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9,846 results on '"Warren Alpert Medical School of Brown University"'

1. Music Therapy at TMH Infusion Center

Author: The Warren Alpert Medical School of Brown University
Published: 2024

2. The Warren Alpert Medical School of Brown University Scholarly Concentrations Program Collection of Abstracts

Author: Program, The Warren Alpert Medical School Of Brown University Scholarly Concentration
Published: 2017
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3. Content validation of the patient-reported outcomes measurement information system (PROMIS) framework in women with urinary incontinence

Author: Departments of Anesthesiology, Medicine, Psychiatry and Psychology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan, The Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, ; Division of Urogynecology and Reconstructive Pelvic Surgery, Women and Infants' Hospital/Warren Alpert Medical School at Brown University, 695 Eddy Street, Providence, RI 02903., The Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, The Division of Urogynecology, Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, Departments of Community Health and Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, Sung, Vivian W., Marques, Felisha, Rogers, Rebecca R., Williams, David A., Myers, Deborah L., Clark, Melissa A., Departments of Anesthesiology, Medicine, Psychiatry and Psychology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, Michigan, The Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, ; Division of Urogynecology and Reconstructive Pelvic Surgery, Women and Infants' Hospital/Warren Alpert Medical School at Brown University, 695 Eddy Street, Providence, RI 02903., The Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, The Division of Urogynecology, Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, Departments of Community Health and Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, Rhode Island, Sung, Vivian W., Marques, Felisha, Rogers, Rebecca R., Williams, David A., Myers, Deborah L., and Clark, Melissa A.
Abstract: Aims To assess whether the existing National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) conceptual framework and item banks sufficiently capture the concerns of women with urinary incontinence (UI). Methods Thirty-five women with UI were recruited between February-April 2009 for 4 structured focus groups to develop and assess the content validity of a conceptual framework for the impact of UI. This framework included domains from the NIH PROMIS framework and item banks including broad domains of physical and social function and mental health. All sessions were transcribed, coded, and qualitatively and quantitatively analyzed using analytic induction and deductive analysis to identify new themes and domains relevant to women with UI. Results The focus groups provided information that confirmed the relevance of existing PROMIS domains and identified new outcome domains that are important to this patient population. The groups confirmed the relevance of the physical and social functioning, and mental health domains. Additional themes that emerged included the distinction between ability versus participation and satisfaction, role functioning, external mediators, re-calibration/coping, cognitive function and new possibilities. Participants also felt strongly that not all domains and items apply to all women with UI and an option to tailor questionnaires and skip non-relevant items was important. Conclusions The PROMIS framework domains are relevant to women with UI, but additional patient-important themes are identified that may improve the comprehensiveness of this assessment framework for measuring outcomes important to women with UI. These results will inform future item content development for UI. 30:503???509, 2011. ?? 2011 Wiley-Liss, Inc.
Published: 2011

4. Beta-Agonist Versus OnabotulinumtoxinA Trial for Urgency Urinary Incontinence (BEST)

Author: University of New Mexico, University of Alabama at Birmingham, University of California, San Diego, Howard University, Brown University, Patient-Centered Outcomes Research Institute, and Vivian Sung, MD, MPH, Professor of Obstetrics & Gynecology, The Warren Alpert Medical School of Brown University; Director of Research, Division of Urogynecology, Women & Infants Hospital of Rhode Island
Published: 2023

5. Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels

Author: Erin Rooney Riggs, Taylor I. Bingaman, Carrie-Ann Barry, Andrea Behlmann, Krista Bluske, Bret Bostwick, Alison Bright, Chun-An Chen, Amanda R. Clause, Avinash V. Dharmadhikari, Mythily Ganapathi, Claudia Gonzaga-Jauregui, Andrew R. Grant, Madeline Y. Hughes, Se Rin Kim, Amanda Krause, Jun Liao, Aimé Lumaka, Michelle Mah, Caitlin M. Maloney, Shruthi Mohan, Ikeoluwa A. Osei-Owusu, Emma Reble, Olivia Rennie, Juliann M. Savatt, Hermela Shimelis, Rebecca K. Siegert, Tam P. Sneddon, Courtney Thaxton, Kelly A. Toner, Kien Trung Tran, Ryan Webb, Emma H. Wilcox, Jiani Yin, Xinming Zhuo, Masa Znidarsic, Christa Lese Martin, Catalina Betancur, Jacob A.S. Vorstman, David T. Miller, Christian P. Schaaf, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), Drexel University, Invitae Corporation, Illumina, Baylor College of Medicine (BCM), Baylor University, Natera [San Carlos, CA, USA], Children’s Hospital Los Angeles [Los Angeles], Keck School of Medicine [Los Angeles], University of Southern California (USC), Columbia University Irving Medical Center (CUIMC), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], New York Medical College (NYMC), University of Illinois [Chicago] (UIC), University of Illinois System, National Human Genome Research Institute (NHGRI), University of the Witwatersrand [Johannesburg] (WITS), Université de Liège, Trillium Health Partners - Mississauga Hospital [Mississauga, ON, Canada] (THP-MH), University of Washington [Seattle], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), St. Michael's Hospital, The Hospital for sick children [Toronto] (SickKids), Garvan Institute of medical research, Warren Alpert Medical School of Brown University, University of California [Los Angeles] (UCLA), University of California (UC), The Jackson Laboratory [Bar Harbor] (JAX), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Heidelberg University Hospital [Heidelberg], This work was supported by the National Human Genome Research Institute of the National Institutes of Health under award number U24HG006834., and Betancur, Catalina
Subjects: ClinGen, MESH: Humans, Autism Spectrum Disorder, Autism, MESH: Autism Spectrum Disorder* / genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Autism Spectrum Disorder* / diagnosis, MESH: Intellectual Disability* / diagnosis, MESH: Intellectual Disability* / genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, Intellectual Disability, MESH: Autistic Disorder* / genetics, MESH: Autistic Disorder* / diagnosis, Humans, Autistic Disorder, MESH: Neurodevelopmental Disorders* / genetics, Genetics (clinical), Gene–disease validity
Abstract: International audience; Purpose: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not.Methods: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship.Results: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants.Conclusion: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.
Published: 2022
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6. Consensus guidelines for the definition of time-to-event end points in image-guided tumor ablation

Author: Puijk, Robbert, Ahmed, Muneeb, Adam, Andreas, Arai, Yasuaki, Arellano, Ronald, de Baère, Thierry, Bale, Reto, Bellera, Carine, Binkert, Christoph, Brace, Christopher, Breen, David, Brountzos, Elias, Callstrom, Matthew, Carrafiello, Gianpaolo, Chapiro, Julius, de Cobelli, Francesco, Coupé, Veerle, Crocetti, Laura, Denys, Alban, Dupuy, Damian, Erinjeri, Joseph, Filippiadis, Dimitris, Gangi, Afshin, Gervais, Debra, Gillams, Alice, Greene, Tissy, Guiu, Boris, Helmberger, Thomas, Iezzi, Roberto, Kang, Tae Wook, Kelekis, Alexis, Kim, Hyun, Kröncke, Thomas, Kwan, Sharon, Lee, Min Woo, Lee, Fred, Lee, Edward, Liang, Ping, Lissenberg-Witte, Birgit, Lu, David, Madoff, David, Mauri, Giovanni, Meloni, Maria Franca, Morgan, Robert, Nadolski, Gregory, Narayanan, Govindarajan, Newton, Isabel, Nikolic, Boris, Orsi, Franco, Pereira, Philippe, Pua, Uei, Rhim, Hyunchul, Ricke, Jens, Rilling, William, Salem, Riad, Scheffer, Hester, Sofocleous, Constantinos, Solbiati, Luigi, Solomon, Stephen, Soulen, Michael, Sze, Daniel, Uberoi, Raman, Vogl, Thomas, Wang, David, Wood, Bradford, Goldberg, S Nahum, Meijerink, Martijn, Goldberg, S. Nahum, Amsterdam UMC - Amsterdam University Medical Center, Harvard Medical School [Boston] (HMS), Guy's and St Thomas' Hospital [London], National Cancer Center Hospital (NCCJ), Department of radiology (Massachusetts General Hospital), Massachusetts General Hospital [Boston], Institut Gustave Roussy (IGR), Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institut Bergonié [Bordeaux], UNICANCER, Kantonsspital Winterthur (KSW), University of Wisconsin School of Medicine and Public Health, University Hospital Southampton NHS Foundation Trust, National and Kapodistrian University of Athens (NKUA), Mayo Clinic [Rochester], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Yale University [New Haven], IRCCS Ospedale San Raffaele [Milan, Italy], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Pisa - Università di Pisa, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Warren Alpert Medical School of Brown University, Memorial Sloan Kettering Cancer Center (MSKCC), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, The London Clinic cancer, Society of Interventional Oncology (SIO), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), and Kiel University
Subjects: Ablation Techniques, medicine.medical_specialty, Consensus, [SDV]Life Sciences [q-bio], MESH: Societies, Medical, MEDLINE, Outcome (game theory), Session (web analytics), Quality of life (healthcare), Humans, Neoplasms, Reproducibility of Results, Societies, Medical, Medical, medicine, MESH: Neoplasms, Radiology, Nuclear Medicine and imaging, Medical physics, ddc:610, MESH: Consensus, License, MESH: Humans, Health economics, business.industry, MESH: Ablation Techniques, Opinion leadership, MESH: Reproducibility of Results, Clinical trial, business, Societies
Abstract: International audience; There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.
Published: 2021
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7. SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Author: Amélie Cordovado, Martina Schaettin, Médéric Jeanne, Veranika Panasenkava, Anne-Sophie Denommé-Pichon, Boris Keren, Cyril Mignot, Martine Doco-Fenzy, Lance Rodan, Keri Ramsey, Vinodh Narayanan, Julie R Jones, Eloise J Prijoles, Wendy G Mitchell, Jillian R Ozmore, Kali Juliette, Erin Torti, Elizabeth A Normand, Leslie Granger, Andrea K Petersen, Margaret G Au, Juliann P Matheny, Chanika Phornphutkul, Mary-Kathryn Chambers, Joaquín-Alejandro Fernández-Ramos, Eduardo López-Laso, Michael C Kruer, Somayeh Bakhtiari, Marcella Zollino, Manuela Morleo, Giuseppe Marangi, Davide Mei, Tiziana Pisano, Renzo Guerrini, Raymond J Louie, Anna Childers, David B Everman, Betrand Isidor, Séverine Audebert-Bellanger, Sylvie Odent, Dominique Bonneau, Brigitte Gilbert-Dussardier, Richard Redon, Stéphane Bézieau, Frédéric Laumonnier, Esther T Stoeckli, Annick Toutain, Marie-Laure Vuillaume, Jonchère, Laurent, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Zürich [Zürich] = University of Zurich (UZH), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), The Translational Genomics Research Institute (TGen), The Greenwood Genetic Center, Keck School of Medicine [Los Angeles], University of Southern California (USC), Dartmouth Hitchcock Medical Center [Lebanon], Gillette Children's Specialty Healthcare [St Paul], GeneDx [Gaithersburg, MD, USA], Randall Children's Hospital [Portland], University of Kentucky (UK), Warren Alpert Medical School of Brown University, Rhode Island Hospital [Providence, RI, États-Unis], Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Barrow Neurological Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), Università degli Studi di Firenze = University of Florence (UniFI), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Funding for HUGODIMS (Western France exome-based trio approach project to identifygenes involved in intellectual disability) was supported by a grant from the French Ministryof Health and from the Health Regional Agency from Poitou-Charentes [HUGODIMS, 2013,RC14_0107]. [A.C.] is a research student recipient of a grant from the University of Tours., Cordovado, Amélie, Schaettin, Martina, Jeanne, Médéric, Panasenkava, Veranika, Denommé-Pichon, Anne-Sophie, Keren, Bori, Mignot, Cyril, Doco-Fenzy, Martine, Rodan, Lance, Ramsey, Keri, Narayanan, Vinodh, Jones, Julie R, Prijoles, Eloise J, Mitchell, Wendy G, Ozmore, Jillian R, Juliette, Kali, Torti, Erin, Normand, Elizabeth A, Granger, Leslie, Petersen, Andrea K, Au, Margaret G, Matheny, Juliann P, Phornphutkul, Chanika, Chambers, Mary-Kathryn, Fernández-Ramos, Joaquín-Alejandro, López-Laso, Eduardo, Kruer, Michael C, Bakhtiari, Somayeh, Zollino, Marcella, Morleo, Manuela, Marangi, Giuseppe, Mei, Davide, Pisano, Tiziana, Guerrini, Renzo, Louie, Raymond J, Childers, Anna, Everman, David B, Isidor, Betrand, Audebert-Bellanger, Séverine, Odent, Sylvie, Bonneau, Dominique, Gilbert-Dussardier, Brigitte, Redon, Richard, Bézieau, Stéphane, Laumonnier, Frédéric, Stoeckli, Esther T, Toutain, Annick, and Vuillaume, Marie-Laure
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Epilepsy, Dendritic Spines, [SDV]Life Sciences [q-bio], Intellectual disability, Chick Embryo, Semaphorins, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Medicine, Settore MED/03 - GENETICA MEDICA, Axon Guidance, [SDV] Life Sciences [q-bio], HEK293 Cells, SEMA6B, Intellectual Disability, Genetics, Animals, Humans, Original Article, Molecular Biology, Genetics (clinical)
Abstract: Intellectual disability (ID) is a neurodevelopmental disorder frequently caused by monogenic defects. In this study, we collected 14 SEMA6B heterozygous variants in 16 unrelated patients referred for ID to different centers. Whereas, until now, SEMA6B variants have mainly been reported in patients with progressive myoclonic epilepsy, our study indicates that the clinical spectrum is wider and also includes non-syndromic ID without epilepsy or myoclonus. To assess the pathogenicity of these variants, selected mutated forms of Sema6b were overexpressed in Human Embryonic Kidney 293T (HEK293T) cells and in primary neuronal cultures. shRNAs targeting Sema6b were also used in neuronal cultures to measure the impact of the decreased Sema6b expression on morphogenesis and synaptogenesis. The overexpression of some variants leads to a subcellular mislocalization of SEMA6B protein in HEK293T cells and to a reduced spine density owing to loss of mature spines in neuronal cultures. Sema6b knockdown also impairs spine density and spine maturation. In addition, we conducted in vivo rescue experiments in chicken embryos with the selected mutated forms of Sema6b expressed in commissural neurons after knockdown of endogenous SEMA6B. We observed that expression of these variants in commissural neurons fails to rescue the normal axon pathway. In conclusion, identification of SEMA6B variants in patients presenting with an overlapping phenotype with ID and functional studies highlight the important role of SEMA6B in neuronal development, notably in spine formation and maturation and in axon guidance. This study adds SEMA6B to the list of ID-related genes.
Published: 2022
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8. TU-E-213-03: Tools for Ensuring Quality and Safety

