| 1. |
- Leifsdottir, Kristin, et al.
(författare)
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The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome
- 2022
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurvival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. MethodsTwenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. ResultsThe CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. ConclusionOur data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.
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| 2. |
- Lindblad, Caroline, et al.
(författare)
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Fluid proteomics of CSF and serum reveal important neuroinflammatory proteins in blood-brain barrier disruption and outcome prediction following severe traumatic brain injury : a prospective, observational study
- 2021
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls. Methods: We conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6-12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (Q(A)), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort. Results: TBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated with Q(A), among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained similar to 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, Delta R-2 = 7.4%) and complement factor B in serum (p = 0.003, Delta R-2 = 9.2%) were independent outcome predictors also following step-down modelling. Conclusions: This represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.
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| 3. |
- Fletcher-Sandersjoo, Alexander, et al.
(författare)
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Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI) : study protocol for a multicentre, retrospective, observational cohort study
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. Methods and analysis This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (>= 15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission >= 48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. Ethics and dissemination The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences.
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| 4. |
- Fletcher-Sandersjöö, Alexander, et al.
(författare)
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Absolute Contusion Expansion Is Superior to Relative Expansion in Predicting Traumatic Brain Injury Outcomes : A Multi-Center Observational Cohort Study
- 2024
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 41:5-6, s. 705-713
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Tidskriftsartikel (refereegranskat)abstract
- Contusion expansion (CE) is a potentially treatable outcome predictor in traumatic brain injury (TBI), and a suitable end-point for hemostatic therapy trials. However, there is no consensus on the definition of clinically relevant CE, both in terms of measurement criteria (absolute vs. relative volume increase) and cutoff values. In light of this, the aim of this study was to assess the predictive abilities of different CE definitions on outcome. We performed a multi-center observational cohort study of adults with moderate-to-severe TBI treated in an intensive care unit. The exposure of interest was CE, defined as the absolute and relative volume change between the first and second computed tomography scan. The primary outcome was the Glasgow Outcome Scale (GOS) at 6–12 months post-injury, dichotomized into unfavorable (GOS ≤3) or favorable (GOS ≥4). The secondary outcome was all-cause mortality. In total, 798 patients were included, with a median duration of 7.0 h between the first and second CT scan. The median absolute and relative CE was 1.5 mL (interquartile range [IQR] 0.1–8.3 mL) and 100% (IQR 10–530%), respectively. Both CE forms were independently associated with unfavorable GOS. Absolute CE outperformed relative CE in predicting both unfavorable GOS (area under the curve [AUC]: 0.65 vs. 0.60, p = 0.002) and all-cause mortality (AUC: 0.66 vs. 0.60, p = 0.003). For dichotomized CE, absolute cutoffs of 1–10 mL yielded the best results. We conclude that absolute CE demonstrates stronger outcome correlation than relative CE. In studies focusing on lesion progression in TBI, it may be advantageous to use absolute CE as the primary outcome metric. For dichotomized outcomes, cutoffs between 1 and 10 mL are suggested, depending on the desired sensitivity-specificity balance.
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| 5. |
- Needham, Edward J, et al.
(författare)
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Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury.
- 2021
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 207:1, s. 90-100
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Tidskriftsartikel (refereegranskat)abstract
- Most of the variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognized prognostic factors. Neuroinflammation may account for some of this difference. We hypothesized that TBI generated variable autoantibody responses between individuals that would contribute to outcome. We developed a custom protein microarray to detect autoantibodies to both CNS and systemic Ags in serum from the acute-phase (the first 7 d), late (6-12 mo), and long-term (6-13 y) intervals after TBI in human patients. We identified two distinct patterns of immune response to TBI. The first was a broad response to the majority of Ags tested, predominantly IgM mediated in the acute phase, then IgG dominant at late and long-term time points. The second was responses to specific Ags, most frequently myelin-associated glycopeptide (MAG), which persisted for several months post-TBI but then subsequently resolved. Exploratory analyses suggested that patients with a greater acute IgM response experienced worse outcomes than predicted from current known risk factors, suggesting a direct or indirect role in worsening outcome. Furthermore, late persistence of anti-MAG IgM autoantibodies correlated with raised serum neurofilament light concentrations at these time points, suggesting an association with ongoing neurodegeneration over the first year postinjury. Our results show that autoantibody production occurs in some individuals following TBI, can persist for many years, and is associated with worse patient outcome. The complexity of responses means that conventional approaches based on measuring responses to single antigenic targets may be misleading.
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| 6. |
- Wood, Sara, et al.
(författare)
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Predictors of intracranial hemorrhage in neonatal patients on extracorporeal membrane oxygenation
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Extracorporeal membrane oxygenation (ECMO) is a life-supportive treatment in neonatal patients with refractory lung and/or heart failure. Intracranial hemorrhage (ICH) is a severe complication and reliable predictors are warranted. The aims of this study were to explore the incidence and possible predictors of ICH in ECMO-treated neonatal patients. We performed a single-center retrospective observational cohort study. Patients aged <= 28 days treated with ECMO between 2010 and 2018 were included. Exclusion criteria were ICH, ischemic stroke, cerebrovascular malformation before ECMO initiation or detected within 12 h of admission, ECMO treatment < 12 h, or prior treatment with ECMO at another facility > 12 h. The primary outcome was a CT-verified ICH. Logistic regression models were employed to identify possible predictors of the primary outcome. Of the 223 patients included, 29 (13%) developed an ICH during ECMO treatment. Thirty-day mortality was 59% in the ICH group and 16% in the non-ICH group (p < 0.0001). Lower gestational age (p < 0.01, odds ratio (OR) 0.96; 95%CI 0.94-0.98), and higher pre-ECMO lactate levels (p = 0.017, OR 1.1; 95%CI 1.01-1.18) were independently associated with increased risk of ICH-development. In the clinical setting, identification of risk factors and multimodal neuromonitoring could help initiate steps that lower the risk of ICH in these patients.
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