Publications by authors named "Jussi P Posti"

48 Publications

How do we identify the crashing traumatic brain injury patient - the neurosurgeon's view.

Curr Opin Crit Care 2021 Apr;27(2):87-94

Department of Neurosurgery, Tampere University Hospital and Tampere University, Tampere, Finland.

Purpose Of Review: To provide an overview on recent advances in the field of assessment and monitoring of patients with severe traumatic brain injury (sTBI) in neurocritical care from a neurosurgical point of view.

Recent Findings: In high-income countries, monitoring of patients with sTBI heavily relies on multimodal neurocritical parameters, nonetheless clinical assessment still has a solid role in decision-making. There are guidelines and consensus-based treatment algorithms that can be employed in both absence and presence of multimodal monitoring in the management of patients with sTBI. Additionally, novel dynamic monitoring options and machine learning-based prognostic models are introduced. Currently, the acute management and treatment of secondary injury/insults is focused on dealing with the objective evident pathology. An ongoing paradigm shift is emerging towards more proactive treatment of neuroworsening as soon as premonitory signs of deterioration are detected.

Summary: Based on the current evidence, serial clinical assessment, neuroimaging, intracranial and cerebral perfusion pressure and brain tissue oxygen monitoring are key components of sTBI care. Clinical assessment has a crucial role in identifying the crashing patient with sTBI, especially from a neurosurgical standpoint. Multimodal monitoring and clinical assessment should be seen as complementary evaluation methods that support one another.
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http://dx.doi.org/10.1097/MCC.0000000000000799DOI Listing
April 2021

Trends in mortality from external causes in the Republic of Seychelles between 1989 and 2018.

Sci Rep 2020 12 17;10(1):22186. Epub 2020 Dec 17.

Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany.

Data on injury-related mortality are scarce in the African region. Mortality from external causes in the Seychelles was assessed, where all deaths are medically certified and the population is regularly enumerated. The four fields for underlying causes of death recorded were reviewed in the national vital statistics register. The age-standardised mortality rates were estimated (per 100,000 person-years) from external causes in 1989-1998, 1999-2008, and 2009-2018. Mortality rates per 100,000 person-years from external causes were 4-5 times higher among males than females, and decreased among males over the three 10-year periods (127.5, 101.4, 97.1) but not among females (26.9, 23.1, 26.9). The contribution of external causes to total mortality did not change markedly over time (males 11.6%, females 4.3% in 1989-2018). Apart from external deaths from undetermined causes (males 14.6, females 2.4) and "other unintentional injuries" (males 14.1, females 8.0), the leading external causes of death in 2009-2018 were drowning (25.9), road traffic injuries (18.0) and suicide (10.4) among males; and road traffic injuries (4.6), drowning (3.4) and poisoning (2.6) among females. Mortality from broad categories of external causes did not change consistently over time but rates of road traffic injuries increased among males. External causes contributed approximately 1 in 10 deaths among males and 1 in 20 among females, with no marked change in cause-specific rates over time, except for road traffic injuries. These findings emphasise the need for programs and policies in various sectors to address this large, but mostly avoidable health burden.
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http://dx.doi.org/10.1038/s41598-020-79228-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746745PMC
December 2020

Cerebral Venous Thrombosis: Finnish Nationwide Trends.

Stroke 2021 01 4;52(1):335-338. Epub 2020 Dec 4.

Neurocenter, Department of Neurology, Clinical Neurosciences (J.O.R., J.O.T.S.), University of Turku, Finland.

Background And Purpose: Epidemiology of cerebral venous thrombosis (CVT) has been reported to be changing. Because long-term nationwide data are needed to confirm this, we studied CVT occurrence between 2005 and 2014 in Finland.

Methods: All acute CVT admissions were retrieved from a mandatory registry covering mainland Finland. Patients aged ≥18 years were included. One admission per patient was allowed.

Results: We identified 563 patients with CVT (56.5% women). Overall incidence was 1.32/100 000 (95% CI, 1.21-1.43) per year with a 5.0% annual increase. In people <55 years of age, incidence was 0.92/100 000 (0.76-1.10) for men and 1.65/100 000 (1.43-1.89) for women, whereas for those 55 years or older incidence was 1.61 (1.34-1.91) for men and 1.17 (0.96-1.41) for women. In-hospital mortality was 2.1% with no sex difference. One-year mortality was 7.9%. Long-term mortality was higher in men (adjusted hazard ratio, 1.61 [1.09-2.38]) and in older patients (1.95 [1.69-2.24]; per 10-year increment).

Conclusions: Overall incidence of CVT in Finland was similar to that reported in the Netherlands and in Australia. There was a 5.0% yearly increase in the rate of admissions while in-hospital mortality was low. Sex-specific incidence rates differed markedly between younger and older people. Long-term mortality increased with age and was higher in men.
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http://dx.doi.org/10.1161/STROKEAHA.120.031026DOI Listing
January 2021

Admission Levels of Interleukin 10 and Amyloid β 1-40 Improve the Outcome Prediction Performance of the Helsinki Computed Tomography Score in Traumatic Brain Injury.

