@article{MTMT:3120851, title = {Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group}, url = {https://m2.mtmt.hu/api/publication/3120851}, author = {Dreier, JP and Fabricius, M and Ayata, C and Sakowitz, OW and William, Shuttleworth C and Dohmen, C and Graf, R and Vajkoczy, P and Helbok, R and Suzuki, M and Schiefecker, AJ and Major, S and Winkler, MK and Kang, EJ and Milakara, D and Oliveira-Ferreira, AI and Reiffurth, C and Revankar, GS and Sugimoto, K and Dengler, NF and Hecht, N and Foreman, B and Feyen, B and Kondziella, D and Friberg, CK and Piilgaard, H and Rosenthal, ES and Westover, MB and Maslarova, A and Santos, E and Hertle, D and Sanchez-Porras, R and Jewell, SL and Balanca, B and Platz, J and Hinzman, JM and Lückl, János and Schoknecht, K and Scholl, M and Drenckhahn, C and Feuerstein, D and Eriksen, N and Horst, V and Bretz, JS and Jahnke, P and Scheel, M and Bohner, G and Rostrup, E and Pakkenberg, B and Heinemann, U and Claassen, J and Carlson, AP and Kowoll, CM and Lublinsky, S and Chassidim, Y and Shelef, I and Friedman, A and Brinker, G and Reiner, M and Kirov, SA and Andrew, RD and Farkas, Eszter and Guresir, E and Vatter, H and Chung, LS and Brennan, KC and Lieutaud, T and Marinesco, S and Maas, AI and Sahuquillo, J and Dahlem, MA and Richter, F and Herreras, O and Boutelle, MG and Okonkwo, DO and Bullock, MR and Witte, OW and Martus, P and van den Maagdenberg, AM and Ferrari, MD and Dijkhuizen, RM and Shutter, LA and Andaluz, N and Schulte, AP and MacVicar, B and Watanabe, T and Woitzik, J and Lauritzen, M and Strong, AJ and Hartings, JA}, doi = {10.1177/0271678X16654496}, journal-iso = {J CEREBR BLOOD F MET}, journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM}, volume = {37}, unique-id = {3120851}, issn = {0271-678X}, abstract = {Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.}, year = {2017}, eissn = {1559-7016}, pages = {1595-1625}, orcid-numbers = {Lückl, János/0000-0001-8094-771X; Farkas, Eszter/0000-0002-8478-9664} } @article{MTMT:3250359, title = {Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management}, url = {https://m2.mtmt.hu/api/publication/3250359}, author = {Maegele, M and Schochl, H and Menovsky, T and Marechal, H and Marklund, N and Büki, András and Stanworth, S}, doi = {10.1016/S1474-4422(17)30197-7}, journal-iso = {LANCET NEUROL}, journal = {LANCET NEUROLOGY}, volume = {16}, unique-id = {3250359}, issn = {1474-4422}, abstract = {Normal haemostasis depends on an intricate balance between mechanisms of bleeding and mechanisms of thrombosis, and this balance can be altered after traumatic brain injury (TBI). Impaired haemostasis could exacerbate the primary insult with risk of initiation or aggravation of bleeding; anticoagulant use at the time of injury can also contribute to bleeding risk after TBI. Many patients with TBI have abnormalities on conventional coagulation tests at admission to the emergency department, and the presence of coagulopathy is associated with increased morbidity and mortality. Further blood testing often reveals a range of changes affecting platelet numbers and function, procoagulant or anticoagulant factors, fibrinolysis, and interactions between the coagulation system and the vascular endothelium, brain tissue, inflammatory mechanisms, and blood flow dynamics. However, the degree to which these coagulation abnormalities affect TBI outcomes and whether they are modifiable risk factors are not known. Although the main challenge for management is to address the risk of hypocoagulopathy with prolonged bleeding and progression of haemorrhagic lesions, the risk of hypercoagulopathy with an increased prothrombotic tendency also warrants consideration.