Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.
Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.
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DOI：
10.1371/journal.pmed.1002352
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发表时间：
2017-07
期刊：
影响因子：
15.8
通讯作者：
Brohi K
中科院分区：
文献类型：
--
作者：
Cabrera CP;Manson J;Shepherd JM;Torrance HD;Watson D;Longhi MP;Hoti M;Patel MB;O'Dwyer M;Nourshargh S;Pennington DJ;Barnes MR;Brohi K
严重的创伤会引起免疫系统的广泛反应。这种“基因组风暴”可能导致不良后果，包括多器官功能障碍综合征（MODS）。MODS具有高死亡率和发病率，并对长期健康结果产生不利影响。MODS的当代管理完全是支持性的，没有特定的治疗方法被证明在降低发病率或严重程度方面有效。MODS的发病机制尚不清楚，目前提出了几种模型，如过度炎症、二次损伤或促炎途径与抗炎途径之间的不平衡。我们假设创伤后的超急性窗口期可能是理解基因组风暴如何启动的关键，并可能导致对MODS发病机制的新认识。我们对伦敦皇家医院70例损伤严重程度评分≥25的危重患者在损伤后2小时内的超急性期进行了全血转录组和流式细胞术分析。我们比较了36例重伤患者和6例轻伤患者（ISS≤4）的转录组研究结果。随后，我们对34名重伤患者进行了流式细胞术分析，并与9名健康志愿者的结果进行了比较。损伤后，只有1239个基因转录本（4%）在重伤患者中差异表达。损伤后24小时，6294个转录本（21%）与超急性期相比差异表达。在损伤后24小时，只有202个（16%）基因在超急性期差异表达时仍向相同方向表达。通路分析显示，模式识别和先天炎症通路主要上调，适应性反应下调。免疫反褶积、流式细胞术和模块化分析表明，中性粒细胞和自然杀伤细胞（NK）具有中心作用，T细胞和B细胞反应表达不足。在转录组队列中，20名重伤患者后来发展为MODS。与16例未发生MODS （NoMODS）的患者相比，最大的差异表达出现在超急性窗期。在MODS和NoMODS中，入院时有363个基因差异表达，而损伤后24小时只有33个基因差异表达。在超急性窗口中差异表达的MODS转录本在与细胞存活和机体死亡相关的疾病和生物学功能中而不是炎症途径中表现出富集。在后来发展为MODS的患者中，NK细胞信号通路和标志物存在差异上调，而中性粒细胞反褶积标志物则下调。该研究受到样本量的限制，无法对超急性反应的驱动因素和不同MODS表型进行更详细的分析，并且需要在其他危重损伤队列中进行验证。在这项研究中，我们展示了超急性损伤后时间窗口是如何包含对严重损伤反应的一个集中的、特定的特征，从而导致广泛的基因组激活。在这个超急性窗口期，出现了MODS后期发展的转录组特征；它显示了细胞死亡和存活途径的强烈信号，并涉及NK细胞和中性粒细胞群体在这种差异反应中。在一项前瞻性队列研究中，Joanna Shepherd及其同事使用全血转录组和流式细胞术分析来鉴定与损伤后早期集中免疫反应相关的细胞群和基因，这些免疫反应发展为广泛的免疫失调和多器官功能障碍。多器官功能障碍综合征（MODS）常见于危重伤存活患者，并与患者预后不良相关，包括死亡、感染和延长重症监护住院时间。MODS是指多器官系统（包括肺、心脏、肾脏和肝脏）的衰竭，创伤后免疫反应过度或功能失调与MODS的发生有关。导致MODS的确切免疫机制尚不完全清楚，但严重损伤后的最初几分钟到几小时可能对“正常”或“失调”免疫反应的发展至关重要。我们的研究旨在研究对严重损伤的早期免疫反应，以确定是否在导致广泛失调和MODS的超急性时间框架内发生特异性免疫反应。我们研究了36名重伤患者入院时（受伤2小时内）全血样本中的29385个免疫细胞基因，并将其与受伤后24小时和72小时的样本进行了比较。我们分析了发生MODS的重症患者与未发生MODS的重症患者之间的差异，并将其与6例轻伤患者进行了比较。我们还使用流式细胞术分析了34名重伤患者的循环免疫细胞群数量，并将其与健康志愿者进行了比较。我们的研究发现，入院时危重患者和对照患者之间只有1239个（4%）免疫细胞基因不同；然而，这随后在损伤后24小时发展为广泛的反应。将MODS患者与非MODS患者进行比较，我们发现入院时有363个基因存在差异，但在损伤后24小时，两组之间只有33个基因存在差异。对超急性时间框架的进一步分析表明，与MODS患者细胞死亡相关的基因通路富集，并涉及中性粒细胞和自然杀伤免疫细胞在这种反应中。超急性时间框架对于理解对创伤的免疫反应及其随后如何发展为MODS至关重要。在超急性时间框架内，对创伤有集中的免疫反应，随后发展为广泛的免疫反应。MODS信号在超急性窗期最强，在这种反应中涉及细胞死亡途径和先天免疫细胞。
Severe trauma induces a widespread response of the immune system. This “genomic storm” can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response. In a prospective cohort study, Joanna Shepherd and colleagues use whole blood transcriptome and flow cytometry analyses to identify cell populations and genes associated with a focused immune response very early after injury that develops into a widespread immune dysregulation and multiple organ dysfunction. Multiple Organ Dysfunction Syndrome (MODS) is common in patients who survive critical