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Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

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The Lancet Global Health 2023年第3期11卷 e385-e413页

作者： Micah, Angela E. Bhangdia, Kayleigh Cogswell, Ian E. Lasher, Dylan Lidral-Porter, Brendan Maddison, Emilie R. Nguyen, Trang Nhu Ngoc Patel, Nishali Pedroza, Paola Solorio, Juan Stutzman, Hayley Tsakalos, Golsum Wang, Yifeng Warriner, Wesley Zhao, Yingxi Zlavog, Bianca S. Abbafati, Cristiana Abbas, Jaffar Abbasi-Kangevari, Mohsen Abbasi-Kangevari, Zeinab Abdelmasseh, Michael Abdulah, Deldar Morad Abedi, Aidin Abegaz, Kedir Hussein Abhilash, E.S. Aboagye, Richard Gyan Abolhassani, Hassan Abrigo, Michael R.M. Abubaker Ali, Hiwa Abu-Gharbieh, Eman Adem, Mohammed Hussien Afzal, Muhammad Sohail Ahmadi, Ali Ahmed, Haroon Ahmed Rashid, Tarik Aji, Budi Akbarialiabad, Hossein Akelew, Yibeltal Al Hamad, Hanadi Alam, Khurshid Alanezi, Fahad Mashhour Alanzi, Turki M. Al-Hanawi, Mohammed Khaled Alhassan, Robert Kaba Aljunid, Syed Mohamed Almustanyir, Sami Al-Raddadi, Rajaa M. Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Amare, Azmeraw T. Ameyaw, Edward Kwabena Amini-Rarani, Mostafa Amu, Hubert Ancuceanu, Robert Andrei, Tudorel Anwar, Sumadi Lukman Appiah, Francis Aqeel, Muhammad Arabloo, Jalal Arab-Zozani, Morteza Aravkin, Aleksandr Y. Aremu, Olatunde Aruleba, Raphael Taiwo Athari, Seyyed Shamsadin Avila-Burgos, Leticia Ayanore, Martin Amogre Azari, Samad Baig, Atif Amin Bantie, Abere Tilahun Barrow, Amadou Baskaran, Pritish Basu, Sanjay Batiha, Abdul-Monim Mohammad Baune, Bernhard T. Berezvai, Zombor Bhardwaj, Nikha Bhardwaj, Pankaj Bhaskar, Sonu Boachie, Micheal Kofi Bodolica, Virginia Botelho, João Silva Botelho Braithwaite, Dejana Breitborde, Nicholas J.K. Busse, Reinhard Cahuana-Hurtado, Lucero Catalá-López, Ferrán Chansa, Collins Charan, Jaykaran Chattu, Vijay Kumar Chen, Simiao Chukwu, Isaac Sunday Dadras, Omid Dandona, Lalit Dandona, Rakhi Dargahi, Abdollah Debela, Sisay Abebe Denova-Gutiérrez, Edgar Desye, Belay Dharmaratne, Samath Dhamminda Diao, Nancy Doan, Linh Phuong Dodangeh, Milad dos Santos, Wendel Mombaque Doshmangir, Leila Dube, John Eini, Ebrahim El Sayed Zaki, Maysaa El Tantawi, Maha Enyew, Daniel Berhanie Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Applied Mathematics University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Nuffield Department of Medicine University of Oxford Oxford United Kingdom Department of Juridical and Economic Studies La Sapienza University Rome Italy Antai College of Economics Shanghai Jiao Tong University Shanghai China Non-communicable Diseases Research Center Tehran University of Medical Sciences Tehran Iran Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Multiple Sclerosis Research Center Tehran University of Medical Sciences Tehran Iran Children’s Medical Center Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran Tehran Heart Center Tehran University of Medical Sciences Tehran Iran Faculty of Medicine Tehran University of Medical Sciences Tehran Iran National Institute for Health Research Tehran University of Medical Sciences Tehran Iran Department of Pharmacology Tehran University of Medical Sciences Tehran Iran Department of Cardiology Tehran University of Medical Sciences Tehran Iran Sina Trauma and Surgery Research Center Tehran University of Medical Sciences Tehran Iran Digestive Diseases Research Institute Tehran University of Medical Sciences Tehran Iran Department of Neurology Tehran University of Medical Sciences Tehran Iran Social Determinants of Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Epidemiology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Health Economics and Statistics Shahid Beheshti University of Medical Sciences Tehran Iran Department of Neurosurgery Shahid Beheshti University of Medical Sciences Tehran Iran Ophthalmic R

Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic;characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic;and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019;293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided

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Cover Image, Volume 58, Issue 5

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molecular Carcinogenesis 2019年第5期58卷

作者： Ariel L. Hernandez Ying Wang Hilary L. Somerset Stephen B. Keysar Dara L. Aisner Carrie Marshall Daniel W. Bowles Sana D. Karam David Raben Antonio Jimeno Marileila Varella-Garcia Xiao-Jing Wang Department of Pathology School of Medicine Molecular Biology Program Medical Scientist Training Program University of Colorado Aurora Colorado University of Colorado Cancer Center Molecular Pathology/Cytogenetics Shared Resource University of Colorado Aurora Colorado Department of Medical Oncology University of Colorado Aurora Colorado Veterans Affairs Medical Center VA Eastern Colorado Health Care System Aurora Colorado Department of Radiation Oncology University of Colorado Aurora Colorado

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Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study (vol 2, pg 144, 2021)

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LANCET GLOBAL HEALTH 2021年第4期9卷 E408-E408页

作者： Steinmetz, Jaimie D. Vision and Eye Research Institute Anglia Ruskin University Cambridge United Kingdom Biomedical Informatics Seoul National University Hospital Seoul South Korea Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Institute of Health Services Research Yonsei University Seoul South Korea Department of Ophthalmology University of Washington Seattle WA United States Department of Mathematics Imperial College London London United Kingdom WHO Collaborating Centre for Public Health Education and Training Imperial College London London United Kingdom Department of Primary Care and Public Health Imperial College London London United Kingdom School of Population and Global Health University of Melbourne Carlton VIC Australia School of Optometry and Vision Science UNSW Sydney NSW Australia Brien Holden Vision Institute Sydney Australia Department of Ophthalmology University of Adelaide Adelaide SA Australia Department of Parasitology and Mycology Jahrom University of Medical Sciences Jahrom Iran Department of Clinical Sciences University of Sharjah Sharjah United Arab Emirates Ophthalmic Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Ophthalmology Shahid Beheshti University of Medical Sciences Tehran Iran Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences Tehran Iran Ophthalmic Epidemiology Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Health Services Management Department Qazvin University of Medical Sciences Qazvin Iran Department of Systems Populations and Leadership University of Michigan Ann Arbor MI United States Department of Medicine Sofia Ismail Memorial Medical Centre Bogura Bangladesh The Fred Hollows Foundation Sydney NSW Australia Berhan Public Health & Eye Care Consultancy Addis A

Hospital El Salvador: a novel paradigm of intensive care in response to COVID-19 in central America. Lancet Glob Health 2021;9: e241?42?In this Comment, the conflict of interest statement should have included the following: ?By virtue of their roles within a public hospital or the Ministry of Health, MB, LC, WH, and XS are government employees. The findings and conclusions in the Comment are only those of the authors.? This correction has been made as of Feb 26, 2021.

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Author Correction: Regulation of sister chromatid cohesion by nuclear PD-L1

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Cell research 2020年第9期30卷 823页

作者： Jia Yu Bo Qin Ann M Moyer Somaira Nowsheen Xinyi Tu Haidong Dong Judy C Boughey Matthew P Goetz Richard Weinshilboum Zhenkun Lou Liewei Wang Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN 55905 USA. Department of Oncology Mayo Clinic Rochester MN 55905 USA. Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN 55905 USA. Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic School of Medicine and the Mayo Clinic Medical Scientist Training Program Mayo Clinic Rochester MN 55905 USA. Departments of Urology and Immunology Mayo Clinic Rochester MN 55905 USA. Department of Surgery Mayo Clinic Rochester MN 55905 USA. Department of Oncology Mayo Clinic Rochester MN 55905 USA. Lou.Zhenkun@mayo.edu. Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN 55905 USA. Wang.Liewei@mayo.edu.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Cardiovascular Concerns in BRCA1 and BRCA2 Mutation Carriers