}, keywords = {FACTOR-XIII DEFICIENCY; PLACEBO-CONTROLLED TRIAL; CRITICALLY-ILL PATIENTS; MOLECULAR-WEIGHT HEPARIN; RECOMBINANT FACTOR VIIA; Prothrombin complex concentrate; BLOOD-CELL TRANSFUSION; RANDOMIZED-CLINICAL-TRIAL; DIRECT ORAL ANTICOAGULANTS; VENOUS THROMBOEMBOLISM PROPHYLAXIS}, year = {2017}, eissn = {1474-4465}, pages = {630-647} } @article{MTMT:3248575, title = {Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain injury Dynamics: A Systematic Review}, url = {https://m2.mtmt.hu/api/publication/3248575}, author = {Thelin, EP and Zeiler, FA and Ercole, A and Mondello, S and Büki, András and Bellander, BM and Helmy, A and Menon, DK and Nelson, DW}, doi = {10.3389/fneur.2017.00300}, journal-iso = {FRONT NEUR}, journal = {FRONTIERS IN NEUROLOGY}, volume = {8}, unique-id = {3248575}, issn = {1664-2295}, year = {2017}, eissn = {1664-2295} } @article{MTMT:31999947, title = {Variation in structure and process of care in traumatic brain injury: Provider profiles of European Neurotrauma Centers participating in the CENTER-TBI study}, url = {https://m2.mtmt.hu/api/publication/31999947}, author = {Cnossen, M.C. and Polinder, S. and Lingsma, H.F. and Maas, A.I.R. and Menon, D. and Steyerberg, E.W.}, doi = {10.1371/journal.pone.0161367}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {31999947}, issn = {1932-6203}, year = {2016}, eissn = {1932-6203}, orcid-numbers = {Barzó, Pál/0000-0001-8717-748X; Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:2995757, title = {Hypothermia for Intracranial Hypertension after Traumatic Brain Injury}, url = {https://m2.mtmt.hu/api/publication/2995757}, author = {Andrews, PJ and Sinclair, HL and Rodriguez, A and Harris, BA and Battison, CG and Rhodes, JK and Murray, GD}, doi = {10.1056/NEJMoa1507581}, journal-iso = {NEW ENGL J MED}, journal = {NEW ENGLAND JOURNAL OF MEDICINE}, volume = {373}, unique-id = {2995757}, issn = {0028-4793}, abstract = {BACKGROUND: In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. METHODS: We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35 degrees C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). RESULTS: We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). CONCLUSIONS: In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).}, keywords = {Adult; Middle Aged; Humans; Treatment Outcome; Combined Modality Therapy; intensive care units; *Hypothermia, Induced; Intention to Treat Analysis; Intracranial Pressure/physiology; Decompressive craniectomy; Intracranial Hypertension/etiology/*therapy; Brain Injuries/*complications/mortality/physiopathology/therapy; Barbiturates/therapeutic use; Arterial Pressure/physiology}, year = {2015}, eissn = {1533-4406}, pages = {2403-2412}, orcid-numbers = {Barzó, Pál/0000-0001-8717-748X} } @article{MTMT:2906963, title = {Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): a prospective longitudinal observational study}, url = {https://m2.mtmt.hu/api/publication/2906963}, author = {Maas, AI and Menon, DK and Steyerberg, EW and Citerio, G and Lecky, F and Manley, GT and Hill, S and Legrand, V and Sorgner, A}, doi = {10.1227/NEU.0000000000000575}, journal-iso = {NEUROSURGERY}, journal = {NEUROSURGERY}, volume = {76}, unique-id = {2906963}, issn = {0148-396X}, abstract = {BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20,000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management.}, year = {2015}, eissn = {1524-4040}, pages = {67-80}, orcid-numbers = {Barzó, Pál/0000-0001-8717-748X; Czeiter, Endre/0000-0002-9578-6944} } @article{MTMT:2349651, title = {The Challenge of Mild Traumatic Brain Injury: Role of Biochemical Markers in Diagnosis of Brain Damage.