Front Neurol 2020 30;11:549527. Epub 2020 Oct 30.

Department of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI). To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI. Eighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale-Extended 5-8, = 49) and unfavorable (Glasgow Outcome Scale-Extended 1-4, = 33) groups. The outcome was assessed 6-12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90-100%. The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9-100) and specificity of 22.4% (95% CI: 10.2-32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1-4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were Aβ40, Aβ42, and neurofilament light. The optimal panel included IL-10, Aβ40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7-6.2) with a sensitivity of 90.9% (95% CI: 81.8-100) and specificity of 59.2% (95% CI: 40.8-69.4). Admission plasma levels of IL-10 and Aβ40 significantly improve the prognostication ability of the HCTS after TBI.
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http://dx.doi.org/10.3389/fneur.2020.549527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661930PMC
October 2020

Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults.

Front Neurol 2020 18;11:1054. Epub 2020 Sep 18.

Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA, United States.

Identification and validation of blood-based biomarkers for the diagnosis and prognosis of mild traumatic brain injury (mTBI) is of critical importance. There have been calls for more research on mTBI in older adults. We compared blood-based protein marker glial fibrillary acidic protein (GFAP) concentrations in serum and in plasma within the same cohort of older adults and assessed their ability to discriminate between individuals based on intracranial abnormalities and functional outcome following mTBI. A sample of 121 older adults [≥50 years old with head computed tomography (CT), = 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 ( = 6; 5.0%) or 15 ( = 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h ( = 2.1; range = 0.5-11.7). Serum GFAP concentration was measured first using the Human Neurology 4-Plex Assay, while plasma GFAP concentration was later measured using the GFAP Discovery Kit, both on an HD-1 Single molecule array (Simoa) instrument. Glasgow Outcome Scale-Extended was assessed 1 week after injury. Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma: = 1,198, < 0.001; serum: = 1,253, < 0.001). The ability to discriminate those with and without intracranial abnormalities was comparable between serum (AUC = 0.814) and plasma (AUC = 0.778). In the total sample, GFAP concentrations were considerably higher in plasma than in serum (Wilcoxon signed-rank test = 0.42, < 0.001, = 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman's range: 0.826-0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: = 1,625, = 0.002; plasma: = 1,539, = 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury. Despite differences in concentration, serum and plasma GFAP levels were highly correlated and had similar discriminability between those with and without intracranial abnormalities on head CT following an mTBI. Neither serum nor plasma GFAP had adequate discriminability to identify patients who would have poor functional outcome.
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http://dx.doi.org/10.3389/fneur.2020.01054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530818PMC
September 2020

A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes.

Sci Rep 2020 09 11;10(1):14984. Epub 2020 Sep 11.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Hämeentie 11, P.O. Box 52, 20521, Turku, Finland.

P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR's related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.
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http://dx.doi.org/10.1038/s41598-020-72061-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486379PMC
September 2020

Volume Change in Frontal Cholinergic Structures After Traumatic Brain Injury and Cognitive Outcome.

Front Neurol 2020 13;11:832. Epub 2020 Aug 13.

Division of Clinical Neurosciences, Turku Brain Injury Centre, Turku University Hospital, Turku, Finland.

The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI ( = 114) and controls with acute orthopedic injuries ( = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.
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http://dx.doi.org/10.3389/fneur.2020.00832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438550PMC
August 2020

Reliability of serum S100B measurement following mild traumatic brain injury: a comparison of assay measurements from two laboratories.

Brain Inj 2020 07 3;34(9):1237-1244. Epub 2020 Aug 3.

Department of Neurosurgery, Tampere University Hospital and University of Tampere , Tampere, Finland.

Objective: There is enormous research and clinical interest in blood-based biomarkers of mild traumatic brain injury (MTBI) sustained in sports, daily life, or military service. We examined the reliability of a commercially available assay for S100B used on the same samples by two different laboratories separated by 2 years in time.

Methods And Procedures: A cohort of 163 adult patients (head CT-scanned, n = 110) with mild head injury were enrolled from the emergency department (ED). All had Glasgow Coma Scale scores of 14 or 15 in the ED (94.4% = 15). The mean time between injury and venous blood sampling was 2.9 h (SD = 1.4; Range = 0.5-6.0 h). Serum S100B was measured at two independent centers using the same high throughput clinical assay (Elecsys S100B®; Roche Diagnostics).

Results: The Spearman correlation between the two assays in the total sample (N = 163) was r = 0.93. A Wilcoxson Signed Ranks test indicated that the median scores for the values differed (Z = 2,082, < .001, Cohen's d = 0.151, small effect size). The values obtained from the two laboratories were very similar for identifying traumatic intracranial abnormalities (sensitivity = 80.1% versus 85.7%).

Conclusions: The serum S100B results measured using the same assay in different laboratories yielded highly correlated and clinically similar, but clearly not identical, results.
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http://dx.doi.org/10.1080/02699052.2020.1800092DOI Listing
July 2020

Multiple formin proteins participate in glioblastoma migration.

