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Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.
Background and Purpose: In the setting of acute ischemic stroke, increased blood-brain barrier permeability (BBBP) as a sign of injury is believed to be associated with increased risk of poor outcome. Pre-clinical studies show that selected serum biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), matrix metallopeptidases (MMP), and vascular endothelial growth factors (VEGFs) may play a role in BBBP post-stroke. In the subacute phase of stroke, increased BBBP may also be caused by regenerative mechanisms such as vascular remodeling and therefore may improve functional recovery. Our aim was to investigate the evolution of BBBP in ischemic stroke using contrast-enhanced (CE) magnetic resonance imaging (MRI) and to analyze potential associations with blood-derived biomarkers as well as functional recovery in subacute ischemic stroke patients.
Methods: This is an exploratory analysis of subacute ischemic stroke patients enrolled in the BAPTISe study nested within the randomized controlled PHYS-STROKE trial (interventions: 4 weeks of aerobic fitness training vs. relaxation). Patients with at least one CE-MRI before (v1) or after (v2) the intervention were eligible for this analysis. The prevalence of increased BBBP was visually assessed on T1-weighted MR-images based on extent of contrast-agent enhancement within the ischemic lesion. The intensity of increased BBBP was assessed semi-quantitatively by normalizing the mean voxel intensity within the region of interest (ROI) to the contralateral hemisphere (“normalized CE-ROI”). Selected serum biomarkers (high-sensitive CRP, IL-6, TNF-α, MMP-9, and VEGF) at v1 (before intervention) were analyzed as continuous and dichotomized variables defined by laboratory cut-off levels. Functional outcome was assessed at 6 months after stroke using the modified Rankin Scale (mRS).
Results: Ninety-three patients with a median baseline NIHSS of 9 [IQR 6–12] were included into the analysis. The median time to v1 MRI was 30 days [IQR 18–37], and the median lesion volume on v1 MRI was 4 ml [IQR 1.2–23.4]. Seventy patients (80%) had increased BBBP visible on v1 MRI. After the trial intervention, increased BBBP was still detectable in 52 patients (74%) on v2 MRI. The median time to v2 MRI was 56 days [IQR 46–67]. The presence of increased BBBP on v1 MRI was associated with larger lesion volumes and more severe strokes. Aerobic fitness training did not influence the increase of BBBP evaluated at v2. In linear mixed models, the time from stroke onset to MRI was inversely associated with normalized CE-ROI (coefficient −0.002, Standard Error 0.007, p < 0.01). Selected serum biomarkers were not associated with the presence or evolution of increased BBBP. Multivariable regression analysis did not identify the occurrence or evolution of increased BBBP as an independent predictor of favorable functional outcome post-stroke.
Conclusion: In patients with moderate-to-severe subacute stroke, three out of four patients demonstrated increased BBB permeability, which decreased over time. The presence of increased BBBP was associated with larger lesion volumes and more severe strokes. We could not detect an association between selected serum biomarkers of inflammation and an increased BBBP in this cohort. No clear association with favorable functional outcome was observed.
Trial registration: NCT01954797.
Die vorliegende Arbeit hatte das Ziel, die Entwicklung der offenen und geschlossenen enossalen Implantationsverfahren unter besonderer Berücksichtigung der Zahn-, Mund- und Kieferheilkunde der Greifswalder Universität darzustellen. Speziell wurde auf die Geschichte der Stiftverbolzung/endodontischen Stiftimplantation nach Staegemann näher eingegangen. Alle Patienten, bei denen in der Poliklinik Mund-, Kiefer- und Gesichtschirurgie der Ernst-Moritz-Arndt-Universität Greifswald im Zeitraum von 1990 bis 1999 offene und geschlossene enossale Implantate inseriert wurden, sind in die vorliegende Studie konsekutive aufgenommen worden. Insgesamt 274 Patienten wurden mit 269 offenen und 129 geschlossenen enossalen Implantaten versorgt. Zur Bestimmung der Überlebenswahrscheinlichkeit mit dem Kriterium Implantatverlust wurde die Analyse nach Kaplan-Meier angewendet. Die Überlebenswahrscheinlichkeit der offenen Implantate betrug 92,5 % nach maximaler Liegedauer von 9,5 Jahren, der geschlossenen - 56,6 % nach maximaler Liegedauer von 9,3 Jahren. Eine akute apikale Parodontitis war dabei die häufigste Ursache für den Verlust der transdental fixierten Zähne. Laut Ergebnissen unserer Studie scheinen die geschlossenen enossalen Implantationsverfahren ihre ursprüngliche Bedeutung zur heutigen Zeit verloren zu haben.
Subterranean estuaries the, subsurface mixing zones of terrestrial groundwater and seawater, substantially influence solute fluxes to the oceans. Solutes brought by groundwater from land and solutes brought from the sea can undergo biogeochemical reactions. These are often mediated by microbes and controlled by reactions with coastal sediments, and determine the composition of fluids discharging from STEs (i.e., submarine groundwater discharge), which may have consequences showing in coastal ecosystems. While at the local scale (meters), processes have been intensively studied, the impact of subterranean estuary processes on solute fluxes to the coastal ocean remains poorly constrained at the regional scale (kilometers). In the present communication, we review the processes that occur in STEs, focusing mainly on fluid flow and biogeochemical transformations of nitrogen, phosphorus, carbon, sulfur and trace metals. We highlight the spatio-temporal dynamics and measurable manifestations of those processes. The objective of this contribution is to provide a perspective on how tracer studies, geophysical methods, remote sensing and hydrogeological modeling could exploit such manifestations to estimate the regional-scale impact of processes in STEs on solute fluxes to the coastal ocean.