Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity.

Large-vessel-occlusion in patients with previous ischemic stroke: an analysis of adherence to secondary preventive medication for different etiologies.

BACKGROUND: Large vessel occlusion (LVO) is a severe condition that carries a high risk of morbidity and mortality, underscoring the importance of effective prevention strategies. This retrospective study aimed to analyze the intake of preventive medication at the time of hospitalization in a cohort of recurrent stroke patients presenting with acute LVO. METHODS: The study assessed the intake of either platelet aggregation inhibitors (PAI), oral anticoagulants (OAC) or statins at admission in patients with recurrent stroke and correlated it with the final classification of LVO. The frequency of those secondary preventive medication in recurrent stroke patients was defined as primary endpoint. The Modified Rankin Scale (mRS) at discharge was used as a functional outcome and defined as a secondary outcome measure. RESULTS: This study included 866 patients who were treated for LVO between 2016 and 2020, of whom 160 (18.5%) had a recurrent ischemic stroke. OAC (25.6% vs. 14.1%, p < 0.01), PAI (50.0% vs. 26.0%, p < 0.01), or statin therapy (50.6% vs. 20.8%, p < 0.01) at admission were significantly more frequent in recurrent stroke patients compared to patients with a first-time stroke. Concerning LVO etiology in recurrent stroke patients, OAC at admission was taken in 46.8% of cardioembolic LVO, whereas PAI and statin at admission in macroangiopathic LVO were administered to 40.0%; neither PAI nor OAC was taken in 26.0%, 28.3%, and 31.6% of cardioembolic, macroangiopathic, or cryptogenic strokes, respectively. Regardless of stroke recurrence or etiology, there was an increase in mRS at discharge. CONCLUSIONS: Despite high-quality healthcare, this study suggested a significant proportion of patients with recurrent stroke who were either non-adherent or insufficiently adherent to secondary preventive medication. Given the disability associated with LVO, improving patients' medication adherence and identifying unknown stroke causes are crucial for effective prevention strategies.

Reduction of Ischemic Stroke Associated Disability in the Population: A State-Wide Stroke Registry Analysis over a Decade.

(Background): Effective prevention strategies and acute therapies have been established and distributed in recent years to reduce the global burden of stroke. However, beyond randomized clinical trials, limited data exist on the real-world impact of these measures. Our goal was to analyze whether the stroke-associated disability in the population decreased over time based on a state-wide stroke registry analysis. (Methods): Consecutive data from a state-wide inpatient stroke registry covering the entire federal state of Hesse, Germany, were obtained. The clinical data of 141,287 patients with ischemic stroke (ICD-10: I63) admitted between 2010 and 2019 were included. The primary outcome was the odds ratio for a change of modified Ranking Scale (mRS) at discharge over time, estimated by ordinary logistic regression and adjusted for age and sex. The secondary outcome was the odds ratio for a lower National Institutes of Health Stroke Scale (NIHSS) score at hospital admission. (Results): The absolute number of severely disabled (mRS 4−5) stroke patients at discharge decreased over time (2010: 3223 (equivalent to 53/100,000 population); 2019: 2429 [39/100,000 population]). The odds at hospital admission for a higher mRS at discharge decreased significantly by 3.7% per year (OR 0.963 (95% CI 0.960−0.966), p < 0.001). The absolute number of severely affected stroke patients (NIHSS > 15) at admission declined over time (2010: 1589 [26/100,000]; 2019: 1185 [19/100,000]; p < 0.001). The odds for a higher NIHSS score at admission to hospital decreased by 3.8% per year (OR 0.962 (95% CI 0.959−0.965), p < 0.001). Trends were most prominent for patients aged 80 years and older and for patients with atrial fibrillation but absent in patients <60 years. (Conclusions): Stroke-associated disability in the population steadily decreased between 2010 and 2019. The improved prevention of severe strokes in elderly patients may be a major driver of this observation.

