| 1. |
- Bartek, Jiri, Jr., et al.
(författare)
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Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study : Study Protocol for a Multinational Population-Based Consecutive Cohort
- 2019
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Ingår i: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 84:3, s. 799-803
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDTraumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.OBJECTIVETo evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.METHODS This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.EXPECTED OUTCOMESWe expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.DISCUSSION An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.
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| 2. |
- Krakau, Karolina, 1968-, et al.
(författare)
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Energy balance and metabolism after severe traumatic brain injury : A pilot study using doubly labelled water
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To explore the course of energy balance in patients with severe traumatic brain injury, from time of injury until twelve weeks post injury. Method: This prospective desriptive study included six patients with isolated, closed severe traumatic brain injury and an expected hospital stay of ≥2-3 months. Energy balance was calculated from energy intake compared to total energy expenditure measured by continuous indirect calorimetry and doubly labelled water. Clinical and laboratory variables with possible influence on metabolism and nutritional delivery were recorded simultaneously. Intermittent indirect calorimetry measurements were used to differentiate components of the energy expended. Results: Patients were roughly in energy balance while on mechanical ventilation, but in negative energy balance from the 3rd week post injury. The total energy expenditure then increased while the daily energy intake declined. Concurrent with this period were difficulties in retaining enteral and/or parenteral nutrition delivery routes until oral feeding was satisfactory. Nitrogen balance was back to normal at about 1.5 months and the inflammatory period with increased C-reactive protein levels continued for 12 to 58 days from time of injury. During the first and second month post injury, patients lost 8-19% of their initial body weight. Conclusion: Data suggests that negative energy balance after a severe TBI could not only be explained by the elevated metabolic rate and catabolism induced by the trauma, but also by difficulties in securing alternative nutritional routes in the distressed patient.
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| 3. |
- Nelson, David W., et al.
(författare)
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Multivariate outcome prediction in traumatic brain injury with focus on laboratory values
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 29:17, s. 2613-2624
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Identifying factors relevant to outcome can provide a better understanding of TBI pathophysiology, in addition to aiding prognostication. Many common laboratory variables have been related to outcome but may not be independent predictors in a multivariate setting. In this study, 757 patients were identified in the Karolinska TBI database who had retrievable early laboratory variables. These were analyzed towards a dichotomized Glasgow Outcome Scale (GOS) with logistic regression and relevance vector machines, a non-linear machine learning method, univariately and controlled for the known important predictors in TBI outcome: age, Glasgow Coma Score (GCS), pupil response, and computed tomography (CT) score. Accuracy was assessed with Nagelkerke's pseudo R2. Of the 18 investigated laboratory variables, 15 were found significant (p<0.05) towards outcome in univariate analyses. In contrast, when adjusting for other predictors, few remained significant. Creatinine was found an independent predictor of TBI outcome. Glucose, albumin, and osmolarity levels were also identified as predictors, depending on analysis method. A worse outcome related to increasing osmolarity may warrant further study. Importantly, hemoglobin was not found significant when adjusted for post-resuscitation GCS as opposed to an admission GCS, and timing of GCS can thus have a major impact on conclusions. In total, laboratory variables added an additional 1.3-4.4% to pseudo R2.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Bellander, Bo-Michael
(författare)
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On the role of complement activation following traumatic brain injury
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI) is one of the leading causes of early death and disability among young people in the industrial world. The final clinical outcome in terms of morbidity/mortality is not only related to the "primary brain injury", but also seems to be dependent on the potential development of so called "secondary injuries", that may occur in the brain the days after the initial impact. Several biochemical mechanisms have been suggested to be involved in these secondary events, like release of free radicals, glutamate, proteases and nitric oxide. During recent years neuroinflammation has gained a growing interest as a mediator of such secondary injuries. One important immunological entity is the complement system, which when activated results in a cascade of events leading to increased vascular permeability, induction of cytokine production which further triggers the inflammatory response, facilitation of phagocytosis by chemotactical recruitment of macrophages and opsonization. The terminal pathway of the complement cascade results in formation of the membrane attack complex (MAC), a protein complex, with capacity to damage basically any target cell by creating pores in the cell membrane, which in turn allows intracellular influx of water and ions, e.g. calcium, that eventually may cause cell death. In this thesis we have shown that the complement cascade is activated in the border zone ("penumbra") of a brain contusion in the adult rat as well as in the human brain. Clusters of MAC, the cytolytic end-product of the complement cascade, were shown to accumulate at membrane surfaces of viable neurons located in the immediate vicinity to the primary brain injury and may thus contribute to additional damages, so called secondary brain injuries. Reactive microglia/macrophages seem to have a key role in complement activation by synthesis of at least complement factor C3. Resident microglial cells which in vivo are difficult to distinguish from peripherally derived monocytes/macrophages were shown in this thesis to contribute to the pool of reactive macrophages surrounding the lesion using an experimental blood/serum free brain slice model. The subsequent neuronal degeneration that follows TBI was found to be more severe in a rat strain that, based on its genetic features, presents a more pronounced neuroinflammatory response, including complement activation, supporting the hypothesis that this biological cascade is involved in the development of secondary brain injuries. Furthermore, in humans suffering from severe traumatic brain injuries, the occurrences of hypoxia, hypotension and other so called "secondary insults" is followed by higher levels of MAC as well as higher levels of the tissue damage marker S100B, in the cerebrospinal fluid, suggesting that secondary insults further enhance complement activation resulting in more and perhaps avoidable secondary injuries, provided that a thorough and systematic monitoring of these patients are undertaken as they are being treated in the neurointensive care unit. In summary, a traumatic brain injury causes a primary necrotic area surrounded by a "penumbra like" border zone where reactive microglial cells accumulate and transform into macrophages. These macrophages synthesize complement factor C3 and thus contribute to the activation of the complement cascade in the immediate vicinity to the contusion. The cytolytic end product of the complement system, MAC, may in turn induce secondary neuronal injuries by its membrane destructive effects, a process that is further enhanced by secondary insults. Future neuroprotective therapies might be based not only on avoiding secondary insults by careful monitoring, but also on specific regulatory compounds acting selectively on specific parts of the neuroinflammatory process, e.g. the terminal pathway of the complement systern.