BMC Cancer 2020 Jul 29;20(1):710. Epub 2020 Jul 29.

Laboratory Division, Department of Pathology, Turku University Hospital, Turku, Finland.

Background: The prognosis of glioblastoma remains poor, related to its diffuse spread within the brain. There is an ongoing search for molecular regulators of this particularly invasive behavior. One approach is to look for actin regulating proteins that might be targeted by future anti-cancer therapy. The formin family of proteins orchestrates rearrangement of the actin cytoskeleton in multiple cellular processes. Recently, the formin proteins mDia1 and mDia2 were shown to be expressed in glioblastoma in vitro, and their function could be modified by small molecule agonists. This finding implies that the formins could be future therapeutic targets in glioblastoma.

Methods: In cell studies, we investigated the changes in expression of the 15 human formins in primary glioblastoma cells and commercially available glioblastoma cell lines during differentiation from spheroids to migrating cells using transcriptomic analysis and qRT-PCR. siRNA mediated knockdown of selected formins was performed to investigate whether their expression affects glioblastoma migration. Using immunohistochemistry, we studied the expression of two formins, FHOD1 and INF2, in tissue samples from 93 IDH-wildtype glioblastomas. Associated clinicopathological parameters and follow-up data were utilized to test whether formin expression correlates with survival or has prognostic value.

Results: We found that multiple formins were upregulated during migration. Knockdown of individual formins mDia1, mDia2, FHOD1 and INF2 significantly reduced migration in most studied cell lines. Among the studied formins, knockdown of INF2 generated the greatest reduction in motility in vitro. Using immunohistochemistry, we demonstrated expression of formin proteins FHOD1 and INF2 in glioblastoma tissues. Importantly, we found that moderate/high expression of INF2 was associated with significantly impaired prognosis.

Conclusions: Formins FHOD1 and INF2 participate in glioblastoma cell migration. Moderate/high expression of INF2 in glioblastoma tissue is associated with worse outcome. Taken together, our in vitro and tissue studies suggest a pivotal role for INF2 in glioblastoma. When specific inhibiting compounds become available, INF2 could be a target in the search for novel glioblastoma therapies.
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http://dx.doi.org/10.1186/s12885-020-07211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391617PMC
July 2020

Alterations in Microstructure and Local Fiber Orientation of White Matter Are Associated with Outcome after Mild Traumatic Brain Injury.

J Neurotrauma 2020 12 17;37(24):2616-2623. Epub 2020 Aug 17.

Department of Clinical Neurosciences, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Turku, Finland.

Mild traumatic brain injury (mTBI) can have long-lasting consequences. We investigated white matter (WM) alterations at 6-12 months following mTBI using diffusion tensor imaging (DTI) and assessed if the alterations associate with outcome. Eighty-five patients with mTBI underwent diffusion-weighted magnetic resonance imaging (MRI) on average 8 months post-injury and patients' outcome was assessed at the time of imaging using the Glasgow Outcome Scale-Extended (GOS-E). Additionally, 30 age-matched patients with extracranial orthopedic injuries were used as control subjects. Voxel-wise analysis of the data was performed using a tract-based spatial statistics (TBSS) approach and differences in microstructural metrics between groups were investigated. Further, the susceptibility of the abnormalities to specific fiber orientations was investigated by analyzing the first eigenvector of the diffusion tensor in the voxels with significant differences. We found significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in patients with mTBI compared with control subjects, whereas no significant differences were observed in axial diffusivity (AD) between the groups. The differences were present bilaterally in several WM regions and correlated with outcome. Moreover, multiple clusters were found in the principal fiber orientations of the significant voxels in anisotropy, and similar orientation patterns were found for the diffusivity metrics. These directional clusters correlated with patients' functional outcome. Our study showed that mTBI is associated with WM changes at the chronic stage and these alterations occur in several WM regions. In addition, several significant clusters of WM alterations in specific fiber orientations were found and these clusters were associated with outcome.
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http://dx.doi.org/10.1089/neu.2020.7081DOI Listing
December 2020

Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam.

Acta Anaesthesiol Scand 2020 10 15;64(9):1278-1286. Epub 2020 Jul 15.

Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku, Turku, Finland.

Background: Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH.

Methods: Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4 μg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20 mm Hg above the baseline.

Results: Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean ± SD) 1.20 ± 0.14, 1.17 ± 0.13 (P = .93), 1.14 ± 0.09 (P = .72) and 1.19 ± 0.18 (P = 1.0) and sROR% was 150.89 ± 84.37, 75.22 ± 27.75 (P = .08), 128.25 ± 58.35 (P = .84) and 104.82 ± 36.92 (P = .42) at baseline and during 0.7, 1.0 and 1.4 μg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0 μg/kg/h dexmedetomidine (P = .02).

Conclusions: Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.
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http://dx.doi.org/10.1111/aas.13663DOI Listing
October 2020

Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury.

