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      Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy

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          Abstract

          Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.

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          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.

          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. 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.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. 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). 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. UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Cytokine pathways and joint inflammation in rheumatoid arthritis.

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              The IL-1 family: regulators of immunity.

              Over recent years it has become increasingly clear that innate immune responses can shape the adaptive immune response. Among the most potent molecules of the innate immune system are the interleukin-1 (IL-1) family members. These evolutionarily ancient cytokines are made by and act on innate immune cells to influence their survival and function. In addition, they act directly on lymphocytes to reinforce certain adaptive immune responses. This Review provides an overview of both the long-established and more recently characterized members of the IL-1 family. In addition to their effects on immune cells, their involvement in human disease and disease models is discussed.
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                Author and article information

                Contributors
                ee291@cam.ac.uk
                sv377@cam.ac.uk
                peter.whitfield@nhs.net
                klc1000@wbic.cam.ac.uk
                pjah2@cam.ac.uk
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central (London )
                1742-2094
                30 May 2017
                30 May 2017
                2017
                : 14
                : 108
                Affiliations
                [1 ]ISNI 0000000121885934, GRID grid.5335.0, Division of Neurosurgery, Department of Clinical Neurosciences, , University of Cambridge, ; Box 167, Cambridge Biomedical Campus, Cambridge, CB2 0QQ UK
                [2 ]ISNI 0000 0001 0575 1952, GRID grid.418670.c, Southwest Neurosurgical Centre, , Plymouth Hospitals NHS Trust, ; Plymouth, PL6 8DH UK
                Author information
                http://orcid.org/0000-0002-7253-9115
                Article
                881
                10.1186/s12974-017-0881-y
                5450087
                28558815
                3bc52d76-b42e-4d67-b24e-0470b17e3896
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 February 2017
                : 15 May 2017
                Funding
                Funded by: National Institute for Health Research (GB)
                Award ID: NIHR Research Professorship
                Award Recipient :
                Funded by: National Institute for Health Research (GB)
                Award ID: Biomedical Research Centre, Cambridge
                Award Recipient :
                Funded by: Royal College of Surgeons of England (GB)
                Award ID: RCS Research Fellowship
                Award Recipient :
                Funded by: Rosetrees Trust (GB)
                Award ID: Research Fellowship
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Neurosciences
                angiogenesis,chronic subdural haematoma,inflammation,head injury,drug therapy
                Neurosciences
                angiogenesis, chronic subdural haematoma, inflammation, head injury, drug therapy

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