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Current Treatment Options in Cardiovascular medicine 2018年第2期20卷 18-18页

作者： Gast, Kelly C. Viscuse, Paul V. Nowsheen, Somaira Haddad, Tufia C. Mutter, Robert W. Wahner Hendrickson, Andrea E. Couch, Fergus J. Ruddy, Kathryn J. Department of Internal Medicine Mayo Clinic School of Graduate Medical Education Rochester MN United States Mayo Clinic Graduate School of Biomedical Sciences Medical Scientist Training Program Mayo Clinic School of Medicine Rochester MN United States Department of Oncology Division of Medical Oncology Mayo Clinic 200 First Street SW Rochester 55095 MN United States Department of Radiation Oncology Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States

Purpose of review: BRCA1 and BRCA2 mutation carriers can be at increased cardiovascular risk. The goal of this review is to provide information about factors associated with increased cardiovascular risk, methods to prevent cardiovascular toxicities, and recommended screening guidelines. Recent findings: BRCA1/2 mutation carriers who are diagnosed with cancer are often exposed to chemotherapy, chest radiotherapy, and/or HER2 directed therapies, all of which can be cardiotoxic. In addition, BRCA1/2 carriers often undergo prophylactic salpingoopherectomies, which may also increase cardiovascular risks. Summary: Understanding the potential for increased cardiovascular risk in individuals with a BRCA1 or BRCA2 mutation, as well as gold standard practices for prevention, detection, and treatment of cardiac concerns in this population, is important. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

关键词： BRCA mutation Cardio-oncology Chemotherapy cardiotoxicity Radiation cardiotoxicity

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Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

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The Lancet 2020年第10258期396卷 1204-1222页