}, url = {https://m2.mtmt.hu/api/publication/2349651}, author = {Mondello, S and Schmid, K and Berger, RP and Kobeissy, F and Italiano, D and Jeromin, A and Hayes, RL and Tortella, FC and Büki, András}, doi = {10.1002/med.21295}, journal-iso = {MED RES REV}, journal = {MEDICINAL RESEARCH REVIEWS}, volume = {34}, unique-id = {2349651}, issn = {0198-6325}, abstract = {During the past decade there has been an increasing recognition of the incidence of mild traumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficits that may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteria for mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detect brain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss the current research on serum biomarkers for mTBI including their rationale and diagnostic performances. Sensitive and specific biomarkers reflecting brain injury can provide important information regarding TBI pathophysiology and serve as candidate markers for predicting abnormal computed tomography findings and/or the development of residual deficits in patients who sustain an mTBI. We also outline the roles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and military injuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emerging proteomics-based strategies for identifying novel markers will be discussed.}, year = {2014}, eissn = {1098-1128}, pages = {503-531} } @article{MTMT:2564842, title = {Human Traumatic Brain Injury Induces Autoantibody Response against Glial Fibrillary Acidic Protein and Its Breakdown Products.}, url = {https://m2.mtmt.hu/api/publication/2564842}, author = {Zhang, Z and Zoltewicz, JS and Mondello, S and Newsom, KJ and Yang, Z and Yang, B and Kobeissy, F and Guingab, J and Glushakova, O and Robicsek, S and Heaton, S and Büki, András and Hannay, J and Gold, MS and Rubenstein, R and Lu, XC and Dave, JR and Schmid, K and Tortella, F and Robertson, CS and Wang, KK}, doi = {10.1371/journal.pone.0092698}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {2564842}, issn = {1932-6203}, abstract = {The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.}, year = {2014}, eissn = {1932-6203} } @article{MTMT:2424624, title = {Toward an international initiative for traumatic brain injury research.}, url = {https://m2.mtmt.hu/api/publication/2424624}, author = {Tosetti, P and Hicks, RR and Theriault, E and Phillips, A and Koroshetz, W and Draghia-Akli, R}, doi = {10.1089/neu.2013.2896}, journal-iso = {J NEUROTRAUM}, journal = {JOURNAL OF NEUROTRAUMA}, volume = {30}, unique-id = {2424624}, issn = {0897-7151}, abstract = {The European Commission (EC) and the National Institutes of Health (NIH) jointly sponsored a workshop on October 18-20, 2011 in Brussels to discuss the feasibility and benefits of an international collaboration in the field of traumatic brain injury (TBI) research. The workshop brought together scientists, clinicians, patients, and industry representatives from around the globe as well as funding agencies from the EU, Spain, the United States, and Canada. Sessions tackled both the possible goals and governance of a future initiative and the scientific questions that would most benefit from an integrated international effort: how to optimize data collection and sharing; injury classification; outcome measures; clinical study design; and statistical analysis. There was a clear consensus that increased dialogue and coordination of research at an international level would be beneficial for advancing TBI research, treatment, and care. To this end, the EC, the NIH, and the Canadian Institutes of Health Research expressed interest in developing a framework for an international initiative for TBI Research (InTBIR). The workshop participants recommended that InTBIR initially focus on collecting, standardizing, and sharing clinical TBI data for comparative effectiveness research, which will ultimately result in better management and treatments for TBI.