| 1. |
- Dickens, Alex Mountfort, et al.
(författare)
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Serum Metabolites Associated with Computed TomographyFindings after Traumatic Brain Injury
- 2018
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:22, s. 2673-2683
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Tidskriftsartikel (refereegranskat)abstract
- 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 between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). 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 (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). Furthermore, 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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| 2. |
- Hossain, Iftakher, et al.
(författare)
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Early Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein in Predicting the Outcome of Mild Traumatic Brain Injury
- 2019
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Ingår i: Journal of neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 36:10, s. 1551-1560
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Tidskriftsartikel (refereegranskat)abstract
- 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). 107 patients with mTBI [Glasgow Coma Scale (GCS) ≥13] having the blood samples for GFAP and NF-L available within 24 hrs from 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) vs. incomplete (GOSE <8), and favorable (GOSE 5-8) vs. 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 to those with complete recovery (p=0.005). The levels of GFAP and NF-L were significantly higher in patients with unfavorable outcome than in patients with favorable outcome (p=0.002 for GFAP and p <0.001 for NF-L). For predicting favorable outcome, the area under the ROC curve for GFAP and NF-L was 0.755 and 0.826, respectively. In a multivariate logistic regression model, the level of NF-L was still a significant predictor for complete recovery (OR=1.008, 95%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 hrs from arrival has a significant predictive value in mTBI also in a multivariate model.
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| 3. |
- Korhonen, Otto, et al.
(författare)
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Outlier analysis for acute blood biomarkers of moderate and severe traumatic brain injury
- 2024
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Ingår i: Journal of Neurotrauma. - 0897-7151 .- 1557-9042. ; 41:1-2, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI (n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-Type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-Tau), amyloid b40 (Ab40) and amyloid b42 (Ab42), within 24 h of admission. Similar analyses were conducted for controls (n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5-8) versus unfavorable (GOSE <5) (n = 38/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1-1.5 interquartile range (IQR) or Q3 + 1.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were > Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-Trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-Tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).
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| 4. |
- Newcombe, Virginia F J, et al.
(författare)
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Post-acute blood biomarkers and disease progression in traumatic brain injury.
- 2022
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:6, s. 2064-2076
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Tidskriftsartikel (refereegranskat)abstract
- There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein and neurofilament light have been widely explored in characterising acute traumatic brain injury, their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following traumatic brain injury. Two-hundred and three patients were recruited in two separate cohorts; six months post-injury (n=165); and >5 years post-injury (n=38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n=199) and magnetic resonance imaging (n=172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualised Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at six months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualised brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. Glial fibrillary acid protein and neurofilament light levels can remain elevated months to years after traumatic brain injury, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify traumatic brain injury survivors who are at high risk of progressive neurological damage.
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| 5. |
- Oresic, Matej, 1967-, et al.
(författare)
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Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury
- 2016
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 12, s. 118-126
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new venue for the development of diagnostic and prognostic markers of broad spectrum of TBIs. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 6. |
- Posti, Jussi P., et al.
(författare)
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SERUM METABOLITES ASSOCIATE WITH HEAD COMPUTED TOMOGRAPHY FINDINGS FOLLOWING TRAUMATIC BRAIN INJURY
- 2018
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:16, s. A67-A67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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 bio-markers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminalhydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein bio-markers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, thre esugar 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). Furthermore, 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 pa-tients). 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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| 7. |
- Tuure, Juho, et al.
(författare)
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Late Blood Levels of Neurofilament Light Correlate With Outcome in Patients With Traumatic Brain Injury.
- 2024
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Ingår i: Journal of neurotrauma. - 1557-9042. ; 41:3-4, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NF-L) is an axonal protein that has shown promise as a traumatic brain injury (TBI) biomarker. Serum NF-L shows a rather slow rise after injury, peaking after 1-2 weeks, although some studies suggest that it may remain elevated for months after TBI. The aim of this study was to examine if plasma NF-L levels several months after the injury correlate with functional outcome in patients who have sustained TBIs of variable initial severity. In this prospective study of 178 patients with TBI and 40 orthopedic injury controls, we measured plasma NF-L levels in blood samples taken at the follow-up appointment on average 9 months after injury. Patients with TBI were divided into two groups (mild [mTBI] vs. moderate-to-severe [mo/sTBI]) according to the severity of injury assessed with the Glasgow Coma Scale upon admission. Recovery and functional outcome were assessed using the Extended Glasgow Outcome Scale (GOSE). Higher levels of NF-L at the follow-up correlated with worse outcome in patients with moderate-to-severe TBI (Spearman's rho=-0.18; p<0.001). In addition, in computed tomography-positive mTBI group, the levels of NF-L were significantly lower in patients with GOSE 7-8 (median 18.14; interquartile range [IQR] 9.82, 32.15) when compared with patients with GOSE <7 (median 73.87; IQR 32.17, 110.54; p=0.002). In patients with mTBI, late NF-L levels do not seem to provide clinical benefit for late-stage assessment, but in patients with initially mo/sTBI, persistently elevated NF-L levels are associated with worse outcome after TBI and may reflect ongoing brain injury.