作者： Abbafati, Cristiana Abbas, Kaja M. Abbasi, Mohammad Abbasifard, Mitra Abbasi-Kangevari, Mohsen Abbastabar, Hedayat Abd-Allah, Foad Abdelalim, Ahmed Abdollahi, Mohammad Abdollahpour, Ibrahim Abedi, Aidin Abedi, Parisa Abegaz, Kedir Hussein Abolhassani, Hassan Abosetugn, Akine Eshete Aboyans, Victor Abrams, Elissa M. Abreu, Lucas Guimarães Abrigo, Michael R.M. Abu Haimed, Abdulaziz Khalid Abualhasan, Ahmed Abu-Gharbieh, Eman Abu-Raddad, Laith Jamal Abushouk, Abdelrahman I. Acebedo, Alyssa Ackerman, Ilana N. Adabi, Maryam Adair, Tim Adamu, Abdu A. Adebayo, Oladimeji M. Adedeji, Isaac Akinkunmi Adekanmbi, Victor Adelson, Jaimie D. Adeoye, Abiodun Moshood Adetokunboh, Olatunji O. Adham, Davoud Advani, Shailesh M. Afarideh, Mohsen Afshari, Mahdi Afshin, Ashkan Agardh, Emilie E. Agarwal, Gina Agasthi, Pradyumna Agesa, Kareha M. Aghaali, Mohammad Aghamir, Seyed Mohammad Kazem Agrawal, Anurag Ahmad, Tauseef Ahmadi, Alireza Ahmadi, Keivan Ahmadi, Mehdi Ahmadieh, Hamid Ahmadpour, Ehsan Ahmed, Muktar Beshir Aji, Budi Akalu, Temesgen Yihunie Akinyemi, Rufus Olusola Akinyemiju, Tomi Akombi, Blessing Akunna, Chisom Joyqueenet Alahdab, Fares Al-Aly, Ziyad Alam, Khurshid Alam, Noore Alam, Samiah Alam, Tahiya Alanezi, Fahad Mashhour Alanzi, Turki M. Albertson, Samuel B. Alcalde-Rabanal, Jacqueline Elizabeth Alema, Niguse Meles Alemu, Biresaw Wassihun Alemu, Yihun Mulugeta Alhabib, Khalid F. Alhassan, Robert Kaba Ali, Muhammad Ali, Saqib Alicandro, Gianfranco Alijanzadeh, Mehran Alinia, Cyrus Alipour, Vahid Alizade, Hesam Aljunid, Syed Mohamed Alla, François Allebeck, Peter Almadi, Majid Abdulrahman Hamad Almasi, Ali Almasi-Hashiani, Amir Almasri, Nihad A. Al-Mekhlafi, Hesham M. Almulhim, Abdulaziz M. Alonso, Jordi Al-Raddadi, Rajaa M. Altirkawi, Khalid A. Alumran, Arwa Khalid Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Amare, Azmeraw T. Amare, Bekalu Amini, Saeed Amini-Rarani, Mostafa Aminorroaya, Arya Amiri, Fatemeh Amit, Arianna Maever L. Amugsi, Dickson A. Amul, Gianna Gayle Herrera Anbesu, Etsay Woldu Ancuceanu, Robert Anderl Department of Juridical and Economic Studies La Sapienza University Rome Italy Department of Infectious Disease Epidemiology London School of Hygiene and Tropical Medicine London United Kingdom Social Determinants of Health Research Center Tehran Iran Department of Neurology Cairo University Cairo Egypt School of Pharmacy Tehran Iran The Institute of Pharmaceutical Sciences (TIPS) Tehran Iran Neuroscience Research Center Isfahan University of Medical Sciences Isfahan Iran Biostatistics Department Near East University Nicosia Cyprus Biostatistics and Health Informatics Madda Walabu University Bale Robe Ethiopia Research Center for Immunodeficiencies Tehran Iran Karolinska University Hospital Huddinge Sweden Department of Cardiology Dupuytren University Hospital Limoges France University of Limoges Limoges France Department of Pediatric Dentistry Federal University of Minas Gerais Belo Horizonte Brazil Department of Research Philippine Institute for Development Studies Quezon City Philippines Department of Healthcare Policy and Research Weill Cornell Medical College in Qatar Doha Qatar Harvard Medical School Boston MA United States Department of Medicine Ain Shams University Cairo Egypt Hamadan University of Medical Sciences Hamadan Iran School of Medicine Cardiff University Cardiff United Kingdom School of Laboratory Medicine and Science University College Hospital Ibadan Ibadan Nigeria Institute of Cardiovascular Diseases University of Ibadan Ibadan Nigeria Centre of Excellence for Epidemiological Modelling and Analysis Stellenbosch University Cape Town South Africa Department of Global Health Stellenbosch University Cape Town South Africa School of Health Ardabil University of Medical Science Ardabil Iran Social Behavioral Research Branch National Institute of Health Bethesda MD United States Department of Oncology Georgetown University Washington DC DC United States Department of Health Metrics Sciences School of Medicine Seattle WA

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw value

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Author Correction: Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk

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Nature genetics 2022年第8期54卷 1259页

作者： Adam W Turner Shengen Shawn Hu Jose Verdezoto Mosquera Wei Feng Ma Chani J Hodonsky Doris Wong Gaëlle Auguste Yipei Song Katia Sol-Church Emily Farber Soumya Kundu Anshul Kundaje Nicolas G Lopez Lijiang Ma Saikat Kumar B Ghosh Suna Onengut-Gumuscu Euan A Ashley Thomas Quertermous Aloke V Finn Nicholas J Leeper Jason C Kovacic Johan L M Björkegren Chongzhi Zang Clint L Miller Center for Public Health Genomics University of Virginia Charlottesville VA USA. Department of Biochemistry and Molecular Genetics University of Virginia Charlottesville VA USA. Medical Scientist Training Program University of Virginia Charlottesville VA USA. Department of Pathology University of Virginia Charlottesville VA USA. Robert M. Berne Cardiovascular Research Center University of Virginia Charlottesville VA USA. Genome Analysis & Technology Core University of Virginia Charlottesville VA USA. Genome Sciences Laboratory University of Virginia Charlottesville VA USA. Department of Genetics Stanford University School of Medicine Stanford CA USA. Department of Computer Science Stanford University Stanford CA USA. Division of Vascular Surgery Department of Surgery Stanford University Stanford CA USA. Department of Genetics and Genomic Sciences Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai New York NY USA. CVPath Institute Gaithersburg MD USA. Department of Public Health Sciences University of Virginia Charlottesville VA USA. Division of Cardiovascular Medicine Department of Medicine Stanford University Stanford CA USA. Cardiovascular Research Institute Icahn School of Medicine at Mount Sinai New York NY USA. Victor Chang Cardiac Research Institute Darlinghurst New South Wales Australia. St. Vincent's Clinical School University of New South Wales Sydney New South Wales Australia. Integrated Cardio Metabolic Centre Department of Medicine Karolinska Institutet Huddinge Sweden. Center for Public Health Genomics University of Virginia Charlottesville VA USA. zang@virginia.edu. Department of Biochemistry and Molecular Genetics University of Virginia Charlottesville VA USA. zang@virginia.edu. Department of Public Health Sciences University of Virginia Charlottesville VA USA. zang@virginia.edu. Center for Public Health Genomics University of Virginia Charlottesville VA USA. clintm@virg