Author: Price, M. [Rhode Island Hospital / Warren Alpert Medical School of Brown University (United States)]
Published: 2015
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9. TH-A-12A-01: Medical Physicist's Role in Digital Information Security: Threats, Vulnerabilities and Best Practices

Author: Curran, B [The Warren Alpert Medical School of Brown University, Providence, RI (United States)]
Published: 2014
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10. The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis

Author: Juliana Campos Junqueira, Patrícia Pimentel de Barros, Rodnei Dennis Rossoni, Eleftherios Mylonakis, Valéria de Lima Kaminski, Beth Burgwyn Fuchs, Flávio V. Loures, Maíra Terra Garcia, Universidade Estadual Paulista (UNESP), Federal University of Rio Grande do Norte (UFRN), Universidade de São Paulo (USP), and Warren Alpert Medical School at Brown University
Subjects: 0301 basic medicine, Microbiology (medical), CAPE (caffeic acid phenethyl ester), 030106 microbiology, Immunology, Drug resistance, Microbiology, 03 medical and health sciences, Minimum inhibitory concentration, chemistry.chemical_compound, In vivo, Hemolymph, Candida albicans, oral candidiasis, Caffeic acid phenethyl ester, biology, Propolis, biology.organism_classification, Corpus albicans, QR1-502, 030104 developmental biology, Infectious Diseases, β-defensin 3, chemistry, Galleria mellonella, Biofilms, gene expression
Abstract: Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 μg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (pALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (pin vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of β-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.
Published: 2021

11. The SOFA score—development, utility and challenges of accurate assessment in clinical trials

Author: Bruno François, Mitchell M. Levy, Simon Lambden, Pierre-François Laterre, Francois, Bruno [0000-0002-2531-1652], Apollo - University of Cambridge Repository, Bodescot, Myriam, Department of Medicine [Cambridge, Royaume-Uni], University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK], Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Rhode Island Hospital [Providence, RI, États-Unis], Warren Alpert Medical School of Brown University, Intensive care unit [Limoges], CHU Limoges, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), SL is a NIHR Clinical Lecturer funded through the University of Cambridge., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs
Subjects: medicine.medical_specialty, Surrogate endpoints, Organ Dysfunction Scores, health care facilities, manpower, and services, Psychological intervention, Context (language use), Review, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Severity of Illness Index, Sepsis, 03 medical and health sciences, Sequential Organ Failure Assessment, 0302 clinical medicine, Critical Care trials, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, health services administration, medicine, Humans, SOFA, Clinical Trials, 030212 general & internal medicine, Program Development, Intensive care medicine, Clinical Trials as Topic, Surrogate endpoint, Sequential organ failure assessment, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, Multiple organ failure, 3. Good health, respiratory tract diseases, Clinical trial, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Healthcare settings, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, SOFA score, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients’ SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials.
Published: 2019
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12. Surgical management of pelvic organ prolapse

Author: Matthew D. Barber, J. J. van Iersel, C. Cheong, Robert E. Gutman, Viviane Dietz, Vivian W. Sung, Kevin Cooper, Charles W. Nager, Xavier Deffieux, E. C. J. Consten, Kaven Baessler, Christopher G. Maher, R. de Tayrac, University of Queensland [Brisbane], Franziskus Krankenhaus Berlin, Duke University [Durham], Queen Elizabeth Hospital [Hong Kong] (QEH), Meander Medisch Centrum, Aberdeen Royal Infirmary, Aberdeen, Paris South University Hospitals, AP-HP, Clamart, Catharina Hospital Eindhoven, Georgetown University Medical Center, University of Twente [Netherlands], University of California [San Diego] (UC San Diego), University of California, Warren Alpert Medical School of Brown University, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: medicine.medical_specialty, Decision Making, 030209 endocrinology & metabolism, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Gynecologic Surgical Procedures / statistics & numerical data, Incidence, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, surgery, 03 medical and health sciences, Gynecologic Surgical Procedures, 0302 clinical medicine, Intervention (counseling), Humans, Medicine, Pelvic organ, 030219 obstetrics & reproductive medicine, business.industry, pathway, General surgery, Age Factors, Obstetrics and Gynecology, General Medicine, n/a OA procedure, 3. Good health, Pelvic organ prolapse, Female, business
Abstract: International audience; Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.
Published: 2019
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13. De novo and biallelic DEAF1 variants cause a phenotypic spectrum

Author: Elysa J. Marco, Heather C Mefford, Stacey McGee, Christèle Dubourg, Edmund Cauley, Randi J Hagerman, Maria J. Nabais Sá, Bert B.A. de Vries, Rüdiger Lorenz, Elizabeth E. Palmer, Michael J. Parker, Arjan P.M. de Brouwer, Hester Y. Kroes, M. Chiara Manzini, Abbey A. Scott, Tara Montgomery, Naama Orenstein, Jeanne Amiel, Delphine Héron, Leonie A. Menke, Jonathan Berg, Sylvie Odent, Rachel Harrison, Philip J. Jensik, Rani Sachdev, Miranda Splitt, Tyler Mark Pierson, Jan Maarten Cobben, Ehsan Ghayoor Karimiani, Anneke T. Vulto-vanSilfhout, Roberto Colombo, Nayana Lahiri, Julian A. Martinez-Agosto, Evan P. McNeil, Boris Keren, John M. Graham, Chanika Phornphutkul, Reza Maroofian, Radboud University Medical Center [Nijmegen], Southern Illinois University [Carbondale] (SIU), Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, St George's, University of London, Geisel School of Medicine at Dartmouth, University Medical Center [Utrecht], University of California [Davis] (UC Davis), University of California, Nottingham University Hospitals NHS Trust, Northern Genetics Service, Newcastle University [Newcastle], University of New South Wales [Sydney] (UNSW), Department of Pediatrics [Seattle, WA, USA] (Division of Genetic Medicine), University of Washington [Seattle]-Seattle Children’s Hospital, University of California [Los Angeles] (UCLA), Tel Aviv University [Tel Aviv], University of Dundee, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Amsterdam [Amsterdam] (UvA), Cedars-Sinai Medical Center, The George Washington University (GW), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Warren Alpert Medical School of Brown University, University of California (UC), Nottingham University Hospitals NHS Trust (NUH), Department of Pediatrics [Seattle, WA, USA], Tel Aviv University (TAU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), General Paediatrics, Paediatric Genetics, Amsterdam Reproduction & Development (AR&D), Sheffield Children's Hospital, St George‘s, University of London, University of Washington [Seattle]-Seattle Children’s Hospital [Seattle, WA, USA], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], George Washington University (GW), and AMS - Sports
Subjects: Adult, Male, Microcephaly, Adolescent, phenotype, Developmental Disabilities, genotype, [SDV]Life Sciences [q-bio], Mutation, Missense, Biology, Young Adult, 03 medical and health sciences, Neurodevelopmental disorder, All institutes and research themes of the Radboud University Medical Center, Genotype, medicine, Humans, Exome, Language Development Disorders, Autistic Disorder, Allele, Child, Alleles, Genetic Association Studies, Genetics (clinical), 030304 developmental biology, Genetics, 0303 health sciences, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], 030305 genetics & heredity, medicine.disease, Phenotype, neurodevelopmental disorder, Human genetics, DEAF1, DNA-Binding Proteins, intellectual disability, Child, Preschool, Speech delay, Autism, Female, medicine.symptom, Transcription Factors
Abstract: International audience; Purpose To investigate the effect of different DEAF1 variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and on DEAF1 activity in vitro. Methods We assembled a cohort of 23 patients with de novo and biallelic DEAF1 variants, described the genotype–phenotype correlation, and investigated the differential effect of de novo and recessive variants on transcription assays using DEAF1 and Eif4g3 promoter luciferase constructs. Results The proportion of the most prevalent phenotypic features, including intellectual disability, speech delay, motor delay, autism, sleep disturbances, and a high pain threshold, were not significantly different in patients with biallelic and pathogenic de novo DEAF1 variants. However, microcephaly was exclusively observed in patients with recessive variants (p < 0.0001). Conclusion We propose that different variants in the DEAF1 gene result in a phenotypic spectrum centered around neurodevelopmental delay. While a pathogenic de novo dominant variant would also incapacitate the product of the wild-type allele and result in a dominant-negative effect, a combination of two recessive variants would result in a partial loss of function. Because the clinical picture can be nonspecific, detailed phenotype information, segregation, and functional analysis are fundamental to determine the pathogenicity of novel variants and to improve the care of these patients. © 2019, American College of Medical Genetics and Genomics.
Published: 2019
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14. Obesity and risk of catheter-related infections in the ICU. A post hoc analysis of four large randomized controlled trials

