Zirkulierende Mikrovesikel und kardiovaskuläres Risiko nach ischämischem Schlaganfall

Microvesicles are released by various cell types upon activation by outward-blebbing of the cell membrane and contain surface markers and contents of the parent cell. In an experiemental setting, endothelial microvesicles (EMV) have been shown to mediate endothelial dysfunction. Clinical studies have shown an association with cardiovascular risk factors and poor outcome in cardiovascular diseases such as myocardial infarction. In ischemic stroke patients, as well as other neurological diseases, microvesicle (MV) levels are elevated after the acute event compared to healthy controls. The potential prognostic role of circulating EMV and MV of other origins for long-term cardiovascular outcome after ischemic stroke has not yet been studied. The PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) is an observational cohort study enrolling patients with first-ever ischemic stroke with a follow-up period of three years. The primary combined endpoint was predefined as recurrent stroke, myocardial infarction (MI), and all-cause mortality. Citrate-blood samples were taken on day 4 (IQR 3-5) after stroke. Levels of endothelial (Annexin V+ CD45- CD41- CD31+/CD144+/CD146+), leukocyte-derived (LMV) (Annexin V+ CD45+ CD41-), monocytic (MMV) (Annexin V+ CD14+ CD41-), and platelet-derived microvesicles (PMV) (Annexin V+ CD41+) were measured using flow cytometry. Kaplan-Meier survival analysis, the log-rank test and Cox proportional hazards models were used to calculate the impact of MV levels on the combined endpoint within three years after adjustment for potential confounding variables. Between January 2010 and June 2013, 621 patients with mild to moderate stroke were recruited of whom 571 had MV measurements (median age 69 years, 39% female, median National Institutes of Health Stroke Scale (NIHSS) 2, interquartile range (IQR) 1-4). During the follow-up period, 95 endpoints (42 recurrent strokes, 5 MI and 48 deaths) occurred. Ischemic stroke patients with levels of EMV (hazard ratio (HR) 2.5, 95% confidence interval (CI) 1.2-4.9) or LMV (HR 3.1, 95% CI 1.4-6.8) in the top quartile suffered more often a combined endpoint than participants with lower levels. This relationship was weaker for PMV (HR 1.7, 95% CI 0.9-3.2) and for MMV (HR 1.1, 95% CI 0.6-1.8) it was not detectable. In the present study, high levels of EMV and LMV were associated with an increased incidence of secondary cardiovascular events or death after mild to moderate ischemic stroke in the long term. These results enhance the significance of endothelial dysfunction and vascular inflammation for post-stroke outcome. EMV and LMV therefore might be potential cofactors for risk prediction after ischemic stroke.Mirkovesikel werden von unterschiedlichen Zelltypen bei Aktivierung durch Ausstülpung der Zellmembran freigesetzt und enthalten Oberflächenmarker und teilweise Inhalte der Ursprungszelle. Endotheliale Mikrovesikel sind durch experimentelle Studien als Surrogatmarker für endotheliale Dysfunktion etabliert und in kardiovaskulären Erkrankungen wie dem Myokardinfarkt mit schlechtem Outcome assoziiert. In der Akutphase ischämischer Schlaganfälle sind Mikrovesikelkonzentrationen verglichen zu gesunden Kontrollen deutlich erhöht und zeigen einen Zusammenhang mit Schlaganfallschwere. Die Bedeutung zirkulierender Mikrovesikel verschiender Ursprungszellen im kardiovaskulären Langzeit-Outcome nach ischämischem Schlaganfall ist derzeit noch unklar. In der Studie PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) wurden PatientInnen mit erstmaligem ischämischen Schlaganfall für drei Jahre beobachtet. Der vordefinierte primäre kombinierte Endpunkt beinhaltete Rezidivschlaganfälle, Myokardinfarkte und Gesamtmortalität. Die Konzentrationen von endothelialen (Annexin V+ CD45- CD41- CD31+/CD144+/CD146+), leukozytären (Annexin V+ CD45+ CD41-), monozytären (Annexin V+ CD14+ CD41-) und thrombozytären Mikrovesikeln (Annexin V+ CD41+) wurden mittels Durchflusszytometrie im Median am 4. Tag (IQR 3-4) nach Schlaganfall im Citratplasma bestimmt. Zur Berechnung der Effektstärke von Mikrovesikeln auf den kombinierten Endpunkt innerhalb drei Jahre wurden die Kaplan-Meier Überlebensanalyse, der Log-Rank Test und die adjustierte Cox Regressionsanalyse angewendet. Zwischen Januar 2010 und Juni 2013 wurden 621 Patienten mit milden bis moderaten Schlaganfällen rekrutiert, von denen 571 Mikrovesikelmessungen erhielten (medianes Alter 69 Jahre, 39% weiblich, medianer NIHSS 2, IQR 1-4). Im Beobachtungszeitraum traten 95 Endpunkte (42 sekundäre Schlaganfälle, 5 Myokardinfarkte, 48 Todesfälle) auf. Schlaganfallpatienten mit Konzentrationen in den höchsten Quartilen von endothelialen (HR 2.5, 95% CI 1.2-4.9) oder leukozytären Mirkovesikeln (HR 3.1, 95% CI 1.4-6.8) erlitten häufiger einen kombinierten Endpunkt als Patienten mit niedrigeren Konzentrationen. Dieser Zusammenhang war für thrombozytäre Mirkovesikel weniger deutlich (HR 1.7, 95% CI 0.9-3.2) und für monozytäre nicht erkennbar (HR 1.1, 95% CI 0.6-1.8). In dieser Studie waren hohe Konzentrationen endothelialer und leukozytärer Mikrovesikel mit einer langfristig erhöhten Inzidenz sekundärer kardiovaskulärer Ereignisse oder Tod nach mildem bis moderatem Schlaganfall assoziiert. Diese Ergebnisse verdeutlichen die Signifikanz endothelialer Dysfunktion und vaskulärer Inflammation für das Outcome nach Schlaganfall. In der Risikoprädiktion nach ischämischem Schlaganfall könnten endotheliale und leukozytäre Mikrovesikel daher potenziell eine wichtige Rolle spielen

