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- Kelsen, Jesper, et al.
(författare)
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Copenhagen Head Injury Ciclosporin Study : A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients
- 2019
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:23, s. 3253-3263
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4-8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.
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| 3. |
- Unden, Johan, et al.
(författare)
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Clinical significance of serum S100B levels in neurointensive care
- 2007
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Ingår i: Neurocritical Care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 6:2, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- Objective S100B is viewed as the most promising biomarker for brain damage. It has been proposed that this marker is useful in a Neurointensive Care Unit (NICU) as a monitoring parameter. This study aims to examine the clinical usefulness of daily serum S100B measurements in this setting. Design Prospective consecutive inclusion of patients. Patients A total of 79 patients with confirmed or suspected head injury or cerebrovascular insults (CVIs) (based upon patient history, computed tomography (CT) and/or magnetic resonance imaging (MRI) and neurological examination including coma scoring) who required neurointensive care were included in the study. Interventions Sampling for S100B was performed at admission and daily until patients were discharged from the NICU. S100B measurements were statistically compared to occurrence of secondary complications and outcome according to Glasgow Outcome Scale (GOS), with focus on clinical prediction. Measurements and main results 17 of 79 patients (22%) had secondary neurological complications. Mean S100B levels were found to be an independent parameter associated with these complications (P = 0.03). Mean S100B levels were higher in patients with complications compared to those without on both the complication day (P = 0.033) and the day after (P = 0.015), but not the day prior to the complication (P = 0.62). S100B did not predict secondary neurological complication. Neither mean (P = 0.182) nor peak (P = 0.370) S100B levels were associated with or predicted outcome according to dichotornised GOS. Conclusion Daily S100B measurements are associated with secondary complications but not to outcome. However, daily S100B levels do not predict secondary complications, which limit the usefulness of this brain biomarker in this setting.
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| 6. |
- Åstrand, Ramona
(författare)
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Clinical Aspects of Pediatric Head Injury
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic head injury is one of the leading causes to severe morbidity and death among children. Specific and national management guidelines for pediatric head injuries are lacking in Sweden, and management routines are consequently based on adult guidelines or local guidelines. The objectives of this thesis were to investigate the current management of pediatric head injury in Sweden and to explore the possibility of introducing a brain injury marker, protein S100B, for optimizing pediatric head injury management. Paper I, a survey in 51 Swedish hospitals, shows that the management routines vary from hospital to hospital, especially concerning criteria for computed tomography, admission, and discharge. The children are initially managed by general surgeons and pediatricians, although several other departments are involved after the admission of the child. Less than one third of the hospitals reported the use of a standardized observation scheme. The study concludes the urgent need for standardized and updated routines for pediatric head injury management. Paper II shows that children admitted to a neurosurgical unit after head injury do well. However, pediatric head injury management based solely on adult guidelines, loss of consciousness or amnesia is not reliable, since there is a non-negligible risk of missing a clinically relevant intracranial hematoma. Before a serum marker can be properly evaluated in clinical trials, there is a need for knowing the reference levels of the marker. Capillary sampling in young children is sometimes easier and less painful and time consuming than venous sampling. In Paper III simultaneous capillary, venous and arterial samples were drawn and compared. The results show that analysis of capillary S100B is possible, but differ from venous concentrations by an average of 0.08 µg/L, while arterial and venous samples can be considered nearly equal. Hence, separate reference levels for capillary and venous S100B are required. Paper IV therefore investigates both capillary and venous reference values for S100B in 465 neurologically healthy children. Pediatric S100B reference levels are age-related and higher than those set for adults (venous S100B: 0.14 µg/L for 3-16 year old vs. 0.10 µg/L for adults), while capillary S100B for 3-16 year old is 0.40 µg/L. These reference levels should be used in the evaluation of future studies.
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| 7. |
- Åstrand, Ramona, et al.
