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Olivecrona, Magnus
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Publications (10 of 33) Show all publications
Koskinen, L.-O. D., Sundström, N., Hägglund, L., Eklund, A. & Olivecrona, M. (2019). Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury. Neurocritical Care, 31(3), 494-500
Open this publication in new window or tab >>Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury
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2019 (English)In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 31, no 3, p. 494-500Article in journal (Refereed) Published
Abstract [en]

Background: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way.

Materials and Methods: Patients suffering severe traumatic brain injury (sTBI) were treated according to an intracranial pressure (ICP)-targeted therapy based on the Lund concept and randomized to an add-on treatment with prostacyclin or placebo. Inclusion criteria were verified blunt head trauma, Glasgow Coma Score <= 8, age 15-70 years, and a first measured cerebral perfusion pressure of >= 10 mmHg. Multimodal monitoring was applied. A brain microdialysis catheter was placed on the worst affected side, close to the penumbra zone. Mean (glycerol(mean)) and maximal glycerol (glycerol(max)) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h.

Results: Of the 48 included patients, 45 had valid glycerol and PR measurements available. PR was higher in the placebo group as compared to the prostacyclin group (p = 0.0164). There was a positive correlation between PR and the glycerol(mean) (rho = 0.503, p = 0.01) and glycerol(max) (rho = 0.490, p = 0.015) levels in the placebo group only.

Conclusions: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2019
Keywords
Traumatic brain injury, Pressure reactivity, Autoregulation, Glycerol, Cerebral microdialysis, Prostacyclin
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-167070 (URN)10.1007/s12028-019-00741-4 (DOI)000501700900007 ()31123992 (PubMedID)
Available from: 2020-01-13 Created: 2020-01-13 Last updated: 2020-01-13Bibliographically approved
Olivecrona, M. & Koskinen, L.-O. D. (2016). Comment on: Early CSF and serum S 100B concentrations for outcome prediction in traumatic brain injury and subarachoid haemorrhage [Letter to the editor]. Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), 150, 197-198
Open this publication in new window or tab >>Comment on: Early CSF and serum S 100B concentrations for outcome prediction in traumatic brain injury and subarachoid haemorrhage
2016 (English)In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 150, p. 197-198Article in journal, Letter (Refereed) Published
Abstract [en]

Background and methods

In the letter the authors discuss the findings in Kellerman and co-worker’s paper: Early CSF and Serum S 100B Concentrations for Outcome Prediction in Traumatic Brain Injury and Subarachoid Haemorrhage published in this journal. Among the findings reported in this paper is that an initial S 100B value of more than 0.7 μg/l would strongly indicate a very poor prognosis. This finding is discussed.

Conclusion

That a use of S 100B as a prognostic tool for clinical decision making is very doubtful and should most probably be refrained from.

Keywords
S 100B, Biomarker, Head injury, Prognosis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-129930 (URN)10.1016/j.clineuro.2016.07.026 (DOI)000386642300035 ()27569027 (PubMedID)
Available from: 2017-01-11 Created: 2017-01-10 Last updated: 2018-06-09Bibliographically approved
Koskinen, L.-O. D., Eklund, A., Sundström, N. & Olivecrona, M. (2015). Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy. Neurocritical Care, 22(1), 26-33
Open this publication in new window or tab >>Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy
2015 (English)In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 22, no 1, p. 26-33Article in journal (Refereed) Published
Abstract [en]

This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

Keywords
ICP, Pressure reactivity, Traumatic brain injury, Prostacyclin, Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-100961 (URN)10.1007/s12028-014-0030-8 (DOI)000348791300005 ()
Available from: 2015-03-18 Created: 2015-03-16 Last updated: 2018-06-07Bibliographically approved
Rodling Wahlström, M., Olivecrona, M., Ahlm, C., Bengtsson, A., Koskinen, L.-O. D., Naredi, S. & Hultin, M. (2014). Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury: a randomised clinical study. SpringerPlus, 3, Article ID 98.
Open this publication in new window or tab >>Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury: a randomised clinical study
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2014 (English)In: SpringerPlus, E-ISSN 2193-1801, Vol. 3, article id 98Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI).

SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23).

TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours.

METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI.

RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1.

CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

Place, publisher, year, edition, pages
Springer, 2014
Keywords
Traumatic brain injury, Epoprostenol, Systemic inflammatory response, Cytokines, Asymmetric dimethylarginine
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-88003 (URN)10.1186/2193-1801-3-98 (DOI)000358950600004 ()24600548 (PubMedID)
Available from: 2014-04-18 Created: 2014-04-18 Last updated: 2018-06-08Bibliographically approved
Hung, N., Chen, Y.-J., Taha, A., Olivecrona, M., Boet, R., Wiles, A., . . . Slatter, T. (2014). Increased paired box transcription factor 8 has a survival function in Glioma. BMC Cancer, 14, 159
Open this publication in new window or tab >>Increased paired box transcription factor 8 has a survival function in Glioma
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2014 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 159-Article in journal (Refereed) Published
Abstract [en]

Background:

The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis.

Methods:

PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression.

Results:

Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.

Conclusions:

PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

Keywords
PAX8, Glioblastoma, Glioma, Telomere maintenance mechanism, Telomerase, ALT, BCL2, Cell survival
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-88287 (URN)10.1186/1471-2407-14-159 (DOI)000333420600003 ()24602166 (PubMedID)
Available from: 2014-05-05 Created: 2014-04-29 Last updated: 2018-06-07Bibliographically approved
Koskinen, L.-O., Olivecrona, M. & Grande, P. O. (2014). Severe traumatic brain injury management and clinical outcome using the Lund concept. Neuroscience, 283, 245-255
Open this publication in new window or tab >>Severe traumatic brain injury management and clinical outcome using the Lund concept
2014 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 283, p. 245-255Article, review/survey (Refereed) Published
Abstract [en]

This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment. This article is part of a Special Issue entitled: Brain compensation. For good?. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Keywords
severe traumatic brain injury, Lund concept, management, outcome
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-98425 (URN)10.1016/j.neuroscience.2014.06.039 (DOI)000345513100018 ()24973658 (PubMedID)2-s2.0-84911911686 (Scopus ID)
Available from: 2015-02-04 Created: 2015-01-22 Last updated: 2018-06-07Bibliographically approved
Kahlow, H. & Olivecrona, M. (2013). Complications of vagal nerve stimulation for drug-resistant epilepsy: A single center longitudinal study of 143 patients. Seizure, 22(10), 827-833
Open this publication in new window or tab >>Complications of vagal nerve stimulation for drug-resistant epilepsy: A single center longitudinal study of 143 patients
2013 (English)In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 22, no 10, p. 827-833Article in journal (Refereed) Published
Abstract [en]

Purpose: To longitudinally study surgical and hardware complications to vagal nerve stimulation (VNS) treatment in patients with drug-resistant epilepsy. Methods: In a longitudinal retrospective study, we analyzed surgical and hardware complications in 143 patients (81 men and 62 women) who between 1994 and 2010 underwent implantation of a VHS-device for drug-resistant epilepsy. The mean follow-up time was 62 +/- 46 months and the total number of patient years 738. Results: 251 procedures were performed on 143 patients. 16.8% of the patients were afflicted by complications related to surgery and 16.8% suffered from hardware malfunctions. Surgical complications were: superficial infection in 3.5%, deep infection needing explantation in 3.5%, vocal cord palsy in 5.6%, which persisted in at least 0.7% for over one year, and other complications in 5.6%. Hardware-related complications were: lead fracture in 11.9% of patients, disconnection in 2.8%, spontaneous turn-off in 1.4% and stimulator malfunction in 1.4%. We noted a tendency to different survival times between the two most commonly used lead models as well as a tendency to increased infection rate with increasing number of stimulator replacements. Conclusion: In this series we report on surgical and hardware complications from our 16 years of experience with VNS treatment. Infection following insertion of the VNS device and vocal cord palsy due to damage to the vagus nerve are the most serious complications related to the surgery. Avoiding unnecessary reoperations in order to reduce the appearances of these complications are of great importance. It is therefore essential to minimize technical malfunctions that will lead to additional surgery. Further studies are needed to evaluate the possible superiority of the modified leads.