Video object detection for privacy-preserving patient monitoring in intensive care

Patient monitoring in intensive care units, although assisted by biosensors, needs continuous supervision of staff. To reduce the burden on staff members, IT infrastructures are built to record monitoring data and develop clinical decision support systems. These systems, however, are vulnerable to artifacts (e.g. muscle movement due to ongoing treatment), which are often indistinguishable from real and potentially dangerous signals. Video recordings could facilitate the reliable classification of biosignals using object detection (OD) methods to find sources of unwanted artifacts. Due to privacy restrictions, only blurred videos can be stored, which severely impairs the possibility to detect clinically relevant events such as interventions or changes in patient status with standard OD methods. Hence, new kinds of approaches are necessary that exploit every kind of available information due to the reduced information content of blurred footage and that are at the same time easily implementable within the IT infrastructure of a normal hospital. In this paper, we propose a new method for exploiting information in the temporal succession of video frames. To be efficiently implementable using off-the-shelf object detectors that comply with given hardware constraints, we repurpose the image color channels to account for temporal consistency, leading to an improved detection rate of the object classes. Our method outperforms a standard YOLOv5 baseline model by +1.7% [email protected] while also training over ten times faster on our proprietary dataset. We conclude that this approach has shown effectiveness in the preliminary experiments and holds potential for more general video OD in the future.Comment: 4 pages, 3 figures, 2023 10th Swiss Conference on Data Science (SDS), code available at https://github.com/raember/yolov5r_autodidact and https://github.com/raember/VideoPro

High‐Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke

Background: Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results: We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions: Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: ; Unique identifier: NCT01363856

Functionalizing tetraphenylpyrazine with perylene diimides (PDIs) as high-performance nonfullerene acceptors

Perylene diimide (PDI)-based small molecular acceptors with a three-dimensional structure are thought to be essential for efficient photocurrent generation and high power conversion efficiencies (PCEs). Herein, a couple of new perylene diimide acceptors (PPDI-O and PPDI-Se) have been designed and successfully synthesized using pyrazine as the core-flanking pyran and selenophene-fused PDIs, respectively. Compared to PPDI-O, PPDI-Se exhibits a blue-shifted absorption in the 400–600 nm range, a comparable LUMO level, and a more distorted molecular geometry. The PPDI-Se-based organic solar cell device with PDBT-T1 as the donor achieved the highest PCE of 7.47% and a high open-circuit voltage (Voc) of up to 1.05 V. The high photovoltaic performance of PPDI-Se-based devices can be attributed to its high LUMO energy level, complementary absorption spectra with donor materials, favorable morphology and balanced carrier transport. The results demonstrate the potential of this type of fullerene-free acceptor for high efficiency organic solar cells

Brain care score and neuroimaging markers of brain health in asymptomatic middle-age persons

Objectives: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury. Methods: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex. Results: We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%–27%] first, 33% [27%–39%] repeat) and higher FA (18% [16%–20%] first, 22% [15%–28%] repeat), with a decrease in MD (9% [7%–11%] first, 10% [4%–16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%–17%] reduction in WMH progression and FA decline over time. Discussion: This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline

The Dynamic of Extracellular Vesicles in Patients With Subacute Stroke: Results of the “Biomarkers and Perfusion—Training-Induced Changes After Stroke” (BAPTISe) Study