Author: Ambre Loiodice, Jean-Christophe Lucet, Stéphane Ruckly, Jean-François Timsit, Niccolò Buetti, Nicolas Mongardon, Leonard A. Mermel, Olivier Mimoz, Bertrand Souweine, Jean-Jacques Parienti, Université de Paris, IAME, INSERM, Paris, France, Infection Control Programme and WHO Collaborating Centre on Patient Safety, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Rhode Island Hospital [Providence, RI, États-Unis], Warren Alpert Medical School of Brown University, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), département d'anesthésiologie, Foie ICU, AP-HP GH Henri Mondor, Créteil, France, Unité de contrôle infectieux [Bichat Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Pharmacovigilance [Hôpital Charles Nicolle, Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Services de Maladies Infectieuses et Tropicales [CHU Bichat]
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, BMI, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Post-hoc analysis, Medicine, 030212 general & internal medicine, Obesity, education, 2. Zero hunger, education.field_of_study, Catheter-related infections, business.industry, Hazard ratio, 030208 emergency & critical care medicine, Dialysis catheter, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Intensive care unit, Intravascular catheter infections, 3. Good health, Catheter, Catheter-related bloodstream infections, business, Body mass index
Abstract: International audience; Purpose: Obesity increases the risk of nosocomial infection, but data regarding the role of body mass index (BMI) in catheter related infections are scarce. We used the data gathered from four randomized, controlled trials (RCTs) to investigate the association between body mass index (BMI) and intravascular catheter infections in critically ill obese patients.Methods: Adult obese patients who required short-term central venous, arterial or dialysis catheter insertion in the intensive care unit (ICU) were analyzed. The association between BMI and major catheter-related infection (MCRI), catheter-related bloodstream infection (CRBSI) and catheter tip colonization was estimated using univariate and multivariate marginal Cox models. Exploratory analysis using dressing disruptions was added.Results: A total of 2282 obese patients and 4275 catheters from 32 centers were included in this post-hoc analysis. Overall, 66 (1.5%) MCRI, 43 (1%) CRBSI and 399 (9.3%) catheter colonizations were identified. The hazard ratio (HR) for MCRI, CRBSI and colonization increased with BMI. After adjustment for well-known infection risk factors, the BMI ≥ 40 group had an increased risk for MCRI (HR 1.88, 95% CI 1.13-3.12, p = 0.015), CRBSI (HR 2.19, 95% CI 1.19-4.04, p = 0.012) and colonization (HR 1.44, 95% CI 1.12-1.84, p = 0.0038) compared to the BMI < 40 group. The mean dressing disruption per catheter was increased in the BMI ≥ 40 group (2.03 versus 1.68 in the BMI < 40 group, p = 0.05).Conclusions: Using the largest dataset ever collected from large multicentric RCTs, we showed that patients with BMI ≥ 40 had an increased risk for intravascular catheter infections. Targeted prevention measures should focus on this population with a particular attention to catheter care and dressing disruption.
Published: 2021
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15. Characterization of the Activity of Croton tiglium Oil in Hetter's Very Heavy Phenol-Croton Oil Chemical Peels

Author: Hélio Amante Miot, Aline da Silva Justo, Leandro Cavalcante Lipinski, Eduardo Bauml Campagnoli, Carlos Gustavo Wambier, Anna Claudia M. O. Capote, Eduardo C. Meurer, Flávio Luís Beltrame, Kevin A. Antunes, Bruna Nunes, Ogechi Ezemma, Janaina Emiliano, Bruna Mikulis Lemes, Medicine, Dentistry, State University of Ponta Grossa, Federal University of Paraná, Warren Alpert Medical School of Brown University, and Universidade Estadual Paulista (UNESP)
Subjects: Male, Croton Oil, Swine, Croton tiglium, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chemexfoliation, Phenols, In vivo, Phenol, Phorbol esters, Animals, Croton oil, Chromatography, Epidermis (botany), biology, General Medicine, biology.organism_classification, Coagulative necrosis, chemistry, Active agent, 030220 oncology & carcinogenesis, Surgery, Female, Dermatologic Agents
Abstract: Made available in DSpace on 2022-04-29T08:30:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 BACKGROUND: Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE: To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS: Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2 > G3. Vascular ectasia: G2 > G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION: Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis. Departments of Pharmaceutical Sciences Medicine Dentistry Laboratory of Research of SEBISA State University of Ponta Grossa Laboratory Fenn of Massachusetts Spectrometry Federal University of Paraná Department of Dermatology Warren Alpert Medical School of Brown University Department of Dermatology and Radiotherapy Sao Paulo State University (UNESP) Department of Dermatology and Radiotherapy Sao Paulo State University (UNESP)
Published: 2021

16. Trichloroacetic acid peels for the treatment of acanthosis nigricans

Author: Erica Lin, Milvia Maria Simões e Silva Enokihara, Felipe Emanuel de Jesus, Carlos Gustavo Wambier, Renato Luiz Baldissera, Juliano Vilaverde Schmitt, Eric J. Yang, Ediléia Bagatin, Universidade Federal de São Paulo (UNIFESP), Warren Alpert Medical School of Brown University, and Universidade Estadual Paulista (Unesp)
Subjects: medicine.medical_specialty, business.industry, Dermatology, medicine.disease, chemistry.chemical_compound, chemistry, Chemabrasion, Medicine, Humans, Acanthosis Nigricans, Trichloroacetic acid, Trichloroacetic Acid, business, Acanthosis nigricans
Abstract: Made available in DSpace on 2021-06-25T10:56:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Department of Dermatology Universidade Federal de São Paulo Escola Paulista de Medicina (UNIFESP-EPM) São Paulo Department of Dermatology Rhode Island Hospital Warren Alpert Medical School of Brown University Discipline of Dermatology São Paulo State University (UNESP) Medical School Botucatu Discipline of Dermatology São Paulo State University (UNESP) Medical School Botucatu
Published: 2021

17. BMI and pneumonia outcomes in critically ill COVID‐19 patients: an international multicenter study

Author: Charles Cerf, M. Jourdain, Julie Helms, Morgane Snacken, Benjamine Sarton, Mikael Chetboun, Mitchell M. Levy, Erwan L'Her, Violeta Raverdy, Romaric Larcher, Fabienne Tamion, Massimo Antonelli, Dror Dicker, Alain Duhamel, Emilie Occhiali, Stein Silva, Simone Piva, Loay Kontar, Florent Wallet, Markos Kalligeros, Dimitrios Karamanis, Shaul Lev, Victoria Dubar, François Pattou, Ferhat Meziani, Mathilde Neuville, Julien Labreuche, Luca Busetto, Eleftherios Mylonakis, Leonidas Palaiodimos, Antonio Artigas, Juliette Perche, Cyrielle Caussy, Gemma Gomà, Kada Klouche, Nicola Latronico, Antoine Riviere, Raphael Krouchi, Arthur Simonnet, Jean-Charles Preiser, 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 Intégré Nord Francilien de l'Obésité (CINFO), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Corporació Sanitària Parc Taulí, CHU Strasbourg, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Rhode Island Hospital [Providence, RI, États-Unis], Warren Alpert Medical School of Brown University, Università degli Studi di Brescia [Brescia], Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Hôpital Foch [Suresnes], 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), CHU Rouen, Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), CHU Amiens-Picardie, Centre Hospitalier d'Abbeville, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CH de Dunkerque, Albert Einstein College of Medicine [New York], University of Piraeus, CH de Roubaix, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Traitement de l'Information Medicale (LaTIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universita degli Studi di Padova, Rabin Medical Center - Beilinson and Hasharon Hospitals [Petach-Tikva, Israel], Tel Aviv University [Tel Aviv], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università degli Studi di Brescia = University of Brescia (UniBs), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Università degli Studi di Padova = University of Padua (Unipd), and Tel Aviv University (TAU)
Subjects: Male, medicine.medical_specialty, Critical Care, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Critical Illness, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), 030209 endocrinology & metabolism, Logistic regression, COVID-19, Obesity, Prevention, Risk Factors, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, COVID‐19, Internal medicine, Diabetes mellitus, Intensive care, medicine, Humans, 030212 general & internal medicine, Israel, Retrospective Studies, Mechanical ventilation, Nutrition and Dietetics, business.industry, Retrospective cohort study, Pneumonia, Middle Aged, medicine.disease, United States, 3. Good health, Europe, Covid‐19 Call for Papers, Female, business, Body mass index
Abstract: International audience; Objective: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19.Methods: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively.Results: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]).Conclusions: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.
Published: 2021
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18. Irreversible Electroporation in a Swine Lung Model

Author: Ng, Thomas [Warren Alpert Medical School of Brown University, Department of Surgery, Rhode Island Hospital (United States)]
Published: 2011
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19. Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells

Author: Kim, Miran [Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI (United States)]
Published: 2011
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20. Streptococcus mutans Secreted Products Inhibit Candida albicans Induced Oral Candidiasis

Author: Jéssica Diane dos Santos, Dulce Helena Siqueira Silva, Felipe de Camargo Ribeiro, Liliana Scorzoni, Patrícia Pimentel de Barros, Luciana Ruano de Oliveira Fugisaki, Mariana de Sá Alves, Rebeca Previate Medina, Eleftherios Mylonakis, Juliana Campos Junqueira, Beth Burgwyn Fuchs, Universidade Estadual Paulista (Unesp), and Warren Alpert Medical School of Brown University
Subjects: Microbiology (medical), Hypha, lcsh:QR1-502, Microbiology, biofilm, lcsh:Microbiology, Streptococcus mutans, 03 medical and health sciences, Candida albicans, oral candidiasis, 030304 developmental biology, Original Research, 0303 health sciences, biology, 030306 microbiology, Chemistry, Biofilm, biology.organism_classification, Corpus albicans, Galleria mellonella, filamentation, Quorum sensing, Bacteria
Abstract: Made available in DSpace on 2020-12-12T02:17:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-15 In the oral cavity, Candida species form mixed biofilms with Streptococcus mutans, a pathogenic bacterium that can secrete quorum sensing molecules with antifungal activity. In this study, we extracted and fractioned culture filtrate of S. mutans, seeking antifungal agents capable of inhibiting the biofilms, filamentation, and candidiasis by Candida albicans. Active S. mutans UA159 supernatant filtrate components were extracted via liquid-liquid partition and fractionated on a C-18 silica column to resolve S. mutans fraction 1 (SM-F1) and fraction 2 (SM-F2). We found anti-biofilm activity for both SM-F1 and SM-F2 in a dose dependent manner and fungal growth was reduced by 2.59 and 5.98 log for SM-F1 and SM-F2, respectively. The SM-F1 and SM-F2 fractions were also capable of reducing C. albicans filamentation, however statistically significant differences were only observed for the SM-F2 (p = 0.004). SM-F2 efficacy to inhibit C. albicans was confirmed by its capacity to downregulate filamentation genes CPH1, EFG1, HWP1, and UME6. Using Galleria mellonella as an invertebrate infection model, therapeutic treatment with SM-F2 prolonged larvae survival. Examination of the antifungal capacity was extended to a murine model of oral candidiasis that exhibited a reduction in C. albicans colonization (CFU/mL) in the oral cavity when treated with SM-F1 (2.46 log) and SM-F2 (2.34 log) compared to the control (3.25 log). Although both SM-F1 and SM-F2 fractions decreased candidiasis in mice, only SM-F2 exhibited significant quantitative differences compared to the non-treated group for macroscopic lesions, hyphae invasion, tissue lesions, and inflammatory infiltrate. Taken together, these results indicate that the SM-F2 fraction contains antifungal components, providing a promising resource in the discovery of new inhibitors for oral candidiasis. Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) Division of Infectious Diseases Rhode Island Hospital Warren Alpert Medical School of Brown University Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)
Published: 2020
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21. Drum training induces long-term plasticity in the cerebellum and connected cortical thickness

