BackgroundPost-stroke cognitive impairment (PSCI) severely affects quality of life and prognosis in stroke survivors, yet reliable predictive, diagnostic and prognostic tools remain limited. Recent advances suggest that molecular, genetic, and imaging-based biomarkers may improve prediction and management of PSCI. The purpose of this systematic review was to provide a synthesis of the current evidence on biomarkers related to PSCI, aiming to highlight knowledge gaps and future research directions.MethodsWe conducted a systematic review of observational cohort, cross-sectional, case-control and interventional studies investigating biomarkers associated with PSCI and post-stroke dementia. Eligible studies enrolled patients with acute ischemic or hemorrhagic stroke and reported cognitive outcomes with biomarker assessments in blood, or other body fluids, or neuroimaging. Screening followed PRISMA guidelines. Data extraction included study design, population characteristics, biomarkers, and cognitive outcomes. Biomarkers were clustered by type for evidence synthesis.ResultsOf 834 screened studies, 154 were included (99 cohorts, 19 case-control, 35 cross-sectional, 1 interventional; n = 114,474). The most frequently studied biomarkers were imaging biomarkers, such as infarct volume, brain atrophy, and white matter hyperintensities, which showed consistent associations with PSCI, whereas blood-based biomarkers, notably markers of inflammation (e.g., CRP, IL-6), metabolism (e.g., HbA1c, homocysteine), and neuronal damage (e.g., amyloid-β1–42, plasma neurofilament light chain), yielded more variable results, thereby limiting their applicability in clinical practice. Genetic markers (e.g., related to APOE ε4, MMP-9, microRNAs) showed moderate evidence of association with PSCI. We found substantial heterogeneity in timing of sampling or acquisition, cognitive assessment tools and population characteristics.ConclusionSeveral body-fluid-based, genetic, and imaging biomarkers demonstrate potential for the prediction of PSCI. However, clinical utility remains constrained by study heterogeneity, lack of standardization and residual confounding. Standardized protocols for cognitive assessments and biomarker timing, as well as multi-center longitudinal studies, are essential to validate and translate these biomarkers into routine clinical care.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42025642710, identifier CRD42025642710.

A significant proportion of ischemic strokes are classified as embolic stroke of undetermined source (ESUS), complicating secondary prevention. Nitric oxide metabolism is regulated by L-arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), contributing to increased cardiovascular risk. Previous studies suggest that SDMA and the ratio of Arg/SDMA help to detect atrial fibrillation (AF). We hypothesized that SDMA and Arg/SDMA improve diagnosis of cardioembolic stroke (CES), which may enable more accurate secondary prevention. This prospective nested case-control study included ischemic stroke patients (CES or ESUS) at Hannover Medical School between January 2022 and July 2023. Blood samples were collected after 24 h of stroke onset. ADMA, SDMA and Arg concentrations were measured and relevant biomarker ratios were calculated. Logistic regression and receiver operating curve analyses examined discriminatory biomarker performances for CES versus ESUS, alongside established clinical risk scores. 235 patients (107 CES, 128 ESUS) were analyzed. Arg/SDMA ratio and SDMA values showed comparable or better discriminatory power between CES and ESUS than clinical AF scores (AUC SDMA = 0.71 (95

Abstract Background and aims Despite advances in stroke treatment, recurrence risk remains largely unchanged over two decades. In the multicenter CiRculating mEdiators of Stroke reCurrENce anD aetiOlogies (CRESCENDO) consortium, we conducted the first large-scale proteomic analysis of 5,400 targets to characterize post-stroke blood-based proteomic signatures associated with 90-day recurrence. Methods CRESCENDO compiled comprehensive prospective cohorts from Hannover (Germany), Barcelona/Seville (Spain), and Zurich/Basel (Switzerland), comprising 4,854 patients sampled within 24 hours of ischemic stroke. A subset of 175 patients (75 recurrent, 100 non-recurrent), balanced for age, sex, NIHSS, was profiled using the Olink Explore HT panel. Protein levels were compared between recurrent and nonrecurrent cases, and their predictive values were evaluated. Results Across all etiologies, G kinase anchoring protein-1 (GKAP1) was elevated in recurrent cases (logFC = 0.72, adjusted P = 0.02). Etiology-stratified analyses revealed upregulation of Carboxylesterase 1 (CES1) in patients with atherosclerotic index stroke and recurrence (logFC = 1.19, adjusted P = 0.02), and enrichment of Centromere Protein F (CENPF), Biliverdin Reductase B (BLVRB), and Parkinson disease protein 7 (PARK7) patients with cardioembolic index stroke and recurrence (logFC = 1.13, 0.99, 0.98, adjusted P = 0.02, 0.03, 0.04). Recurrence prediction using clinical data alone had an accuracy of 0.55, which increased to 0.61 when etiology-specific proteins were added. Conclusions High-throughput proteomics identified novel, etiology-specific proteins associated with 90-day recurrence. The improvement in predictive accuracy when integrating these markers suggests that etiology-stratified proteomic profiling can uncover distinct biological drivers of recurrence, warranting larger studies to refine targeted secondary prevention. Conflict of interest nothing to disclose.