Front Neurol 2020 2;11:376. Epub 2020 Jun 2.

Department of Specialities of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100β, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Blood samples from patients with acute TBI (all severities) were collected <24 h post trauma. The outcome was measured >6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE≥5)/unfavorable outcome (GOSE ≤ 4) and complete (GOSE = 8)/incomplete (GOSE ≤ 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. When sensitivity was set at 95-100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100β and clinical parameters improves outcome prediction models in TBI.
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http://dx.doi.org/10.3389/fneur.2020.00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280446PMC
June 2020

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years.

J Neurol 2020 Nov 13;267(11):3223-3234. Epub 2020 Jun 13.

Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.

Background: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials.

Objective: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling.

Methods: Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years.

Results: Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3-6 months.

Interpretation: Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment.
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http://dx.doi.org/10.1007/s00415-020-09979-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578150PMC
November 2020

Admission Levels of Total Tau and β-Amyloid Isoforms 1-40 and 1-42 in Predicting the Outcome of Mild Traumatic Brain Injury.

Front Neurol 2020 13;11:325. Epub 2020 May 13.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland.

The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI). A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6-12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters. The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = -0.231, = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = -0.288, = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores. The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI.
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http://dx.doi.org/10.3389/fneur.2020.00325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237639PMC
May 2020

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

J Head Trauma Rehabil 2020 Nov/Dec;35(6):E513-E523

University Division of Anaesthesia, Department of Medicine (Drs Carroll, Menon, and Newcombe and Mss Manktelow, Outtrim, Chatfield, and Forsyth), Academic Department of Neurosurgery, Department of Clinical Neurosciences (Dr Hutchinson), Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (Drs Sahakian, Menon, and Newcombe), Department of Psychiatry (Dr Sahakian), and Behavioural & Clinical Neuroscience Institute (Dr Sahakian), University of Cambridge, Cambridge, United Kingdom; Turku Brain Injury Center, University of Turku, Turku, Finland (Drs Tenovuo and Posti); Turku University Hospital, Turku, Finland (Drs Tenovuo and Posti); Department of Neurosurgery, Turku University Hospital, Turku, Finland (Dr Posti); and Division of Psychology, University of Stirling, Stirling, United Kingdom (Dr Wilson).

Objective: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI.

Participants/setting: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99).

Design: Case-control observational study.

Main Measures: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility.

Results: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI.

Conclusion: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.
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http://dx.doi.org/10.1097/HTR.0000000000000575DOI Listing
May 2020

Biomaterial and implant induced ossification: in vitro and in vivo findings.

J Tissue Eng Regen Med 2020 08 8;14(8):1157-1168. Epub 2020 Jul 8.

International Clinical Research Center of St. Anne's University Hospital Brno, Brno, Czech Republic.

Material-induced ossification is suggested as a suitable approach to heal large bone defects. Fiber-reinforced composite-bioactive glasses (FRC-BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC-BG implant in vivo from the perspective of material-induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly-formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC-BG, we cultured human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) in the presence of two different BGs (45S5 and S53P4) and Al O control. AD-MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro-osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC-BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC-BG implant demonstrated material-induced ossification both in vitro and in vivo.
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http://dx.doi.org/10.1002/term.3056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496445PMC
August 2020

A decade of geriatric traumatic brain injuries in Finland: population-based trends.

Age Ageing 2020 08;49(5):779-785

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Background: we investigated trends of traumatic brain injury (TBI)-related hospitalisations, deaths, acute neurosurgical operations (ANO), and lengths of hospital stay (LOS) in patients aged ≥70 years in Finland using a population-based cohort.

Methods: nationwide databases were searched for all admissions with a TBI diagnosis as well as later deaths for persons ≥70 years of age during 2004-2014.

Results: the study period included 20,259 TBI-related hospitalisations (mean age = 80.7 years, men = 48.9%). The incidence of TBI-related hospitalisations was 283/100,000 person-years with an estimated overall annual increase of 2.9% (95% CI: 0.4-5.9%). There was an annual decrease of 2.2% in in-hospital mortality (IHM) in men (95% CI: 0.1-4.3%), with no change in women or overall. There was an annual decrease of 1.1% in odds for ANOs among hospitalised overall (95% CI: 0.1-2.1%) and of 1.4% in men (95% CI: 0.0-2.7%), while no change was observed in women. LOS decreased annually by 2.5% (95% CI: 2.1-2.9%). The incidence of TBI-related deaths was 70/100,000 person-years with an estimated annual increase of 1.6% in women (95% CI: 0.2-2.9%), but no change in men or overall. Mean ages of TBI-related admissions and deaths increased (P < 0.001).

Interpretation: the incidence rate of geriatric TBI-related hospitalisations increased, especially in women, but LOS and the rate of ANOs among hospitalised decreased. The overall TBI-related mortality remained stable, and IHM decreased in men, while in women, the overall mortality increased and IHM remained stable. However, the overall incidence rates of TBI-related hospitalisations and deaths and the number of cases of IHM were still higher in men.
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http://dx.doi.org/10.1093/ageing/afaa037DOI Listing
August 2020

Integrative Analysis of Circulating Metabolite Profiles and Magnetic Resonance Imaging Metrics in Patients with Traumatic Brain Injury.

