominique Debray, Monique Fabre, Karine Mention, Eric Bauchard, Dries Dobbelaere, Manuel Schiff, Nathalie Seta, Sandrine Vuillaumier-Barrot, Claire Douillard, Florence Lacaille, Stéphanie Torre, Delphine Borgel, Valérie A. McLin, Alice Kuster, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geneva University Hospitals and Geneva University, Hospital Bichat Paris, Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse (INSERM UMR1193), Université Paris-Saclay, and European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014)
Subjects: Liver Cirrhosis, Male, [SDV]Life Sciences [q-bio], diarrhea, Administration, Oral, Gastroenterology, Congenital Disorders of Glycosylation, Enteropathy, Portal hypertension, Child, Genetics (clinical), Venous Thrombosis, 0303 health sciences, ddc:618, 030305 genetics & heredity, Transferrin, portal hypertension, Thrombosis, 3. Good health, Venous thrombosis, Diarrhea, Treatment Outcome, Child, Preschool, Hypertension, Congenital hepatic fibrosis, Female, medicine.symptom, D-mannose, medicine.medical_specialty, Renal function, Hypoglycemia, Medication Adherence, 03 medical and health sciences, congenital disorder of glycosylation, Internal medicine, Genetics, medicine, congenital hepatic fibrosis, Humans, coagulation, Retrospective Studies, 030304 developmental biology, Coagulation, Mannose-6-Phosphate Isomerase, business.industry, Congenital disorder of glycosylation, Infant, medicine.disease, MPI-CDG, business, Mannose
Abstract: International audience; Mannose phosphate isomerase MPI-CDG (formerly CDG-1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D-mannose. We retrospectively reviewed long-term outcomes of patients with MPI-CDG, all but one of whom were treated with D-mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D-mannose treatment. Nine patients were diagnosed with MPI-CDG at a median age of 3 months. The presenting symptoms were diarrhea (n = 9), hepatomegaly (n = 9), hypoglycemia (n = 8), and protein loosing enteropathy (n = 7). All patients survived except the untreated one who died at 2 years of age. Oral D-mannose was started in eight patients at a median age of 7 months (mean 38 months), with a median follow-up on treatment of 14 years 9 months (1.5-20 years). On treatment, two patients developed severe portal hypertension, two developed venous thrombosis, and 1 displayed altered kidney function. Poor compliance with D-mannose was correlated with recurrence of diarrhea, thrombosis, and abnormal biological parameters including coagulation factors and transferrin profiles. Liver fibrosis persisted despite treatment, but two patients showed improved liver architecture during follow-up. This study highlights (i) the efficacy and safety of D-mannose treatment with a median follow-up on treatment of almost 15 years (ii) the need for life-long treatment (iii) the risk of relapse with poor compliance, (iii) the importance of portal hypertension screening (iv) the need to be aware of venous and renal complications in adulthood.
Published: 2020
Full Text: View/download PDF

41. Invasive Aspergillosis associated with Covid-19: A word of caution

Author: Odile Eloy, Jean-Pierre Bedos, Theophile Cocherie, F. Bruneel, Alexis Ferré, Stéphanie Marque-Juillet, Christelle Simon, Stéphane Legriel, Laura Gouzien, Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, This work has been supported by: Centre Hospitalier de Versailles André Mignot ., This work has been supported by: Centre Hospitalier de Versailles Andr? Mignot., and HAL UVSQ, Équipe
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pulmonary Aspergillosis/diagnosis, diagnosis, [SDV]Life Sciences [q-bio], Critical Illness, Aspergillosis, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Coronavirus Infections/pathology, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Aged, Retrospective Studies, Invasive Pulmonary Aspergillosis, 0303 health sciences, 030306 microbiology, business.industry, Critically ill, Incidence (epidemiology), Incidence, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Coinfection, pathology, Female, Pulmonary Aspergillosis, Complication, business, Coronavirus Infections, Cohort study
Abstract: International audience; Introduction: Invasive pulmonary aspergillosis is a well-known complication of acute respiratory distress syndrome, the most serious manifestation of COVID-19. Four recent studies have reported its incidence among ICU COVID-19 patients. However, they do not share the same case definition, and have provided conflicting results. In this paper we have aimed at reported the incidence of invasive pulmonary aspergillosis for COVID-19 patients in our ICU, and at comparing the different definitions in order to assess their respective relevance. Methods: Retrospective cohort study of critically ill patients with severe COVID-19 requiring ICU management between 1st March and 30th April 2020. Results: Our results showed significantly lower incidence of invasive pulmonary aspergillosis (1.8%;1/53), compared to three out of four previous studies, and wide variation in the numbers of cases with regard to the different definitions. Conclusion: Large-scale studies are needed for a better definition and a more accurate estimation of invasive pulmonary aspergillosis coinfection during COVID-19.
Published: 2020
Full Text: View/download PDF

