Background
Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients.
Methods
We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed.
Results
Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals.
Conclusions
Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke.
Trial registration
DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278
Technical dysfunctions of stimulation electrodes or extension leads are rare but important sources of unsatisfying DBS efficacy. In the majority of cases DBS programming or reprogramming allows avoiding surgical revision.
Background:Aim of our study was to determine the predictive impact of certain serum immunological markers on overall survival (OS) in patients with glioblastoma multiforme (GBM).Methods:We assayed prospectively values of interleukin 2 (IL-2), immunoglobulin G (IgG), C4, CD3+, CD4+ and CD8+ cells via flow cytometry, enzyme-linked immunosorbent assay (ELISA) and radial immunodiffusion in preoperative sera of adult patients with de novo histologically confirmed supratentorial GBM. Kaplan-Meier method and Cox proportional hazards models were used to assess clinical, laboratory, and treatment prognostic factors for OS.Results:Twenty-six consecutive patients were identified with a mean age of 59.6 years. Median follow up was 12 months. Lower IL-2 values (<7.97 pg/ml vs. ≥7.97 pg/ml, P = 0.029) und CD4+ counts (<200 cells/μl vs. ≥200 cells/μl, P < 0.001) correlated significantly with a shorter OS. The independent prognostic relevance of CD4 + counts was confirmed by the multivariate analysis (HR = 0.010, 95% CI 0.001-0.226, P = 0.011). Further independent prognostic factors for OS were type of resection (resection vs. biopsy) and administration of radiotherapy (yes/no).Conclusion:Preoperative values IL-2 and CD4+ cells in sera may carry a prognostic impact. Novel diagnostic models prior to histopathological confirmation may be used to predict prognosis of patients with GBM. Future studies should investigate whether targeting immune factors, such as CD4+ and IL-2, may improve the prognosis of patients with GBM.
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