Safety of the Solitaire 4 × 40 mm Stent Retriever in the Treatment of Ischemic Stroke.

PURPOSE Stent retrievers apply mechanical force to the intracranial vasculature. Our aim was to evaluate the safety and efficacy of the long Solitaire 4 × 40 mm stent retriever for large vessel occlusion in stroke patients. METHODS We conducted a retrospective analysis of all patients treated for acute ischemic large vessel occlusion stroke with the Solitaire 2 FR 4 × 40 device between May and October 2016 at our institution. Patient-specific data at baseline and at discharge were documented. Reperfusion was graded with the thrombolysis in cerebral infarction (TICI) classification. Postinterventional angiograms and follow-up cross-sectional imaging were used to evaluate complications. RESULTS TICI 2b/3 recanalization was achieved in 20 of 23 patients (87.0%), in 17 patients with the first retriever pass. NIHSS improved from a mean score at presentation of 16 (range 4-36) to 11 (range 0-41) at discharge. Mean mRS score at discharge was 3 (range 0-6) and 3 (range 0-6) at 90 days post-treatment. No infarcts in other territories were observed. One patient showed a (reversible) vasospasm in the postinterventional angiogram and another a small contrast extravasation in follow-up imaging. CONCLUSION The Solitaire 2 FR 4 × 40 stent retriever is a safe and efficient device for large vessel occlusion acute ischemic stroke with a high recanalization rate and a low peri- and postinterventional complication rate together with a good clinical outcome. Despite potentially higher friction and shearing forces, no increased incidence of visible damage to the vessel wall was observed

Temporal Trends and Risk Factors for Delayed Hospital Admission in Suspected Stroke Patients.

(1) Background: The benefit of acute ischemic stroke (AIS) treatment declines with any time delay until treatment. Hence, factors influencing the time from symptom onset to admission (TTA) are of utmost importance. This study aimed to assess temporal trends and risk factors for delays in TTA. (2) Methods: We included 1244 consecutive patients from 2015 to 2018 with suspected stroke presenting within 24 h after symptom onset registered in our prospective, pre-specified hospital database. Temporal trends were assessed by comparing with a cohort of a previous study in 2006. Factors associated with TTA were assessed by univariable and multivariable regression analysis. (3) Results: In 1244 patients (median [IQR] age 73 [60-82] years; 44% women), the median TTA was 96 min (IQR 66-164). The prehospital time delay reduced by 27% in the last 12 years and the rate of patients referred by Emergency medical services (EMS) increased from 17% to 51% and the TTA for admissions by General Practitioner (GP) declined from 244 to 207 min. Factors associated with a delay in TTA were stroke severity (beta-1.9; 95% CI-3.6 to -0.2 min per point NIHSS score), referral by General Practitioner (GP, beta +140 min, 95% CI 100-179), self-admission (+92 min, 95% CI 57-128) as compared to admission by emergency medical services (EMS) and symptom onset during nighttime (+57 min, 95% CI 30-85). Conclusions: Although TTA improved markedly since 2006, our data indicates that continuous efforts are mandatory to raise public awareness on the importance of fast hospital referral in patients with suspected stroke by directly informing EMS, avoiding contact of a GP, and maintaining high effort for fast transportation also in patients with milder symptoms

Heterogeneity of the Relative Benefits of TICI 2c/3 over TICI 2b50/2b67 : Are there Patients who are less Likely to Benefit?

PURPOSE Incomplete reperfusion after mechanical thrombectomy (MT) is associated with a poor outcome. Rescue therapy would potentially benefit some patients with an expanded treatment in cerebral ischemia score (eTICI) 2b50/2b67 reperfusion but also harbors increased risks. The relative benefits of eTICI 2c/3 over eTICI 2b50/67 in clinically important subpopulations were analyzed. METHODS Retrospective analysis of our institutional database for all patients with occlusion of the intracranial internal carotid artery (ICA) or the M1/M2 segment undergoing MT and final reperfusion of ≥eTICI 2b50 (903 patients). The heterogeneity in subgroups of different time metrics, age, National Institutes of Health Stroke Scale (NIHSS), number of retrieval attempts, Alberta Stroke Programme Early CT Score (ASPECTS) and site of occlusion using interaction terms (pi) was analyzed. RESULTS The presence of eTICI 2c/3 was associated with better outcomes in most subgroups. Time metrics showed no interaction of eTICI 2c/3 over eTICI 2b50/2b67 and clinical outcomes (onset to reperfusion pi = 0.77, puncture to reperfusion pi = 0.65, onset to puncture pi = 0.63). An eTICI 2c/3 had less consistent association with mRS ≤2 in older patients (>82 years, pi = 0.038) and patients with either lower NIHSS (≤9) or very high NIHSS (>19, pi = 0.01). Regarding occlusion sites, the beneficial effect of eTICI 2c/3 was absent for occlusions in the M2 segments (aOR 0.73, 95% confidence interval [CI] 0.33-1.59, pi = 0.018). CONCLUSION Beneficial effect of eTICI 2c/3 over eTICI 2b50/2b67 only decreased in older patients, M2-occlusions and patients with either low or very high NIHSS. Improving eTICI 2b50/2b67 to eTICI 2c/3 in those subgroups may be more often futile