Int J Mol Sci 2020 Feb 19;21(4). Epub 2020 Feb 19.

School of Medical Sciences, Örebro University, 702 81 Örebro, Sweden.

Recent evidence suggests that patients with traumatic brain injuries (TBIs) have a distinct circulating metabolic profile. However, it is unclear if this metabolomic profile corresponds to changes in brain morphology as observed by magnetic resonance imaging (MRI). The aim of this study was to explore how circulating serum metabolites, following TBI, relate to structural MRI (sMRI) findings. Serum samples were collected upon admission to the emergency department from patients suffering from acute TBI and metabolites were measured using mass spectrometry-based metabolomics. Most of these patients sustained a mild TBI. In the same patients, sMRIs were taken and volumetric data were extracted (138 metrics). From a pool of 203 eligible screened patients, 96 met the inclusion criteria for this study. Metabolites were summarized as eight clusters and sMRI data were reduced to 15 independent components (ICs). Partial correlation analysis showed that four metabolite clusters had significant associations with specific ICs, reflecting both the grey and white matter brain injury. Multiple machine learning approaches were then applied in order to investigate if circulating metabolites could distinguish between positive and negative sMRI findings. A logistic regression model was developed, comprised of two metabolic predictors (erythronic acid and -inositol), which, together with neurofilament light polypeptide (NF-L), discriminated positive and negative sMRI findings with an area under the curve of the receiver-operating characteristic of 0.85 (specificity = 0.89, sensitivity = 0.65). The results of this study show that metabolomic analysis of blood samples upon admission, either alone or in combination with protein biomarkers, can provide valuable information about the impact of TBI on brain structural changes.
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http://dx.doi.org/10.3390/ijms21041395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073036PMC
February 2020

Machine learning-based dynamic mortality prediction after traumatic brain injury.

Sci Rep 2019 11 27;9(1):17672. Epub 2019 Nov 27.

Department of Neurosurgery, Helsinki University Hospital and University of Helsinki, Topeliuksenkatu 5, PB 266, 00029 HUS, Helsinki, Finland.

Our aim was to create simple and largely scalable machine learning-based algorithms that could predict mortality in a real-time fashion during intensive care after traumatic brain injury. We performed an observational multicenter study including adult TBI patients that were monitored for intracranial pressure (ICP) for at least 24 h in three ICUs. We used machine learning-based logistic regression modeling to create two algorithms (based on ICP, mean arterial pressure [MAP], cerebral perfusion pressure [CPP] and Glasgow Coma Scale [GCS]) to predict 30-day mortality. We used a stratified cross-validation technique for internal validation. Of 472 included patients, 92 patients (19%) died within 30 days. Following cross-validation, the ICP-MAP-CPP algorithm's area under the receiver operating characteristic curve (AUC) increased from 0.67 (95% confidence interval [CI] 0.60-0.74) on day 1 to 0.81 (95% CI 0.75-0.87) on day 5. The ICP-MAP-CPP-GCS algorithm's AUC increased from 0.72 (95% CI 0.64-0.78) on day 1 to 0.84 (95% CI 0.78-0.90) on day 5. Algorithm misclassification was seen among patients undergoing decompressive craniectomy. In conclusion, we present a new concept of dynamic prognostication for patients with TBI treated in the ICU. Our simple algorithms, based on only three and four main variables, discriminated between survivors and non-survivors with accuracies up to 81% and 84%. These open-sourced simple algorithms can likely be further developed, also in low and middle-income countries.
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http://dx.doi.org/10.1038/s41598-019-53889-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881446PMC
November 2019

Prospective Validation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults.

J Neurotrauma 2019 10 10;36(20):2904-2912. Epub 2019 Jul 10.

Department of Neurosurgery, Tampere University Hospital and Tampere University, Tampere, Finland.

The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults (Scandinavian guidelines) are the first to incorporate serum measurement of the S100 astroglial calcium-binding protein B (S100B) to emergency department (ED) triage of patients with head injury (HI). This prospective validation study was conducted in the ED of the Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with HI presenting to the ED within 24 h from injury were eligible for inclusion. Venous blood for S100B sampling was drawn from all patients, and the result was available at the ED. Computed tomography (CT) scans of the head were performed according to the on-call physician's evaluation. Only the samples collected within 6 h after injury were used. A one-week follow-up was conducted to identify possible HI-related complications. A total of 295 patients (median age, 67.0 years, range, 18-100; women, 48.8%) were enrolled. Of those, 196 (66.4%) underwent scanning. Acute traumatic lesions were detected on 31 (15.8%) of the scans. Two of the CT-positive patients were scanned without a guidelines-based indication. These lesions did not require any specific treatment or repeated imaging. The guidelines-based sensitivity was 0.94 (95% confidence interval [CI], 0.77-0.99) and specificity 0.19 (95% CI, 0.13-0.26) for predicting traumatic intracranial CT abnormalities. The positive and negative predictive value for positive head CT was 0.18 (95% CI, 0.12-0.25) and 0.94 (95% CI, 0.78-0.99), respectively. In the mild-low risk group, no false negative S100B values were recorded. Thirteen patients (4.4%) were re-admitted to the ED, and two patients (0.7%) died one week after the primary HI. The deaths were unrelated to the injury. None of these adverse events were directly caused by a primarily undiagnosed intracranial injury. The Scandinavian guidelines incorporated with S100B are a valid means of screening clinically significant acute traumatic lesions after HI and have the potential to reduce unnecessary CT scanning.
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http://dx.doi.org/10.1089/neu.2018.6351DOI Listing
October 2019