}, year = {2013}, eissn = {1557-9042}, pages = {1211-1222} } @article{MTMT:2802038, title = {The economic cost of brain disorders in Europe}, url = {https://m2.mtmt.hu/api/publication/2802038}, author = {Olesen, J and Gustavsson, A and Svensson, M and Wittchen, HU and Jonsson, B}, doi = {10.1111/j.1468-1331.2011.03590.x}, journal-iso = {EUR J NEUROL}, journal = {EUROPEAN JOURNAL OF NEUROLOGY}, volume = {19}, unique-id = {2802038}, issn = {1351-5101}, abstract = {Background and purpose: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries. Methods: One-year prevalence and annual cost per person of 19 major groups of disorders are based on 'best estimates' derived from systematic literature reviews by panels of experts in epidemiology and health economics. Our cost estimation model was populated with national statistics from Eurostat to adjust to 2010 values, converting all local currencies to Euros (sic), imputing cost for countries where no data were available, and aggregating country estimates to purchasing power parityadjusted estimates of the total cost of brain disorders in Europe in 2010. Results: Total European 2010 cost of brain disorders was sic 798 billion, of which direct health care cost 37%, direct non-medical cost 23%, and indirect cost 40%. Average cost per inhabitant was sic 5.550. The European average cost per person with a disorder of the brain ranged between sic 285 for headache and sic 30 000 for neuromuscular disorders. Total annual cost per disorder (in billion sic 2010) was as follows: addiction 65.7; anxiety disorders 74.4; brain tumor 5.2; child/adolescent disorders 21.3; dementia 105.2; eating disorders 0.8; epilepsy 13.8; headache 43.5; mental retardation 43.3; mood disorders 113.4; multiple sclerosis 14.6; neuromuscular disorders 7.7; Parkinson's disease 13.9; personality disorders 27.3; psychotic disorders 93.9; sleep disorders 35.4; somatoform disorder 21.2; stroke 64.1; and traumatic brain injury 33.0. Conclusion: Our cost model revealed that brain disorders overall are much more costly than previously estimated constituting a major health economic challenge for Europe. Our estimate should be regarded as conservative because many disorders or cost items could not be included because of lack of data.}, keywords = {Europe; DISEASE; IMPACT; burden; cost; brain disorder}, year = {2012}, eissn = {1468-1331}, pages = {155-162}, orcid-numbers = {Vécsei, László/0000-0001-8037-3672} } @article{MTMT:2222547, title = {Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2). A randomised, placebo-controlled trial}, url = {https://m2.mtmt.hu/api/publication/2222547}, author = {Olldashi, F and Kerçi, M and Zhurda, T and Ruçi, K and Banushi, A and Traverso, MS and Jiménez, J and Balbi, J and Dellera, C and Svampa, S and Quintana, G and Piñero, G and Teves, J and Seppelt, I and Mountain, D and Hunter, J and Balogh, Zsolt and Zaman, M and Druwé, P and Rutsaert, R and Mazairac, G and Pascal, F and Yvette, Z and Chancellin, D and Okwen, P and Djokam-Liapoe, J and Jangwa, E and Mbuagbaw, L and Fointama, N and Pascal, N and Baillie, F and Jiang, J-Y and Gao, G-Y and Bao, Y-H and Morales, C and Sierra, J and Naranjo, S and Correa, C and Gómez, C and Herrera, J and Caicedo, L and Rojas, A and Pastas, H and Miranda, H and Constaín, A and Perdomo, M and Muñoz, D and Duarte, A and Vásquez, E and Ortiz, C and Ayala, B and Delgado, H and Benavides, G and Rosero, L and Mejía-Mantilla, J and Varela, A and Calle, M and Castillo, J and García, A and Ciro, J and Villa, C and Panesso, R and Flórez, L and Gallego, A and Puentes-Manosalva, F and Medina, L and Márquez, K and Romero, AR and Hernández, R and Martínez, J and Gualteros, W and Urbina, Z and Velandia, J and Benítez, F and Trochez, A and Villarreal, A and Pabón, P and López, H and Quintero, L and Rubiano, A and Tamayo, J and Piñera, M and Navarro, Z and Rondón, D and Bujan, B and Palacios, L and Martínez, D and Hernández, Y and Fernández, Y and Casola, E and Delgado, R and Herrera, C and Arbolaéz, M and Domínguez, M and Iraola, M and Rojas, O and Enseñat, A and