Background:During the COVID-19 pandemic, it became evident that an infection with SARS-CoV-2 is associated with an increased predisposition for thrombembolic events. Recent studies suggest an excessive neutrophil extracellular trap (NET)-formation in response to SARS-CoV-2, which is considered a hallmark in immunothrombosis. A better understanding of the (dys)regulation of NET-formation in COVID-19 may provide the basis for new therapeutic strategies. Methods:We conducted a pilot study with a total of 84 patients in three groups matched in a 1:1:1 fashion: Group 1: patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and SARS-CoV-2 infection, Group 2: patients with AIS and no SARS-CoV-2 infection and Group 3: patients with SARS-CoV-2 infection and no AIS or TIA. Venous blood samples were collected from all patients and subsequently analyzed for NET-specific markers, NET regulators (Deoxyribonuclease (DNase) activity) and a panel of cytokines. Results:Citrullinated histone3 (H3cit) and elastase levels were higher in groups with SARS-CoV-2 infection (Groups 1 and 3) compared to patients without ((group 1: H3cit = 2.9 (1.11-6.89) ng/mL, elastase = 312.1 (162-435.4) ng/mL and group 3: H3cit = 3.31 (2.03-7.97) ng/mL and elastase = 433.1 (281-783.8) ng/mL) vs. group 2: H3cit = 1.17 (0.61-2.15) ng/mL), elastase = 195.1 (91.99-386.9) ng/mL). No relevant differences were found regarding other measured NET-marker (myeloperoxidase, LL-37). DNase activity was lower in group 1 (6.12 (4.97-6.78) pmol/mL/min) compared to both other groups (group 2: (7.16 (5.88-7.85) pmol/mL/min) (p=0.018) and group 3 (7.19 (5.52-8.54) pmol/mL/min) (p=0.013). Conclusion:This pilot data suggest that a disturbed regulation of NETs in patients with SARS-CoV-2 infection may play a role in SARS-CoV-2 associated cerebral ischemia. These results highlight the importance of further investigating the role of NETs in immunothrombosis in the context of viral infections, to better understand its potential as a target for therapeutic strategies.

Abstract Background and aims The TNF-α promoter variant rs1800629 and TNF-α serum levels could indicate inflammatory pathways across stroke subtypes, aiding precise etiology assignment. In this phenotype-genotype association study investigating embolic stroke of undetermined source (ESUS) (PHEGAESUS), we performed targeted analyses to elucidate the role of TNF-α and its genetic variants in stroke etiologies. Methods Within the PHEGAESUS study, ischemic stroke patients were consecutively recruited at Hannover Medical School between December 2020 and July 2023. Genotyping was performed using Axiom myDesign Custom Genotyping Array. TNF-α serum concentrations were measured by chemiluminescence immunoassay in samples obtained >24h after stroke onset. We performed explorative analyses between rs1800629 and ESUS, and between rs1800629 and TNF-α serum concentration. Results After quality control, data from 1,001 patients with both SNP and clinical information were available. Comparing 288 ESUS patients to 713 patients assigned to another defined etiology, rs1800629 carriers in a dominant model (GA+AA) showed a higher prevalence in ESUS than in other stroke etiologies (35.8% vs. 29.2%, p-chi2: 0.042, OR 1.35, 95%CI 1.01-1.8). No difference across genotypes was observed for TNF-α serum concentration in ESUS (median (IQR) GA+AA (n=46) vs. GG (n=96): 10.7 (4.4)pg/ml vs. 9.8 (5.3)pg/ml, p Mann-Whitney-U: 0.36). Conclusions TNF-α promoter variant rs1800629 is enriched in ESUS patients but does not appear to influence TNF-α serum levels. These findings suggest a complex relationship between biomarker and genetic variation. Further investigation of the genomic region of TNF-α is warranted to clarify the potential pathophysiological role of inflammatory pathways in ESUS. Conflict of interest Ricarda Siegel: nothing to disclose, Johannes Teller: nothing to disclose, Gerrit M. Grosse: nothing to disclose, Ramona Schuppner: nothing to disclose, Johanna Ernst: nothing to disclose, Ralf Lichtinghagen: nothing to disclose, Karin Weissenborn: nothing to disclose, Gesa Wilde: nothing to disclose, Hannelore Ehrenreich: nothing to disclose, Anika Grosshennig: nothing to disclose