Divergence and Convergence of Sex-Specific Time Trends in Ischemic Stroke: 10-Year Analysis of a State-Wide Registry in Germany.

Background The incidence of ischemic stroke was previously expected to rise among countries with an aging population. Lately, several studies from developed countries have reported a decline in certain cohorts. Whether this applies to all sexes, however, is uncertain, with limited data on the temporal development in incidence, treatment, and recovery. Methods and Results We analyzed a prospective stroke inpatient quality-assurance registry of the federal state of Hesse, Germany. Recruitment of all patients with a final diagnosis of ischemic stroke at hospital discharge (International Classification of Diseases, Tenth Revision [ICD-10]: I63) is mandatory by law. Incidence rates were calculated based on census data of all inhabitants and stratified according to age. Between 2010 and 2019, there were 141 277 patients included, 73 770 (52.2%) male patients and 67 507 (47.8%) female patients. Overall, the incidence of ischemic stroke was 228 per 100 000 in 2010 and 226 per 100 000 in 2019 (-0.8%; odds ratio [OR], 0.99 [95% CI, 0.96-1.02]; P=0.50). For male patients, the incidence increased continuously from 236 per 100 000 to 245 per 100 000 (+3.8%); in female patients it decreased from 220 per 100 000 to 208 per 100 000 (-5.6%). After adjusting for age, the OR for ischemic stroke between male and female patients was 1.40 in 2010 (95% CI, 1.35-1.44; P<0.001) and 1.48 in 2019 (95% CI, 1.43-1.53; P<0.001). This development was most pronounced in male patients aged 45 to 59 years with an increase from 151 per 100 000 to 176 per 100 000. In this age group, male patients showed increasing rates of prior strokes and atrial fibrillation, surpassing the prevalence in female patients over time. After multivariable regression analysis, male patients had a lower modified Rankin Scale at discharge compared with female patients, but this difference has decreased since 2015 (common OR in 2010, 0.83 [95% CI, 0.78-0.88]; common OR in 2019, 0.90 [95% CI, 0.84-0.95]), which coincided with rising rates of endovascular treatment. Conclusions Over the past decade in the federal state of Hesse, the overall incidence of ischemic stroke has declined predominantly in the female population. In contrast, for male patients, the incidence has risen by about 4%, with a steeper increase of 16% in male patients aged 45 to 59 years, which might be related to increasing rates of recurrent strokes and atrial fibrillation in this cohort. This finding provides a cautionary tale for effective secondary prevention. Female patients were generally less likely to achieve a favorable outcome, but since the introduction of endovascular treatment, the outcome gap is decreasing.

Endovascular treatment for ischemic stroke with the drip-and-ship model-Insights from the German Stroke Registry.

Background: Endovascular therapy (EVT) in acute ischemic stroke has been widely established. Globally, stroke patients are transferred either directly to a thrombectomy center (DC) or a peripheral stroke unit with a "drip-and-ship" (DS) model. We aimed to determine differences between the DS and DC paradigms after EVT of acute stroke patients with large-vessel-occlusion (LVO) in the database of the German Stroke Registry (GSR). Methods: We performed a retrospective analysis of GSR patients between June 2015 and December 2019 in 23 German centers. Primary outcome was an ordinal shift analysis of modified Rankin Scale (mRS) 90 days after index event. Secondary endpoints included time from symptom onset to recanalization and complications. Tertiary endpoint was the association of imaging strategies in DS admissions with outcome. Results: 2,813 patients were included in the DS and 3,819 in the DC group. After propensity score matching mRS after 90 days was higher in DS than DC admissions (OR 1.26; 95%-CI 1.13-1.40). Time from symptom-onset to flow-restoration was shorter in DC than DS (median 199.0 vs. 298.0 min; p < 0.001). DS patients undergoing magnetic resonance imaging (MRI; n=183) before EVT had a lower 90-day mRS than without (n = 944) (OR 0.63; 95%-CI 0.45-0.88). ASPECTS assessed on MRI correlated with 90-day mRS (ρ = -0.326; p < 0.001). Conclusions: Clinical outcome was worse for EVT-eligible patients in the DS setting, even though patients were in a better state of health prior to stroke. A potentially mutable factor was the time delay of 99 min from symptom-onset to successful recanalization. Performing MRI before thrombectomy was associated with good outcome and MRI-ASPECTS was negatively correlated with mRS after 90 days.

Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia.

(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.

Predicting Poststroke Pneumonia in Patients With Anterior Large Vessel Occlusion: A Prospective, Population-Based Stroke Registry Analysis.

OBJECTIVE: To assess predictive factors for poststroke pneumonia (PSP) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, with special regard to the impact of intravenous thrombolysis (IVT) and endovascular treatment (EVT) on the risk of PSP. As a secondary goal, the validity of the A2DS2, PNEUMONIA, and ISAN scores in LVO will be determined. METHODS: Analysis was based on consecutive data for the years 2017 to 2019 from the prospective inpatient stroke registry covering the entire federal state of Hesse, Germany, using the Kruskal-Wallis test and binary logistic regression. RESULTS: Data from 4,281 patients with LVO were included in the analysis (54.8% female, median age = 78 years, range = 18-102), of whom 66.4% (n = 2,843) received recanalization therapy (RCT). In total, 19.4% (n = 832) of all LVO patients developed PSP. Development of PSP was associated with an increase in overall in-hospital mortality of 32.1% compared with LVO patients without PSP (16.4%; p < 0.001). Incidence of PSP was increased in 2132 patients with either EVT (n = 928; 25.9% PSP incidence) or combined EVT plus IVT (n = 1,204; 24.1%), compared with 2,149 patients with IVT alone (n = 711; 15.2%) or conservative treatment only (n = 1,438; 13.5%; p < 0.001). Multivariate analysis identified EVT (OR 1.5) and combined EVT plus IVT (OR 1.5) as significant independent risk factors for PSP. Furthermore, male sex (OR 1.9), age ≥ 65 years (OR 1.7), dysphagia (OR 3.2) as well as impaired consciousness at arrival (OR 1.7) and the comorbidities diabetes (OR 1.4) and atrial fibrillation (OR 1.3) were significantly associated risk factors (each p < 0.001). Minor stroke (NIHSS ≤ 4) was associated with a significant lower risk of PSP (OR 0.5). Performance of risk stratification scores varied between A2DS2 (96.1% sensitivity, 20.7% specificity), PNEUMONIA (78.2% sensitivity and 45.1% specificity) and ISAN score (98.0% sensitivity, 20.0% specificity). CONCLUSION: Nearly one in five stroke patients with LVO develops PSP during acute care. This risk of PSP is further increased if an EVT is performed. Other predictive factors are consistent with those previously described for all AIS patients. Available risk stratification scores proved to be sensitive tools in LVO patients but lack specificity.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.

Measuring Patient Safety Climate in Acute Stroke Therapy.

Background: Treatment of acute stroke is highly time-dependent and performed by a multiprofessional, interdisciplinary team. Interface problems are expectable and issues relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety climate. The objective of this study was to evaluate the SAQ for the first time in the context of acute stroke care. Methods: A survey was carried out during the STREAM trial (NCT00032282) at seven university hospitals in Germany from October 2017 to October 2018. The anonymous survey included 33 questions (5-point Likert scale, 1 = disagree to 5 = agree) and addressed the entire multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. Results: 164 questionnaires were completed yielding a response rate of 66.4%. 67.7% of respondents were physicians and 25.0% were nurses. Confirmatory Factor Analysis revealed that the original 6-factor structure fits the data adequately. The SAQ for acute stroke care showed strong internal consistency (α = 0.88). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing physicians to nurses and when comparing physicians according to their duration of professional experience. Conclusion: The SAQ is a helpful and well-applicable tool to measure patient safety in acute stroke care. In comparison to other high-risk fields in medicine, patient safety climate in acute stroke care seems to be on a similar level with the potential for further improvements. Trial registration: www.ClinicalTrials.gov Identifier: NCT032282.