42. Serum bikunin isoforms in congenital disorders of glycosylation and linkeropathies

Author: Arnaud Bruneel, Walid Haouari, Johanne Dubail, Nathalie Seta, Pierre Prada, Charles Roseau, Valérie Cormier-Daire, Estelle Colin, Céline Huber, François Foulquier, Samra Lounis-Ouaras, Sandrine Vuillaumier-Barrot, Christian Poüs, Rizk Bennani, Alexandra Afenjar, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-15-RAR3-0004,EURO-CDG-2,A European research network directed towards improving diagnosis and treatment of inborn glycosylation disorders.(2015), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gene isoform, congenital, hereditary, and neonatal diseases and abnormalities, Glycosylation, [SDV]Life Sciences [q-bio], linkeropathies, Golgi Apparatus, Context (language use), Antiporters, Glycosaminoglycan, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, Congenital Disorders of Glycosylation, Alpha-Globulins, Genetics, Humans, Protein Isoforms, inter‐α‐trypsin inhibitor, Chondroitin sulfate, Cation Transport Proteins, Genetics (clinical), 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, bikunin, 030305 genetics & heredity, Golgi apparatus, 3. Good health, Enzyme, Biochemistry, chemistry, TMEM165, GAG tetrasaccharide, Nucleotide Transport Proteins, symbols, CDG, SLC35A3, Glycoprotein, Biomarkers
Abstract: Bikunin (Bkn) isoforms are serum chondroitin sulfate (CS) proteoglycans synthesized by the liver. They include two light forms, that is, the Bkn core protein and the Bkn linked to the CS chain (urinary trypsin inhibitor [UTI]), and two heavy forms, that is, pro‐α‐trypsin inhibitor and inter‐α‐trypsin inhibitor, corresponding to UTI esterified by one or two heavy chains glycoproteins, respectively. We previously showed that the Western‐blot analysis of the light forms could allow the fast and easy detection of patients with linkeropathy, deficient in enzymes involved in the synthesis of the initial common tetrasaccharide linker of glycosaminoglycans. Here, we analyzed all serum Bkn isoforms in a context of congenital disorders of glycosylation (CDG) and showed very specific abnormal patterns suggesting potential interests for their screening and diagnosis. In particular, genetic deficiencies in V‐ATPase (ATP6V0A2‐CDG, CCDC115‐CDG, ATP6AP1‐CDG), in Golgi manganese homeostasis (TMEM165‐CDG) and in the N‐acetyl‐glucosamine Golgi transport (SLC35A3‐CDG) all share specific abnormal Bkn patterns. Furthermore, for each studied linkeropathy, we show that the light abnormal Bkn could be further in‐depth characterized by two‐dimensional electrophoresis. Moreover, besides being interesting as a specific biomarker of both CDG and linkeropathies, Bkn isoforms' analyses can provide new insights into the pathophysiology of the aforementioned diseases.
Published: 2020
Full Text: View/download PDF

43. Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients

Author: Alexandre Demoule, Isabelle Vinatier, Virginie Lemiale, Anne-Pascale Meert, Samir Jaber, Dominique Benoit, Elie Azoulay, Guillaume Dumas, Djamel Mokart, Michael Darmon, Christine Lebert, Audrey De Jong, Achille Kouatchet, Fabrice Bruneel, Frédéric Pène, Magali Bisbal, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Gouvernance et Contrôle Organisationnel (LGCO), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département d'anesthésiologie et de soins intensifs [Institut Paoli-Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
Subjects: Organ Dysfunction Scores, medicine.medical_treatment, Critical Illness, mechanical ventilation, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Severity of Illness Index, high-flow oxygen, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Clinical endpoint, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Intubation, Intratracheal, Intubation, neutropenia, Humans, Lung, Mechanical ventilation, Cross Infection, business.industry, Mortality rate, Oxygen Inhalation Therapy, noninvasive ventilation, 030208 emergency & critical care medicine, Odds ratio, Oxygenation, Length of Stay, 3. Good health, Intensive Care Units, 030228 respiratory system, Anesthesia, business, Respiratory Insufficiency, Nasal cannula, radiography, Cohort study
Abstract: International audience; Objectives: To assess the response to initial oxygenation strategy according to clinical variables available at admission.Design: Multicenter cohort study.Setting: Thirty French and Belgium medical ICU.Subjects: Immunocompromised patients with hypoxemic acute respiratory failure.Interventions: None.Measurements and Main Results: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03–2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07–3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23–10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73–4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27–3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10–4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11–11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35–4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26–3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates.Conclusions: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.
Published: 2020
Full Text: View/download PDF

44. Impact of early ICU admission for critically ill cancer patients: Post-hoc analysis of a prospective multicenter multinational dataset

Author: René López, Elie Azoulay, Yannick Hourmant, Julien Mayaux, Anne Renault, Anne-Pascale Meert, Michael Darmon, Dominique Benoit, Virginie Lemiale, Christine Lebert, Djamel Mokart, Achille Kouatchet, Fabrice Bruneel, and Frédéric Pène
Subjects: medicine.medical_specialty, Soins intensifs réanimation, health care facilities, manpower, and services, Critical Illness, Critical Care and Intensive Care Medicine, Early admission, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Neoplasms, Post-hoc analysis, Outcome assessment (health care), Medicine, Humans, Intensive care medicine, Hospital Mortality, Prospective Studies, Mortality, Retrospective Studies, Time-to-treatment, business.industry, Confounding, 030208 emergency & critical care medicine, Intensive care unit, Triage, Intensive Care Units, 030228 respiratory system, Propensity score matching, Emergency medicine, Cohort, SOFA score, business
Abstract: Objectives: Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP. Design: Retrospective analysis of a prospective multicenter dataset. Early admission was defined as admission in the ICU < 24 h of hospital admission. We assessed the association between early ICU admission and hospital mortality in CICP via survival analysis and propensity score matching. Results: Of the 1011patients in our cohort, 1005 had data available regarding ICU admission timing and were included. Overall, early ICU admission occurred in 455 patients (45.3%). Crude hospital mortality in patients with early and delayed ICU admission was 33.6% (n = 153) vs. 43.1% (n = 237), respectively (P = 0.02). After adjustment for confounders, early compared to late ICU admission was not associated with hospital mortality (HR 0.92; 95%CI 0.76–1.11). After propensity score matching, hospital mortality did not differ between patients with early (35.2%) and late (40.6%) ICU admission (P = 0.13). In the matched cohort, early ICU admission was not associated with mortality after adjustment on SOFA score (HR 0.89; 95%CI 0.71–1.12). Similar results were obtained after adjustment for center effect. Conclusion: In this cohort, early ICU admission was not associated with a better outcome after adjustment for confounder and center effect. The uncertainty with regard to the beneficial effect of early ICU on hospital mortality suggests the need for an interventional study., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

