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  • 1
    Online Resource
    Online Resource
    Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 11 ( 2022-11-21), p. 4097-4107
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 11 ( 2022-11-21), p. 4097-4107
    Abstract: COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac321
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
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    Online Resource
    Responses of Posttraumatic Pericontusional Cerebral Blood Flow and Blood Volume to an Increase in Cerebral Perfusion Pressure
    SAGE Publications ; 2003
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 23, No. 11 ( 2003-11), p. 1371-1377
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 23, No. 11 ( 2003-11), p. 1371-1377
    Abstract: In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1097/01.WCB.0000090861.67713.10
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2003
    detail.hit.zdb_id: 2039456-1
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  • 3
    Online Resource
    Online Resource
    Is there a broader role for independent mental capacity advocates in critical care? An exploratory study
    Wiley ; 2018
    In:  Nursing in Critical Care Vol. 23, No. 2 ( 2018-03), p. 82-87
    Details
    In: Nursing in Critical Care, Wiley, Vol. 23, No. 2 ( 2018-03), p. 82-87
    Abstract: This research explores the current and potential future role of independent mental capacity advocates ( IMCAs ) in critical care. The Mental Capacity Act ( MCA ) of 2005 introduced IMCAs as advocates for patients without anyone to represent their best interests, but research suggests that this role is not well understood or implemented. No existing research explores the role of IMCAs in critical care or their potential use when families are judged ‘appropriate to act’ on the patient's behalf. It is suggested that families may not be best placed to advocate for their sick family member when they themselves are in a state of shock. Aim To investigate existing levels of knowledge and awareness of the MCA and understanding of the role of IMCAs in critical care as a prelude to considering whether the role of IMCAs might usefully be extended. The concept of ‘ IMCA clinics’ is introduced and explored. Design and methods A small‐scale qualitative study using thematic analysis of 15 interviews across two NHS sites and a survey of IMCA services were undertaken. Results Some knowledge of the MCA was evident across both study sites, but training on MCA remains unsatisfactory, with confusion about the role of IMCAs and when they should become involved. Overall, participants felt that the broader involvement of IMCAs on a regular basis within critical care could be useful. Conclusions There was evidence of good practice when instructing IMCAs , but further work needs to be conducted to ensure that critical care staff are informed about the referral process. It was clear that expanding the role of an advocate warrants further investigation. Relevance to clinical practice Further training on the role of IMCAs within critical care is required, and good practice examples should be shared with other units to improve referral rates to the IMCA service and ensure that vulnerable patients are properly represented.
    Type of Medium: Online Resource
    ISSN: 1362-1017 , 1478-5153
    URL: Issue
    URL: Article
    DOI: 10.1111/nicc.2018.23.issue-2
    DOI: 10.1111/nicc.12290
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2106066-6
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  • 4
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    Online Resource
    Mental Capacity Act 2005 and Research
    SAGE Publications ; 2011
    In:  Journal of the Intensive Care Society Vol. 12, No. 3 ( 2011-07), p. 190-195
    Details
    In: Journal of the Intensive Care Society, SAGE Publications, Vol. 12, No. 3 ( 2011-07), p. 190-195
    Abstract: This article is the second of two describing the impact of the Mental Capacity Act on the practice of intensive care medicine in the UK. This article concentrates on the impact on clinical research. Intrusive research in incapacitated patients that does not involve trials of medicines or non-identifiable data is covered by the Act. Research must have Ethics Committee approval and must have some chance of benefiting the research subject or provide information about the disease without causing risk to the patient or being unduly invasive or restricting the patient's freedom. It is the responsibility of those engaged in clinical research to be aware of the requirements of the Act and to interpret and implement it appropriately.