Quality assurance data for regional drip-and-ship strategies- gearing up the transfer process.

BACKGROUND: Stroke patients with large vessel occlusion (LVO) require endovascular therapy (EVT) provided by comprehensive stroke centers (CSC). One strategy to achieve fast stroke symptom 'onset to treatment' times (OTT) is the preclinical selection of patients with severe stroke for direct transport to CSC. Another is the optimization of interhospital transfer workflow. Our aim was to investigate the dynamics of the OTT of 'drip-and-ship' patients as well as the current 'door-in-door-out' time (DIDO) and its determinants at representative regional German stroke units. METHODS: We determined the numbers of all EVT treatments, 'drip-and-ship' and 'direct-to-center' patients and their median OTT from the mandatory quality assurance registry of the federal state of Hesse, Germany (2012-2019). Additionally, we captured process time stamps from primary stroke centers (PSC) in a consecutive registry of patients referred for EVT in our regional stroke network over a 3 months period. RESULTS: Along with an increase of the EVT rate, the proportion of drip-and-ship patients grew steadily from 19.4% in 2012 to 31.3% in 2019. The time discrepancy for the median OTT between 'drip-and-ship' and 'direct-to-center' patients continuously declined from 173 to 74 min. The largest share of the DIDO (median 92, IQR 69-110) is spent with the organization of EVT and consecutive patient transfer. CONCLUSIONS: 'Drip-and-ship' patients are an important and growing proportion of stroke patients undergoing EVT. The discrepancy in OTT for EVT between 'drip-and-ship' and 'direct-to-center' patients has been reduced considerably. Further optimization of the DIDO primarily aiming at the processes after the detection of LVO is urgently needed to improve stroke patient care.

Simulation-based training improves patient safety climate in acute stroke care (STREAM).

BACKGROUND: Treatment of acute stroke performed by a multiprofessional, interdisciplinary team is highly time dependent. Interface problems are preprogrammed and pitfalls relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety. The objective of this study was to evaluate the influence of Simulation-based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM) on patient safety measured by SAQ in the context of acute stroke care. METHODS: During the STREAM trial at seven university hospitals in Germany from October 2017 to October 2018, an anonymous survey was conducted before and after the STREAM intervention centering around interdisciplinary simulation training. The questionnaire, based on the SAQ, included 33 items (5-point Likert scale, 1 = disagree to 5 = agree) and was addressed at the whole multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. RESULTS: In total 167 questionnaires were completed representing an overall response rate of 55.2%, including especially physicians (65.2%) and nurses (26.3%). Safety climate was significantly improved (pre-interventional: 3.34 ± .63 vs. post-interventional: 3.56 ± .69, p = .028). The same applies for teamwork climate among stroke teams (pre-interventional: 3.76 ± .59 vs. post-interventional: 3.84 ± .57, p = .001). The perceived benefit was most relevant among nurses. CONCLUSIONS: The STREAM intervention centering around interdisciplinary simulation training increases perceived patient safety climate assessed by the SAQ in acute stroke therapy. These results have the potential to be a basis for future quality improvement programs.

Evaluation of Endovascular Treatment for Acute Basilar Occlusion in a State-Wide Prospective Stroke Registry.