injuries and is associated with poor patient outcomes, including death, infection, and prolonged critical care admission. MODS describes a failure of multiple organ systems (including lung, heart, kidney, and liver), and an excessive or dysfunctional immune response has been implicated in its development after trauma. The precise immune mechanisms leading to MODS are not fully understood, but the first minutes to hours after severe injury are likely to be pivotal to the development of a “normal” or “dysregulated” immune response. Our study was designed to investigate the very early immune responses to critical injury to determine whether a specific immune reaction occurs in the hyperacute timeframe that leads to widespread dysregulation and MODS. We studied 29,385 immune cell genes within whole blood samples obtained from 36 critically injured patients at admission (within 2 hours of injury) and compared these to samples obtained at 24 and 72 hours following injury. We analysed the differences between critically injured patient who developed MODS and those who did not and compared these to 6 patients who had minor injuries. We also used flow cytometry to analyse the numbers of circulating immune cell populations in 34 critically injured patients and compared these to healthy volunteers. Our study identified only 1,239 (4%) immune cell genes that were different between critical and control patients at admission; however, this subsequently developed into a widespread reaction by 24 hours postinjury. Comparing patients with MODS to those without MODS, we found 363 genes were different at admission, but by 24 hours postinjury, only 33 genes differentiated between the groups. Further analysis of the hyperacute timeframe demonstrated enrichment of gene pathways associated with cell death in patients with MODS and implicated neutrophils and natural killer immune cells in this response. The hyperacute timeframe is crucial to understanding the immune response to trauma and how this subsequently develops into MODS. There is a focused immune response to trauma in the hyperacute timeframe, which subsequently develops into a widespread immune reaction. The MODS signal was strongest in the hyperacute window and implicated cell death pathways and innate immune cells in this response.
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影响因子：
168.9
作者：