Author: Muriel M K Bruchhage, Flavio Dell'Acqua, Ali Amad, Pedro Luque Laguna, Andrew Robertson, Luis Miguel Lacerda, Jade Seidman, Marcus S. Smith, James Wheeler, Ruth G. Lowry, Stephen B. Draper, Steven Williams, King‘s College London, Rhode Island Hospital [Providence, RI, États-Unis], Warren Alpert Medical School of Brown University, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hartpury University [Hartpury, Royaume-Uni], University College of London [London] (UCL), University of Essex, University of Chichester [Chichester, Royaume-Uni], Queen Mary University of London (QMUL), The authors would like to thank The Waterloo Foundation for their financial support, guidance and enthusiasm during the course of this project. We also would like to express our deepest gratitude to the NIHR Biomedical Research Centre for Mental Health at the South London and the Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London for their on-going support of our translational imaging research programme. M. B. has received funding from the European Community’s Seventh Framework (FP7/2007–2013) TACTICS. A. A held a postdoctoral fellowship from the 'Fondation Thérèse et René Planiol'. A.R. was funded by a Royal academy of Engineering/EPSRC Fellowship. F. d. A. received funding from Wellcome Trust., European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), Lille Neurosciences & Cognition - U 1172 (LilNCog), Bodescot, Myriam, and Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes - TACTICS - - EC:FP7:HEALTH2012-01-01 - 2016-12-31 - 278948 - VALID
Subjects: Male, 0301 basic medicine, Cerebellum, Inferior cerebellar peduncle, Adolescent, Motor training, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:Medicine, Motor Activity, Plasticity, Biology, Article, Long term plasticity, Cerebellar Cortex, Young Adult, 03 medical and health sciences, Sensorimotor processing, 0302 clinical medicine, Parietal Lobe, Image Processing, Computer-Assisted, medicine, Humans, lcsh:Science, Music Therapy, Brain Mapping, Neuronal Plasticity, Multidisciplinary, lcsh:R, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain, Anatomy, QP, Magnetic Resonance Imaging, White Matter, White matter microstructure, 030104 developmental biology, medicine.anatomical_structure, nervous system, MT, Female, lcsh:Q, Left superior, Right precuneus, 030217 neurology & neurosurgery, Neuroscience
Abstract: It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as well as cortical thickness of 15 healthy non-musicians before and after learning to drum, and 16 age matched novice control participants. After 8 weeks of group drumming instruction, 3 ×30 minutes per week, we observed the cerebellum significantly changing its grey (volume increase of left VIIIa, relative decrease of VIIIb and vermis Crus I volume) and white matter microstructure in the inferior cerebellar peduncle. These plastic cerebellar changes were complemented by changes in cortical thickness (increase in left paracentral, right precuneus and right but not left superior frontal thickness), suggesting an interplay of cerebellar learning with cortical structures enabled through cerebellar pathways.
Published: 2020
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22. Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel

Author: Siew C. Ng, Herbert Tilg, Harry Sokol, Colleen R. Kelly, Faming Zhang, Giovanni Cammarota, Antonio Gasbarrini, Gianluca Ianiro, Samuel P Costello, Benjamin H. Mullish, Monika Fischer, Luca Masucci, Jessica R. Allegretti, Zain Kassam, Josbert J. Keller, Maurizio Sanguinetti, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Imperial College London, Warren Alpert Medical School of Brown University, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Group of Faecal microbiota Transplantation [Paris] (FGFT), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Finch Therapeutics Group, The Chinese University of Hong Kong [Hong Kong], Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Harvard Medical School [Boston] (HMS), Nanjing Medical University, Haaglanden Medical Center [La Haye, Pays-Bas] (HMC), Leiden University Medical Center (LUMC), University of Adelaide, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Bodescot, Myriam, Università cattolica del Sacro Cuore [Roma] (Unicatt), and Innsbruck Medical University [Austria] (IMU)
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Settore MED/12 - GASTROENTEROLOGIA, Pneumonia, Viral, MEDLINE, Transplant Donors, Betacoronavirus, Feces, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Living Donors, medicine, Humans, Mass Screening, Intensive care medicine, Pandemics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Hepatology, SARS-CoV-2, business.industry, Viral Epidemiology, Settore MED/09 - MEDICINA INTERNA, Gastroenterology, COVID-19, Outbreak, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fecal Microbiota Transplantation, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Pneumonia, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Coronavirus Infections, business
Abstract: International audience
Published: 2020
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23. Pseudomonas Causing Catheter Infection in the Groin Area

Author: Parienti, Jean-Jacques, Join-Lambert, Olivier, Mermel, Leonard, Unité de Biostatistique et de Recherche Clinique (UBRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Service de Microbiologie [CHU Caen], and Warren Alpert Medical School of Brown University
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience
Published: 2020
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24. MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent

Author: Chung, Maureen [Department of Surgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 2 Dudley Street, MOC 470, Providence, RI 02905 (United States)]
Published: 2008

25. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock

Author: Laterre, Pierre-François, Berry, Scott, Blemings, Allan, Carlsen, Jan, Francois, Bruno, Graves, Todd, Jacobsen, Karsten, Lewis, Roger, Opal, Steven, Perner, Anders, Pickkers, Peter, Russell, James, Windeløv, Nis, Yealy, Donald, Asfar, Pierre, Bestle, Morten, Muller, Grégoire, Bruel, Cédric, Brule, Noëlle, Decruyenaere, Johan, Dive, Alain-Michel, Dugernier, Thierry, Krell, Kenneth, Lefrant, Jean-Yves, Mégarbane, Bruno, Mercier, Emmanuelle, Mira, Jean-Paul, Quenot, Jean-Pierre, Rasmussen, Bodil Steen, Thorsen-Meyer, Hans-Christian, Vander Laenen, Margot, Vang, Marianne Lauridsen, Vignon, Philippe, Vinatier, Isabelle, Wichmann, Sine, Wittebole, Xavier, Kjolbye, Anne Louise, Angus, Derek, Cliniques universitaires St Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Ferring Pharmaceuticals A/S, Centre d'Investigation Clinique de Limoges (CIC1435), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Los Angeles Biomedical Research Institute (LA BioMed), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Warren Alpert Medical School of Brown University, Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], University of British Columbia (UBC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Ghent University Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Cochin [AP-HP], Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ziekenhuis Oost-Limburg (ZOL), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, University of Pittsburgh (PITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Importance: Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects.Objective: To test whether selepressin improves outcome in septic shock.Design, setting, and participants: An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 μg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018.Interventions: Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters.Main outcomes and measures: Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days.Results: Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, -1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, -6.5% to 8.8%]; P = .77; kidney replacement therapy-free days: 18.5 vs 18.2; difference, 0.3 [95% CI, -2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, -1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%).Conclusions and relevance: Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock.Trial registration: ClinicalTrials.gov Identifier: NCT02508649.
Published: 2019
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26. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Author: Douglas Cunningham, D. Ward, Mamta K. Jain, Faiza Ajana, Magda Opsomer, Anita Rachlis, Sharon Walmsley, Frank A. Post, Anders Blaxhult, Amanda Clarke, M. J. Galindo, Marcel Stoeckle, P.-M. Girardy, Karam Mounzer, David Shamblaw, U. F. Bredeek, L. Bhatti, J. J. Eron, Andrew Ustianowski, Mar Gutierrez, John Jezorwski, Javier O Morales-Ramirez, Antonio Rivero, M.A. Johnson, Gatell Jm, Erika Van Landuyt, Stéphane De Wit, A. Wilkin, Laurent Cotte, Cheryl McDonald, D. Murphy, Cynthia Brinson, Romana Petrovic, Olayemi Osiyemi, J. de Vente, I. Poizot-Martin, Juan Berenguer, Robin Dretler, J. Bailey, B. Rashbaum, Moti Ramgopal, A. Scribner, Yazdan Yazdanpanah, Eric Florence, A. Piekarska, Brian Gazzard, Chloe Orkin, W. Halota, Gary Richmond, Jacques Reynes, C. Ricart, C. Lucasti, Ignacio Pérez-Valero, Jason Brunetta, S. Shafran, Daniel Podzamczer, Franco Antonio Felizarta, Claudia Martorell, F. Post, Peter Ruane, Edwin DeJesus, J. Portilla Sogorb, C. Orkin, K. Tashima, Federico Pulido, Bernard Vandercam, F. Pulido, José L. Casado, Christine Katlama, Kimberley Brown, J Gasiorowski, A. Witor, Joseph J. Eron, Brian Conway, Andri Rauch, Jose R. Arribas, Michel Moutschen, H. Olivet, A. Scarsella, Leo Flamholc, A. Horban, D. Cunningham, Ronald Nahass, Félix Gutiérrez, G. Huhn, W.K. Henry, A. Thalme, S De Wit, Jan Fehr, Debbie Hagins, José Antonio Iribarren, J.-M. Molina, S. Henn, F Raffi, Juan A. Pineda, Marina B. Klein, Eugenia Negredo, Hernando Knobel, J. Slim, P. Benson, L. Waters, E. Teicher, Linos Vandekerckhove, Craig A. Dietz, Magnus Gisslén, Joel E. Gallant, J. Gathe, P. Shalit, D. Prelutsky, G. Voskuhl, D. Rey, E. Van Wijngaerden, Anthony Mills, Erkki Lathouwers, Carl J. Fichtenbaum, I. Brar, Gordon Crofoot, Veerle Hufkens, I. Santos Gil, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Queen Mary University of London (QMUL), Pueblo Family Physicians, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), King's College Hospital (KCH), Université libre de Bruxelles (ULB), Janssen Pharmaceutica [Beerse], Janssen Research & Development, Institute of Tropical Medicine [Antwerp] (ITM), Department of Infectious and Parasitic Diseases (University Liege), Université de Liège, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Living Hope Foundation, Ghent University Hospital, Cliniques Universitaires Saint-Luc [Bruxelles], Maple Leaf Clinic, Vancouver Infectious Diseases Centre, McGill University = Université McGill [Montréal, Canada], University of Toronto, Sunnybrook Health Sciences Centre, University of Alberta, University Health Network, Services des maladies infectieuses [Tourcoing], Centre Hospitalier de Tourcoing, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Wrocław [Poland] (UWr), Faculty of Medicine [Bydgoszcz, Poland], Nicolaus Copernicus University [Toruń], Medical University of Warsaw - Poland, Medical University of Łódź (MUL), Regional Hospital [Chorzow, Poland], La Paz Hospital, IdiPAZ, Hospital General Universitario 'Gregorio Marañón' [Madrid], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Infectious Diseases Service, AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain., Hospital Universitario de Elche, Hospital Universitario de Valencia, Hospital de la Santa Creu i Sant Pau, Donostia Hospital Universitario San Sebastian, IMIM-Hospital del Mar, Generalitat de Catalunya, LLuita contra la Sida Fdn-HIV Unit, Germans Trias i Pujol University Hospital- Universitat Autònoma de Barcelona, Hospital Universitario de Valme, Hospital Universitari de Bellvitge, Universitat de València (UV), Hospital Universitario Reina Sofía, Hospital La Princesa, Madrid, Karolinska Institutet, Södersjukhuset, Skane University Hospital [Malmo], Lund University [Lund], University of Gothenburg (GU), Karolinska University Hospital [Stockholm], University hospital of Zurich [Zurich], Bern University Hospital [Berne] (Inselspital), University Hospital Basel [Basel], Royal Sussex County Hospital, Chelsea and Westminster Hospital, North Manchester General Hospital, University College of London [London] (UCL), Johns Hopkins University School of Medicine [Baltimore], Be Well, AIDS healthcare foundation [California], Henry Ford Hospital, Metropolis Medical, Central Texas Clinical Research, The Crofoot Research Center, Orlando Immunology Center, Kansas City Free Health Clinic, University of Cincinnati (UC), University of Minnesota System, University of Texas Southwestern Medical Center, South Jersey Infectious Disease, Infectious Disease, Tarrant County Infectious Disease Associates, Southern California Men’s Medical Group, Clinical Research Puerto Rico Inc, Philadelphia FIGHT, ID care, Community Research Initiative of New England, Triple O Research Institute PA, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Midway Immunology Center, Capital Medical Associates, Broward General Medical Center, Ruane Clinical Research Group, Pacific Oaks Medical Group, DCOL Center for Clinical Research, Peter Shalit MD and Associates, La Playa Medical Group, Seton Hall University, Warren Alpert Medical School of Brown University, AIDS Arms, Inc, Dupont Circle Physicians Group, Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hospital Universitario Donostia [San Sebastian, Spain] (HUD), Universitat Autònoma de Barcelona (UAB), Hospital Universitario de La Princesa, HAL AMU, Administrateur, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service de médecine interne générale
Subjects: Male, DOLUTEGRAVIR, Sustained Virologic Response, HIV Infections, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Medicine and Health Sciences, Emtricitabine, 030212 general & internal medicine, Pharmacology & Pharmacy, Darunavir, 0303 health sciences, Alanine, Drug Substitution, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Lamivudine, Antiretrovirals, Middle Aged, Viral Load, OPEN-LABEL, 3. Good health, WEIGHT-GAIN, Drug Combinations, Treatment Outcome, Dolutegravir, NON-INFERIORITY, Female, Safety, Viral load, Life Sciences & Biomedicine, medicine.drug, Tablets, Adult, medicine.medical_specialty, Efficacy, Anti-HIV Agents, RITONAVIR, TENOFOVIR ALAFENAMIDE, LAMIVUDINE, Tenofovir alafenamide, Single-tablet regimen, 03 medical and health sciences, Internal medicine, Virology, medicine, VIH (Virus), Humans, Switch study, Protease Inhibitors, Tenofovir, Aged, Pharmacology, Science & Technology, 030306 microbiology, business.industry, HIV (Viruses), Adenine, Darunavir/cobicistat/emtricitabine/TAF, Antiretroviral agents, COBICISTAT, MAINTENANCE, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, Ritonavir, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, RESISTANCE
Abstract: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL
Published: 2019
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27. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives

Author: Andrea Olschewski, Ralph T. Schermuly, Peter Dorfmüller, Mark R. Nicolls, Christophe Guignabert, Marlene Rabinovitch, Marc Humbert, Kurt R. Stenmark, Soni Savai Pullamsetti, James R. Klinger, Sébastien Bonnet, Service de Pneumologie et Réanimation Respiratoire [AP-HP Hôpital Bicêtre] (DHU TORINO), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Centre de Référence de l'Hypertension Pulmonaire Sévère, Université Paris-Sud [Le Kremlin-Bicêtre] (Faculté de Médecine), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), Faculté de médecine de l'Université Laval [Québec] (ULaval), Service de pathologie [Hôptital Marie Lannelongue], Hôpital Marie Lannelongue, Warren Alpert Medical School of Brown University, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Wall Center for Pulmonary Vascular Disease [Stanford, CA, USA], Ludwig Boltzmann Institute for Lung Vascular Research [Graz], Medical University Graz, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Justus-Liebig-Universität Gießen (JLU), German Center for Lung Research, Cardio Vascular Pulmonary Research Lab [Denver, CO, USA], University of Colorado [Denver], Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Marie-Lannelongue, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Guignabert, Christophe, and Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Hypertension, Pulmonary, [SDV]Life Sciences [q-bio], Translational research, Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Vascular remodelling in the embryo, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Pulmonary pathology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Series, Antihypertensive Agents, business.industry, Pulmonary vessels, medicine.disease, Pulmonary hypertension, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], 030104 developmental biology, Drug development, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Vascular pathology, World Symposium on Pulmonary Hypertension, business
Abstract: Clinical and translational research has played a major role in advancing our understanding of pulmonary hypertension (PH), including pulmonary arterial hypertension and other forms of PH with severe vascular remodelling (e.g. chronic thromboembolic PH and pulmonary veno-occlusive disease). However, PH remains an incurable condition with a high mortality rate, underscoring the need for a better transfer of novel scientific knowledge into healthcare interventions. Herein, we review recent findings in pathology (with the questioning of the strict morphological categorisation of various forms of PH into pre- or post-capillary involvement of pulmonary vessels) and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of PH. We also discuss ways to improve management and to support and optimise drug development in this research field., State of the art and research perspectives in the cellular and molecular basis and pathology of pulmonary vascular remodelling associated with various forms of pulmonary hypertension http://ow.ly/cjwp30mgzmH
Published: 2019
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28. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Author: Max Nieuwdorp, Colleen R. Kelly, Gianluca Ianiro, Luca Masucci, Dina Kao, E.M. Terveer, Patrizia Kump, Maria J G T Vehreschild, Ailsa Hart, Antonio Gasbarrini, Franco Scaldaferri, Antonio López-Sanromán, Benjamin H. Mullish, Reetta Satokari, Juozas Kupcinskas, Zain Kassam, Josbert J. Keller, Stacy A. Kahn, Lorenza Putignani, Giovanni Cammarota, Perttu Arkkila, Jessica R. Allegretti, Herbert Tilg, Loris Riccardo Lopetuso, Ed J. Kuijper, Monika Fischer, Samuel P Costello, Harry Sokol, Cristina Pintus, Experimental Vascular Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Internal Medicine and Gastroenterology, Day Hospital of Gastroenterology and Intestinal Microbiota Transplantation, Fondazione Policlinico A Gemelli IRCCS, Catholic University of Medicine-Catholic University of Medicine, Warren Alpert Medical School of Brown University, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London-Imperial College London, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School [Boston] (HMS)-Harvard Medical School [Boston] (HMS), Microbiome Informatics, Massachusetts Institute of Technology (MIT), OpenBiome, Parasitology Unit and Human Microbiome Unit, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Medicine, Indiana State University, Department of Gastroenterologyand Hepatology, Haaglanden Medical Center, National Donor Feces Bank, Department of Gastroenterology, The Queen Elizabeth Hospital, University of South Australia [Adelaide]-University of South Australia [Adelaide], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Group of Fecal Microbiota Transplantation, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens-Universität [Graz, Autriche]-Karl-Franzens-Universität [Graz, Autriche], Human Microbiome Research Program, University of Helsinki-University of Helsinki, Hepatology and Nutrition, Boston Children's Hospital-Boston Children's Hospital, University of Alberta-University of Alberta, Department of Clinic of Gastroenterology, University of Helsinki, Department of Medical Microbiology, LeidenUniversity Medical Centre, Department I of Internal Medicine, German Centre for Infection Research, University Hospital of Cologne [Cologne]-University Hospital of Cologne [Cologne], Tissues and Cells Area, Italian National Transplant Center, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Microbiology, VU University Medical Center [Amsterdam], Gastroenterology and Hepatology Department, Hospital Universitario Ramon y Cajal, Partenaires INRAE-Partenaires INRAE, Institute for Digestive Research, Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences-Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences, St Mark's Hospital, Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Innsbruck Medical University [Austria] (IMU), Catholic University of Rome, Line D-1, Service de Gastroenterologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, University of Graz-University of Graz, Reetta Maria Satokari / Principal Investigator, HUMI - Human Microbiome Research, HUS Abdominal Center, University Management, Gastroenterologian yksikkö, Clinicum, and Internal medicine
Subjects: 0301 basic medicine, Delphi method, Donor Feces, Frozen, 0302 clinical medicine, stool bank, Medicine, Gastroenterology, Consensus conference, fecal microbiota transplantation, Metaanalysis, 3. Good health, Clinical Practice, Editorial, 030211 gastroenterology & hepatology, Medical emergency, Recurrent, guideline, Consensus, Efficacy, Settore MED/12 - GASTROENTEROLOGIA, Faecal microbiota transplantation, Donor Selection, Specimen Handling, 03 medical and health sciences, microbiota, Humans, Organ donation, Active Ulcerative-colitis, Gastroenterology & Hepatology, business.industry, 1103 Clinical Sciences, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Guideline, Clostridium difficile, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Workflow, 3121 General medicine, internal medicine and other clinical medicine, Intestinal Microbiota, Insulin Sensitivity, Organ Donation, clostridioides difficile, Clostridium Infections, Fecal Microbiota Transplantation, 1114 Paediatrics and Reproductive Medicine, business, Clostridium-difficile Infection, Clostridioides
Abstract: Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.
Published: 2019
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29. Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells

Author: Charlène, Niogret, S M Shahjahan, Miah, Giorgia, Rota, Nicolas P, Fonta, Haiping, Wang, Werner, Held, Walter, Birchmeier, Veronica, Sexl, Wentian, Yang, Eric, Vivier, Ping-Chih, Ho, Laurent, Brossay, Greta, Guarda, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Microbiology and Immunology, Brown University, Université de Lausanne = University of Lausanne (UNIL), Warren Alpert Medical School of Brown University, Institute for Research in Biomedicine [Ticino, Switzerland], Università della Svizzera italiana = University of Italian Switzerland (USI), Max Delbrueck Center for Molecular Medicine, Helmholtz-Gemeinschaft = Helmholtz Association, Veterinärmedizinische Universität Wien, Hôpital de la Timone [CHU - APHM] (TIMONE), Innate Pharma Research Labs [Marseille], and Innate Pharma
Subjects: Muromegalovirus, Cancer Research, animal structures, Science, Cell Count, Protein Tyrosine Phosphatase, Non-Receptor Type 11, chemical and pharmacologic phenomena, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, Animals, Antigens, Ly, Extracellular Signal-Regulated MAP Kinases, lcsh:Science, Cell Proliferation, Cell Size, Interleukin-15, Mice, Knockout, Integrases, Natural Cytotoxicity Triggering Receptor 1, Receptors, Interleukin-15, Antigens, Ly/metabolism, Cell Proliferation/drug effects, Cell Size/drug effects, Enzyme Activation/drug effects, Extracellular Signal-Regulated MAP Kinases/metabolism, Integrases/metabolism, Interleukin-15/pharmacology, Killer Cells, Natural/drug effects, Killer Cells, Natural/metabolism, Mice, Inbred C57BL, Muromegalovirus/physiology, Natural Cytotoxicity Triggering Receptor 1/metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 11/deficiency, Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism, Receptors, Interleukin-15/metabolism, TOR Serine-Threonine Kinases/metabolism, TOR Serine-Threonine Kinases, hemic and immune systems, Enzyme Activation, Killer Cells, Natural, embryonic structures, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, biological phenomena, cell phenomena, and immunity
Abstract: The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells have reduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically, Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respiration rates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK and mTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together, our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signaling with downstream metabolic burst and NK cell expansion., The phosphatase Shp-2 was implicated in NK cell education due to its reported association with inhibitory receptors, but its function in this context is unclear. Here the authors show that Shp-2 is not required for NK cell function, but is necessary for IL-15-induced metabolic burst and expansion.
Published: 2019
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30. A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill

Author: Olivier Mimoz, Thiago Lisboa, Vineet Chopra, Jean-Jacques Parienti, Jean-François Timsit, Emilio Bouza, Kevin B. Laupland, Walter Zingg, Tarja J. Karpanen, Garyphalia Poulakou, Mark E. Rupp, Leonard A. Mermel, Bertrand Souweine, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), University of Nebraska Medical Center, University of Nebraska System, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital General Universitario 'Gregorio Marañón' [Madrid], University of Michigan [Ann Arbor], University of Michigan System, Queens Elizabeth Hospital [Birmingham], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital de Clínicas de Porto Alegre (HCPA), Warren Alpert Medical School of Brown University, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Unité de Biostatistique et de Recherche Clinique (UBRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université d'Athènes (UOA), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Hôpitaux Universitaires de Genève (HUG), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Microbiology and Infectious Diseases Department, Universidad Complutense de Madrid [Madrid] (UCM), Service d'anesthésie réanimation [Poitiers], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Catheterization, Central Venous, Critical Illness, Intravascular catheter, Critical Care and Intensive Care Medicine, Critical Care Nursing, 03 medical and health sciences, 0302 clinical medicine, Catheters, Indwelling, Multidisciplinary approach, Risk Factors, Anesthesiology, Sepsis, Catheterization, Peripheral, Medicine, Central Venous Catheters, Humans, 030212 general & internal medicine, Intensive care medicine, Pulmonary emboli, Critically ill, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, ddc:616, business.industry, 030208 emergency & critical care medicine, Thrombosis, State of the art review, Process of care, Middle Aged, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Practice Guidelines as Topic, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, business
Abstract: Intravascular catheters are inserted into almost all critically ill patients. This review provides up-to-date insight into available knowledge on epidemiology and diagnosis of complications of central vein and arterial catheters in ICU. It discusses the optimal therapy of catheter-related infections and thrombosis. Prevention of complications is a multidisciplinary task that combines both improvement of the process of care and introduction of new technologies. We emphasize the main component of the prevention strategies that should be used in critical care and propose areas of future investigation in this field.
Published: 2018
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31. Determining the analytical specificity of PCR-based assays for the diagnosis of IA: What is Aspergillus?

