| 1. |
|
|
| 2. |
|
|
| 3. |
- Huie, J. Russell, et al.
(författare)
-
Biomarkers for Traumatic Brain Injury : Data Standards and Statistical Considerations
- 2021
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:18, s. 2514-2529
-
Tidskriftsartikel (refereegranskat)abstract
- Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Canova, C., et al.
(författare)
-
Perinatal and antibiotic exposures and the risk of developing childhood-onset inflammatory bowel disease : A nested case-control study based on a population-based birth cohort
- 2020
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:7
-
Tidskriftsartikel (refereegranskat)abstract
- The role of early-life environmental exposures on Inflammatory Bowel Disease (IBD) onset remains unclear. We aimed to quantify the impact of perinatal conditions and antibiotic use in the first 6 and 12 months of life, on the risk of childhood-onset IBD, in a birth cohort of the region Friuli-Venezia Giulia (Italy). A nested case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate Odds Ratios (OR) with 95% confidence intervals (CI) for all analyzed risk factors. We identified 164 individuals with IBD onset before the age of 18 years and 1640 controls. None of the considered perinatal conditions were associated with IBD. Analyses on antibiotic exposure were based on 70 cases and 700 controls. Risks were significantly higher for children with ≥4 antibiotic prescriptions in the first 6 and 12 months of life (OR = 6.34; 95%CI 1.68–24.02 and OR = 2.91; 95%CI 1.31–6.45, respectively). This association was present only among patients with Crohn’s disease and those with earlier IBD onset. We found that perinatal characteristics were not associated to IBD, while the frequent use of antibiotics during the first year of life was associated to an increased risk of developing subsequent childhood-onset IBD.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Needham, Edward J, et al.
(författare)
-
Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury.
- 2021
-
Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 207:1, s. 90-100
-
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.
|
|