Fatal traumatic brain injuries during 13 years of successive alcohol tax increases in Finland - a nationwide population-based registry study.

Sci Rep 2019 04 1;9(1):5419. Epub 2019 Apr 1.

Heart Center, Turku University Hospital, Turku, Finland.

We sought to investigate how increases in alcohol taxation and changes in alcohol consumption were associated with the incidence rate of fatal traumatic brain injuries (TBI) in Finland during the years 2004-2016. Nationwide, mandatory cause of death database covering all deaths in Finland was searched for all deaths related to TBIs (ICD-10: S06.X) in persons ≥16 years of age during 2004-2016. Study period included 28,657,870 person-years and 325,514 deaths of which 12,110 were TBI-related. Occurrence rates were standardized to European 2013 standard population. Data for alcohol consumption were obtained from the National Institute for Health and Welfare and for alcohol taxation from Ministry of Finance, Finland. Standardized incidence rate of TBI-related death was 22.0 (95% CI 21.61-22.38) per 100,000 person-years. Overall alcohol consumption decreased on average by 1.2% annually. Concurrently, the overall incidence rate of fatal TBIs decreased by 4.1% annually (by 4.3% in men and 2.4% in women). There was an association between overall alcohol consumption and TBI-related mortality rate (p < 0.001). Tax-rate increases of all beverage types were associated with decreased incidence rate of TBI-related death in men (p < 0.001), in women (p < 0.036) and overall (p < 0.001). In this population-based study, we report that during 13 years of successive alcohol tax increases, overall alcohol consumption has decreased in parallel with a reduction in the incidence rate of fatal TBIs in Finland.
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http://dx.doi.org/10.1038/s41598-019-41913-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443785PMC
April 2019

Serum Neurofilament Light Is Elevated Differentially in Older Adults with Uncomplicated Mild Traumatic Brain Injuries.

J Neurotrauma 2019 08 23;36(16):2400-2406. Epub 2019 Apr 23.

6Department of Neurosurgery, Tampere University Hospital and University of Tampere, Tampere, Finland.

Neurofilament light (NF-L) might have diagnostic and prognostic potential as a blood biomarker for mild traumatic brain injury (mTBI). However, elevated NF-L is associated with several neurological disorders associated with older age, which could confound its usefulness as a traumatic brain injury biomarker. We examined whether NF-L is elevated differentially following uncomplicated mTBI in older adults with pre-injury neurological disorders. In a case-control study, a sample of 118 adults (mean age = 62.3 years, standard deviation [SD] = 22.5, range = 18-100; 52.5% women) presenting to the emergency department (ED) with an uncomplicated mTBI were enrolled. All participants underwent head computed tomography in the ED and showed no macroscopic evidence of injury. The mean time between injury and blood sampling was 8.3 h (median [Md] = 3.5; SD = 13.5; interquartile range [IQR] = 1.9-6.0, range = 0.8-67.4, and 90% collected within 19 h). A sample of 40 orthopedically-injured trauma control subjects recruited from a second ED also were examined. Serum NF-L levels were measured and analyzed using Human Neurology 4-Plex A assay on a HD-1 Single Molecule Array (Simoa) instrument. A high correlation was found between age and NF-L levels in the total mTBI sample (r = 0.80), within the subgroups without pre-injury neurological diseases (r = 0.76) and with pre-injury neurological diseases (r = 0.68), and in the trauma control subjects (r = 0.76). Those with mTBIs and pre-injury neurological conditions had higher NF-L levels than those with no pre-injury neurological conditions ( < 0.001, Cohen's d = 1.01). Older age and pre-injury neurological diseases are associated with elevated serum NF-L levels in patients with head trauma and in orthopedically-injured control subjects.
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http://dx.doi.org/10.1089/neu.2018.6341DOI Listing
August 2019

Correlation of Blood Biomarkers and Biomarker Panels with Traumatic Findings on Computed Tomography after Traumatic Brain Injury.

J Neurotrauma 2019 07 5;36(14):2178-2189. Epub 2019 Apr 5.

13 Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative ( = 65) and CT-positive ( = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.
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http://dx.doi.org/10.1089/neu.2018.6254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909751PMC
July 2019

A large calvarial bone defect in a child: osteointegration of an implant.