Naghavi, Mohsen;Wang, Haidong;Lozano, Rafael;Davis, Adrian;Liang, Xiaofeng;Zhou, Maigeng;Vollset, Stein Emil;Ozgoren, Ayse Abbasoglu;Abdalla, Safa;Abd-Allah, Foad;Aziz, Muna I. Abdel;Abera, Semaw Ferede;Aboyans, Victor;Abraham, Biju;Abraham, Jerry P.;Abuabara, Katrina E.;Abubakar, Ibrahim;Abu-Raddad, Laith J.;Abu-Rmeileh, Niveen M. E.;Achoki, Tom;Adelekan, Ademola;Ademi, Zanfi Na;Adofo, Koranteng;Adou, Arsene Kouablan;Adsuar, Jose C.;Arnlov, Johan;Agardh, Emilie Elisabet;Akena, Dickens;Al Khabouri, Mazin J.;Alasfoor, Deena;Albittar, Mohammed;Alegretti, Miguel Angel;Aleman, Alicia V.;Alemu, Zewdie Aderaw;Alfonso-Cristancho, Rafael;Alhabib, Samia;Ali, Mohammed K.;Ali, Raghib;Alla, Francois;Al Lami, Faris;Allebeck, Peter;AlMazroa, Mohammad A.;Salman, Rustam Al-Shahi;Alsharif, Ubai;Alvarez, Elena;Alviz-Guzman, Nelson;Amankwaa, Adansi A.;Amare, Azmeraw T.;Ameli, Omid;Amini, Hassan;Ammar, Walid;Anderson, H. Ross;Anderson, Benjamin O.;Antonio, Carl Abelardo T.;Anwari, Palwasha;Apfel, Henry;Cunningham, Solveig Argeseanu;Arsenijevic, Valentina S. Arsic;Al Artaman;Asad, Majed Masoud;Asghar, Rana J.;Assadi, Reza;Atkins, Lydia S.;Atkinson, Charles;Badawi, Alaa;Bahit, Maria C.;Bakfalouni, Talal;Balakrishnan, Kalpana;Balalla, Shivanthi;Banerjee, Amitava;Barber, Ryan M.;Barker-Collo, Suzanne L.;Barquera, Simon;Barregard, Lars;Barrero, Lope H.;Barrientos-Gutierrez, Tonatiuh;Basu, Arindam;Basu, Sanjay;Basulaiman, Mohammed Omar;Beardsley, Justin;Bedi, Neeraj;Beghi, Ettore;Bekele, Tolesa;Bell, Michelle L.;Benjet, Corina;Bennett, Derrick A.;Bensenor, Isabela M.;Benzian, Habib;Bertozzi-Villa, Amelia;Beyene, Tariku Jibat;Bhala, Neeraj;Bhalla, Ashish;Bhutta, Zulfiqar A.;Bikbov, Boris;Bin Abdulhak, Aref;Biryukov, Stan;Blore, Jed D.;Blyth, Fiona M.;Bohensky, Megan A.;Borges, Guilherme;Bose, Dipan;Boufous, Soufiane;Bourne, Rupert R.;Boyers, Lindsay N.;Brainin, Michael;Brauer, Michael;Brayne, Carol E. G.;Brazinova, Alexandra;Breitborde, Nicholas;Brenner, Hermann;Briggs, Adam D. M.;Brown, Jonathan C.;Brugha, Traolach S.;Buckle, Geoffrey C.;Bui, Linh Ngoc;Bukhman, Gene;Burch, Michael;Nonato, Ismael Ricardo Campos;Carabin, Helesne;Cardenas, Rosario;Carapetis, Jonathan;Carpenter, David O.;Caso, Valeria;Castaneda-Orjuela, Carlos A.;Castro, Ruben Estanislao;Catala-Lopez, Ferrn;Cavalleri, Fiorella;Chang, Jung-Chen;Charlson, Fiona C.;Che, Xuan;Chen, Honglei;Chen, Yingyao;Chen, Jian Sheng;Chen, Zhengming;Chiang, Peggy Pei-Chia;Chimed-Ochir, Odgerel;Chowdhury, Rajiv;Christensen, Hanne;Christophi, Costas A.;Chuang, Ting-Wu;Chugh, Sumeet S.;Cirillo, Massimo;Coates, Matthew M.;Coffeng, Luc Edgar;Coggeshall, Megan S.;Cohen, Aaron;Colistro, Valentina;Colquhoun, Samantha M.;Colomar, Mercedes;Cooper, Leslie Trumbull;Cooper, Cyrus;Coppola, Luis M.;Cortinovis, Monica;Courville, Karen;Cowie, Benjamin C.;Criqui, Michael H.;Crump, John A.;Cuevas-Nasu, Lucia;Leite, Iuri da Costa;Dabhadkar, Kaustubh C.;Dandona, Lalit;Dandona, Rakhi;Dansereau, Emily;Dargan, Paul I.;Dayama, Anand;De la Cruz-Gongora, Vanessa;de la Vega, Shelley F.;De Leo, Diego;Degenhardt, Louisa;del Pozo-Cruz, Borja;Dellavalle, Robert P.;Deribe, Kebede;Jarlais, Don