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| 7. |
- Cacciani, Nicola, et al.
(författare)
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A prospective clinical study on the mechanisms underlying critical illness myopathy : A time-course approach
- 2022
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : John Wiley & Sons. - 2190-5991 .- 2190-6009. ; 13:6, s. 2669-2682
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Tidskriftsartikel (refereegranskat)abstract
- Background: Critical illness myopathy (CIM) is a consequence of modern critical care resulting in general muscle wasting and paralyses of all limb and trunk muscles, resulting in prolonged weaning from the ventilator, intensive care unit (ICU) treatment and rehabilitation. CIM is associated with severe morbidity/mortality and significant negative socioeconomic consequences, which has become increasingly evident during the current COVID-19 pandemic, but underlying mechanisms remain elusive.Methods: Ten neuro-ICU patients exposed to long-term controlled mechanical ventilation were followed with repeated muscle biopsies, electrophysiology and plasma collection three times per week for up to 12 days. Single muscle fibre contractile recordings were conducted on the first and final biopsy, and a multiomics approach was taken to analyse gene and protein expression in muscle and plasma at all collection time points.Results: (i) A progressive preferential myosin loss, the hallmark of CIM, was observed in all neuro-ICU patients during the observation period (myosin:actin ratio decreased from 2.0 in the first to 0.9 in the final biopsy, P < 0.001). The myosin loss was coupled to a general transcriptional downregulation of myofibrillar proteins (P < 0.05; absolute fold change >2) and activation of protein degradation pathways (false discovery rate [FDR] <0.1), resulting in significant muscle fibre atrophy and loss in force generation capacity, which declined >65% during the 12 day observation period (muscle fibre cross-sectional area [CSA] and maximum single muscle fibre force normalized to CSA [specific force] declined 30% [P < 0.007] and 50% [P < 0.0001], respectively). (ii) Membrane excitability was not affected as indicated by the maintained compound muscle action potential amplitude upon supramaximal stimulation of upper and lower extremity motor nerves. (iii) Analyses of plasma revealed early activation of inflammatory and proinflammatory pathways (FDR < 0.1), as well as a redistribution of zinc ions from plasma.Conclusions: The mechanical ventilation-induced lung injury with release of cytokines/chemokines and the complete mechanical silencing uniquely observed in immobilized ICU patients affecting skeletal muscle gene/protein expression are forwarded as the dominant factors triggering CIM.
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| 8. |
- 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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| 9. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 10. |
- Krakau, Karolina, 1968-, et al.
(författare)
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Prediction of energy expenditure in patients with severe traumatic brain injury : A validation study by use of continuous indirect calorimetry and doubly labelled water
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The aim was to evaluate the accuracy of methods to predict energy expenditure (EE) in patients with severe traumatic brain injury (TBI). Method: To this prospective descriptive study, a small cohort of patients (n6) with isolated, severe TBI and an expected hospital stay of ≥2-3 months were included. The EE was measured at two intervals: by continuous indirect calorimetry during mechanical ventilation and by doubly labelled water from 3rd to 5th week post injury. Different equations for prediction of EE and a portable monitor, the SenseWear Armband were compared to the measured EE. Result: The majority of methods for predicting EE agreed poorly with the measured EE during indirect calorimetry period. A good agreement was found only with the three Penn-State equations, but two were biased according to Bland Altman analysis. The Penn-State equation from 1998 was the only valid predictive method, with a mean difference per day close to zero (+22 kcal), an excellent agreement (ICC 0.82) with 72% (n54/75) accurately assessed days (±10% of the measured EE) and with all patients within clinically acceptable levels, i.e. ±15% of the measured EE. During doubly labelled water period, observations were too few for any conclusive statement. Conclusion: These data support use of the Penn-State equation from 1998 to estimate EE in patients with severe TBI while on mechanical ventilation.
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