45. Midazolam sedation in palliative medicine: retrospective study in a French center for cancer control

Author: Stéphanie Villet, Vincent Berry, Chloé Prod’homme, Vincent Gamblin, Michel Reich, Emmanuelle Tresch-Bruneel, Nicolas Penel, and Arlette Da Silva
Subjects: Adult, Male, medicine.medical_specialty, Palliative care, Midazolam, Sedation, Pain medicine, lcsh:Special situations and conditions, Cancer control, Neoplasms, medicine, Humans, Hypnotics and Sedatives, Aged, Retrospective Studies, Aged, 80 and over, Maintenance dose, business.industry, lcsh:RC952-1245, Palliative Care, Retrospective cohort study, General Medicine, Middle Aged, Time of death, Oncology, Emergency medicine, Female, France, medicine.symptom, business, Research Article, medicine.drug
Abstract: BackgroundFrench legislation about sedation in palliative medicine evolved in 2016 with the introduction of a right to deep and continuous sedation, maintained until death. The objective was to describe midazolam sedation at the COL (Centre Oscar Lambret[Oscar Lambret Center], French regional center for cancer control), in order to establish a current overview before the final legislative changes.MethodsDescriptive, retrospective and single-center study, concerning major patients in palliative care hospitalized from 01/01/2014 to 12/31/2015, who had been sedated by midazolam. The proven sedations (explicitly named) and the probable sedations were distinguished.ResultsA total of 54 sedations were identified (48 proven, 6 probable). Refractory symptoms accounted for 48.1% of indications, complications with immediate risk of death 46.3%, existential suffering 5.6%. Titration was performed in 44.4% of cases. Sedation was continuous until death for 98.1% of the cases. Probable sedation had a higher failure rate than proven sedation. Significant differences existed for the palliative care unit compared to other units regarding information to the patient, their consent, anticipation, mention by correspondence and carrying out titrations. When patients had already been treated with midazolam, the induction doses, initial maintenance doses, and doses at the time of death were significantly higher. For those receiving opioids, the maintenance dose at the time of death was higher. No comparison found a difference in overall survival.ConclusionsAfter a sufficient follow-up has enabled teams to familiarize with this new legislation, reflection on sedation should be conducted to adapt to final recommendations.
Published: 2020
Full Text: View/download PDF

46. Reliability results of perceptual ratings of resonance, nasal airflow and speech acceptability in patients with cleft palate by Ugandan speech-language pathologists following a two-day workshop

Author: Daniel Sseremba, Laura Bruneel, Kristiane Van Lierde, Cassandra Alighieri, Imke Kissel, Evelien D'haeseleer, and Anke Adriaansen
Subjects: Adult, Male, medicine.medical_specialty, Speech-Language Pathology, Wilcoxon signed-rank test, Adolescent, media_common.quotation_subject, Nasal emission, Black People, Audiology, Speech Acoustics, Speech Disorders, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Speech Production Measurement, 030225 pediatrics, Perception, Health care, Nose Diseases, otorhinolaryngologic diseases, medicine, Humans, Active listening, Uganda, 030223 otorhinolaryngology, Child, Reliability (statistics), media_common, business.industry, Speech Intelligibility, Reproducibility of Results, General Medicine, medicine.disease, Test (assessment), Cleft Palate, Otorhinolaryngology, Pediatrics, Perinatology and Child Health, Speech Perception, Female, business
Abstract: Introduction To meet the scarcity of training and/or educational initiatives in Uganda regarding state-of-the-art speech diagnosis and treatment in patients with cleft palate, a workshop was organized for all interested speech-language pathologists and health care workers. Objective To evaluate and compare the inter- and intra-rater reliability of the perceptual evaluation of hypernasality, hyponasality, nasal emission, nasal turbulence and speech acceptability before and after a two-day workshop in Ugandan speech-language pathologists. Methods On the first day, perceptual speech evaluation was discussed and practiced. Perceptual exercises included individual ratings of a specific speech variable followed by a group discussion and consensus listening exercises in listener pairs. The second day focused on speech treatment. Ten Ugandan speech-language pathologists rated speech samples of Ugandan patients with a CP ± L before and immediately following the two-day workshop. Inter- and intra-rater reliability of the perceptual ratings of hypernasality, hyponasality, nasal emission, nasal turbulence and speech acceptability were determined by means of the absolute percentage of agreement. The Wilcoxon signed-rank test was used to compare results at both time points. Results Overall inter- and intra-rater reliability improved when observing the absolute percentage agreement. However, median agreement results only showed enhanced reliability for hypernasality, hyponasality and nasal turbulence whereas (limited) deteriorated reliability was observed for nasal emission and speech acceptability. Regarding inter-rater reliability only the median percentage agreement for hyponasality exceeded 50% (median: 56.3%). Overall, better results were found for intra-rater reliability, with only weak results for speech acceptability. Discussion and conclusion Training positively affected reliability results. Nonetheless, this improvement was not achieved for each speech variable and reliability improvements were modest. Findings indicate the need for continued training and the search for the most effective training paradigm and feedback techniques, whilst taking into account clinical relevance and practical considerations.
Published: 2020