C. Des;Dessalegn, Muluken;deVeber, Gabrielle A.;Dharmaratne, Samath D.;Dherani, Mukesh;Diaz-Ortega, Jose-Luis;Diaz-Torne, Cesar;Dicker, Daniel;Ding, Eric L.;Dokova, Klara;Dorsey, E. Ray;Driscoll, Tim R.;Duan, Leilei;Duber, Herbert C.;Durrani, Adnan M.;Ebel, Beth E.;Edmond, Karen M.;Ellenbogen, Richard G.;Elshrek, Yousef;Ermakov, Sergey Petrovich;Erskine, Holly E.;Eshrati, Babak;Esteghamati, Alireza;Estep, Kara;Fuerst, Thomas;Fahimi, Saman;Fahrion, Anna S.;Faraon, Emerito Jose A.;Farzadfar, Farshad;Fay, Derek F. J.;Feigl, Andrea B.;Feigin, Valery L.;Felicio, Manuela Mendonca;Fereshtehnejad, Seyed-Mohammad;Fernandes, Jefferson G.;Ferrari, Alize J.;Fleming, Thomas D.;Foigt, Nataliya;Foreman, Kyle;Forouzanfar, Mohammad H.;Fowkes, F. Gerry R.;Fra Paleo, Urbano;Franklin, Richard C.;Futran, Neal D.;Gaffikin, Lynne;Gambashidze, Ketevan;Gankpe, Fortune Gbetoho;Garcia-Guerra, Francisco Armando;Garcia, Ana Cristina;Geleijnse, Johanna M.;Gessner, Bradford D.;Gibney, Katherine B.;Gillum, Richard F.;Gilmour, Stuart;Abdelmageem, Ibrahim;Ginawi, Mohamed;Giroud, Maurice;Glaser, Elizabeth L.;Goenka, Shifalika;Dantes, Hector Gomez;Gona, Philimon;Gonzalez-Medina, Diego;Guinovart, Caterina;Gupta, Rahul;Gupta, Rajeev;Gosselin, Richard A.;Gotay, Carolyn C.;Goto, Atsushi;Gowda, Hube N.;Graetz, Nicholas;Greenwell, K. Fern;Gugnani, Harish Chander;Gunnell, David;Gutierrez, Reyna A.;Haagsma, Juanita;Hafezi-Nejad, Nima;Hagan, Holly;Hagstromer, Maria;Halasa, Yara A.;Hamadeh, Randah Ribhi;Hamavid, Hannah;Hammami, Mouhanad;Hancock, Jamie;Hankey, Graeme J.;Hansen, Gillian M.;Harb, Hilda L.;Harewood, Heather;Haro, Josep Maria;Havmoeller, Rasmus;Hay, Roderick J.;Hay, Simon I.;Hedayati, Mohammad T.;Pi, Ileana B. Heredia;Heuton, Kyle R.;Heydarpour, Pouria;Higashi, Hideki;Hijar, Martha;Hoek, Hans W.;Hoffman, Howard J.;Hornberger, John C.;Hosgood, H. Dean;Hossain, Mazeda;Hotez, Peter J.;Hoy, Damian G.;Hsairi, Mohamed;Hu, Guoqing;Huang, John J.;Huffman, Mark D.;Hughes, Andrew J.;Husseini, Abdullatif;Huynh, Chantal;Iannarone, Marissa;Iburg, Kim M.;Idrisov, Bulat T.;Ikeda, Nayu;Innos, Kaire;Inoue, Manami;Islami, Farhad;Ismayilova, Samaya;Jacobsen, Kathryn H.;Jassal, Simerjot;Jayaraman, Sudha P.;Jensen, Paul N.;Jha, Vivekanand;Jiang, Guohong;Jiang, Ying;Jonas, Jost B.;Joseph, Jonathan;Juel, Knud;Kabagambe, Edmond Kato;Kan, Haidong;Karch, Andre;Karimkhani, Chante;Karthikeyan, Ganesan;Kassebaum, Nicholas;Kaul, Anil;Kawakami, Norito;Kazanjan, Konstantin;Kazi, Dhruv S.;Kemp, Andrew H.;Kengne, Andre Pascal;Keren, Andre;Kereselidze, Maia;Khader, Yousef Saleh;Khalifa, Shams Eldin Ali Hassan;Khan, Ejaz Ahmed;Khan, Gulfaraz;Khang, Young-Ho;Kieling, Christian;Kinfu, Yohannes;Kinge, Jonas M.;Kim, Daniel;Kim, Sungroul;Kivipelto, Miia;Knibbs, Luke;Knudsen, Ann