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| 8. |
- Hossain, Iftakher, et al.
(författare)
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Tau as a fluid biomarker of concussion and neurodegeneration.
- 2022
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Ingår i: Concussion (London, England). - : Future Medicine Ltd. - 2056-3299. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Concussion is predominant among the vast number of traumatic brain injuries that occur worldwide. Difficulties in timely identification, whether concussion led to neuronal injury or not, diagnosis and the lack of prognostic tools for adequate management could lead this type of brain injury to progressive neurodegenerative diseases. Tau has been extensively studied in recent years, particularly in repetitive mild traumatic brain injuries and sports-related concussions. Tauopathies, the group of neurodegenerative diseases, have also been studied with advanced functional imaging. Nevertheless, neurodegenerative diseases, such as chronic traumatic encephalopathy, are still conclusively diagnosed at autopsy. Here, we discuss the diagnostic dilemma and the relationship between concussion and neurodegenerative diseases and review the literature on tau as a promising biomarker for concussion.
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| 9. |
- Huebschmann, Nathan A, et al.
(författare)
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Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults.
- 2020
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: 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. Methods: A sample of 121 older adults [≥50 years old with head computed tomography (CT), n = 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 (n = 6; 5.0%) or 15 (n = 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h (SD = 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. Results: Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma: U = 1,198, p < 0.001; serum: U = 1,253, p < 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 z = 0.42, p < 0.001, r = 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman's rho range: 0.826-0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: U = 1,625, p = 0.002; plasma: U = 1,539, p = 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury. Conclusions: 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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| 10. |
- Iaccarino, Corrado, et al.
(författare)
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Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel
- 2024
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Ingår i: Brain & spine. - : Elsevier. - 2772-5294. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance.RESEARCH QUESTION: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems.METHODS: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction."RESULTS: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain."DISCUSSION AND CONCLUSION: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.
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| 11. |
- Iverson, Grant L, et al.
(författare)
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Examining four blood biomarkers for the detection of acute intracranial abnormalities following mild traumatic brain injury in older adults.
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based biomarkers have been increasingly studied for diagnostic and prognostic purposes in patients with mild traumatic brain injury (MTBI). Biomarker levels in blood have been shown to vary throughout age groups. Our aim was to study four blood biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NF-L), and total tau (t-tau), in older adult patients with MTBI. The study sample was collected in the emergency department in Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with head injury were eligible for inclusion. Serum samples were collected from the enrolled patients, which were frozen and later sent for biomarker analyses. Patients aged 60 years or older with MTBI, head computed tomography (CT) imaging, and available biomarker levels were eligible for this study. A total of 83 patients (mean age = 79.0, SD = 9.58, range = 60-100; 41.0% men) were included in the analysis. GFAP was the only biomarker to show statistically significant differentiation between patients with and without acute head CT abnormalities [U(83) = 280, p < 0.001, r = 0.44; area under the curve (AUC) = 0.79, 95% CI = 0.67-0.91]. The median UCH-L1 values were modestly greater in the abnormal head CT group vs. normal head CT group [U (83) = 492, p = 0.065, r = 0.20; AUC = 0.63, 95% CI = 0.49-0.77]. Older age was associated with biomarker levels in the normal head CT group, with the most prominent age associations being with NF-L (r = 0.56) and GFAP (r = 0.54). The results support the use of GFAP in detecting abnormal head CT findings in older adults with MTBIs. However, small sample sizes run the risk for producing non-replicable findings that may not generalize to the population and do not translate well to clinical use. Further studies should consider the potential effect of age on biomarker levels when establishing clinical cut-off values for detecting head CT abnormalities.
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| 12. |
- Janigro, Damir, et al.
(författare)
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GFAP and S100B : What You Always Wanted to Know and Never Dared to Ask
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools.
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| 13. |
- Keski-Pukkila, Mira, et al.
(författare)
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Preliminary Evaluation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries with Glial Fibrillary Acidic Protein
- 2024
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Ingår i: NEUROTRAUMA REPORTS. - 2689-288X. ; 5:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- Glial fibrillary acidic protein (GFAP) has become the most promising biomarker for detecting traumatic abnormalities on head computed tomography (CT) in patients with traumatic brain injury (TBI), but most studies have not addressed the potential added value of combining the biomarker with clinical variables that confer risk for intracranial injuries. The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults were the first clinical decision rules in the field with an incorporated biomarker, the S100 astroglial calcium-binding protein B (S100B), which is used in the Mild (Low Risk) group defined by the guidelines. Our aim was to evaluate the performance of the guidelines when S100B was substituted with GFAP. The sample (N = 296) was recruited from the Tampere University Hospital's emergency department between November 2015 and November 2016, and there were 49 patients with available GFAP results who were stratified in the Mild (Low Risk) group (thus patients undergoing biomarker triaging). A previously reported cutoff of plasma GFAP >= 140 pg/mL was used. Within the Mild (Low Risk) group (n = 49), GFAP sensitivity (with 95% confidence intervals in parentheses) for detecting traumatic CT abnormalities was 1.0 (0.40-1.00), specificity 0.34 (0.19-0.53), the negative predictive value (NPV) 1.0 (0.68-1.00), and the positive predictive value (PPV) 0.16 (0.05-0.37). The sensitivity and specificity of the modified guidelines with GFAP, when applied to all imaged patients (n = 197) in the whole sample, were 0.94 (0.77-0.99) and 0.20 (0.15-0.28), respectively. NPV was 0.94 (0.80-0.99) and PPV 0.18 (0.13-0.25). In the Mild (Low Risk) group, none of the patients with GFAP results below 140 pg/mL had traumatic abnormalities on their head CT. These findings were derived from a small patient subgroup. Future researchers should replicate these findings in larger samples and assess whether GFAP has added or comparable value to S100B in acute TBI management.