47. Tryptophan pathway catabolites (serotonin, 5-hydroxyindolacetic acid, kynurenine) and enzymes (monoamine oxidase and indole amine 2,3 dioxygenase) in patients with septic shock

Author: Troché, Gilles, Henry-Lagarrigue, Matthieu, Soppelsa, Frédérique, Legriel, Stephane, Yehia, Aihem, Bruneel, Fabrice, Bédos, Jean-Pierre, and Spreux-Varoquaux, Odile
Subjects: Male, Serotonin, Organ Dysfunction Scores, Tryptophan, Observational Study, Hydroxyindoleacetic Acid, Middle Aged, mortality, Shock, Septic, Survival Rate, human septic shock, tryptophan catabolites, Case-Control Studies, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, organ failure, Female, Prospective Studies, Monoamine Oxidase, Kynurenine, Research Article, Aged
Abstract: Septic shock is associated with a strong inflammatory response that induces vasodilation and vascular hyporeactivity. We investigated the role for tryptophan-pathway catabolites of proinflammatory cytokines in septic shock. We prospectively included 30 patients with very recent-onset septic shock and 30 healthy volunteers. The following were assayed once in the controls and on days 1, 2, 3, 7, and 14 in each patient: plasma free and total tryptophan, platelet and plasma serotonin, total blood serotonin, urinary serotonin, plasma and urinary 5-hydroxyindolacetic acid, plasma kynurenine, monoamine oxidase activity, and total indole amine 2,3-dioxygenase activity. Organ-system failure and mortality were recorded. Compared with the healthy controls, the patients with septic shock had 2-fold to 3-fold lower total tryptophan levels throughout the 14-day study period. Platelet serotonin was substantially lower, while monoamine oxidase activity and 5-hydroxyindolacetic acid were markedly higher in the patients than in the controls, consistent with the known conversion of tryptophan to serotonin, which is then promptly and largely degraded to 5-hydroxyindolacetic acid. Plasma kynurenine was moderately increased and indole amine 2,3-dioxygenase activity markedly increased in the patients versus the volunteers, reflecting conversion of tryptophan to kynurenine. Changes over time in tryptophan metabolites were not associated with survival in the patients but were associated with the Sequential Organ Failure Assessment score and hemodynamic variables including hypotension and norepinephrine requirements. Our results demonstrate major tryptophan pathway alterations in septic shock. Marked alterations were found compared with healthy volunteers, and tryptophan metabolite levels were associated with organ failure and hemodynamic alterations. Tryptophan metabolite levels were not associated with surviving septic shock, although this result might be ascribable to the small sample size. Trial registration: ClinicalTrials.gov; No: NCT00684736; URL: www.clinicaltrials.gov.
Published: 2020

48. Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation

Author: Onland, W., Cools, F., Kroon, A., Rademaker, K., Merkus, M.P., Dijk, P.H., Straaten, H.L. van, Pas, A.B.T., Mohns, T., Bruneel, E., Heijst, A.F. van, Kramer, B.W., Debeer, A., Zonnenberg, I., Marechal, Y., Blom, H., Plaskie, K., Offringa, M., Kaam, A.H. van, Nuytemans, D.H., Loo, M.V. de, Kemper, E.M., Vereeck, I., Heide-Jalving, M. van der, Kort, E. de, Cavartorta, E., Rassart, A., Eerdekens, A., Stuijvenberg, M., Matthijsse, R., Boode, W. de, Niemarkt, H., Hattum, I. van, Jebbink, L.G., Mulder-de Tollenaer, S.M., Tan, R., Theyskens, C., Weissenbruch, M. van, Dierckx, E., Rigo, V., Vrijlandt, E., Tweel, I. van der, Baal, C. van, Wildt, S. de, STOP-BPD Study Grp, Data Safety Monitoring Comm, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, STOP-BPD Study Grp, Data Safety Monitoring Comm, Clinical sciences, Growth and Development, Neonatology, Pediatrics, Groningen Research Institute for Asthma and COPD (GRIAC), ARD - Amsterdam Reproduction and Development, APH - Methodology, APH - Quality of Care, Other Research, Clinical Research Unit, and APH - Health Behaviors & Chronic Diseases
Subjects: Hydrocortisone, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Anti-Inflammatory Agents, CHILDREN, Infant, Premature, Diseases, 01 natural sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, Medicine, Infant, Very Low Birth Weight, 030212 general & internal medicine, Treatment Failure, Original Investigation, Bronchopulmonary Dysplasia, Incidence, TREAT, Gestational age, General Medicine, Female, Life Sciences & Biomedicine, Infant, Premature, medicine.medical_specialty, Birth weight, Placebo, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Time-to-Treatment, 03 medical and health sciences, MORBIDITY, Medicine, General & Internal, All institutes and research themes of the Radboud University Medical Center, Double-Blind Method, General & Internal Medicine, Intensive care, Internal medicine, Intensive Care Units, Neonatal, Humans, 0101 mathematics, Science & Technology, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], 010102 general mathematics, Postmenstrual Age, Infant, Newborn, PREVENT, Odds ratio, medicine.disease, Respiration, Artificial, Bronchopulmonary dysplasia, RISK-FACTORS, Human medicine, POSTNATAL CORTICOSTEROIDS, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract: IMPORTANCE: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking. OBJECTIVE: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017. INTERVENTIONS: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190). MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age. RESULTS: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%). CONCLUSIONS AND RELEVANCE: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication. TRIAL REGISTRATION: Netherlands National Trial Register Identifier: NTR2768. ispartof: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION vol:321 issue:4 pages:354-363 ispartof: location:United States status: published
Published: 2019
Full Text: View/download PDF

49. Better speech outcomes after very early palatal repair?—A longitudinal case-control study in Ugandan children with cleft palate

