| 1. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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β-Blocker after severe traumatic brain injury is associated with better long-term functional outcome : a matched case control study
- 2017
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Berlin/Heidelberg. - 1863-9933 .- 1863-9941. ; 43:6, s. 783-789
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Severe traumatic brain injury (TBI) is the predominant cause of death and disability following trauma. Several studies have observed improved survival in TBI patients exposed to β-blockers, however, the effect on functional outcome is poorly documented.METHODS: Adult patients with severe TBI (head AIS ≥ 3) were identified from a prospectively collected TBI database over a 5-year period. Patients with neurosurgical ICU length of stay <48 h and those dying within 48 h of admission were excluded. Patients exposed to β-blockers ≤ 48 h after admission and who continued with treatment until discharge constituted β-blocked cases and were matched to non β-blocked controls using propensity score matching. The outcome of interest was Glasgow Outcome Scores (GOS), as a measure of functional outcome up to 12 months after injury. GOS ≤ 3 was considered a poor outcome. Bivariate analysis was deployed to determine differences between groups. Odds ratio and 95% CI were used to assess the effect of β-blockers on GOS.RESULTS: 362 patients met the inclusion criteria with 21% receiving β-blockers during admission. After propensity matching, 76 matched pairs were available for analysis. There were no statistical differences in any variables included in the analysis. Mean hospital length of stay was shorter in the β-blocked cases (18.0 vs. 26.8 days, p < 0.01). The risk of poor long-term functional outcome was more than doubled in non-β-blocked controls (OR 2.44, 95% CI 1.01-6.03, p = 0.03).CONCLUSION: Exposure to β-blockers in patients with severe TBI appears to improve functional outcome. Further prospective randomized trials are warranted.
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| 2. |
- Al Nimer, Faiez, et al.
(författare)
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Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R-2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R-2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R-2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that SNF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further
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| 3. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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The Role of Glycerol-Containing Drugs in Cerebral Microdialysis : A Retrospective Study on the Effects of Intravenously Administered Glycerol
- 2019
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Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 30:3, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral microdialysis (CMD) is a valuable tool for monitoring compounds in the cerebral extracellular fluid (ECF). Glycerol is one such compound which is regarded as a marker of cell membrane decomposition. Notably, in some acutely brain-injured patients, CMD-glycerol levels rise without any other apparent indication of cerebral deterioration. The aim of this study was to investigate whether this could be due to an association between CMD-glycerol levels and the administration of glycerol-containing drugs.METHODS: Microdialysis data were retrospectively retrieved from the hospital's intensive care unit patient data management system (PDMS). All patients who were monitored with CMD for ≥ 96 h were included. Administered drug doses were retrieved from the PDMS and converted to exact doses of glycerol. Cross-correlation analyses were performed between the free, metabolized as well as total administered dose of glycerol and the detrended and differenced CMD-glycerol concentration. These analyses were repeated for two sets of subgroups based upon the individual catheter's graphical trend and its location in relation to the lesion.RESULTS: There was no significant correlation between the differenced CMD-glycerol levels and drug-administered glycerol. Furthermore, there was no significant correlation between CMD-glycerol and catheter location or graphical trend. However, if the CMD-glycerol levels were detrended, significant but clinically non-relevant correlations were identified (maximum correlation coefficient of 0.1 (0.04-0.15, 95% CI) at a lag of 7 h using the total administered dose of glycerol).CONCLUSIONS: Glycerol-containing drugs routinely administered intravenously in the clinical setting appear to have a minimal and clinically insignificant effect on levels of glycerol in the cerebral ECF.
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| 4. |
- Mohseni, Shahin, 1978-, et al.
(författare)
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The Effect of beta-blockade on Survival After Isolated Severe Traumatic Brain Injury
- 2015
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 39:8, s. 2076-2083
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Tidskriftsartikel (refereegranskat)abstract
- Several North American studies have observed survival benefit in patients exposed to beta-blockers following traumatic brain injury (TBI). The purpose of this study was to evaluate the effect of beta-blockade on mortality in a Swedish cohort of isolated severe TBI patients.The trauma registry of an urban academic trauma center was queried to identify patients with an isolated severe TBI between 1/2007 and 12/2011. Isolated severe TBI was defined as an intracranial injury with an Abbreviated Injury Scale (AIS) a parts per thousand yen3 excluding extra-cranial injuries AIS a parts per thousand yen3. Multivariable logistic regression analysis was used to determine the effect of beta-blocker exposure on mortality. Also, a subgroup analysis was performed to investigate the risk of mortality in patients on pre-admission beta-blocker versus not and the effect of specific type of beta-blocker on the overall outcome.Overall, 874 patients met the study criteria. Of these, 33 % (n = 287) were exposed to beta-blockers during their hospital admission. The exposed patients were older (62 +/- A 16 years vs. 49 +/- A 21 years, p < 0.001), and more severely injured based on their admission GCS, ISS, and head AIS scores (GCS a parts per thousand currency sign8: 32 % vs. 28 %, p = 0.007; ISS a parts per thousand yen16: 71 % vs. 59 %, p = 0.001; head AIS a parts per thousand yen4: 60 % vs. 45 %, p < 0.001). The crude mortality was higher in patients who did not receive beta-blockers (17 % vs. 11 %, p = 0.007) during their admission. After adjustment for significant confounders, the patients not exposed to beta-blockers had a 5-fold increased risk of in-hospital mortality (AOR 5.0, CI 95 % 2.7-8.5, p = 0.001). No difference in survival was noted in regards to the type of beta-blocker used. Subgroup analysis revealed a higher risk of mortality in patients naive to beta-blockers compared to those on pre-admission beta-blocker therapy (AOR 3.0 CI 95 % 1.2-7.1, p = 0.015).Beta-blocker exposure after isolated severe traumatic brain injury is associated with significantly improved survival. We also noted decreased mortality in patients on pre-admission beta-blocker therapy compared to patients naive to such treatment. Further prospective studies are warranted.
