Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry

Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone.Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days.Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v.-rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864).Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT

Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts

Replicative senescence of human fibroblasts in vitro has been used as a model for in vivo aging. The onset of replicative senescence varies between several months to years. A colony formation assay, critically dependent on growth speed, can be performed within weeks, and has been reported being an indicator for the onset of replicative senescence. Earlier we could not find a correlation between growth speed in mass cultures and onset of replicative senescence of human fibroblast strains. Therefore, we studied the colony formation assay in 23 fibroblast strains that varied widely in their replicative capacity. Neither the number nor the size of colonies was related to the onset of replicative senescence. The number of cells within the colonies was modestly correlated to the growth speed of the mass cultures. We conclude that the colony formation assay does not reflect the onset of replicative senescence in human fibroblasts

Doppler flow morphology characteristics of epiaortic arteries in aortic valve pathologies: a retrospective study on a cohort of patients with ischemic stroke

Abstract Background and aims Neurovascular ultrasound (nvUS) of the epiaortic arteries is an integral part of the etiologic workup in patients with ischemic stroke. Aortic valve disease shares similar vascular risk profiles and therefore not only presents a common comorbidity, but also an etiologic entity. The aim of this study is to investigate the predictive value of specific Doppler curve flow characteristics in epiaortic arteries and the presence of aortic valve disease. Methods Retrospective, single-center analysis of ischemic stroke patients, both receiving full nvUS of the extracranial common- (CCA), internal- (ICA) and external carotid artery (ECA) and echocardiography (TTE/TEE) during their inpatient stay. A rater blinded for the TTE/TEE results investigated Doppler flow curves for the following characteristics: ‘pulsus tardus et parvus’ for aortic valve stenosis (AS) and ‘bisferious pulse’, ‘diastolic reversal’, ‘zero diastole’ and ‘no dicrotic notch’ for aortic valve regurgitation (AR). Predictive value of these Doppler flow characteristics was investigated using multivariate logistic regression models. Results Of 1320 patients with complete examination of Doppler flow curves and TTE/TEE, 75 (5.7%) showed an AS and 482 (36.5%) showed an AR. Sixty-one (4.6%) patients at least showed a moderate-to-severe AS and 100 (7.6%) at least showed a moderate-to-severe AR. After adjustment for age, coronary artery disease, arterial hypertension, diabetes mellitus, smoking, peripheral arterial disease, renal failure and atrial fibrillation, the following flow pattern predicted aortic valve disease: ‘pulsus tardus et parvus’ in the CCA and ICA was highly predictive for a moderate-to-severe AS (OR 1158.5, 95% CI 364.2–3684.8, p < 0.001). ‘No dicrotic notch’ (OR 102.1, 95% CI 12.4–839.4, p < 0.001), a ‘bisferious pulse’ (OR 10.8, 95% CI 3.2–33.9, p < 0.001) and a ‘diastolic reversal’ (OR 15.4, 95% CI 3.2–74.6, p < 0.001) in the CCA and ICA predicted a moderate-to-severe AR. The inclusion of Doppler flow characteristics of the ECA did not increase predictive value. Conclusions Well defined, qualitative Doppler flow characteristics detectable in the CCA and ICA are highly predictive for aortic valve disease. The consideration of these flow characteristics can be useful to streamline diagnostic and therapeutic measures, especially in the outpatient setting

Effect of beta-blocker therapy on post-stroke infections stratified by statin therapy.

<p>*p-value for interaction based on a Likelihood Ratio Test comparing a model with interaction term with the corresponding model without interaction term</p><p>Effect of beta-blocker therapy on post-stroke infections stratified by statin therapy.</p

Baseline characteristics of patients with and without beta-blocker therapy (n = 625).

<p>SD: Standard deviation, IQR: Interquartile range,</p><p>*t-tests, Wilcoxon rank-sum tests and chi-square tests as appropriate</p><p>Baseline characteristics of patients with and without beta-blocker therapy (n = 625).</p

Influence of beta-blocker therapy on the risk of infections and death in patients at high risk for stroke induced immunodepression.