Abstract Background and aims Acute ischemic stroke treatment is a time-sensitive, interdisciplinary workflow demanding efficient communication and standardized protocols to ensure rapid and safe care. Smartphone applications offer the potential to enhance communication within the acute workflow. Modifying this high-risk process requires structured implementation. We aim to evaluate the impact of app-based single call activation (SCA) introduced via stroke team training (STT) on door-to-needle-times (DNT) at our comprehensive stroke center. Methods A comprehensive stroke center implemented STT prior to launching an app-based SCA using “Join” in April 2024. The neurologist alerts the stroke team (neurologists, ED nurses, radiology technicians, neuroradiologists, stroke unit nurses) via app-based SCA and conveys key information, enabling preemptive resource preparation. Weekly one-hour STT sessions, comprising briefing, simulation, and debriefing, began before app-start in clinical routine. Median DNT for patients receiving intravenous thrombolysis (IVT) was compared before (T1) and after (T2) implementing STT and SCA. Results SCA and STT were successfully integrated. N=316 SCAs were conducted in clinical routine and n=184 professionals participated in 23 STTs. Among 225 IVT-treated patients analyzed (T1: n=111; T2: n=114), median DNT decreased significantly from 27 minutes (IQR 16–46) to 19.5 minutes (IQR 14–36). Linear regression adjusted for imaging modality (CT/MRI), trichotomized NIHSS, time window (<4.5h/>4.5h), and SCA status(yes/no) identified SCA as an independent predictor of reduced DNT [β −0.187; CI: −18.769 to −0.600]. Conclusions App-based SCA implementation introduced by STT allows the stroke team to act in concert, significantly shortening DNT. Linear regression reveals SCA as an independent factor for reduced DNT. Conflict of interest TN: nothing to disclose; HW: nothing to disclose; MS: nothing to disclose; CF: nothing to disclose; IA: nothing to disclose; WP : reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses STROKE TEAM-Training (LAERDAL medical); payment or honoraria from LAERDAL medical, Alexion, Pfizer-BMS, Boehringer Ingelheim and AstraZeneca; support for attending meetings and/or travel from LAERDAL medical, Alexion and Pfizer-BMS; OA-F: nothing to disclose; RS: nothing to disclose; AB: nothing to disclose; JE: nothing to disclose Figure 1 - belongs to Results

Abstract Background and aims Neutrophil extracellular traps (NETs) have been implicated in vascular inflammation and thromboinflammatory processes that contribute to atherosclerotic plaque vulnerability and athero-thrombosis. However, their role in human carotid plaques associated with ischemic stroke remains insufficiently characterized. Methods Carotid endarterectomy specimens from patients with symptomatic and asymptomatic carotid stenosis as well as peripheral venous blood samples taken prior to intervention and at a 90-day follow-up were analyzed. Blood-based NETs markers (cfDNA, DNase activity, H3cit) were determined. Immunohistochemical staining for established NET markers DNA-histone-1 complexes and myeloperoxidase (MPO) was performed and analyzed in carotid plaque samples. A semi-quantitative NETs score was established to investigate the association between NETs burden and clinical as well as histopathological features of plaque vulnerability. Results 48 patients (mean age: 69 years, 25% female) were included. Symptomatic carotid plaques (n= 22) exhibited markedly higher NETs burden compared to asymptomatic plaques (n=24): p=0.03. Moreover, the NETs score correlated with histopathological features of plaque vulnerability (rs=0.333, p=0.029). No differences were found in blood-based NETs markers between symptomatic and asymptomatic patients at baseline. At 90 days, DNase activity tended to be lower in blood samples of symptomatic patients with a significant delta to baseline (DNase activity 90d [pmol/min/ml]: symp= 16.56 vs. asymp=16.88, p=0.083, Delta DNase activity: symp= 1.47 vs asymp= -1.51, p=0.012). Conclusions Plaque-based burden of NETs is associated with vulnerability and stroke in carotid artery stenosis. The findings of this pilot study therefore underscore the potential role of NETs in stroke in carotid artery disease. Conflict of interest Ramona Schuppner: nothing to disclose, Ricarda D. Stauss: nothing to disclose, Claudia Schrimpf: nothing to disclose, Mathias Wilhelmi: nothing to disclose, Maria M. Gabriel: nothing to disclose, Lavinia Neubert´: nothing to disclose, Danny D. Jonigk: nothing to disclose, Karin Weissenborn: nothing to disclose, Nicole de Buhr: nothing to disclose, Gerrit M. Grosse: nothing to disclose