Author: Massimo Cogliati, Yvette J. Debets-Ossenkopp, Juergen Loeffler, Birgit Willinger, Petr Hamal, Catriona Halliday, Angela M. Caliendo, Rosemary Ann Barnes, Martina Lengerová, C. Orla Morrissey, Melinda Paholcsek, Katia Jaton, Katrien Lagrou, Willem J. G. Melchers, Lena Klingspor, Kathleen Harvey-Wood, Laurence Millon, Gemma Johnson, Cornelia Lass-Flörl, Carlo Mengoli, Stéphane Bretagne, Sarah E. Kidd, J. Peter Donnelly, Markus Ruhnke, Alida Fe Talento, Rebecca Gorton, Christopher J. Linton, P. Lewis White, Ferry Hagen, Manuel Cuenca-Estrella, C. Oliver Morton, Western Sydney University, Public Health Wales Microbiology Cardiff, School of Medicine [Cardiff], Institute of Medical Genetics [Cardiff]-Cardiff University, Karolinska University Hospital [Stockholm], Instituto de Salud Carlos III [Madrid] (ISC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Radboud University Medical Center [Nijmegen], Regional Reference Centre of Infectious Diseases,Microbiology and Virology Unit,University of Padova, Warren Alpert Medical School of Brown University, Università degli Studi di Milano [Milano] (UNIMI), Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Royal Free Hospital, London, Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Clinical Mycology Reference Laboratory, Pathology West, Westmead, Australia, Palacky University Olomouc, Southern General Hospital, Glasgow, University of Lausanne and University Hospital Centre, School of Biological and Chemical Sciences, Queen Mary University of London, National Mycology Reference Centre, SA Pathology, Adelaide, University Hospital Brno, Innsbruck Medical University [Austria] (IMU), Public Health England [London], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Alfred Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, Trinity College Dublin, Abt. Onkologie und Hämatologie, Med. Klinik u. Poliklinik II, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medizinische Universität Wien = Medical University of Vienna, and University of Würzburg = Universität Würzburg
Subjects: 0301 basic medicine, 030106 microbiology, Klinikai orvostudományok, Aspergillosis, medicine.disease_cause, Polymerase Chain Reaction, Sensitivity and Specificity, Cross-reactivity, Microbiology, law.invention, Aspergillus PCR, 03 medical and health sciences, law, Biopsy, medicine, Humans, Gene, Polymerase chain reaction, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Invasive Pulmonary Aspergillosis, Aspergillus, biology, medicine.diagnostic_test, Orvostudományok, General Medicine, Assay sensitivity, Ribosomal RNA, biology.organism_classification, medicine.disease, analytical specificity, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Infectious Diseases, Molecular Diagnostic Techniques, cross reactivity, detection range, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract: Contains fulltext : 175113.pdf (Publisher’s version ) (Closed access) A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive samples (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P < .0001) than assays specific for individual Aspergillus species (47.2%). For genus specific assays the most often missed species were A. lentulus (25.0%), A. versicolor (24.1%), A. terreus (16.1%), A. flavus (15.2%), A. niger (13.4%), and A. fumigatus (6.2%). There was a significant positive association between accuracy and using an Aspergillus genus PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential.
Published: 2017
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32. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Author: Robert J. Wilkinson, James E. Bower, Liliana K. Rutaihwa, W. Henry Boom, Matthias Egger, Philip Noel Suffys, Elisabeth Sanchez-Padilla, Linda Gail-Bekker, Sebastien Gagneux, Issam Alani, Marie Ballif, Kathleen D. Eisenach, Jennifer L. Guthrie, Ana Gil-Brusola, Eddie M. Wampande, Willy Ssengooba, Nyanda E. Ntinginya, Rita Macedo, Petras Stakenas, Bijaya Malla, Adwoa Asante-Poku, Stefan Niemann, Lynsey Stewart-Isherwood, Mireia Coscolla, Perpetual Wangui Ndung'u, Florian Gehre, Daniela Maria Cirillo, E. Jane Carter, Sidra Ezidio Gonçalves Vasconcellos, Moses Joloba, Midori Kato-Maeda, Indira Basu, Andrea Rachow, Bouke C. de Jong, Serej D. Ley, Andrej Trauner, Hans-Peter Beck, Jackson Thomas, Dorothy Yeboah-Manu, Qingyun Liu, Tao Luo, Francesca Barletta, Véronique Penlap Beng, Janet A. M. Fyfe, Anastasia Koch, Margarida Saraiva, Sven Hoffner, Daniela Brites, Sahal Al-Hajoj, Griselda Tudo Vilanova, Maria Globan, Qian Gao, Helmi Mardassi, Maryline Bonnet, Philip Supply, Iñaki Comas, Valeriu Crudu, Girts Skenders, Francine Ntoumi, Frances B. Jamieson, Olga Domnica Moldovan, Leïla Jeljeli, Gunturu Revathi, Milagros Moreno, Suriya Akter, Sonia Borrell, Kadri Toit, Matthias Frank, Michael Hoelscher, Lameck Diero, Daiva Bakonyte, David Stucki, Lukas Fenner, Larissa Otero, Roland Diel, University of Basel (Unibas), Swiss Tropical Institute, Swiss Tropical and Public Health Institute [Basel], Forschungszentrum Borstel - Research Center Borstel, German Center for Infection Research, Borstel Site, Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Fudan University, Laboratory of Infection and Immunity, School of Basic Medical Science, West China Center of Medical Sciences, Sichuan University [Chengdu] (SCU), University of California at San Francisco, University of California [San Francisco] (UCSF), University of California-University of California, School of Medicine, Laboratorio Nacional de Saude Publica, Hospital Nossa Senhora da Paz, Servei de Microbiologia, Hospital Clínic–ISGlobal, Barcelona, Victorian Infectious Diseases Reference Laboratory, Public Health Ontario - Santé publique Ontario, Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana, Makerere University College of Health Sciences, Department of Global Health, University of Amsterdam [Amsterdam] (UvA), Department of Molecular Biology and Microbiology, Case Western Reserve University [Cleveland], Lab Plus, Auckland City Hospital, ICVS/3B's—PT Government Associate Laboratory, Braga, Molecular Biology Applied to Mycobacteria / Biologia Molecular Aplicada a Micobactérias [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute of Infectious Disease and Molecular Medicine, and Department of Clinical Laboratory Sciences, University of Cape Town, Department of Medicine, Imperial College London, Francis Crick Institute Mill Hill Laboratory, London, Papua New Guinea Institute of Medical Research (PNG-IMR), Institute of Tropical Medicine [Antwerp] (ITM), Tartu University Hospital United Laboratories, Mycobacteriology, Epicentre [Paris] [Médecins Sans Frontières], Institute of Tropical Medicine and Infectious Diseases (ITROMID), Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Department of Microbiology, University Hospital La Fe, Valencia, University of Tübingen [Germany], Fondation Congolaise pour la Recherche Médicale, Université Marien Gouabi, Brazzaville, University of Yaoundé [Cameroun], University of Arkansas for Medical Sciences (UAMS), Department of Medical Laboratory Technology, Faculty of Medical Technology, Baghdad, Department of Pathology, Aga Khan University Hospital (AKUH), Nairobi, Medical Research Council, Fajara, Right to Care and the Clinical HIV Research Unit, University of the Witwatersrand [Johannesburg] (WITS), Division of Infectious Diseases and Tropical Medicine = Abteilung für infektions und tropenmedizin [Munich, Germany], Klinikum der Universität [München]-Ludwig-Maximilians-Universität München (LMU), National Institute of Medical Research, Mbeya Medical Research Centre (NIMR-MMRC), Mbeya, Emerging Bacterial Pathogen Unit, San Raffaele Scientific Institute, WHO Supranational TB Reference Laboratory, Department of Microbiology, Public Health Agency of Sweden, Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University [Vilnius], Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Marius Nasta Institute of Pneumology, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit–Tuberculosis, Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH)-Universidad Peruana Cayetano Heredia (UPCH), Warren Alpert Medical School of Brown University, Moi University School of Medicine, Eldoret, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiology and Public Health, Madrid, [et. al.], Universidade do Minho, Wellcome Trust, Universität Bern [Bern] (UNIBE), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Victorian Infectious Diseases Reference Laboratory [Melbourne, Australia] (VIDRL), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Ludwig-Maximilians-Universität München (LMU)-Klinikum der Universität [München], King Faisal Specialist Hospital and Research Centre (KFSH & RC), 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 National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Infecções Respiratórias, [SDV]Life Sciences [q-bio], Generalist and specialist species, Global Health, ANTIGENIC VARIATION, Polymorphism, Genetic/genetics, POPULATION, ComputingMilieux_MISCELLANEOUS, Genetics & Heredity, education.field_of_study, RESISTANT TUBERCULOSIS, Human migration, Ecology, 11 Medical And Health Sciences, Genomics, SOUTH-AFRICA, 3. Good health, Mycobacterium tuberculosis/classification/genetics/isolation & purification, Phylogeography, GENETIC DIVERSITY, Life Sciences & Biomedicine, DNA, Bacterial, Lineage (genetic), Genotype, Niche, Population, Tuberculosis/genetics/microbiology, Biology, Article, Host Specificity, 03 medical and health sciences, HIV-INFECTION, Genetics, Humans, Tuberculosis, DNA, Bacterial/analysis, education, Ecological niche, PATHOGENS, Science & Technology, Polymorphism, Genetic, Obligate, business.industry, Mycobacterium tuberculosis, 06 Biological Sciences, biology.organism_classification, PAPUA-NEW-GUINEA, EVOLUTION, Genomics/methods, 030104 developmental biology, Evolutionary biology, business, GENOMIC DIVERSITY, purl.org/pe-repo/ocde/ford#1.06.07 [https], Developmental Biology, Mycobacterium
Abstract: Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration., We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.).
Published: 2016
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33. Mutations in the GIGYF2 (TNRC15) Gene at the PARK11 Locus in Familial Parkinson Disease

Author: Corinne Lautier, Alexandra Durr, William G. Tsiaras, Gianni Pezzoli, Robert J. Smith, Alexis Brice, Stefano Goldwurm, Barbara Giovannone, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Parkinson Institute, Istituti Clinici di Perfezionamento, Department of Endocrinology, Warren Alpert Medical School of Brown University, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR, ANR-05-NEUR-0019,LRRK2 in PD,Pathologie moléculaire et modèles murins du gène LRRK2, impliqué dans la maladie de Parkinson(2005), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, MESH: Mutation, MESH: Pedigree, DNA Mutational Analysis, MESH: Chromosomes, Human, Pair 2, Locus (genetics), MESH: Carrier Proteins, Biology, Article, 03 medical and health sciences, Exon, 0302 clinical medicine, Genetics, Missense mutation, Humans, Genetics(clinical), MESH: DNA Mutational Analysis, Gene, Index case, Genetics (clinical), Exome sequencing, 030304 developmental biology, Aged, MESH: Aged, 0303 health sciences, MESH: Humans, MESH: Middle Aged, Parkinson Disease, MESH: Adult, Middle Aged, LRRK2, Penetrance, MESH: Male, Pedigree, Chromosomes, Human, Pair 2, Mutation, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Carrier Proteins, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract: The genetic basis for association of the PARK11 region of chromosome 2 with familial Parkinson disease (PD) is unknown. This study examined the GIGYF2 (Grb10-Interacting GYF Protein-2) (TNRC15) gene, which contains the PARK11 microsatellite marker with the highest linkage score (D2S206, LOD 5.14). The 27 coding exons of the GIGYF2 gene were sequenced in 123 Italian and 126 French patients with familial PD, plus 131 Italian and 96 French controls. A total of seven different GIGYF2 missense mutations resulting in single amino acid substitutions were present in 12 unrelated PD index patients (4.8%) and not in controls. Three amino acid insertions or deletions were found in four other index patients and absent in controls. Specific exon sequencing showed that these ten sequence changes were absent from a further 91 controls. In four families with amino acid substitutions in which at least one other PD case was available, the GIGYF2 mutations (Asn56Ser, Thr112Ala, and Asp606Glu) segregated with PD. There were, however, two unaffected carriers in one family, suggesting age-dependent or incomplete penetrance. One index case (PD onset age 33) inherited a GIGYF2 mutation (Ile278Val) from her affected father (PD onset age 66) and a previously described PD-linked mutation in the LRRK2 gene (Ile1371Val) from her affected mother (PD onset age 61). The earlier onset and severe clinical course in the index patient suggest additive effects of the GIGYF2 and LRRK2 mutations. These data strongly support GIGYF2 as a PARK11 gene with a causal role in familial PD.
Published: 2008
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34. The quest for a better insight into physiology of fluids and barriers of the brain: the exemplary career of Joseph D. Fenstermacher

