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1.
  • Clarke, Gerard Janez Brett, et al. (författare)
  • Chronic immunosuppression across 12 months and high ability of acute and subacute CNS-injury biomarker concentrations to identify individuals with complicated mTBI on acute CT and MRI.
  • 2024
  • Ingår i: Journal of Neuroinflammation. - 1742-2094. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The main aims of our study were (1) to assess the temporal evolution of blood biomarkers of CNS injury and inflammation in individuals with complicated mTBI determined on computer tomography (CT) and magnetic resonance imaging (MRI); (2) to assess the corresponding discriminability of both single- and multi-biomarker panels, from acute to chronic phases after injury.Patients with mTBI (n=207), defined as Glasgow Coma Scale score between 13 and 15, loss of consciousness<30min and post-traumatic amnesia<24h, were included. Complicated mTBI - i.e., presence of any traumatic intracranial injury on neuroimaging - was present in 8% (n=16) on CT (CT+) and 12% (n=25) on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72h), 2 weeks (±3 days), 3 months (±2 weeks) and 12 months (±1 month). CNS biomarkers included were glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, along with 12 inflammation markers.The most discriminative single biomarkers of traumatic intracranial injury were GFAP at admission (CT+:AUC=0.78; MRI+:AUC=0.82), and NFL at 2 weeks (CT+:AUC=0.81; MRI+:AUC=0.89) and 3 months (MRI+:AUC=0.86). MIP-1β and IP-10 concentrations were significantly lower across follow-up period in individuals who were CT+and MRI+. Eotaxin and IL-9 were significantly lower in individuals who were MRI+only. FGF-basic concentrations increased over time in MRI- individuals and were significantly higher than MRI+individuals at 3 and 12 months. Multi-biomarker panels improved discriminability over single biomarkers at all timepoints (AUCs>0.85 for admission and 2-week models classifying CT+and AUC≈0.90 for admission, 2-week and 3-month models classifying MRI+).The CNS biomarkers GFAP and NFL were useful single diagnostic biomarkers of complicated mTBI, especially in acute and subacute phases after mTBI. Several inflammation markers were suppressed in patients with complicated versus uncomplicated mTBI and remained so even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints, though at acute and 2-week timepoints, the single biomarkers GFAP and NFL, respectively, displayed similar accuracy compared to multi-biomarker panels.
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2.
  • Clarke, Gerard, et al. (författare)
  • Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury Following Mild Traumatic Brain Injury
  • 2024
  • Ingår i: Journal of neurotrauma. - 1557-9042. ; 41:7-8, s. 862-878
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (n = 192, 16-60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC)<30 min and post-traumatic amnesia (PTA)<24 hours were included. Blood samples were collected at admission (within 72 hours), 2 weeks and 3 months. From the blood, concentrations of blood biomarkers associated with CNS damage (GFAP, NFL and tau) and inflammation (IFN, IL-8, eotaxin, MIP-1, MCP-1, IP-10, IL-17A, IL-9, TNF, FGF-basic PDGF and IL-1ra) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on MRI (within 72 hours), and extracranial injuries. Delta values, i.e., timepoint differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multivariable models, female sex, longer PTA duration, MRI findings and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFN were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A and FGF-basic at 2 weeks compared to admission, MCP-1 at 3 months compared to admission and TNF at 2 weeks and 3 months compared to admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both timepoint comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, while the optimal combination of biomarkers yielded AUCs between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling timepoint after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.
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3.
  • Kristoffersen, Laila, et al. (författare)
  • Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants
  • 2019
  • Ingår i: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 108:8, s. 1434-1440
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity.METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination.RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91).CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.
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