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Back Cover, Volume 43, Issue 7

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Human Mutation 2022年第7期43卷

作者： Ariadne R. Lima Barbara M. Ferreira Chaofan Zhang Angad Jolly Haowei Du Janson J. White Moez Dawood Tulio C. Lins Marcela A. Chiabai Ellen van Beusekom Mara S. Cordoba Erica C.C. Caldas Rosa Hulya Kayserili Virginia Kimonis Erica Wu Cecilia Mellado Vineet Aggarwal Antonio Richieri-Costa Décio Brunoni Talyta M. Canó Alexander A. L. Jorge Chong A. Kim Rachel Honjo Débora R. Bertola Raissa M. Dandalo-Girardi Yavuz Bayram Alper Gezdirici Elif Yilmaz-Gulec Evren Gumus Gülay C. Yilmaz Nobuhiko Okamoto Hirofumi Ohashi Zeynep Coban–Akdemir Tadahiro Mitani Shalini N. Jhangiani Donna M. Muzny Neysa A.P. Regattieri Robert Pogue Rinaldo W. Pereira Paulo A. Otto Richard A. Gibbs Bassam R. Ali Hans van Bokhoven Han G. Brunner V. Reid Sutton James R. Lupski Angela M. Vianna-Morgante Claudia M. B. Carvalho Juliana F. Mazzeu Programa de Pós-Graduação em Ciências da Saúde Universidade de Brasília Brasília DF Brasil Programa de Pós-Graduação em Ciências Médicas Universidade de Brasília Brasília DF Brasil Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas USA Medical Scientist Training Program Baylor College of Medicine Houston Texas USA Department of Pediatrics University of Washington Seattle Washington USA Human Genome Sequencing Center Baylor College of Medicine Houston Texas USA Programa de Pós-graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília Brasília DF Brasil Radboud University Nijmegen Medical Centre Nijmegen The Netherlands Faculdade de Medicina Universidade de Brasília Brasília DF Brasil Hospital Universitário de Brasília Brasília Brasil Medical Genetics Department School of Medicine (KUSoM) Koç University Istanbul Turkey Division of Genetics and Genomic Medicine Department of Pediatrics University of California-Irvine Irvine California USA Obstetrics and Gynecology Stanford University Stanford California USA Unidad de Genética División de Pediatría Pontificia Universidad Católica de Chile Santiago Chile Department of Orthopedics Indira Gandhi Medical College Snowdon India Hospital de Reabilitação de Anomalias Craniofaciais Bauru Brasil In memoriam. Universidade Presbiteriana Mackenzie–UPM São Paulo Brasil Núcleo de Genética–SESDF Brasília DF Brasil Laboratório de Endocrinologia Celular e Molecular LIM25 Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo Unidade de Endocrinologia Genética São Paulo Brasil Unidade de Genética Instituto da Criança-Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de São Paulo São Paulo Brasil Departamento de Genética e Biologia Evolutiva Instituto de Biociências Universidade de São Paulo São Paulo Brasil Programa de Mestrado Profissional em Aconselhamento Genético e Genômica Humana Instituto de Biociências U

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Human genetic and immunological determinants of critical COVID-19 pneumonia

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四川生理科学杂志 2021年第11期43卷 1947-1947页