Author: Charles Nicholson, Joanna Szmydynger-Chodobska, Jean-François Ghersi-Egea, Tavarekere N. Nagaraja, Adam Chodobski, BMC, BMC, Neurotrauma and Brain Barriers Research Laboratory, Warren Alpert Medical School of Brown University, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology and Neuroscience, New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Department of Anesthesiology, and Henry Ford Hospital
Subjects: [SDV]Life Sciences [q-bio], education, Review, 030218 nuclear medicine & medical imaging, Diffusion, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Brain extracellular space, MRI contrast agent, Radiolabelled tracers, Cognitive science, Cerebrospinal fluid dynamics, General Medicine, Cerebral blood flow, humanities, 3. Good health, [SDV] Life Sciences [q-bio], Ventriculocisternal perfusion, Cerebrospinal fluid, Neurology, Tumour therapy, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; In June 2014 Dr. Joseph D. Fenstermacher celebrated his 80th birthday, which was honored by the symposium held in New London, NH, USA. This review discusses Fenstermacher's contribution to the field of fluids and barriers of the CNS. Specifically, his fundamental work on diffusion of molecules within the brain extracellular space and the research on properties of the blood-brain barrier in health and disease are described. Fenstermacher's early research on cerebrospinal fluid dynamics and the regulation of cerebral blood flow is also reviewed, followed by the discussion of his more recent work involving the use of magnetic resonance imaging.
Published: 2014
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35. Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits

Author: Jatin Relan, Bernd Jung, Manfred Zehender, Gerlind Franke, David Ziupa, Marius Menza, Gideon Koren, Michael Brunner, Stefanie Perez Feliz, Daniela Föll, Katja E. Odening, Corinna N. Lang, Christoph Bode, Maxime Sermesant, Rocio Cabrera Lozoya, Department of Cardiology and Angiology I, University Heart Centre Freiburg - Bad Krozingen, Department of Radiology, Medical Physics, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik)-University Hospital Freiburg, Analysis and Simulation of Biomedical Images (ASCLEPIOS), 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), Division of Cardiology [Providence], and Warren Alpert Medical School of Brown University
Subjects: medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Pyridines, Transgene, Long QT syndrome, Diastole, Action Potentials, QT interval, Animals, Genetically Modified, Piperidines, Physiology (medical), Internal medicine, medicine, Repolarization, Animals, Systole, medicine.diagnostic_test, business.industry, Cardiac electrophysiology, Magnetic resonance imaging, Arrhythmias, Cardiac, medicine.disease, Magnetic Resonance Imaging, Long QT Syndrome, Cardiology, cardiovascular system, Female, Rabbits, Cardiology and Cardiovascular Medicine, business, Anti-Arrhythmia Agents
Abstract: Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias.To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS.Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments.In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P.01) and APD dispersion was greater than that in LMC rabbits (P.01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P.01; E4031-treated: -3.24 ± 0.6 cm/s, P.0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P.05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P.001; E4031-treated: 199.5 ± 2.2 ms, P.0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P.01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data.The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder.
Published: 2013
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36. Programmed death-1 levels correlate with increased mortality nosocomial infection and immune dysfunctions in septic shock patients

Author: Hakim Kherouf, Bernard Allaouchiche, Laure Denis, Guillaume Monneret, Alfred Ayala, Alain Lepape, Aurélie Cheron, Françoise Poitevin, François Gueyffier, Xin Huang, Caroline Guignant, Christophe Malcus, Fabienne Venet, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], 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 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)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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), Laboratoire d'Immunologie, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Service de Réanimation, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Division of Surgical Research, Department of Surgery-Warren Alpert Medical School of Brown University, Centre d'Investigation Clinique (CIC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de Lyon, This research was supported by funds from the Hospices Civils de Lyon, by DHOS-Inserm 'Recherche Clinique Translationnelle 2009' (to GM and FG), by Fondation Innovation en Infectiologie (FINOVI) (to GM and FV), by the French Ministry of Health (PHRC 2008) (to GM and AL), and by US National Institutes of Health grants R01s GM46354 and GM53209 (to AA)., and BMC, Ed.
Subjects: Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Time Factors, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], T-Lymphocytes, Lymphocyte Activation, Critical Care and Intensive Care Medicine, Monocytes, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Prospective Studies, Receptor, Prospective cohort study, 030304 developmental biology, Aged, Cell Proliferation, 0303 health sciences, Cross Infection, business.industry, Septic shock, Research, Case-control study, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, 3. Good health, Interleukin-10, Interleukin 10, Case-Control Studies, Immunology, Female, Programmed death 1, Mitogens, business, Apoptosis Regulatory Proteins
Abstract: International audience; INTRODUCTION: Septic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients. METHODS: This prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed. RESULTS: We observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration. CONCLUSIONS: These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.
Published: 2011
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37. Outcome of Surgery for Hypothalamic Hamartoma-Related Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis.

Author: Niazi F, Goel K, Chen JS, Hadjinicolaou A, Keezer MR, Nguyen DK, Gallagher A, Shlobin N, Yuan-Mou Yang J, Soeby L, Webster E, Desnous B, Scavarda D, Perry MS, Mithani K, Ibrahim GM, Gaillard WD, Mathieu D, Kerrigan JF, Fallah A, and Weil AG
Subjects: Humans, Treatment Outcome, Neurosurgical Procedures methods, Hamartoma surgery, Hamartoma complications, Hypothalamic Diseases surgery, Hypothalamic Diseases complications, Epilepsy surgery
Abstract: Background and Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy., Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted. The PubMed, Embase, and Scopus online databases were searched without any date restrictions for original studies with more than 1 participant reporting on patients with HH-related epilepsy who underwent surgical treatment. Random-effects modeling was used to calculate the pooled proportions of seizure freedom (Engel I) at the last follow-up. IPD were used to perform mixed-effects logistic regression to identify predictors of seizure freedom and major postoperative complications., Results: Sixty-four studies were included, and IPD on 517 patients were obtained. The overall quality of evidence was low. After the index procedure, the pooled proportion of overall seizure freedom was 50.0% (95% CI 42.7%-57.4%), which increased to 64.5% (95% CI 57.2%-71.5%) after multiple treatments. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) and radiofrequency thermocoagulation (RFTC) demonstrated the highest efficacy at the last follow-up, with seizure freedom rates of 74.5% (95% CI 66.8%-81.7%) and 78.5% (95% CI 71.6%-84.8%), respectively. Factors independently associated with a lower likelihood of seizure freedom included multiple seizure types (odds ratio [OR] 0.296, 95% CI 0.140-0.624, p = 0.001) and previous surgery (OR 0.418, 95% CI 0.198-0.884, p = 0.023). Stereotactic radiosurgery (SRS) was the safest approach, with a pooled proportion of major complications of 0.0% (95% CI 0.0%-1.4%). Only surgical technique emerged as an independent predictor of major complications, with SRS (OR 0.024, 95% CI 0.002-0.292, p = 0.004), RFTC (OR 0.133, 95% CI 0.026-0.692, p = 0.017), and MRgLITT (OR 0.234, 95% CI 0.056-0.968, p = 0.045) being associated with a lower likelihood of major complications., Discussion: MRgLITT and RFTC offer superior efficacy and safety compared with open microsurgery and should be considered as first-line options. Despite its lower efficacy, SRS is associated with few reported long-term complications, making it a viable alternative for select cases, such as small HHs with good baseline functioning. Direct comparisons between techniques are limited by short follow-up durations in RFTC and MRgLITT cohorts. Further large-scale, multicenter studies directly comparing these modalities are warranted.
Published: 2024
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38. Treatment of Acne Vulgaris With a 650-ms, 1064-nm Nd:YAG Laser: A Retrospective Study.

Author: Olugbade ID, Petty AC, and Imahiyerobo-Ip J
Abstract: Background: The 650-ms, 1064-nm Nd:YAG laser device may provide superior efficacy and tolerability for the treatment of acne vulgaris over conventional treatments., Aim: To evaluate the efficacy and tolerability of a 650-ms laser for the treatment of mild to severe facial acne vulgaris., Patients/methods: Records of 225 subjects with mild to severe facial acne vulgaris and treated with a 650-ms laser were reviewed., Results: Subjects required a median of 3 treatments to achieve clearance. Clearance was achieved in 108/225 (48%) subjects. Adverse effects were limited to acne flare-ups and dryness. Treatment with isotretinoin was not required in 180/209 (80%) of subjects. A variety of topical and oral medications and non-laser procedures may be used in conjunction with the 650-ms laser without adverse effects. At the 6-month follow-up visit, the median Investigator Global Scale (IGA) score was 1.0 (almost clear). For most IGA-rated parameters differences between white patients and patients with skin of color were not statistically significant., Conclusion: The 650-ms, 1064-nm Nd:YAG laser provides a safe and efficacious treatment of mild to severe acne in patients with white skin and skin of color., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)
Published: 2024
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39. Strengths-Based Assessment and Inclusive Language for Patients With Intellectual and Developmental Disabilities.

Author: Jain S, Shah K, Woo S, Dykman M, Fung LK, and Rork JF
Abstract: Pediatric dermatology patients with intellectual and developmental disabilities (IDD) and comorbid cutaneous conditions often face barriers to effective healthcare due to differences in communication preferences and sensitivities to environmental factors. The clinical intake process serves as a potential intervention point to help better understand and meet patients' needs. Strengths-based assessment and considerations around identity-first versus person-first language are tools that can improve the clinical intake process in pediatric dermatology. We provide examples of intake questions and recommendations to help guide IDD-informed care., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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40. Antisemitism in American Healthcare: A Survey Study of Reported Experiences.

Author: Michelson KN, Fishman AC, Feinberg EC, Ross S, Wald HS, Auerbach C, and Roth S
Abstract: Competing Interests: Declarations:. Conflict of Interest:: Hedy S. Wald, PhD is a Commissioner of the Lancet Commission on medicine, Nazism, and the Holocaust. The views presented in this article do not represent other members of the Lancet Commission on Medicine, Nazism, and the Holocaust, but rather the views of the authors only. Dr. Roth is President of the Healthcare Council of the Coalition for Jewish Values, Baltimore, MD, and Director of the Publications Committee, American Jewish Medical Association, New York, NY. Both of Dr. Roth’s positions are unpaid and voluntary.
Published: 2024
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41. Evolutionary trajectories of β-lactam resistance in Enterococcus faecalis strains.