Pastrana, I and Rodríguez, D and De La Campa, SA and Fortún, T and Larrea, M and Aragón, L and Madrazo, A and Svoboda, P and Izurieta, M and Daccach, A and Altamirano, M and Ortega, A and Cárdenas, B and González, L and Ochoa, M and Ortega, F and Quichimbo, F and Guiñanzaca, J and Zavala, I and Segura, S and Jerez, J and Acosta, D and Yánez, F and Camacho, R and Khamis, H and Shafei, H and Kheidr, A and Nasr, H and Mosaad, M and Rizk, S and El, Sayed H and Moati, T and Hokkam, E and Amin, M and Lowis, H and Fawzy, M and Bedir, N and Aldars, M and Rodríguez, V and Tobar, J and Alvarenga, J and Shalamberidze, B and Demuria, E and Rtveliashvili, N and Chutkerashvili, G and Dotiashvili, D and Gogichaishvili, T and Ingorokva, G and Kazaishvili, D and Melikidze, B and Iashvili, N and Tomadze, G and Chkhikvadze, M and Khurtsidze, L and Lomidze, Z and Dzagania, D and Kvachadze, N and Gotsadze, G and Kaloiani, V and Kajaia, N and Dakubo, J and Naaeder, S and Sowah, P and Yusuf, A and Ishak, A and Selasi-Sefenu, P and Sibiri, B and Sarpong-Peprah, S and Boro, T and Bopaiah, K and Shetty, K and Subbiah, R and Mulla, L and Doshi, A and Dewan, Y and Grewal, S and Tripathy, P and Mathew, J and Gupta, B and Lal, A and Choudhury, M and Gupta, S and Gupta, S and Chug, A and Pamidimukkala, V and Jagannath, P and Maharaj, M and Vommi, R and Gudipati, N and Chhang, WH and Patel, P and Suthar, N and Banker, D and Patel, J and Dharap, S and Kamble, R and Patkar, S and Lohiya, S and Saraf, R and Kumar, D and Parihar, S and Gupta, R and Mangual, R and Kooper, D and Mohapatra, C and David, S and Rajaleelan, W and Pangi, A and Saraf, V and Chikareddy, S and Mankar, S and Golhar, A and Sakhare, R and Wagh, N and Hazarika, D and Chaudhuri, P and Ketan, P and Purohit, G and Purohit, Y and Pandya, M and Gupta, R and Kiran, S and Walia, S and Goyal, S and Goyal, S and Goyal, S and Attri, A and Sharma, R and Oberai, A and Oberai, M and Oberoi, S and Tripathi, GK and Peettakkandy, V and Karuthillath, P and Vadakammuriyil, P and Pol, J and Pol, S and Saste, M and Raul, S and Tiwari, S and Nelly, N and Chidambaram, M and Kollengode, V and Thampan, S and Rajan, S and Rajan, S and Raju, S and Sharma, R and Babu, SV and Sumathi, C and Chatterjee, P and Agarwal, A and Magar, H and Magar, M and Singh, M and Gupta, D and Haloi, K and Sagdeo, V and Giri, P and Verma, N and Jariwala, R and Goti, A and Prabhu-Gaonkar, A and Utagi, S and Joshi, M and Agrawal, R and Sharma, G and Saini, G and Tewari, V and Yadav, Y and Parihar, V and Venkataramana, N and Rao, S and Reddy, N and Chander, SG and Hathila, V and Das, V and Agaja, K and Purohit, A and Lahari, A and Bhagchandani, R and Vidyasagar, B and Sachan, PK and Das, T and Vyas, S and Bhattacharjee, S and Sancheti, P and Manoj, T and Moideen, M and Pansey, K and Chandrasekaran, VP and Saikia, K and Tata, H and Vhora, S and Shah, A and Rangad, G and Rajasekaran, S and Shankarlal, ST and Devadoss, S and Saleem, M and Pillay, H and Hazarika, Z and Deshmukh, P and Murugappan, SP and Jaiswal, A and Vangani, D and Modha, P and Chonzik, C and Praveen, M and Sethurayar, V and Ipe, S and Shetty, N and Jain, V and Shah, K and Dwikoryanto, M and Golden, N and Atmadjaya, K and Wiargitha, K and Sudiasa, K and Suwedagatha, G and Bal'afif, F and Budipramana, V and Lemuel, A and Chandra, S and Ama, F and Sherafatkazemzadeh, E and Moradi, E and Sheikhi, A and Ziaee, A and Fanaei, A and Hajinasrollah, E and Amini, A and Mohammad, B and Hadi, N and Perone, G and De Peri, E and Volpi, A and Johnson, J and Abe, M and Mutiso, V and Okanga, B and Ojuka, D and Abdullah, B and Rahman, H and Noh, Y and Jamaluddin, S and Dawal, H and Roslani, A and Law, C-W and Devashanti, P and Wahab, Y and Velaiutham, S and Dato, R and Loría, J and Montes, E and Gómez, E and Cazales, V and Bautista, P and Bautista, R and Ahumada, D and Hernández, E and Velásquez, G and Ortega, P and Lira, G and Estrada, F and Martínez, J and Martínez, J and Olaomi, O and Abubakar, Y and Apollo, K and Badejo, O and Ihekire, O and Casasola, J and Iribhogbe, P and Oludiran, O and Obeta, E and Okojie, C and Agbon, EU and Komolafe, E and Olaleye, P and Uzochukwu, T and Onakpoya, U and Dongo, A and Uhunmwagho, O and Eighemerio, E and Morgan, E and Thanni, L and Afolabi, A and Akinola, T and Ademola, A and Akute, O and Khalid, L and Abubakar, L and Aminu, M and Ogirima, M and Attansey, A and Michael, D and Aremu, O and Olugbenga, O and Ukpong, U and Salman, Y and Obianyo, N and Ani, C and Ezeadawi, R and Kehinde, O and Olaide, A and Jogo, A and Bitto, T and Anyanwu, S and Mbonu, O and Oludara, M and Somoye, M and Shehu, B and Ismail, N and Katchy, A and Ndoma-Egba, R and Grace-Inah, N and Songden, Z and Abdulraheem, A and Otu, A and Nottidge, T and Inyang, D and Idiapho, D and Giebel, H and Hassan, R and Adisa, A and Akinkuolie, A and Okam, K and Musa, A and Falope, I and Eze, J and Caballero, J and Azabache, W and Salirrosas, O and Soto, A and Torres, E and Ramírez, G and Pérez, M and Malca, C and Velez, J and Yepez, R and Yupanqui, H and Lagos, P and Rodriguez, D and Flores, J and Moya, A and Barrionuevo, A and Gonzales-Portillo, M and Nunez, E and Eldawlatly, A and Al, Naami M and Delvi, B and Alyafi, W and Djurovic, B and Ng, I and Yaghi, A and Laincz, A and Trenkler, S and Valky, J and Modiba, M and Legodi, P and Rangaka, T and Wallis, L and Muñoz, A and Serrano, A and Misis, M and Rubi, M and De La Torre, V and Ellawala, R and Wijeratna, S and Gunaratna, L and Wijayanayaka, C and Nungu, K and Haonga, B and Mtapa, G and Yutthakasemsunt, S and Kittiwattanagul, W and Piyavechvirat, P and Impool, T and Thummaraj, S and Salaeh, R and Tangchitvittaya, S and Wattanakrai, K and Soonthornthum, C and Jiravongbunrod, T and Meephant, S and Subsompon, P and Pensuwan, P and Chamnongwit, W and Jerbi, Z and Cherif, A and Nash, M and Harris, T and Banerjee, J and Freij, R and Kendall, J and Moore, S and Townend, W and Cottingham, R and Becker, D and Lloyd, S and Burdett-Smith, P and Mirza, K and Webster, A and Brady, S and Grocutt, A and Thurston, J and Lecky, F and Goodacre, S and Mulla, Y and Sakala, D and Chengo, C}, doi = {10.1016/S0140-6736(10)60835-5}, journal-iso = {LANCET}, journal = {LANCET}, volume = {376}, unique-id = {2222547}, issn = {0140-6736}, abstract = {Background Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. Methods This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919. Findings 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14·5%] tranexamic acid group vs 1613 [16·0%] placebo group; relative risk 0·91, 95% CI 0·85-0·97; p=0·0035). The risk of death due to bleeding was significantly reduced (489 [4·9%] vs 574 [5·7%]; relative risk 0·85, 95% CI 0·76-0·96; p=0·0077). Interpretation Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. Funding UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.}, keywords = {Adult; Female; Male; Humans; HEMORRHAGE; INJURY; THROMBOSIS; DEATH; ARTICLE; MORTALITY; INFUSION; human; risk assessment; priority journal; major clinical study; controlled study; drug effect; randomized controlled trial; controlled clinical trial; clinical trial; outcome assessment; multicenter study; placebo; drug safety; blood transfusion; multiple organ failure; Glasgow coma scale; head injury; thorax surgery; heart infarction; cause of death; abdominal surgery; clinical assessment; hospital; blunt trauma; bleeding; antifibrinolytic agent; tranexamic acid; deep vein thrombosis; loading drug dose; Wounds and Injuries; blood vessel occlusion; lung embolism; neurosurgery; penetrating trauma; Antifibrinolytic Agents; pelvis surgery}, year = {2010}, eissn = {1474-547X}, pages = {23-32} }