作者： Qian Zhang St Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France University of Paris Imagine Institute Paris France Department of Pediatrics Necker Hospital for Sick Children Paris France Howard Hughes Medical Institute Paris France Cemil Taşcıoglu City Hospital Istanbul Turkey Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France Imagine Institute University of Paris Paris France Al Jalila Children’s Hospital Dubai United Arab Emirates San Raffaele Telethon Institute for Gene Therapy IRCCS Ospedale San Raffaele and Vita Salute San Raffaele University Milan Italy Hospices Civils de Lyon Lyon France Helix San Mateo CA USA Department of Intensive Care Medicine Critical Care Center CHU Lille Lille France Univ. Lille CNRS Inserm CHU Lille Institut Pasteur de Lille U1019-UMR9017-CIIL-Centre d’Infection et d’Immunité deLille Lille France Shupyk National Medical Academy for Postgraduate Education Kiev Ukraine Department of Medical Microbiology University Medical Center Utrecht Utrecht The Netherlands Sidra Medicine Doha Qatar Primary Immunodeficiencies Group Department of Microbiology and Parasitology School of Medicine University of Antioquia Medellín Colombia School of Microbiology University of Antioquia Medellín Colombia IIBB-CSIC IDIBAPS Barcelona Spain Department of Immunology Second Faculty of Medicine Charles University University Hospital in Motol Prague Czech Republic Department of Immunology Dmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology Moscow Russia Pulmonology Department Cliniques Universitaires Saint-Luc Brussels Belgium Institut de Recherche Expérimentale et Clinique (IREC) Université Catholique de Louvain Brussels Belgium

SARS-CoV-2 infection is benign in most individuals but,in-10%of cases,it triggers hypoxemic COVID-19 pneumonia,which becomes critical in-3%of *** ensuing risk of death(-1%)doubles every five years from childhood onward and is-1.5 times greater in men than in *** are the molecular and cellular determinants of critical COVID-19 pneumonia?Inborn errors of type I IFNs,including autosomal TLR3 and X-linked TLR7 deficiencies,are found in-1-5%of patients with critical pneumonia under 60 years old.

关键词： pneumonia critical cases

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IMMU-12. T-CELL THERAPIES DEMONSTRATE EFFICACY WITHOUT TOXICITY IN IMMUNOCOMPETENT MODELS OF BRAINSTEM TUMORS

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Neuro-Oncology 2018年第SUPPL_2期20卷 i101-i101页

作者： Schuelke, Matt Evgin, Laura Wongthida, Phonphimon Thompson, Jill Kottke, Tim Sanchez-Perez, Luis Sampson, John Vile, Richard Mayo Clinic Medical Scientist Training Program Rochester MN USA Mayo Clinic Department of Molecular Medicine Rochester MN USA Duke University Department of Neurosurgery Durham NC USA

Diffuse intrinsic pontine glioma (DIPG) is a pediatric brainstem tumor with a dismal prognosis and no curative treatments. Immunotherapy has been considered as a treatment for these tumors because of its ability to provide specific and sustained tumor killing. By nature, this approach is inflammatory and remains controversial due to the potential for catastrophic inflammatory toxicity in the brainstem. In order to address whether this approach should be considered as a clinical option, we characterized the efficacy/toxicity profile of transgenic and chimeric antigen receptor (CAR) T-cell therapies in the brainstem using immunocompetent, syngeneic mouse models. We first adoptively transferred naïve transgenic T-cells recognizing the model tumor antigens gp100 or ovalbumin to treat established aggressive, transplantable murine tumors in the brainstem. Encouragingly, this therapy significantly extended median survival (16 to 32 days; p<.001) with no signs of therapeutic toxicity. We plan to expand these studies by incorporating hgp100 into a spontaneously-occurring, engineered model of DIPG, followed by transgenic T-cell treatment. Lastly and most clinically-relevant, we have used CAR T-cell therapy to treat B16 melanoma engineered to express EGFRvIII and implanted into the brainstem. This therapy extended median survival from 14 to 30 days (p<.001). We plan to evaluate whether combinatorial approaches using checkpoint inhibitors or oncolytic viruses can further enhance survival. Together these data from immunocompetent mouse models demonstrate that T-cell immunotherapies are well- tolerated and efficacious against tumors located in the brainstem, opening the door for future clinical trials.

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