World Neurosurg 2019 Jan 23. Epub 2019 Jan 23.

Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; PO Box 23, 90029 OYS, Finland; Medical Research Center Oulu, and PEDEGO Research Unit, University of Oulu, Oulu, Finland.

Background: This is an original report describing the long-term follow-up outcome of a cranioplasty. A large calvarial bone defect of a child was reconstructed with a bioactive and biostable non-metallic implant.

Case Description: This is a case study of a young child with an infantile fibrosarcoma of occipital bone. The malignancy in an occipital bone was removed from a child of 2.5 years of age, and the defect site was reconstructed with an on-lay glass fibre-reinforced composite - bioactive glass implant. After 5 years and 7 months, the follow-up examination showed no signs of a recidive. During the follow-up period, the contour of the reconstructed area followed skull anatomical development. Computed tomography demonstrated considerably large areas (approximately 70 % of the total area) of bone on-growth to the peridural surface of the implant.

Conclusions: In the future, a synthetic cranioplasty material that is capable to integrate with cranial bone may be considered superior to cryopreserved bone grafts in younger age groups.
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http://dx.doi.org/10.1016/j.wneu.2019.01.028DOI Listing
January 2019

Risk Factors for Recurrent Hematoma After Surgery for Acute Traumatic Subdural Hematoma.

World Neurosurg 2019 Jan 10. Epub 2019 Jan 10.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Turku, Finland; Neurovascular Surgery Program, Section of Neurosurgery, University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA. Electronic address:

Objective: The development of postcraniotomy hematoma (PCH) after surgery for acute traumatic subdural hematoma (aSDH) has been associated with an increased risk of a poor outcome. The risk factors contributing to PCH remain poorly understood. Our aim was to study the potential risk factors for PCH in a consecutive series of surgically evacuated patients with aSDH.

Methods: A total of 132 patients with aSDH treated at Turku University Hospital (Turku, Finland) from 2008 to 2012 were enrolled in the present retrospective cohort study. The demographic, clinical, laboratory, and imaging data were collected from the medical records. A comprehensive analysis of the data using 6 different univariate methods, including machine learning and multivariate analyses, was conducted to identify the factors related to PCH.

Results: The incidence of PCH after primary surgery for traumatic aSDH was 10.6%. The patients experiencing PCH were younger (P = 0.04). No difference was found in the use of anticoagulant or antiplatelet medication for the patients with and without PCH. Multivariate analyses identified alcohol inebriation at the time of injury (odds ratio [OR], 12.67; P = 0.041) and hypocapnia (OR, 26.09; P = 0.003) as independent risk factors for PCH. The patients with PCH had had hyponatremia (OR, 0.08; P = 0.018) less often, and their maximal systolic blood pressure was lower (OR, 0.94; P = 0.009). The area under the curve for the multivariate model was 0.96 (P = 0.049), with a Youden index of 0.88.

Conclusions: The results suggest that alcohol inebriation at the time of injury and hypocapnia during hospitalization are risk factors for the development of PCH.
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http://dx.doi.org/10.1016/j.wneu.2018.12.155DOI Listing
January 2019

TBIcare Investigators' Response to Papa and Wang (doi: 10:1089/neu.2017.5030): Raising the Bar for Traumatic Brain Injury Biomarker Research: Methods Make a Difference.

J Neurotrauma 2019 05 25;36(10):1680-1681. Epub 2019 Feb 25.

2 Turku Brain Injury Centre, Turku University Hospital, Turku, Finland.

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http://dx.doi.org/10.1089/neu.2017.5209DOI Listing
May 2019

Early Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein in Predicting the Outcome of Mild Traumatic Brain Injury.

J Neurotrauma 2019 05 8;36(10):1551-1560. Epub 2019 Jan 8.

1 Department of Neurosurgery, Turku University Hospital, Turku, Finland.

The purpose of this study was to correlate the early levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NF-L) with outcome in patients with mild traumatic brain injury (mTBI). A total of 107 patients with mTBI (Glasgow Coma Scale ≥13) who had blood samples for GFAP and NF-L available within 24 h of arrival were included. Patients with mTBI were divided into computed tomography (CT)-positive and CT-negative groups. Glasgow Outcome Scale-Extended (GOSE) was used to assess the outcome. Outcomes were defined as complete (GOSE 8) versus incomplete (GOSE <8), and favorable (GOSE 5-8) versus unfavorable (GOSE 1-4). GFAP and NF-L concentrations in blood were measured using ultrasensitive single molecule array technology. Patients with incomplete recovery had significantly higher levels of NF-L compared with those with complete recovery ( = 0.005). The levels of GFAP and NF-L were significantly higher in patients with unfavorable outcome than in patients with favorable outcome ( = 0.002 for GFAP and  < 0.001 for NF-L). For predicting favorable outcome, the area under the receiver operating characteristic curve for GFAP and NF-L was 0.755 and 0.826, respectively. In a multi-variate logistic regression model, the level of NF-L was still a significant predictor for complete recovery (odds ratio [OR] = 1.008; 95% confidence interval [CI], 1.000-1.016). Moreover, the level of NF-L was a significant predictor for complete recovery in CT-positive patients (OR = 1.009; 95% CI, 1.001-1.016). The early levels of GFAP and NF-L are significantly correlated with the outcome in patients with mTBI. The level of NF-L within 24 h from arrival has a significant predictive value in mTBI also in a multi-variate model.
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http://dx.doi.org/10.1089/neu.2018.5952DOI Listing
May 2019

Stroke hospitalization trends of the working-aged in Finland.