Kristin;Kokubo, Yoshihiro;Kosen, Sowarta;Kotagal, Meera;Kravchenko, Michael A.;Krishnaswami, Sanjay;Krueger, Hans;Defo, Barthelemy Kuate;Kuipers, Ernst J.;Bicer, Burcu Kucuk;Kulkarni, Chanda;Kulkarni, Veena S.;Kumar, Kaushalendra;Kumar, Ravi B.;Kwan, Gene F.;Kyu, Hmwe;Lai, Taavi;Balaji, Arjun Lakshmana;Lalloo, Ratilal;Lallukka, Tea;Lam, Hilton;Lan, Qing;Lansingh, Van C.;Larson, Heidi J.;Larsson, Anders;Lavados, Pablo M.;Lawrynowicz, Alicia E. B.;Leasher, Janet L.;Lee, Jong-Tae;Leigh, James;Leinsalu, Mall;Leung, Ricky;Levitz, Carly;Li, Bin;Li, Yichong;Li, Yongmei;Liddell, Chelsea;Lim, Stephen S.;de Lima, Graca Maria Ferreira;Lind, Maggie L.;Lipshultz, Steven E.;Liu, Shiwei;Liu, Yang;Lloyd, Belinda K.;Lofgren, Katherine T.;Logroscino, Giancarlo;London, Stephanie J.;Lortet-Tieulent, Joannie;Lotufo, Paulo A.;Lucas, Robyn M.;Lunevicius, Raimundas;Lyons, Ronan Anthony;Ma, Stefan;Machado, Vasco Manuel Pedro;MacIntyre, Michael F.;Mackay, Mark T.;MacLachlan, Jennifer H.;Magis-Rodriguez, Carlos;Mahdi, Abbas A.;Majdan, Marek;Malekzadeh, Reza;Mangalam, Srikanth;Mapoma, Christopher Chabila;Marape, Marape;Marcenes, Wagner;Margono, Christopher;Marks, Guy B.;Marzan, Melvin Barrientos;Masci, Joseph R.;Mashal, Mohammad Taufi Q.;Masiye, Felix;Mason-Jones, Amanda J.;Matzopolous, Richard;Mayosi, Bongani M.;Mazorodze, Tasara T.;McGrath, John J.;Mckay, Abigail C.;Mckee, Martin;McLain, Abigail;Meaney, Peter A.;Mehndiratta, Man Mohan;Mejia-Rodriguez, Fabiola;Melaku, Yohannes Adama;Meltzer, Michele;Memish, Ziad A.;Mendoza, Walter;Mensah, George A.;Meretoja, Atte;Mhimbira, Francis A.;Miller, Ted R.;Mills, Edward J.;Misganaw, Awoke;Mishra, Santosh K.;Mock, Charles N.;Moffitt, Terrie E.;Ibrahim, Norlinah Mohamed;Mohammad, Karzan Abdulmuhsin;Mokdad, Ali H.;Mola, Glen Liddell;Monasta, Lorenzo;Monis, Jonathan de la Cruz;Hernandez, Julio C. Montaez;Montico, Marcella;Montine, Thomas J.;Mooney, Meghan D.;Moore, Ami R.;Moradi-Lakeh, Maziar;Moran, Andrew E.;Mori, Rintaro;Moschandreas, Joanna;Moturi, Wilkister Nyaora;Moyer, Madeline L.;Mozaffarian, Dariush;Mueller, Ulrich O.;Mukaigawara, Mitsuru;Mullany, Erin C.;Murray, Joseph;Mustapha, Adetoun;Naghavi, Paria;Naheed, Aliya;Naidoo, Kovin S.;Naldi, Luigi;Nand, Devina;Nangia, Vinay;Narayan, K. M. Venkat;Nash, Denis;Nasher, Jamal;Nejjari, Chakib;Nelson, Robert G.;Neuhouser, Marian;Neupane, Sudan Prasad;Newcomb, Polly A.;Newman, Lori;Newton, Charles R.;Ng, Marie;Ngalesoni, Frida Namnyak;Nguyen, Grant;Nhung Thi Trang Nguyen;Nisar, Muhammad Imran;Nolte, Sandra;Norheim, Ole F.;Norman, Rosana E.;Norrving, Bo;Nyakarahuka, Luke;Odell, Shaun;O'Donnell, Martin;Ohkubo, Takayoshi;Ohno, Summer Lockett;Olusanya, Bolajoko O.;Omer, Saad B.;Opio, John Nelson;Orisakwe, Orish Ebere;Ortblad, Katrina F.;Ortiz, Alberto;Otayza, Maria Lourdes K.;Pain, Amanda