Background: Timely treatment of ischaemic stroke with intravenous thrombolysis (IVT) and endovascular treatment (EVT) depends on efficient communication within a multiprofessional team. Mobile applications can streamline communication and documentation processes in acute stroke care. Objective: This study aims to implement a mobile app to facilitate digital documentation and communication in acute stroke care and evaluate its impact on documentation rates and treatment times. Furthermore, a user experience survey was performed to gather information about the app usage in an acute medical process. Design: The study is designed as an observational post-market clinical follow-up cohort study. Methods: The mobile app ‘Join’ was implemented in a tertiary stroke care centre. Feasibility was assessed by monitoring documentation rates and process times, that is, ‘door-to-needle time’ (DNT) and ‘door-to-groin time’ (DGT). All patients treated for suspected stroke or transitory ischaemic attack were included in a 6-month period prior to (T1) and a 3-month period after (T2) implementation of the Join app. User experience was evaluated through a standardized survey including technical features. Results: The interface between the mobile application, hospital information, picture archiving and communication, and quality assurance system as well as various magnetic resonance imaging/computer tomography scanners was implemented for acute stroke care. A total of 504 stroke patients was treated, 334 in T1 and 170 in T2. Of these, 65 received IVT and 87 received endovascular treatment (EVT). DNT (T1 vs T2, 27.5 vs 32 min, p = 0.987) and DGT (T1 vs T2, 50 vs 61.5 min, p = 0.481) were numerically longer during T2. Documentation rates increased threefold for all patients and 1.5 times for those receiving recanalization therapy. The survey revealed that documentation (76%) and case information retrieval (52%) were the most used app features, while other functionalities were less frequently utilized. Conclusion: Implementing a mobile app facilitated real-time digital documentation accessible to the entire stroke care team. The introduction of the app did not improve treatment times for patients receiving acute recanalizing therapies. We recommend systematic training programmes to promote user acceptance and effective use.

Purpose With an incidence of 2-5 per million adults, cerebral venous and sinus thrombosis (CVST) is a rarity in the spectrum of cerebrovascular diseases. The etiology and symptomatic presentation are heterogeneous and diverse. CSVT is, therefore, often underdiagnosed. In addition to therapeutic anticoagulation, venous thrombectomy is a last-resort therapy in individual cases. Case Description A 42-year-old woman was admitted to the hospital with postural headache following an unsuccessful lumbar puncture. On suspicion of post-puncture syndrome, analgesic therapy with adjuvant caffeine tablets was initially chosen, leading to rapid improvement and short-term discharge. However, only one day later, the patient presented with a significant worsening of her symptoms and new onset of paresthesia. Since distally accentuated paresis of the left arm also occurred within a very short period of time, a cerebral MRI examination was performed. This revealed an extensive CVST. Due to the extensive CVST and progressive worsening of symptoms, mechanical venous thrombectomy was discussed and performed on an interdisciplinary basis. Mechanical thrombectomy was successful and resulted in complete improvement of symptoms. Discussion The pathophysiological diagnosis is cerebrospinal fluid leak syndrome after unsuccessful lumbar puncture. According to the Monroe-Kellie doctrine, the loss of CSF leads to compensatory dilatation and venous stasis, which in combination can lead to venous insufficiency and promote prothrombotic conditions. Although the available data on the performance of venous thrombectomy suggest caution, there should always be sufficient discretion for individual decision making. As our experience shows, there is a chance of successful venous thrombectomy in the early phase of CVST.

Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)-based and IFN-free therapy. HCV-infected patients who underwent neuropsychological assessment in previous studies were invited to a follow-up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self-report questionnaires addressing health-related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling "d" test, Word-Figure-Memory Test and computer-based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow-up. Our data can be considered as a hint that HCV eradication-independent of therapy regimen-does not substantially ameliorate neuropsychiatric symptoms in HCV-afflicted patients.

Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients’ blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke.