PLoS One 2018 1;13(8):e0201633. Epub 2018 Aug 1.

Heart Center, Turku University Hospital, Turku, Finland.

Background: The age-standardized incidence of stroke has decreased globally but, for reasons unknown, conflicting results have been observed regarding trend in incidence of major stroke subtypes in young adults. We studied these trends among people of working age in a population-based setting in Finland, where cardiovascular risk factor profiles have developed favorably.

Methods: All hospitalizations for stroke in 2004-2005 and 2013-2014 for persons 18-64 years of age were identified from a national register. The search included all hospitals that provide acute stroke care on mainland Finland.

Results: Hospitalizations for both intracerebral hemorrhage (ICH; -15.2%; p = 0.0008) and subarachnoid hemorrhage (SAH; -26.5%; p<0.0001) decreased overall and for both sexes separately. Concerning IS, hospitalizations decreased only for men (-6.3%; p = 0.0190) but not for women or overall. However, there was an increase in IS hospitalizations in men 35-44 years of age (+37.5%; p = 0.0019). The length of stay (LOS) of IS patients declined in nearly all subgroups (overall -20.8%, p<0.0001) whereas no change in LOS was observed for patients with ICH or SAH. In-hospital mortality decreased in patients with IS (-42.8%; p = 0.0092) but remained unchanged in patients with ICH or SAH.

Conclusions: Stroke hospitalizations of young people declined in Finland, except for men 35-44 years of age for whom IS hospitalizations increased. Declining LOS and in-hospital mortality of IS patients suggests admission of less severe cases, improved care or both.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201633PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070270PMC
February 2019

Serum Metabolites Associated with Computed Tomography Findings after Traumatic Brain Injury.

J Neurotrauma 2018 11 21;35(22):2673-2683. Epub 2018 Aug 21.

1 Turku Centre for Biotechnology, University of Turku , Turku, Finland .

There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish among different types of injuries observed. Logistical regression models using metabolite data from the discovery cohort (n = 144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and those with negative findings on head CT. The resultant models were then tested in the validation cohort (n = 66, Cambridge, United Kingdom). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (area under the curve [AUC] = 0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives, and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC = 0.77 in Turku patients and AUC = 0.73 in Cambridge patients). Further, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC = 0.87 in Turku patients and AUC = 0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
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http://dx.doi.org/10.1089/neu.2017.5272DOI Listing
November 2018

Predictors of primary autograft cranioplasty survival and resorption after craniectomy.

J Neurosurg 2018 May 1:1-8. Epub 2018 May 1.

6Department of Biomaterials Science, Institute of Dentistry, University of Turku and City of Turku, Welfare Division, Turku.

OBJECTIVECraniectomy is a common neurosurgical procedure that reduces intracranial pressure, but survival necessitates cranioplasty at a later stage, after recovery from the primary insult. Complications such as infection and resorption of the autologous bone flap are common. The risk factors for complications and subsequent bone flap removal are unclear. The aim of this multicenter, retrospective study was to evaluate the factors affecting the outcome of primary autologous cranioplasty, with special emphasis on bone flap resorption.METHODSThe authors identified all patients who underwent primary autologous cranioplasty at 3 tertiary-level university hospitals between 2002 and 2015. Patients underwent follow-up until bone flap removal, death, or December 31, 2015.RESULTSThe cohort comprised 207 patients with a mean follow-up period of 3.7 years (SD 2.7 years). The overall complication rate was 39.6% (82/207), the bone flap removal rate was 19.3% (40/207), and 11 patients (5.3%) died during the follow-up period. Smoking (OR 3.23, 95% CI 1.50-6.95; p = 0.003) and age younger than 45 years (OR 2.29, 95% CI 1.07-4.89; p = 0.032) were found to independently predict subsequent autograft removal, while age younger than 30 years was found to independently predict clinically relevant bone flap resorption (OR 4.59, 95% CI 1.15-18.34; p = 0.03). The interval between craniectomy and cranioplasty was not found to predict either bone flap removal or resorption.CONCLUSIONSIn this large, multicenter cohort of patients with autologous cranioplasty, smoking and younger age predicted complications leading to bone flap removal. Very young age predicted bone flap resorption. The authors recommend that physicians extensively inform their patients of the pronounced risks of smoking before cranioplasty.
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http://dx.doi.org/10.3171/2017.12.JNS172013DOI Listing
May 2018