Context: Despite overwhelming evidence for endovascular therapy in anterior circulation ischemic stroke due to large-vessel occlusion, data regarding the treatment of acute basilar artery occlusion (BAO) are still equivocal. The BASICS trial failed to show an advantage of endovascular therapy (EVT) over best medical treatment (BMT). In contrast, data from the recently published BASILAR registry showed a better outcome in patients receiving EVT. Objective: The aim of the study was to investigate the safety and efficacy of EVT plus BMT vs. BMT alone in acute BAO. Methods: We analyzed the clinical course and short-term outcomes of patients with radiologically confirmed BAO dichotomized by BMT plus EVT or BMT only as documented in a state-wide prospective registry of consecutive patients hospitalized due to acute stroke. The primary endpoint was a favorable functional outcome (mRS 0-3) at hospital discharge assessed as common odds ratio using binary logistic regression. Secondary subgroup analyses and propensity score matching were added. Safety outcomes included mortality, the rate of intracerebral hemorrhages, and complications during hospitalization. Results: We included 403 patients with acute BAO (2017-2019). A total of 270 patients (67%) were treated with BMT plus EVT and 133 patients (33%) were treated with BMT only. A favorable outcome (mRS 0-3) was observed in 33.8% of the BMT and 26.7% of the BMT plus EVT group [OR.770, CI (0.50-1.2)]. Subgroup analyses for patients with a NIHSS score > 10 at admission to the hospital revealed a benefit from EVT [OR 3.05, CI (1.03-9.01)]. Conclusions: In this prospective, quasi population-based registry of patients hospitalized with acute BAO, BMT plus EVT was not superior to BMT alone. Nevertheless, our results suggest that severely affected BAO patients are more likely to benefit from EVT.

Diagnostic Accuracy of Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase-L1 Serum Concentrations for Differentiating Acute Intracerebral Hemorrhage from Ischemic Stroke.

BACKGROUND: Biomarkers indicative of intracerebral hemorrhage (ICH) may help triage acute stroke patients in the pre-hospital phase. We hypothesized that serum concentration of glial fibrillary acidic protein (GFAP) in combination with ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), measured by a rapid bio-assay, could be used to distinguish ICH from ischemic stroke. METHODS: This prospective two-center study recruited patients with a clinical diagnosis of acute stroke both in the pre-hospital phase and at hospital admission (within 4 and 6 h after symptom onset, respectively). Blood samples were analyzed for concentrations of GFAP and UCH-L1 using ELISA techniques. The reference standard was the diagnosis of ICH, ischemic stroke, or stroke mimicking condition achieved after clinical workup including brain imaging. RESULTS: A total of 251 patients were included (mean age [± SD] 72 ± 15 years; 5 ICH, 23 ischemic strokes and 14 stroke mimics in the pre-hospital part; and 59 ICH, 148 ischemic strokes and 2 stroke mimics in the in-hospital part). Mean delay (± SD) from symptom onset to blood withdrawal was 130 ± 79 min for the pre-hospital patients and 136 ± 86 min for the in-hospital patients. Both GFAP and UCH-L1 serum concentrations were higher in patients having ICH as compared to other diagnoses (GFAP: median 330 ng/L [interquartile range 64-7060, range 8-56,100] vs. 27.5 ng/L [14-57.25, 0-781], p < 0.001; UCH-L1: 401 ng/L [265-764, 133-1812] vs. 338 ng/L [213-549.5, 0-2950], p = 0.025). Area-under-the-curve values were 0.866 (95% CI 0.809-0.924, p < 0.001) for GFAP, and 0.590 (0.511-0.670, p = 0.033) for UCH-L1. Regarding overall diagnostic accuracy, UCH-L1 did not add significantly to the performance of GFAP. CONCLUSIONS: GFAP may differentiate ICH from ischemic stroke and stroke mimics. A point-of-care test to distinguish between ischemic and hemorrhagic strokes might facilitate triage to different treatment pathways or locations, or be used to select patients for trials of ultra-early interventions.

Simulation-Based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM)-A Prospective Single-Arm Multicenter Trial.

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2-3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the "door-to-needle" time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three "STREAM multipliers" from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2-3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings. Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.

A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network.

BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.