Background and Purpose: Cell-free DNA (cfDNA) and endogenous deoxyribonuclease activity are opposing mediators and might influence the inflammatory response following acute ischemic stroke. In this cohort study, we investigated the relation between these markers, circulating inflammatory mediators and clinical course including occurrence of stroke-associated infections (SAI) in patients with acute stroke. Methods: Ninety-two patients with stroke due to large vessel occlusion undergoing mechanical thrombectomy were prospectively recruited at Hannover Medical School from March 2018 to August 2019. Deoxyribonuclease activity, cfDNA, damage-associated molecular patterns, and circulating cytokines were measured in venous blood collected immediately before mechanical thrombectomy and 7 days later. Reperfusion status was categorized (sufficient/insufficient). Clinical outcome was evaluated using the modified Rankin Scale after 90 days, where a score of 3 to 6 was considered unfavorable. To validate findings regarding SAI, another stroke cohort (n=92) was considered with blood taken within 24 hours after stroke onset. Results: Patients with unfavorable clinical outcome had higher cfDNA concentrations. After adjustment for confounders (Essen Stroke Risk Score, National Institutes of Health Stroke Scale, and sex), 7-day cfDNA was independently associated with clinical outcome and especially mortality (adjusted odds ratio: 3.485 [95% CI, 1.001–12.134] and adjusted odds ratio: 9.585 [95% CI, 2.006–45.790]). No association was found between reperfusion status and cfDNA or deoxyribonuclease activity. While cfDNA concentrations correlated positively, deoxyribonuclease activity inversely correlated with distinct biomarkers. Baseline deoxyribonuclease activity was lower in patients who developed SAI compared with patients without SAI. This association was confirmed after adjustment for confounding factors (adjusted odds ratio: 0.447 [95% CI, 0.237–0.844]). In cohort 2, differences of deoxyribonuclease activity between patients with and without SAI tended to be higher with higher stroke severity. Conclusions: The interplay of endogenous deoxyribonuclease activity and cfDNA in acute stroke entails interesting novel diagnostic and potential therapeutic approaches. We confirm an independent association of cfDNA with a detrimental clinical course after stroke due to large vessel occlusion. This study provides first evidence for lower endogenous deoxyribonuclease activity as risk factor for SAI after severe stroke.

Background: In patients with left ventricular assist devices (LVADs), ischemic and hemorrhagic stroke are dreaded complications. Predictive markers for these events are lacking. This study aimed to investigate the prevalence and predictive value of microembolic signals (MES) for stroke, detected by Transcranial Doppler sonography (TCD) in patients with HeartMate 3 (HM 3) or HeartWare (HW). Methods: A thirty-minute bilateral TCD monitoring of the middle cerebral artery (MCA) was performed in 62 outpatients with LVAD (HM 3 N = 31, HW N = 31) and 31 healthy controls. Prevalence and quantity of MES were investigated regarding clinical and laboratory parameters. Cerebrovascular events (CVE) were recorded on follow-up at 90 and 180 days.Results: MES were detected in six patients with HM 3, three patients with HW, and three controls. Within the LVAD groups, patients on monotherapy with vitamin-K-antagonist (VKA) without antiplatelet therapy were at risk for a higher count of MES (negative binomial regression: VKA: 1; VKA + ASA: Exp(B) = 0.005, 95%CI 0.001-0.044; VKA + clopidogrel: Exp(B) = 0.012, 95%CI 0.002-0.056). There was no association between the presence of MES and CVE or death on follow-up (p > 0.05). Conclusion:For the first time, the prevalence of MES was prospectively investigated in a notable outpatient cohort of patients with HM 3 and HW. Despite optimized properties of the latest LVAD, MES remain detectable depending on antithrombotic therapy. No association between MES and CVE could be detected.

Mechanical thrombectomy (MT) is a highly efficient treatment in patients with acute ischemic stroke due to large vessel occlusion (LVO). However, in a relevant proportion of LVO, no sufficient recanalization can be achieved. The composition of cerebral thrombi is highly heterogeneous and may constitute a relevant factor for insufficient reperfusion. We hypothesized that circulating cytokines and growth factors involved in thrombo-inflammation and platelet activation may be associated with reperfusion status and thrombus composition in patients undergoing MT. An according biomarker panel was measured in plasma specimens taken prior to MT and at a seven-day follow-up. Reperfusion status was categorized into sufficient or insufficient. Composition of retrieved thrombi was histologically analyzed. Differences of baseline biomarker-concentrations between insufficient and sufficient reperfusion were highest for interferon (IFN)-γ, epidermal growth factor (EGF), platelet derived growth factor (PDGF)-AB/BB, and interferon-γ induced protein 10 (IP-10/CXCL10). After applying correction for multiple comparisons and logistic regression analysis adjusting for stroke etiology, intravenous thrombolysis and vascular risk factors, PDGF-AB/BB was identified as an independent predictor of reperfusion status (odds ratio: 0.403 (95%-CI: 0.199–0.819). Histological analysis revealed that the majority of thrombi had a mixed composition. In conclusion, this study provides first evidence that cytokines and growth factors are potential effectors in patients undergoing MT for the treatment of acute ischemic stroke.

Background: In acute ischemic stroke, timely treatment is of utmost relevance. Identification of delaying factors and knowledge about challenges concerning hospital structures are crucial for continuous improvement of process times in stroke care. Objective: In this study, we report on our experience in optimizing the door-to-needle time (DNT) at our tertiary care center by continuous quality improvement. Methods: Five hundred forty patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) at Hannover Medical School were consecutively analyzed in two phases. In study phase I, including 292 patients, process times and delaying factors were collected prospectively from May 2015 until September 2017. In study phase II, process times of 248 patients were obtained from January 2019 until February 2021. In each study phase, a new clinical standard operation procedure (SOP) was implemented, considering previously identified delaying factors. Pre- and post-SOP treatment times and delaying factors were analyzed to evaluate the new protocols. Results: In study phase I, SOP I reduced the median DNT by 15 min. The probability to receive treatment within 30 min after admission increased by factor 5.35 [95% confidence interval (CI): 2.46–11.66]. Further development of the SOP with implementation of a mobile thrombolysis kit led to a further decrease of DNT by 5 min in median in study phase II. The median DNT was 29 (25th–75th percentiles: 18–44) min, and the probability to undergo IVT within 15 min after admission increased by factor 4.2 (95% CI: 1.63–10.83) compared with study phase I. Conclusion: Continuous process analysis and subsequent development of targeted workflow adjustments led to a substantial improvement of DNT. These results illustrate that with appropriate vigilance, there is constantly an opportunity for improvement in stroke care.

BackgroundThe identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors.MethodsWe determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate.ResultsADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = −0.452, p < 0.001) and CHA2DS2VASC (r = −0.375, p < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010).ConclusionADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.