W.;Pandian, Jeyaraj D.;Panelo, Carlo Irwin;Panniyammakal, Jeemon;Papachristou, Christina;Paternina Caicedo, Angel J.;Patten, Scott B.;Patton, George C.;Paul, Vinod K.;Pavlin, Boris;Pearce, Neil;Pellegrini, Carlos A.;Pereira, David M.;Peresson, Sophie C.;Perez-Padilla, Rogelio;Perez-Ruiz, Fernando P.;Perico, Norberto;Pervaiz, Aslam;Pesudovs, Konrad;Peterson, Carrie B.;Petzold, Max;Phillips, Bryan K.;Phillips, David E.;Phillips, Michael R.;Plass, Dietrich;Piel, Frederic Bernard;Poenaru, Dan;Polinder, Suzanne;Popova, Svetlana;Poulton, Richie G.;Pourmalek, Farshad;Prabhakaran, Dorairaj;Qato, Dima;Quezada, Amado D.;Quistberg, D. Alex;Rabito, Felicia;Rafay, Anwar;Rahimi, Kazem;Rahimi-Movaghar, Vafa;Rahman, Sajjad U. R.;Raju, Murugesan;Rakovac, Ivo;Rana, Saleem M.;Refaat, Amany;Remuzzi, Giuseppe;Ribeiro, Antonio L.;Ricci, Stefano;Riccio, Patricia M.;Richardson, Lee;Richardus, Jan Hendrik;Roberts, Bayard;Roberts, D. Allen;Robinson, Margaret;Roca, Anna;Rodriguez, Alina;Rojas-Rueda, David;Ronfani, Luca;Room, Robin;Roth, Gregory A.;Rothenbacher, Dietrich;Rothstein, David H.;Rowley, Jane Tf;Roy, Nobhojit;Ruhago, George M.;Rushton, Lesley;Sambandam, Sankar;Soreide, Kjetil;Saeedi, Mohammad Yahya;Saha, Sukanta;Sahathevan, Ramesh;Sahraian, Mohammad Ali;Sahle, Berhe Weldearegawi;Salomon, Joshua A.;Salvo, Deborah;Samonte, Genesis May J.;Sampson, Uchechukwu;Sanabria, Juan Ramon;Sandar, Logan;Santos, Itamar S.;Satpathy, Maheswar;Sawhney, Monika;Saylan, Mete;Scarborough, Peter;Schoettker, Ben;Schmidt, Juergen C.;Schneider, Ione J. C.;Schumacher, Austin E.;Schwebel, David C.;Scott, James G.;Sepanlou, Sadaf G.;Servan-Mori, Edson E.;Shackelford, Katya;Shaheen, Amira;Shahraz, Saeid;Shakh-Nazarova, Marina;Shangguan, Siyi;She, Jun;Sheikhbahaei, Sara;Shepard, Donald S.;Shibuya, Kenji;Shinohara, Yukito;Shishani, Kawkab;Shiue, Ivy;Shivakoti, Rupak;Shrime, Mark G.;Sigfusdottir, Inga Dora;Silberberg, Donald H.;Silva, Andrea P.;Simard, Edgar P.;Sindi, Shireen;Singh, Jasvinder A.;Singh, Lavanya;Sioson, Edgar;Skirbekk, Vegard;Sliwa, Karen;So, Samuel;Soljak, Michael;Soneji, Samir;Soshnikov, Sergey S.;Sposato, Luciano A.;Sreeramareddy, Chandrashekhar T.;Stanaway, Jeff Rey D.;Stathopoulou, Vasiliki Kalliopi;Steenland, Kyle;Stein, Claudia;Steiner, Caitlyn;Stevens, Antony;Stoeckl, Heidi;Straif, Kurt;Stroumpoulis, Konstantinos;Sturua, Lela;Sunguya, Bruno F.;Swaminathan, Soumya;Swaroop, Mamta;Sykes, Bryan L.;Tabb, Karen M.;Takahashi, Ken;Talongwa, Roberto Tchio;Tan, Feng;Tanne, David;Tanner, Marcel;Tavakkoli, Mohammad;Ao, Braden Te;Teixeira, Carolina Maria;Templin, Tara;Tenkorang, Eric Yeboah;Terkawi, Abdullah Sulieman;Thomas, Bernadette A.;Thorne-Lyman, Andrew L.;Thrift, Amanda G.;Thurston, George D.;Tillmann, Taavi;Tirschwell, David L.;Tleyjeh, Imad