Stroke-induced immunodepression is a well characterized complication of acute ischemic stroke. In experimental studies beta-blocker therapy reversed stroke-induced immunodepression, reduced infection rates and mortality. Recent, heterogeneous studies in stroke patients could not provide evidence of a protective effect of beta-blocker therapy. Aim of this study is to investigate the potential preventive effect of beta-blockers in subgroups of patients at high risk for stroke-induced immunodepression.Data from a prospectively derived registry of major stroke patients receiving endovascular therapy between 2011-2017 in a tertiary stroke center (University Medical Center Göttingen. Germany) was used. The effect of beta-blocker therapy on pneumonia, urinary tract infection, sepsis and mortality was assessed using multivariate logistic regression analysis.Three hundred six patients with a mean age of 72 ± 13 years and a median NIHSS of 16 (IQR 10.75-20) were included. 158 patients (51.6%) had pre-stroke- and continued beta-blocker therapy. Beta-blocker therapy did not reduce the incidence of pneumonia (OR 0.78, 95% CI 0.31-1.92, p = 0.584), urinary tract infections (OR 1.51, 0.88-2.60, p = 0.135), sepsis (OR 0.57, 0.18-1.80, p = 0.334) or mortality (OR 0.59, 0.16-2.17, p = 0.429). Strokes involving the insula and anterio-medial cortex increased the risk for pneumonia (OR 4.55, 2.41-8.56, p<0.001) and sepsis (OR 4.13, 1.81-9.43, p = 0.001), while right hemispheric strokes increased the risk for pneumonia (OR 1.60, 0.92-2.77, p = 0.096). There was a non-significantly increased risk for urinary tract infections in patients with beta-blocker therapy and insula/anterio-medial cortex strokes (OR 3.12, 95% CI 0.88-11.05, p = 0.077) with no effect of beta-blocker therapy on pneumonia, sepsis or mortality in both subgroups.In major ischemic stroke patients, beta-blocker therapy did not lower post-stroke infection rates and was associated with urinary tract infections in a subgroup with insula/anterio-medial strokes

Post-stroke pneumonia, urinary tract infection and mortality in patients with and without beta-blocker therapy (n = 625).

<p>HR/RR: Hazard-Ratio and Rate Ratio (adjusted for age, sex and baseline NIHSS) obtained using Poisson (pneumonia, urinary tract infection) and Cox (death) regression models, CI: Confidence interval,</p><p>*Likelihood Ratio Test,</p><p>‡ competing risk situation</p><p>Post-stroke pneumonia, urinary tract infection and mortality in patients with and without beta-blocker therapy (n = 625).</p

C-reactive protein, leukocyte count, NIHSS, modified ranking scale and Barthel-index in patients with and without beta-blocker therapy (n = 625).

<p>NIHSS: National Institute of Health Stroke Scale; CRP: C-reactive protein; mRS: modified Ranking Scale; SE: Standard error; ANCOVAs adjusted for age, sex, baseline NIHSS and individual follow-up; Change in outcome parameters were calculated as follows: baseline value—follow-up value (for NIHSS) or highest value—baseline value (for CRP and leukocyte count)</p><p>C-reactive protein, leukocyte count, NIHSS, modified ranking scale and Barthel-index in patients with and without beta-blocker therapy (n = 625).</p

Kaplan-Meier plot displaying survival after stroke in patients with and without beta-blocker therapy.

<p>Patients with beta blocker therapy showed a higher 30 days mortality than those without beta blocker therapy in the univariable (log-rank test, p = 0.003) and multivariable analyses (Cox regression model, p = 0.006).</p

Validation of collateral scoring on flat-detector multiphase CT angiography in patients with acute ischemic stroke.

BACKGROUND:The pivotal impact of collateral circulation on outcomes in endovascular therapy has fueled the development of numerous CTA collateral scales, yet synchronized validation with conventional angiography has never occurred. We validated multiphase flat-detector CTA (mpFDCTA) for collateral imaging in patients undergoing endovascular stroke treatment. MATERIALS AND METHODS:Consecutive acute ischemic stroke patient data, including mpFDCTA shortly followed by digital subtraction angiography (DSA), in the setting of acute ICA- or MCA-occlusions were analyzed. An independent core lab scored mpFDCTA with an established collateral scale and separately graded American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score on DSA, blind to all other data. RESULTS:24 consecutive cases (age 76.7 ± 7.3 years; 58.3% women; baseline NIHSS median 17 (4-23)) of acute ICA- or MCA-occlusion were analyzed. Time from mpFDCTA to intracranial DSA was 23.04 ± 7.6 minutes. Median mpFDCTA collateral score was 3 (0-5) and median DSA ASITN collateral score was 2 (0-3), including the full range of potential collateral grades. mpFDCTA and ASITN collateral score were strongly correlated (r = 0.86, p<0.001). mpFDCTA provided more complete collateral data compared to selective DSA injections in cases of ICA-occlusion. ROC analyses for prediction of clinical outcomes revealed an AUC of 0.76 for mpFDCTA- and 0.70 for DSA ASITN collaterals. CONCLUSIONS:mpFDCTA in the angiography suite provides a validated measure of collaterals, offering distinct advantages over conventional angiography. Direct patient transfer to the angiography suite and mpFDCTA collateral grading provides a novel and reliable triage paradigm for acute ischemic stroke