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| 14. |
- Posti, Jussi P., et al.
(författare)
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Metabolomics Profiling As a Diagnostic Tool in Severe Traumatic Brain injury
- 2017
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is a complex disease with a multifaceted pathophysiology. Impairment of energy metabolism is a key component of secondary insults. This phenomenon is a consequence of multiple potential mechanisms including diffusion hypoxia, mitochondrial failure, and increased energy needs due to systemic trauma responses, seizures, or spreading depolarization. The degree of disturbance in brain metabolism is affected by treatment interventions and reflected in clinical patient outcome. Hence, monitoring of these secondary events in peripheral blood will provide a window into the pathophysiological course of severe TBI. New methods for assessing perturbation of brain metabolism are needed in order to monitor on-going pathophysiological processes and thus facilitate targeted interventions and predict outcome. Circulating metabolites in peripheral blood may serve as sensitive markers of pathological processes in TBI. The levels of these small molecules in blood are less dependent on the integrity of the blood-brain barrier as compared to protein biomarkers. We have recently characterized a specific metabolic profile in serum that is associated with both initial severity and patient outcome of TBI. We found that two medium-chain fatty acids, octanoic and decanoic acids, as well as several sugar derivatives are significantly associated with the severity of TBI. The top ranking peripheral blood metabolites were also highly correlated with their levels in cerebral microdialyzates. Based on the metabolite profile upon admission, we have been able to develop a model that accurately predicts patient outcome. Moreover, metabolomics profiling improved the performance of the well-established clinical prognostication model. In this review, we discuss metabolomics profiling in patients with severe TBI. We present arguments in support of the need for further development and validation of circulating biomarkers of cerebral metabolism and for their use in assessing patients with severe TBI.
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| 15. |
- Tefre, Sondre, et al.
(författare)
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Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV)
- 2022
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for EN and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. Methods and analysis The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients >= 18 years of age treated with EN at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. Ethics and dissemination The study is approved by appropriate ethics or patient safety boards in all participating countries.
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| 16. |
- Thomas, Ilias, 1987-, et al.
(författare)
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Integrative Analysis of Circulating Metabolite Profiles and Magnetic Resonance Imaging Metrics in Patients with Traumatic Brain Injury
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- 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 myo-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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| 17. |
- Thomas, Ilias, 1987-, et al.
(författare)
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Serum metabolome associated with severity of acute traumatic brain injury
- 2022
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.
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| 18. |
- Tommiska, Pihla, et al.
(författare)
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Finnish study of intraoperative irrigation versus drain alone after evacuation of chronic subdural haematoma (FINISH) : a study protocol for a multicentre randomised controlled trial
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:6, s. 038275-038275
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Chronic subdural haematomas (CSDHs) are one of the most common neurosurgical conditions. The goal of surgery is to alleviate symptoms and minimise the risk of symptomatic recurrences. In the past, reoperation rates as high as 20%-30% were described for CSDH recurrences. However, following the introduction of subdural drainage, reoperation rates dropped to approximately 10%. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural drainage. Yet, the role of intraoperative irrigation has not been established. If there is no difference in recurrence rates between intraoperative irrigation and no irrigation, CSDH surgery could be carried out faster and more safely by omitting the step of irrigation. The aim of this multicentre randomised controlled trial is to study whether no intraoperative irrigation and subdural drainage results in non-inferior outcome compared with intraoperative irrigation and subdural drainage following burr-hole craniostomy of CSDH. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, parallel group, non-inferiority multicentre trial comparing single burr-hole evacuation of CSDH with intraoperative irrigation and evacuation of CSDH without irrigation. In both groups, a passive subdural drain is used for 48 hours as a standard of treatment. The primary outcome is symptomatic CSDH recurrence requiring reoperation within 6 months. The predefined non-inferiority margin for the primary outcome is 7.5%. To achieve a 2.5% level of significance and 80% power, we will randomise 270 patients per group. Secondary outcomes include modified Rankin Scale, rate of mortality, duration of operation, length of hospital stay, adverse events and change in volume of CSDH. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District (HUS/3035/2019 §238) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04203550.
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