    Type of Medium: Online Resource
    ISSN: 1751-1437
    URL: Article
    DOI: 10.1177/175114371101200305
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2701626-2
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  • 5
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    Online Resource
    Early Metabolic Characteristics of Lesion and Nonlesion Tissue after Head Injury
    SAGE Publications ; 2009
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 29, No. 5 ( 2009-05), p. 965-975
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 29, No. 5 ( 2009-05), p. 965-975
    Abstract: We defined lesion and structurally normal regions using magnetic resonance imaging at follow-up in patients recovering from head injury. Early metabolic characteristics in these regions of interest (ROIs) were compared with physiology in healthy volunteers. Fourteen patients with severe head injury had positron emission tomography within 72 h, and magnetic resonance imaging at 3 to 18 months after injury. Cerebral blood flow (CBF), oxygen utilization (CMRO 2 ), and oxygen extraction fraction (OEF) were all lower in lesion ROIs, compared with nonlesion and control ROIs ( P 〈 0.001); however, there was substantial overlap in physiology. Control ROIs showed close coupling among CBF, blood volume (CBV), and CMRO 2 , whereas relationships within lesion and nonlesion ROIs were abnormal. The relationship between CBF and CMRO 2 generally remained coupled but the slope was reduced; that for CBF and OEF was variable; whereas that between CBF and CBV was highly variable. There was considerable heterogeneity between and within patients. Although irreversibly damaged tissue is characterized by marked derangements in physiology, a more detailed analysis shows acute changes in physiology and physiologic relationships within regions of the brain that appear structurally normal at follow-up. Such pathophysiological derangements may result in selective neuronal loss and impact on functional outcome.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2009.22
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2039456-1
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  • 6
    Online Resource
    Online Resource
    The Mental Capacity Act 2005 and its Impact in Critical Care
    SAGE Publications ; 2011
    In:  Journal of the Intensive Care Society Vol. 12, No. 1 ( 2011-01), p. 47-51
    Details
    In: Journal of the Intensive Care Society, SAGE Publications, Vol. 12, No. 1 ( 2011-01), p. 47-51
    Abstract: The Mental Capacity Act (MCA) 2005, covering England and Wales, provides a statutory framework for people who lack capacity to make decisions for themselves, or who have capacity and want to make preparations for a time when they may lack capacity in the future. The Act came into force during 2007 and applies to everyone ‘habitually resident or present in England and Wales’. Essentially it has translated in to law what has always deemed to be best practice. However it is vital that all healthcare professionals be familiar with the MCA and its accompanying Code of Practice. This article is aimed at those working in the critical care environment and will help to clarify some of the issues raised by the MCA.
    Type of Medium: Online Resource
    ISSN: 1751-1437
    URL: Article
    DOI: 10.1177/175114371101200113
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2701626-2
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  • 7
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    Online Resource
    Post-acute blood biomarkers and disease progression in traumatic brain injury
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 6 ( 2022-06-30), p. 2064-2076
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 6 ( 2022-06-30), p. 2064-2076
    Abstract: There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and & gt;5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to & gt;5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at & gt;5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and & gt;5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over & gt;5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac126
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Variability of SF-36 scores within gose categories
    SAGE Publications ; 2005
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 25, No. 1_suppl ( 2005-08), p. S560-S560
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 25, No. 1_suppl ( 2005-08), p. S560-S560
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/sj.jcbfm.9591524.0560
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2039456-1
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  • 9
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    Online Resource
    Variability and Fractal Analysis of Middle Cerebral Artery Blood Flow Velocity and Arterial Blood Pressure in Subarachnoid Hemorrhage
    SAGE Publications ; 2008
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 28, No. 1 ( 2008-01), p. 64-73
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 28, No. 1 ( 2008-01), p. 64-73
    Abstract: Higher biologic systems operate far from equilibrium resulting in order, complexity, fluctuation of inherent parameters, and dissipation of energy. According to the decomplexification theory, disease is characterized by a loss of system complexity. We analyzed such complexity in patients after subarachnoid hemorrhage (SAH), by applying the standard technique of variability analysis and the novel method of fractal analysis to middle cerebral artery blood flow velocity (FV) and arterial blood pressure (ABP). In 31 SAH –patients, FV (using transcranial Doppler sonography) and direct ABP were measured. The standard deviations (s.d.) and coefficients of variation (CV = relative s.d.) for FV and ABP time series of length 2 10 secs were calculated as measures of variability. The spectral index β low and the Hurst coefficient H bdSWV were analyzed as fractal measures. Outcome was assessed 1 year after SAH according to the Glasgow Outcome Scale (GOS). Both FV (β low = 2.2±0.4, mean±s.d.) and ABP (β low = 2.3±0.4) were classified as nonstationary (fractal Brownian motion) signals. FV showed significantly ( P 〈 0.05) higher variability (CV = 7.2±2.5%) and Hurst coefficient ( H bdSWV = 0.26±0.13) as compared with ABP (CV = 5.5±2.7%, H bdSWV = 0.19±0.11). Better outcome (GOS) correlated significantly ( P 〈 0.05) with higher s.d. of FV (Spearman's r s = 0.51, r s 2 = 0.26) and ABP ( r s = 0.57, r s 2 = 0.32), as well as with a higher Hurst coefficient of ABP ( r s = 0.46, r s 2 = 0.21). Cerebral vasospasm reduced CV of FV, but left H bdSWV unchanged. FV and ABP fluctuated markedly despite homeostatic control. A reduced variability of FV and ABP might indicate a loss of complexity and was associated with a less favorable outcome. Therefore, the decomplexification theory of illness may apply to SAH.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/sj.jcbfm.9600506
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 2039456-1
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