INTRODUCTION/AIMS:Spinal muscular atrophy (SMA) is a multisystem disorder. We assessed metabolic syndrome (MetS) prevalence in adults with SMA and its association with motor function, quality of life (QoL), fatigue, and depression. METHODS:MetS was diagnosed using 2009 consensus criteria. Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and 36-Item Short Form Health Survey (SF-36) were recorded and correlations between muscle function, depression, fatigue, QoL, and MetS were analyzed. RESULTS:We included 36 individuals (18 males; mean age: 38.7 ± 14.6 years). MetS was present in 25.0%. The most common component of MetS was central obesity (69.7%). Nearly half of the SMA individuals exhibited at least one abnormal lipid level result. Individuals with MetS more frequently were SMA type 3 (77.8% vs. 37.0%, p = .02) and had higher levels of fatigue (48.4 ± 6.7 vs. 39.5 ± 11.6, p = .03) than those without MetS. No associations of the presence of MetS with ambulatory status or HFMSE/RULM scores were observed. SMA individuals with MetS scored significantly lower in mental and social domains of QoL and total SF-36 score (p = .04). We observed weak to moderate correlations between the presence of MetS and SMA type, presence of comorbidities, QoL, and fatigue. DISCUSSION:The frequency of MetS was modestly higher among adults with SMA than in the general population, particularly in SMA type 3. MetS was associated with reduced QoL and increased fatigue. Larger studies are needed to fully understand the significance of MetS in adults with SMA.

Background Endovascular therapy (EVT) offers a highly effective therapy for patients with acute ischemic stroke due to large vessel occlusion. Comprehensive stroke centers (CSC) are required to provide permanent accessibility to EVT. However, when affected patients are not located in the immediate catchment area of a CSC, i.e. in rural or structurally weaker areas, access to EVT is not always ensured. Main body Telestroke networks play a crucial role in closing this healthcare coverage gap and thereby support specialized stroke treatment. The aim of this narrative review is to elaborate the concepts for the indication and transfer of EVT candidates via telestroke networks in acute stroke care. The targeted readership includes both comprehensive stroke centers and peripheral hospitals. The review is intended to identify ways to design care beyond those areas with narrow access to stroke unit care to provide the indicated highly effective acute therapies on a region-wide basis. Here, the two different models of care: "mothership" and "drip-and-ship" concerning rates of EVT and its complications as well as outcomes are compared. Decisively, forward-looking new model approaches such as a third model the “flying/driving interentionalists” are introduced and discussed, as far as few clinical trials have investigated these approaches. Diagnostic criteria used by the telestroke networks to enable appropriate patient selection for secondary intrahospital emergency transfers are displayed, which need to meet the criteria in terms of speed, quality and safety. Conclusion The few findings from the studies with telestroke networks are neutral for comparison in the drip-and-ship and mothership models. Supporting spoke centres through telestroke networks currently seems to be the best option for offering EVT to a population in structurally weaker regions without direct access to a CSC. Here, it is essential to map the individual reality of care depending on the regional circumstances.

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.

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 devices, MES remain detectable depending on antithrombotic therapy. No association between MES and CVE could be detected.

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.

Background: 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.

(1) Background: Patients with acute ischaemic stroke (AIS) are at high risk for stroke-associated infections (SAIs). We hypothesised that increased concentrations of systemic inflammation markers predict SAIs and unfavourable outcomes; (2) Methods: In 223 patients with AIS, blood samples were taken at ≤24 h, 3 d and 7d after a stroke, to determine IL-6, IL-10, CRP and LBP. The outcome was assessed using the modified Rankin Scale at 90 d. Patients were thoroughly examined regarding the development of SAIs; (3) Results: 47 patients developed SAIs, including 15 lower respiratory tract infections (LRTIs). IL-6 and LBP at 24 h differed, between patients with and without SAIs (IL-6: p < 0.001; LBP: p = 0.042). However, these associations could not be confirmed after adjustment for age, white blood cell count, reduced consciousness and NIHSS. When considering the subgroup of LRTIs, in patients who presented early (≤12 h after stroke, n = 139), IL-6 was independently associated with LRTIs (OR: 1.073, 95% CI: 1.002–1.148). The ROC-analysis for prediction of LRTIs showed an AUC of 0.918 for the combination of IL-6 and clinical factors; (4) Conclusions: Blood biomarkers were not predictive for total SAIs. At early stages, IL-6 was independently associated with outcome-relevant LRTIs. Further studies need to clarify the use of biochemical markers to identify patients prone to SAIs.