(författare)
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Clinical Factors Associated with Intracranial Complications after Pediatric Traumatic Head Injury: An Observational Study of Children Submitted to a Neurosurgical Referral Unit.
- 2010
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Ingår i: Pediatric Neurosurgery. - : S. Karger AG. - 1016-2291 .- 1423-0305. ; 46:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinically validated guidelines for the management of head injury in children do not exist, and the treatment is often based upon adult management routines. In order to examine the safety of this procedure, an analysis of clinical factors associated with complications after pediatric head injury was attempted. Method: We performed a descriptive retrospective study, including patients who received any S06 diagnosis during treatment in the Neurointensive Care Unit at Lund University Hospital between 2002 and 2007. One hundred children were included during the 6 years. Results: During 6 years, 100 children with head injury needed neurointensive care or neurosurgery for their injury in southern Sweden. Traffic accidents (50%) were the main cause of head trauma, followed by falls (36%). Thirty-two percent of all children were injured in bicycle and motorcycle accidents. Both loss of consciousness and amnesia were absent in 23% of the children with intracranial injury. Seven children with intracranial injury, 6 of them requiring neurosurgery, were classed as having minimal head injury according to the Head Injury Severity Scale (HISS). Interesting differences in intracranial injuries between helmet users and nonusers were observed. Conclusion: Children with minimal head injuries (according to HISS) may develop intracranial complications and may even require neurosurgical intervention. Hence, the HISS classification, as well as other risk classifications based upon unconsciousness and amnesia, are unreliable in children.
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| 8. |
- Åstrand, Ramona, et al.
(författare)
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Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:6, s. 1055-1061
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Tidskriftsartikel (refereegranskat)abstract
- Background: Protein S100B is soon in clinical use as a sensitive marker after mild traumatic head injury in adults. Initial studies of S100B in pediatric head injury have shown promising results. Venous sampling can be challenging in children and capillary samples are often a preferred option. The aim of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples in severely brain-injured patients. Methods: Venous, arterial and capillary blood samples for S100B were collected simultaneously once a day for a maximum of 6 days. Patients were >= 18 years old and admitted to neurointensive care due to severe brain pathology. Results: Capillary S100B samples were on average 0.08 mu g/L higher than venous S100B samples. Prediction of venous concentration from capillary samples yielded a prediction error of 0.07 mu g/L. The mean difference between venous and arterial samples was 0.01 mu g/L. The mean prediction error was 0.03 mu g/L. Conclusions: Capillary and venous serum S100B are not interchangeable, and should be considered as two separate, although related, variables. Arterial measurements of S100B can successfully predict the corresponding venous concentration.
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| 10. |
- Åstrand, Ramona, et al.
(författare)
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Reference values for venous and capillary S100B in children
- 2011
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 412:23-24, s. 2190-2193
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedBackground: The current management guidelines for pediatric mild head injury (MHI) liberally recommend computed tomography (CT) and frequent admission. Serum protein S100B, currently used in management of adult head injury, has recently shown potential for reducing unnecessary CT scans after pediatric mild head injury. Capillary sampling in children is commonly used when venous sampling fails or is inappropriate. We present reference values for both venous and capillary samples of protein S100B in children.Methods: Neurologically healthy children aged 1–16, scheduled for minor surgery requiring general anesthesia, were prospectively included. Samples for S100B were drawn before (venous) and after (venous and capillary) sedation.Results: Serum values of 455 children (255 boys, 200 girls) aged 1–14 were computed. S100B was higher in younger children for both venous (r = − 0.32) and capillary samples (r = − 0.28). Reference levels for children aged 1 and 2 were significantly higher than for children aged 3–14 years (venous 0.15 μg/L, capillary 0.37 μg/L). For capillary blood, a gender difference was found in the youngest age groups.Conclusions: We present reference values for venous and capillary S100B in healthy children. These results can be utilized when considering future studies on pediatric head injury and S100B levels.
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