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| 5. |
- Mondello, Stefania, et al.
(författare)
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Extracellular vesicles : pathogenetic, diagnostic and therapeutic value in traumatic brain injury
- 2018
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Ingår i: Expert Review of Proteomics. - : Taylor & Francis. - 1478-9450 .- 1744-8387. ; 15:5, s. 451-461
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Accurate classification according to injury-specific and patient-specific characteristics is critical to help informed clinical decision-making and to the pursuit of precision medicine in TBI. Reliable biomarker signatures for improved TBI diagnostics are required but still an unmet need. Areas covered: Extracellular vesicles (EVs) represent a new class of biomarker candidates in TBI. These nano-sized vesicles have key roles in cell signaling profoundly impacting pathogenic pathways, progression and long-term sequelae of TBI. As such EVs might provide novel neurobiological insights, enhance our understanding of the molecular mechanisms underlying TBI pathophysiology and recovery, and serve as biomarker signatures and therapeutic targets and delivery systems. Expert commentary: EVs are fast gaining momentum in TBI research, paving the way for new transformative diagnostic and treatment approaches. Their potential to sort out TBI variability and active involvement in the mechanisms underpinning different clinical phenotypes point out unique opportunities for improved classification, risk-stratification ad intervention, harboring promise of predictive, personalized, and even preemptive therapeutic strategies. Although a great deal of progress has been made, substantial efforts are still required to ensure the needed rigorous validation and reproducibility for clinical implementation of EVs.
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| 6. |
- Thelin, Eric
(författare)
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On biomarkers in traumatic brain injury
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI) is a common cause of death and disability. Unfortunately, TBI patients will be affected by secondary insults, such as hypoxia and increased intracranial pressure, which may lead to secondary brain injuries. Because of this, these patients are treated in specialized neuro-intensive care units (NICU) where the brain is monitored in order to prevent secondary lesion development. Cerebral monitoring is limited by its locality and more generalized markers to monitor the injured brain are warranted. Biomarkers have been introduced in the field of TBI, where they may be evaluated to examine potential pathophysiological processes. S100B, a primarily astrocytic protein, is the most studied serum biomarker in TBI, but other candidates exist. The aims of this thesis were to validate biomarkers toward long-term functional outcome, to evaluate the effect of biomarkers and a new global method of microdialysis in multimodal monitoring of NICU patients and in a translational methodology assess how biomarkers may facilitate in the damage analysis in a hypoxic-TBI animal model. In Paper I, a retrospective study including 265 NICU TBI patients, where S100B samples were acquired at admission and every 12 hours the first 48 hours after injury, we detected a significant, and independent, correlation between S100B levels and long-term functional outcome. The predictive capabilities increased sharply after 12 hours and remained high up to 36 hours after injury. S100B levels were only significantly correlated to pathology detected on computerized tomography (CT) and not to extracranial trauma. In Paper II, a retrospective study including 250 NICU TBI patients, we analyzed S100B samples acquired later than 48 hours after injury. We noted that secondary increases of S100B even as low as 0.05μg/L is sensitive and specific enough to detect radiological verified cerebral deteriorations, undetected by conventional monitoring. In Paper III, a prospective study including 14 NICU TBI patients, we monitored patients using microdialysis (MD) in flowing cerebrospinal fluid (CSF) for a more “global” overview of cerebral metabolism. We validated the method using conventional CSF samples, and found that the MD-CSF method yielded adequate results. Also, albeit a small sample size, we noted that lactate and pyruvate levels were significantly elevated in patients with an unfavorable outcome. In Paper IV, a retrospective study including 182 NICU TBI patients, we analyzed serum and CSF levels of Neurofilament light, a protein of axonal origin thus different from S100B. We showed that NFL levels significantly correlated independently to outcome, even in the presence of S100B. However, we could not correlate NFL levels to injuries visible on CT and magnetic resonance imaging (MRI). In Paper V, a preclinical study including 73 Sprague-Dawley rats, we analyzed how hypoxia exacerbates TBI. We detected increased neuronal death using immunohistochemistry and increased lesion size on MRI in the hypoxic animals compared to normoxic animals. A trend was found towards higher S100B levels in serum after 24 hours in the hypoxic group. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF1α) expressions were significantly increased in the normoxic group. In summary, the biomarker S100B provides important information towards long-term outcome, even more so than other known predictors of long-term outcome. Outcome prediction models including both S100B and NFL presents the highest explanatory variance, presumably by monitoring different pathophysiological processes. S100B is a valuable asset in the multimodal monitoring in order to detect secondary cerebral injuries and together with the MD-CSF technique; it could improve conventional NICU care with a more global approach. Hypoxic insults following TBI aggravate injury development and this pathophysiological process could presumably be monitored using S100B as an indicator of injury severity.
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| 7. |
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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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| 9. |
- Thelin, Eric Peter, et al.
(författare)
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Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics : A systematic review
- 2017
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Background: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum.Materials and methods: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations.Results: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use.Conclusion: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.
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