Objective: Extracellular vesicles (EV) are sub-1 μm bilayer lipid coated particles and have been shown play a role in long-term cardiovascular outcome after ischemic stroke. However, the dynamic change of EV after stroke and their implications for functional outcome have not yet been elucidated. Methods: Serial blood samples from 110 subacute ischemic stroke patients enrolled in the prospective BAPTISe study were analyzed. All patients participated in the PHYS-STROKE trial and received 4-week aerobic training or relaxation sessions. Levels of endothelial-derived (EnV: Annexin V+, CD45–, CD41–, CD31+/CD144+/CD146+), leukocyte-derived (LV: Annexin V+, CD45+, CD41–), monocytic-derived (MoV: Annexin V+, CD41–, CD14+), neuronal-derived (NV: Annexin V+, CD41–, CD45–, CD31–, CD144–, CD146–, CD56+/CD171+/CD271+), and platelet-derived (PV: Annexin V+, CD41+) EV were assessed via fluorescence-activated cell sorting before and after the trial intervention. The levels of EV at baseline were dichotomized at the 75th percentile, with the EV levels at baseline above the 75th percentile classified as “high” otherwise as “low.” The dynamic of EV was classified based on the difference between baseline and post intervention, defining increases above the 75th percentile as “high increase” otherwise as “low increase.” Associations of baseline levels and change in EV concentrations with Barthel Index (BI) and cardiovascular events in the first 6 months post-stroke were analyzed using mixed model regression analyses and cox regression. Results: Both before and after intervention PV formed the largest population of vesicles followed by NV and EnV. In mixed-model regression analyses, low NV [−8.57 (95% CI −15.53 to −1.57)] and low PV [−6.97 (95% CI −13.92 to −0.01)] at baseline were associated with lower BI in the first 6 months post-stroke. Patients with low increase in NV [8.69 (95% CI 2.08–15.34)] and LV [6.82 (95% CI 0.25–13.4)] were associated with reduced BI in the first 6 months post-stroke. Neither baseline vesicles nor their dynamic were associated with recurrent cardiovascular events. Conclusion: This is the first report analyzing the concentration and the dynamic of EV regarding associations with functional outcome in patients with subacute stroke. Lower levels of PV and NV at baseline were associated with a worse functional outcome in the first 6 months post-stroke. Furthermore, an increase in NV and LV over time was associated with worse BI in the first 6 months post-stroke. Further investigation of the relationship between EV and their dynamic with functional outcome post-stroke are warranted. Clinical Trial Registration: clinicaltrials.gov/, identifier: NCT01954797

Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke

Background Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post‐stroke exists. Objectives Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Patients/Methods In the Prospective Cohort with Incident Stroke Berlin (PROSCIS‐B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all‐cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. Results In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person‐years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28–3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09–2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49–1.51). Continuous analyses yielded similar results. Conclusions In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3‐year period after first ischemic stroke

A supervised, externally validated machine learning model for artifact and drainage detection in high-resolution intracranial pressure monitoring data

OBJECTIVE: In neurocritical care, data from multiple biosensors are continuously measured, but only sporadically acknowledged by the attending physicians. In contrast, machine learning (ML) tools can analyze large amounts of data continuously, taking advantage of underlying information. However, the performance of such ML-based solutions is limited by different factors, for example, by patient motion, manipulation, or, as in the case of external ventricular drains (EVDs), the drainage of CSF to control intracranial pressure (ICP). The authors aimed to develop an ML-based algorithm that automatically classifies normal signals, artifacts, and drainages in high-resolution ICP monitoring data from EVDs, making the data suitable for real-time artifact removal and for future ML applications. METHODS: In their 2-center retrospective cohort study, the authors used labeled ICP data from 40 patients in the first neurocritical care unit (University Hospital Zurich) for model development. The authors created 94 descriptive features that were used to train the model. They compared histogram-based gradient boosting with extremely randomized trees after building pipelines with principal component analysis, hyperparameter optimization via grid search, and sequential feature selection. Performance was measured with nested 5-fold cross-validation and multiclass area under the receiver operating characteristic curve (AUROC). Data from 20 patients in a second, independent neurocritical care unit (Charité - Universitätsmedizin Berlin) were used for external validation with bootstrapping technique and AUROC. RESULTS: In cross-validation, the best-performing model achieved a mean AUROC of 0.945 (95% CI 0.92–0.969) on the development dataset. On the external validation dataset, the model performed with a mean AUROC of 0.928 (95% CI 0.908–0.946) in 100 bootstrapping validation cycles to classify normal signals, artifacts, and drainages. CONCLUSIONS: Here, the authors developed a well-performing supervised model with external validation that can detect normal signals, artifacts, and drainages in ICP signals from patients in neurocritical care units. For future analyses, this is a powerful tool to discard artifacts or to detect drainage events in ICP monitoring signals

High‐Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke

Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high‐sensitivity cardiac troponin T (hs‐cTnT) are associated with recurrent vascular events and death in patients with first‐ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS‐B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs‐cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all‐cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs‐cTnT above upper reference limit, 39.2%). During a mean follow‐up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all‐cause death. The primary outcome occurred more often in patients with hs‐cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3–3.3), with a dose‐response relationship when the highest and lowest hs‐cTnT quartiles were compared (15.2 versus 1.8 events per 100 person‐years; adjusted hazard ratio, 4.8; 95% CI, 1.9–11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs‐cTnT is dose‐dependently associated with an increased risk of recurrent vascular events and death within 3 years after first‐ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs‐cTnT for individualized risk stratification after stroke