Author: Kim Bettens, Cassandra Alighieri, Laura Bruneel, Evelien D'haeseleer, Anke Luyten, Daniel Sseremba, Duncan Musasizib, Isaac Ojok, Andrew Hodges, George Galiwango, Hubert Vermeersch, and Kristiane Van Lierde
Subjects: Linguistics and Language, Velopharyngeal Insufficiency, Cleft Lip, Cognitive Neuroscience, Infant, Experimental and Cognitive Psychology, LPN and LVN, Cleft Palate, Speech and Hearing, Case-Control Studies, Child, Preschool, Humans, Speech, Uganda, Prospective Studies, Child
Abstract: Children born with cleft palate with or without cleft lip (CP±L) tend to use less oral pressure consonants and more glottal sounds in their babbling. The purpose of very early palatal repair (i.e., one-stage palatal closure prior to 6 months of age) is to make the palate functional before the onset of speech acquisition to reduce the anchoring of wrong patterns in the child's developing phonological system. As a result, less compensatory articulation errors are expected to be present. Currently, no detailed longitudinal speech outcomes after very early palatal closure are available. This study aimed to provide longitudinal speech outcomes in Ugandan children with CP±L who received palatal closure prior to the age of 6 months.Ten children with CP±L were assessed at a mean age of 5 and 10 years old. Speech understandability, speech acceptability, resonance, nasal airflow and articulation were perceptually rated by two experienced speech-language pathologists. Velopharyngeal function was estimated using the velopharyngeal composite score (VPC-sum). Information regarding speech therapy, fistula rate, and secondary (speech) surgery was collected. The outcomes were compared with the longitudinal outcomes of an age- and gender-matched control group of 10 Ugandan children without CP±L.Speech understandability and acceptability improved significantly over time in the group with CP±L (all p's ≤ 0.05, all Z's-2.43). At both test dates, significantly worse judgments were found for the group with CP±L compared to the control group for these variables and variables related to passive speech errors (all p's ≤ 0.05, all Z's2.49). A statistically significant difference with the control group was found for the presence of compensatory articulation errors at the age of 5 years but not at the age of 10 years, indicating a catch up by the children with CP±L.Whether a one-stage palatal closure prior to the age of 6 months is more favorable for speech outcomes compared to one-stage palatal closure at 12 months is still not clear. Speech of the children with CP±L improved over time, but significantly differed from the control group at the age of 5 and 10 years old. Limited access to health care facilities and possible influence of malnutrition on wound healing need to be considered when interpreting the results. Whether palatal closure prior to the age of 6 months is transferable to other countries is subject for further research, including both longitudinal and prospective designs with larger samples.
Published: 2022
Full Text: View/download PDF

50. Clinical Application of a New Approach to Identify Oral–Nasal Balance Disorders Based on Nasalance Scores

Author: Kristiane Van Lierde, Laura Bruneel, Tim Bressmann, Gillian de Boer, and Kim Bettens
Subjects: Orthodontics, Hyponasality, Pharyngeal flap surgery, Voice Quality, business.industry, Balance disorders, 030206 dentistry, Mixed nasality, Nose, Linear discriminant analysis, 03 medical and health sciences, Nasometry, 0302 clinical medicine, Speech Production Measurement, Otorhinolaryngology, Child, Preschool, Nose Diseases, Humans, Medicine, Oral Surgery, Nasalance, Child, 030223 otorhinolaryngology, business, Retrospective Studies
Abstract: Objective: A new approach to classify oral–nasal balance disorders based on instrumental measurements was developed based on linear discriminant analysis (LDA) of nasalance scores of simulated oral–nasal balance disorders by de Boer and Bressmann. The current study aimed to apply the newly developed functions to clinical data to investigate the applicability of this new approach. Design: Retrospective diagnostic accuracy study. Setting: Tertiary university hospital. Participants: Fifty-five Dutch-speaking Flemish children (age 4-12 years) with normal (n = 20), hypernasal (n = 18), hyponasal (n = 12), or mixed nasality (n = 5). Interventions: Nasalance scores of an oral and a nasal text were used to calculate 3 sets of LDA function scores. Predicted classification was consecutively based on the function values of the group centroids originally determined by de Boer and Bressmann and adapted LDA functions and group centroids based on clinical data. Main Outcome Measures: Discriminatory power of the linear discriminant formulas. Results: Based on the original LDA functions, 56% of the speech samples matched the perceptual classification. Applying a correction factor for age and language differences resulted in a 67% correct classification, although 83% of the hyponasal samples were ranked as “normal resonance.” Rederivation of the LDA functions based on current clinical data resulted in an 80% correct classification. Conclusions: The new approach of classifying oral–nasal balance disorders based on a combination of nasalance scores was promising. However, further clinical research is needed to refine the LDA functions and group centroids before clinical application is possible.
Published: 2018
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

327 results on '"Bruneel A"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources