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- Fletcher-Sandersjöö, Alexander, et al.
(författare)
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Absolute Contusion Expansion Is Superior to Relative Expansion in Predicting Traumatic Brain Injury Outcomes : A Multi-Center Observational Cohort Study
- 2024
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 41:5-6, s. 705-713
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Tidskriftsartikel (refereegranskat)abstract
- Contusion expansion (CE) is a potentially treatable outcome predictor in traumatic brain injury (TBI), and a suitable end-point for hemostatic therapy trials. However, there is no consensus on the definition of clinically relevant CE, both in terms of measurement criteria (absolute vs. relative volume increase) and cutoff values. In light of this, the aim of this study was to assess the predictive abilities of different CE definitions on outcome. We performed a multi-center observational cohort study of adults with moderate-to-severe TBI treated in an intensive care unit. The exposure of interest was CE, defined as the absolute and relative volume change between the first and second computed tomography scan. The primary outcome was the Glasgow Outcome Scale (GOS) at 6–12 months post-injury, dichotomized into unfavorable (GOS ≤3) or favorable (GOS ≥4). The secondary outcome was all-cause mortality. In total, 798 patients were included, with a median duration of 7.0 h between the first and second CT scan. The median absolute and relative CE was 1.5 mL (interquartile range [IQR] 0.1–8.3 mL) and 100% (IQR 10–530%), respectively. Both CE forms were independently associated with unfavorable GOS. Absolute CE outperformed relative CE in predicting both unfavorable GOS (area under the curve [AUC]: 0.65 vs. 0.60, p = 0.002) and all-cause mortality (AUC: 0.66 vs. 0.60, p = 0.003). For dichotomized CE, absolute cutoffs of 1–10 mL yielded the best results. We conclude that absolute CE demonstrates stronger outcome correlation than relative CE. In studies focusing on lesion progression in TBI, it may be advantageous to use absolute CE as the primary outcome metric. For dichotomized outcomes, cutoffs between 1 and 10 mL are suggested, depending on the desired sensitivity-specificity balance.
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| 2. |
- Lindblad, Caroline, et al.
(författare)
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Fluid proteomics of CSF and serum reveal important neuroinflammatory proteins in blood-brain barrier disruption and outcome prediction following severe traumatic brain injury : a prospective, observational study
- 2021
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (Q(A)), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort. Results: TBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with Q(A), among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained similar to 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, Delta R-2 = 7.4%) and complement factor B in serum (p = 0.003, Delta R-2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.
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| 6. |
- Rostami, Elham, et al.
(författare)
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Proteomic-based identification of injury-specific patterns of biomarkers in rotational and penetrating TBI
- 2010
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Ingår i: 40th Neuroscience Conference, November 13-17, 2010, San Diego, USA. ; , s. Program 467.14, Poster AA14-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Traumatic Brain Injury (TBI) biomarkers would be highly valuable in the diagnosis of various forms of TBI and also in evaluation and treatment of TBI patients and may even provide prediction of outcome of the future impairments of the patients. Here we use proteomics to investigate the temporal changes of chosen proteins in serum and brain in 2 different animal TBI models. Methods: The first model is a controlled penetration of 2 mm thick needle shaped object, which is accelerated with a bullet from air gun or a pendulum, pen-TBI. In the second model where we produce diffuse axonal injury, the animal is subjected to high-speed sagittal rotation acceleration, rot-TBI. The rats were sacrificed 1 day, 3 days and 14 days post injury. We used 30rats, 15rats in each model, 5 rats for each timepoint where 2 of these where sham, these results were compared with values from normal rats. The FC (FC) and HC (HC) were extracted in addition to serum samples. The tissue extractions were analyzed with reverse capture antibody based proteomics for N-cadherin, S-100B, Tau, NSE, NF200, TNF-a, MBP, BDNF, C3, C9, C5b9,Results: In brain significant changes could be seen in N-cadherin in HC in pen-TBI on day 1, BDNF showed a peak in rot-TBI on day 1 while in pen-TBI the peak was after 14 days. C3 increased significantly in the HC of rot-TBI at day 1. C9 increased significantly in rot-TBI both in FC and HC on day 3 and day1 and 3 respectively. C5b9 had its peak in HC in rot-TBI on day 1 but in pen-TBI at day14. N-cadherin in serum of rot-TBI showed a significant increase in day 1 and 14 with a nadir at day3. The pattern was different in pen-TBI where there was an increase at all timepoint with increase overtime. Tau in serum was significantly increased uniformly at all time points in both models. TNF-a was also increased at all timepoints but in rot-TBI it decreased by day 14. S-100B showed no significant change in rot-TBI while in pen-TBI it was significantly increased at all timepoints. NSE in rot-TBI had a peak at day 1 and declined but in pen-TBI there was a nadir at day 3 and the peak was reached by day14. Similar pattern was seen in NF200. MBP was increased at all timepoints with a peak at day 3 in both models. C3 was increased at all timepoints but in pen-TBI it had a peak in day 3. C9 in rot-TBI increased significantly at day 3 and 14 while in pen-TBI it increased from day1 till day 14. C5b9 was significantly increased at all timepoints in both models however in rot-TBI it increased overtime while in pen-TBI it had a peak on day 14.Conclusion: To the best of our knowledge these are the first results showing TBI – type specific changes in different proteins that can be considered as future biomarkers.
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| 8. |
- Thelin, Eric Peter, et al.
(författare)
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Protein profiling in serum after traumatic brain injury in rats reveals potential injury markers
- 2018
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Ingår i: Behavioural Brain Research. - : Elsevier. - 0166-4328 .- 1872-7549. ; 340, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. Material and methods: Sprague Dawley rats (n = 73) received a 3 mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O-2) or hypoxic (11% O-2) air mixture for 30 min before resuscitation. The rats were sacrificed at day 1, 3, 7, 14 and 28 after trauma. A total of 204 antibodies targeting 143 unique proteins of interest in TBI research, were selected. The sample proteome was analyzed in a suspension bead array set-up. Comparative statistics and factor analysis were used to detect differences as well as variance in the data. Results: We found that complement factor 9 (C9), complement factor B (CFB) and aldolase c (ALDOC) were detected at higher levels the first days after trauma. In contrast, hypoxia inducing factor (HIF)1 alpha, amyloid precursor protein (APP) and WBSCR17 increased over the subsequent weeks. S100A9 levels were higher in hypoxic-compared to normoxic rats, together with a majority of the analyzed proteins, albeit few reached statistical significance. The principal component analysis revealed a variance in the data, highlighting clusters of proteins. Conclusions: Protein profiling of serum following TBI using an antibody based microarray revealed temporal changes of several proteins over an extended period of up to four weeks. Further studies are warranted to confirm our findings.
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