Place, publisher, year, edition, pages
Saunders Elsevier, 2013
Keywords
Vagal nerve stimulation, Complication, Epilepsy
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-85098 (URN)10.1016/j.seizure.2013.06.011 (DOI)000327687300004 ()
Available from: 2014-01-28 Created: 2014-01-28 Last updated: 2018-06-08Bibliographically approved
Koskinen, L.-O. D., Grayson, D. & Olivecrona, M. (2013). The complications and the position of the Codman MicroSensor (TM) ICP device: an analysis of 549 patients and 650 Sensors. Acta Neurochirurgica, 155(11), 2141-2148
Open this publication in new window or tab >>The complications and the position of the Codman MicroSensor (TM) ICP device: an analysis of 549 patients and 650 Sensors
2013 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, no 11, p. 2141-2148Article in journal (Refereed) Published
Abstract [en]

Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. To study complications and the insertion depth of the CMS in a clinical setting. We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 +/- 4.9 days. The mean implantation depth was 21.3 +/- 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

Place, publisher, year, edition, pages
Springer, 2013
Keywords
ICP monitoring, Complications, Position, Codman MicroSensor
National Category
Neurology Surgery
Identifiers
urn:nbn:se:umu:diva-82790 (URN)10.1007/s00701-013-1856-0 (DOI)000325815600019 ()
Available from: 2013-11-12 Created: 2013-11-11 Last updated: 2018-06-08Bibliographically approved
Olivecrona, M. & Olivecrona, Z. (2013). Use of the CRASH study prognosis calculator in patients with severe traumatic brain injury treated with an intracranial pressure-targeted therapy. Journal of clinical neuroscience, 20(7), 996-1001
Open this publication in new window or tab >>Use of the CRASH study prognosis calculator in patients with severe traumatic brain injury treated with an intracranial pressure-targeted therapy
2013 (English)In: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 20, no 7, p. 996-1001Article in journal (Refereed) Published
Abstract [en]

Based on the Corticosteroid Randomisation after Significant Head Injury (CRASH) trial database, a prognosis calculator has been developed for the prediction of outcome in an individual patient with a head injury. In 47 patients with severe traumatic brain injury (sTBI) prospectively treated using an intracranial pressure (ICP) targeted therapy, the individual prognosis for mortality at 14 days and unfavourable outcome at 6 months was calculated and compared with the actual outcome. An overestimation of the risk of mortality and unfavourable outcome was found. The mean risk for mortality and unfavourable outcome were estimated to be 44.6 +/- 32.5% (95% confidence interval [CI], 35.1-54.2%) and 69.3 +/- 23.7% (95% CI, 62.3-76.2%). The actual outcome was 4.3% and 42.6% respectively. The absolute risk reduction (ARR) for mortality was 33.1% and for unfavourable outcome 29.8%. A logistic fit for outcome at 6 months shows a statistically significant difference (p < 0.01). A receiver operating characteristic (ROC) curve analysis shows an area under the curve (AUC) of 0.691. The CRASH prognosis calculator overestimates the risk of mortality and unfavourable outcome in patients with sTBI treated with an ICP-targeted therapy based on the Lund concept. We do not advocate the use of the calculator for treatment decisions in individual patients. We further conclude that patients with blunt sTBI admitted within 8 hours of trauma should be treated regardless of their clinical status as long as the initial cerebral perfusion pressure is > 10 mmHg.

Keywords
CRASH calculator, Intracranial pressure targeted therapy, Lund concept, Prognosis, Severe traumatic brain injury
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-79905 (URN)10.1016/j.jocn.2012.09.015 (DOI)000321463600017 ()
Available from: 2013-09-05 Created: 2013-09-04 Last updated: 2019-11-27Bibliographically approved
Bobinski, L., Olivecrona, M. & Koskinen, L.-O. D. (2012). Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study. Acta Neurochirurgica, 154(6), 1069-1079
Open this publication in new window or tab >>Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study
2012 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 6, p. 1069-1079Article in journal (Refereed) Published
Abstract [en]

The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICPmax), minimal cerebral perfusion pressure (CPPmin), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied. Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CTi) and follow-up scans nearest to 24 h (CT24) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications. There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT24 Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CTi Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes. The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).

Keywords
Traumatic brain injury, Traumatic subarachnoid hemorrhage, Marshall, Morris-Marshall, Rotterdam classification
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-56190 (URN)10.1007/s00701-012-1345-x (DOI)000304113800017 ()
Available from: 2012-06-12 Created: 2012-06-12 Last updated: 2018-06-08Bibliographically approved
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