Author: Ugalde Silva P, Desbonnet C, Rice LB, and García-Solache M
Subjects: Whole Genome Sequencing, Phenotype, Humans, Genome, Bacterial, beta-Lactams pharmacology, Enterococcus faecalis genetics, Enterococcus faecalis drug effects, Anti-Bacterial Agents pharmacology, beta-Lactam Resistance genetics, Ampicillin pharmacology, Evolution, Molecular, Microbial Sensitivity Tests, Imipenem pharmacology, Mutation
Abstract: Resistance to ampicillin and imipenem in Enterococcus faecalis is infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a long-term evolution experiment using four genetically diverse strains of E. faecalis with varying susceptibilities to ampicillin and imipenem. Each strain was subjected to increasing concentrations of either ampicillin or imipenem over 200 days, with three independent replicates for each strain. Selective pressure from imipenem led to the rapid selection of highly resistant lineages across all genetic backgrounds, compared to ampicillin. In addition to high resistance, we describe, for the first time, the evolution of a β-lactam-dependent phenotype observed in lineages from all backgrounds. Whole-genome sequencing and bioinformatic analysis revealed mutations in three main functional classes: genes involved in cell wall synthesis and degradation, genes in the walK/R two-component system, and genes in the c-di-AMP pathway. Our analysis identified new mutations in genes known to be involved in resistance as well as novel genes potentially associated with resistance. Furthermore, the newly described β-lactam-dependent phenotype was correlated with the inactivation of c-di-AMP degradation, resulting in high levels of this second messenger. Together, these data highlight the diverse genetic mechanisms underlying resistance to ampicillin and imipenem in E. faecalis . The emergence of high resistance levels and β-lactam dependency underscores the importance of understanding evolutionary dynamics in the development of antibiotic resistance., Importance: Enterococcus faecalis is a major human pathogen, and treatment is frequently compromised by poor response to first-line antibiotics such as ampicillin. Understanding the factors that play a role in susceptibility/resistance to these drugs will help guide the development of much-needed treatments., Competing Interests: The authors declare no conflict of interest.
Published: 2024
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42. Management and Outcomes of Pulmonary Embolism in Women of Reproductive Age Admitted to Urban Versus Rural Areas Compared to Men.

Author: Bansal M, Mehta A, Ahmad K, Bortnick AE, Nagaraja V, Hyder ON, Dawn Abbott J, and Vallabhajosyula S
Abstract: There are limited and conflicting data on sex and urban-rural disparities in outcomes of patients with pulmonary embolism (PE) in the reproductive age group. Our object was to assess sex disparities in the reproductive age group cohort. All adult non-elective admissions in the reproductive age group (18-49 years) with a primary diagnosis of PE and with no missing sex/age data were identified using the National Inpatient Sample. Females and males were stratified into rural and urban location based on hospital information. Outcomes of interest included in-hospital mortality, complication rates, variations in management, total hospitalization costs, and length of stay. During 01/01/2016 to 12/31/2020, 180,898 PE admissions aged 18-49 years were identified (rural-12,319 [6.8%]). Females comprised 54.8% and 55.1% of the rural and urban cohorts, respectively. Overall, compared to males, females in urban and rural regions had largely comparable rates of definitive PE interventions, except lower rates of catheter directed therapy (4.7 vs. 3.6%, p < 0.001) in females admitted to urban hospitals. Despite younger age, higher comorbidity, and lower utilization of PE interventions, females in both regions had similar unadjusted in-hospital mortality (rural 1.1% vs. 1.0%; p = 0.93 and urban 1.8% vs. 1.7%; p = 0.78) and hospitalization costs compared to males. In conclusion, females of reproductive age group had comparable in-hospital outcomes to males in both urban and rural areas. Females in urban areas had lower utilization of advanced PE interventions, potentially indicating selective management strategies in different settings., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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43. Dietary Inflammatory Index Is Differentially Associated With Cardiometabolic Health After Pregnancy on the Basis of Adverse Pregnancy Outcome Exposure.

Author: Jancsura MK, Wirth MD, Helsabeck NP, Mercer BM, Haas DM, Greenland P, McNeil R, Levine LD, Silver RM, Yee LM, Saade GR, Khan SS, Chung JH, and Grobman WA
Abstract: Background: Inflammatory diets may influence risk of cardiovascular disease. Subsequent cardiovascular disease is also influenced by adverse pregnancy outcomes (APOs) such as preterm birth, small-for-gestational-age birth, gestational diabetes, and hypertensive disorders of pregnancy. However, the associations between inflammatory diet, APOs, and cardiometabolic health remain unclear., Methods and Results: We used data from the nuMoM2b (Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-Be) HHS (Heart Health Study) to assess the relationship between dietary quality and cardiometabolic health. We calculated Energy-Adjusted Dietary Inflammatory Index scores representing the inflammatory burden in a person's diet. We used linear regression to determine the association between Energy-Adjusted Dietary Inflammatory Index score and cardiometabolic outcomes. We performed stratified analyses for outcomes with a significant interaction between Energy-Adjusted Dietary Inflammatory Index and APO. Data were available from 3249 participants at a median of 3.1 years after delivery. Higher Energy-Adjusted Dietary Inflammatory Index scores were associated with higher body mass index (B=0.29 kg/m 2 [95% CI, 0.16-0.42]), waist circumference (0.66 cm [95% CI, 0.39-0.93]), diastolic blood pressure (0.26 mm Hg [95% CI, 0.09-0.44]), mean arterial pressure (0.23 mm Hg [95% CI, 0.06-0.40]), triglycerides (2.11 mg/dL [95% CI, 1.05-3.18]), creatinine (2.78 mg/dL [95% CI, 1.13-4.44]), insulin (exp[B]=1.04 [95% CI, 1.03-1.05]) and C-reactive protein (exp[B]=1.07 [95% CI, 1.04-1.10]), and lower high-density lipoprotein cholesterol (-0.41 mg/dL [95% CI, -0.66 to -0.37]) (all P <0.01). Significant interactions with APO ( P <0.05) were identified for body mass index and waist circumference, with stratified analysis revealing stronger associations for individuals with APOs., Conclusions: A more proinflammatory diet was associated with worse cardiometabolic health measures, and these relationships differed by a person's APO history. Further investigation should establish how dietary modifications after pregnancy may potentially mitigate cardiovascular disease risk.
Published: 2024
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44. Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Author: Ospel JM, Goyal M, Menon BK, Almekhlafi MA, Zerna C, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Joshi M, Kashani N, Heard K, Field TS, Dowlatshahi D, van Adel B, Swartz RH, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, and Hill MD
Abstract: Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume., Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo. Patients not receiving intravenous alteplase were included in this post hoc secondary analysis of the trial data. Final infarct volume was manually segmented on 24-hour noncontrast computed tomography or diffusion-weighted magnetic resonance imaging. Predictors of final infarct volume were identified using multivariable linear regression with cubic-root-transformed infarct volume as the dependent variable. Evidence of treatment-by-predictor interaction was tested by including interaction terms in the model., Results: Four hundred forty-six patients (219 who received nerinetide and 227 who received a placebo) out of a total of 1105 enrolled patients were included in this secondary post hoc analysis of the randomized ESCAPE-NA1 trial. Nerinetide was a strong predictor of smaller infarct volume (adjusted β coefficient, -0.35 [95% CI, -0.67 to -0.02]). Other predictors of smaller infarct volume were history of hypertension, good pial collateral filling on multiphase computed tomography angiography, a middle cerebral artery occlusion compared with an internal carotid artery occlusion, lower baseline National Institutes of Health Stroke Scale score, lower baseline systolic blood pressure, lower baseline serum glucose, shorter onset-to-randomization time, and higher Alberta Stroke Program Early CT Score. There was evidence of a treatment-by-systolic blood pressure and treatment-by-anesthesia interaction: nerinetide attenuated the negative effects of elevated baseline ( P interaction =0.04) systolic blood pressure and use of general anesthesia ( P =0.06) on final infarct volume. We observed a marginally significant interaction with reperfusion status, such that nerinetide may attenuate the harmful effect of poor reperfusion status on infarct volume ( interaction =0.04) systolic blood pressure and use of general anesthesia ( P interaction =0.06) on final infarct volume. We observed a marginally significant interaction with reperfusion status, such that nerinetide may attenuate the harmful effect of poor reperfusion status on infarct volume ( P interaction =0.08)., Conclusions: Nerinetide treatment was strongly associated with smaller final infarct volumes among patients not cotreated with alteplase. The reduction in infarct volume was greater among patients with poor prognostic factors., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02930018.
Published: 2024
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45. Cognitive and Procedural Competencies in the Cardiac Intensive Care Unit.

Author: Applefeld WN, Jentzer JC, and Vallabhajosyula S
Published: 2024
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46. Ethnicity as a Risk Factor for Early Neurological Deterioration: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes Trial.

Author: Goldstein ED, Liew SQR, Shu L, Rocha A, and Yaghi S
Abstract: Objectives: Nearly 25% of those with a small vessel stroke will develop early neurological deterioration (END). The objectives of this study were to identify clinical risk factors for small vessel stroke-related END and its associated impact on functional outcomes in an ethnically diverse data set., Methods: We performed a post hoc analysis of the "Secondary Prevention of Small Subcortical Strokes" trial. The primary outcome was END defined as progressive or stuttering stroke-related neurological symptoms. Standard descriptive and inferential statistical methods were used for analysis. Functional outcomes are reported by modified Rankin Scale score and analyzed by the Wilcoxon signed-rank test., Results: In all, 69 participants met the inclusion criteria; 21 (30%) had END. Of the cohort, Spanish, Hispanic, or Latino ethnicity (grouping per trial definition) most frequently developed END [11 (52.4%) vs 4 (8.3%), P < 0.001] with a higher adjusted likelihood of END (odds ratio: 14.1, 95% CI: 2.57-76.7, P = 0.002). Black or African-American race less commonly had END [3 (14.3%) vs 21 (43.8%), P = 0.03] but lost significance after adjustment (odds ratio: 1.46, 95% CI: 0.26-8.17, P = 0.67) due to powering. END was associated with a higher mean modified Rankin Scale (2.06 ± 0.94 vs 1.17 ± 0.79, P = 0.006) but did not differ in the shift analysis., Conclusions: We found that Spanish, Hispanic, or Latino ethnicity was the most consistent risk factor for END though it was without meaningful functional outcome differences., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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47. How the history of midwifery and obstetrics still affects what you do today in pregnancy care: the American Journal of Obstetrics & Gynecology MFM starts a new "Obstetrical history" series.

Author: Berghella V, Miller ES, Stout M, Lewkowitz AK, Bennett TA, and Fox KA
Published: 2024
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48. Pulsatile GnRH Therapy: does one size fit all?

Author: Kassi LA and Eaton JL
Published: 2024
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49. After COVID-19 diagnosis, risk for incident type 2 diabetes was elevated for up to 2 y.

Author: Vassilopoulos S and Mylonakis E
Abstract: Source Citation: Taylor K, Eastwood S, Walker V, et al. Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people. Lancet Diabetes Endocrinol. 2024;12:558-568. 39054034., Competing Interests: Disclosures: Disclosure forms are available with the article online.
Published: 2024
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50. An Update on Kawasaki Disease.

Author: Goel AR and Yalcindag A
Subjects: Humans, Immunoglobulins, Intravenous therapeutic use, SARS-CoV-2, Mucocutaneous Lymph Node Syndrome epidemiology, Mucocutaneous Lymph Node Syndrome diagnosis, Mucocutaneous Lymph Node Syndrome therapy, Mucocutaneous Lymph Node Syndrome drug therapy, COVID-19 epidemiology, COVID-19 complications
Abstract: Purpose: To summarize advances in research on the epidemiology, pathogenesis, diagnosis, and treatment of Kawasaki Disease (KD), a systemic inflammatory illness of unknown etiology that affects children globally., Recent Findings: The epidemiology of KD was affected by the COVID-19 pandemic and advances in molecular immunology and machine learning have enabled research into its pathogenesis. There is ongoing research into agents that can be used to intensify initial treatment and accumulating evidence supporting the use of certain rescue regimens for refractory disease over others. There is promise surrounding a new coronary artery aneurysm prediction model. Research into the post-acute morbidity of KD continues. The COVID-19 pandemic temporarily reduced the incidence of KD. The NLRP3 inflammasome plays a key role in KD pathogenesis. Intensified initial treatment benefits high-risk patients, yet no intensification regimen shows superiority over another. Corticosteroids, infliximab, or combination therapy with IVIg plus another agent may be superior rescue regimens compared to IVIg alone for refractory KD. The Son score, developed in North America, predicted coronary artery lesions in Japanese and Italian cohorts. Patients with a history of KD may carry long-term physical and emotional burdens that persist into adulthood yet appear to have typical neurocognitive development. Successful transition to adult healthcare presents a challenge., Competing Interests: Declarations. Conflict of Interest: The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2024
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