M.;Tonelli, Marcello;Topouzis, Fotis;Towbin, Jeffrey A.;Toyoshima, Hideaki;Traebert, Jefferson;Tran, Bach X.;Truelsen, Thomas;Trujillo, Ulises;Trillini, Matias;Dimbuene, Zacharie Tsala;Tsilimbaris, Miltiadis;Tuzcu, E. Murat;Ubeda, Clotilde;Uchendu, Uche S.;Ukwaja, Kingsley N.;Undurraga, Eduardo A.;Vallely, Andrew J.;van de Vijver, Steven;van Gool, Coen H.;Varakin, Yuri Y.;Vasankari, Tommi J.;Vasconcelos, Ana Maria Nogales;Vavilala, Monica S.;Venketasubramanian, N.;Vijayakumar, Lakshmi;Villalpando, Salvador;Violante, Francesco S.;Vlassov, Vasiliy Victorovich;Wagner, Gregory R.;Waller, Stephen G.;Wang, JianLi;Wang, Linhong;Wang, XiaoRong;Wang, Yanping;Warouw, Tati Suryati;Weichenthal, Scott;Weiderpass, Elisabete;Weintraub, Robert G.;Wenzhi, Wang;Werdecker, Andrea;Wessells, K. Ryan R.;Westerman, Ronny;Whiteford, Harvey A.;Wilkinson, James D.;Williams, Thomas Neil;Woldeyohannes, Solomon Meseret;Wolfe, Charles D. A.;Wolock, Timothy M.;Woolf, Anthony D.;Wong, John Q.;Wright, Jonathan L.;Wulf, Sarah;Wurtz, Brittany;Xu, Gelin;Yang, Yang C.;Yano, Yuichiro;Yatsuya, Hiroshi;Yip, Paul;Yonemoto, Naohiro;Yoon, Seok-Jun;Younis, Mustafa;Yu, Chuanhua;Jin, Kim Yun;Zaki, Maysaa El Sayed;Zamakhshary, Mohammed Fouad;Zeeb, Hajo;Zhang, Yong;Zhao, Yong;Zheng, Yingfeng;Zhu, Jun;Zhu, Shankuan;Zonies, David;Zou, Xiao Nong;Zunt, Joseph R.;Vos, Theo;Lopez, Alan D.;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
DOI：
10.1136/injuryprev-2015-041616
发表时间：
2016-02
期刊：
Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention
影响因子：
--
作者：
Haagsma JA;Graetz N;Bolliger I;Naghavi M;Higashi H;Mullany EC;Abera SF;Abraham JP;Adofo K;Alsharif U;Ameh EA;Ammar W;Antonio CA;Barrero LH;Bekele T;Bose D;Brazinova A;Catalá-López F;Dandona L;Dandona R;Dargan PI;De Leo D;Degenhardt L;Derrett S;Dharmaratne SD;Driscoll TR;Duan L;Petrovich Ermakov S;Farzadfar F;Feigin VL;Franklin RC;Gabbe B;Gosselin RA;Hafezi-Nejad N;Hamadeh RR;Hijar M;Hu G;Jayaraman SP;Jiang G;Khader YS;Khan EA;Krishnaswami S;Kulkarni C;Lecky FE;Leung R;Lunevicius R;Lyons RA;Majdan M;Mason-Jones AJ;Matzopoulos R;Meaney PA;Mekonnen W;Miller TR;Mock CN;Norman RE;Orozco R;Polinder S;Pourmalek F;Rahimi-Movaghar V;Refaat A;Rojas-Rueda D;Roy N;Schwebel DC;Shaheen A;Shahraz S;Skirbekk V;Søreide K;Soshnikov S;Stein DJ;Sykes BL;Tabb KM;Temesgen AM;Tenkorang EY;Theadom AM;Tran BX;Vasankari TJ;Vavilala MS;Vlassov VV;Woldeyohannes SM;Yip P;Yonemoto N;Younis MZ;Yu C;Murray CJ;Vos T
通讯作者：
Vos T
DOI：
10.1097/00005373-199010000-00003
发表时间：
1990-10-01
影响因子：
--
作者：
COPES, WS;CHAMPION, HR;SCHWAITZBERG, S
通讯作者：
SCHWAITZBERG, S
DOI：
10.1097/00005373-197403000-00001
发表时间：
1974-01-01
影响因子：
--
作者：
BAKER, SP;ONEILL, B;LONG, WB
通讯作者：
LONG, WB
影响因子：
15.9
作者：
Pillay, Janesh;Kamp, Vera M.;Koenderman, Leo
通讯作者：
Koenderman, Leo