Stent-Based Retrieval Techniques in Acute Ischemic Stroke Patients with and Without Susceptibility Vessel Sign.

BACKGROUND AND PURPOSE Randomized controlled trials have challenged the assumption that reperfusion success after mechanical thrombectomy varies depending on the retrieval techniques applied; however, recent analyses have suggested that acute ischemic stroke (AIS) patients showing susceptibility vessel sign (SVS) may respond differently. We aimed to compare different stent retriever (SR)-based thrombectomy techniques with respect to interventional outcome parameters depending on SVS status. METHODS We retrospectively reviewed 497 patients treated with SR-based thrombectomy for anterior circulation AIS. Imaging was conducted using a 1.5 T or 3 T magnetic resonance imaging (MRI) scanner. Logistic regression analyses were performed to test for the interaction of SVS status and first-line retrieval technique. Results are shown as percentages, total values or adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS An SVS was present in 87.9% (n = 437) of patients. First-line SR thrombectomy was used to treat 293 patients, whereas 204 patients were treated with a combined approach (COA) of SR and distal aspiration. An additional balloon-guide catheter (BGC) was used in 273 SR-treated (93.2%) and 89 COA-treated (43.6%) patients. On logistic regression analysis, the interaction variable of SVS status and first-line retrieval technique was not associated with first-pass reperfusion (aOR 1.736, 95% CI 0.491-6.136; p = 0.392), overall reperfusion (aOR 3.173, 95% CI 0.752-13.387; p = 0.116), periinterventional complications, embolization into new territories, or symptomatic intracerebral hemorrhage. The use of BGC did not affect the results. CONCLUSION While previous analyses indicated that first-line SR thrombectomy may promise higher rates of reperfusion than contact aspiration in AIS patients with SVS, our data show no superiority of any particular SR-based retrieval technique regardless of SVS status

Study of an unusually high level of N-glycolylneuraminic acid (NGNA) sialylation on a monoclonal antibody expressed in Chinese hamster ovary cells

Sialic or neuraminic acids of recombinant therapeutic glycoproteins produced in mammalian cells, including monoclonal antibodies, have significant impact on the half-life, stability, and biological activity of these proteins (Hossler et al., 2009; Ghaderi et al., 2012). The predominant sialic acid N-acetylneuraminic acid (NANA or Neu5Ac) is added from precursor CMP-NANA to galactose residues of N-linked glycoproteins by sialytransferases. In most mammals CMP-NANA can also be modified to its hydroxylated derivative CMP-NGNA by CMP-N-acetylneuraminic acid hydroxylase (CMAH). NGNA can then be added from CMP-NGNA to galactose residues of the N-linked glycoproteins, also by sialytransferases. However, humans cannot make functional CMAH due to an inactivating exon deletion mutation in CMAH gene (Okerblom and Varki, 2017), and therefore cannot convert CMP-NANA to CMP-NGNA. Consequently, when injected into human patients, NGNA sialic acid containing mAbs or other recombinant glycoproteins may induce immune responses, which could negatively impact pharmacokinetics or efficacy. Therefore high levels of NGNA on therapeutic mAbs or other recombinant glycoproteins are an undesirable product quality attribute. The level of total sialic acids of recombinant glycoproteins produced in Chinese hamster ovary (CHO) cells is dictated largely by the selected cell lines, upstream process, and to a lesser degree, downstream process. NGNA sialylation is generally rare in CHO cells (Könitzer et al., 2015). Hence, therapeutic glycoproteins manufactured in these cells are considered safe for human use. However, during a first-in-human (FIH) upstream process development for a novel mAb, an initially selected desirable cell line (A) was found to produce the mAb with an unexpectedly high level of the NGNA sialic acid (\u3e30%). To the best of our knowledge such high level of NGNA sialylation on a mAb produced by CHO cells has not been reported. To mitigate potential risks associated with high NGNA in human patients, a new cell line (B) that produces the mAb with very low NGNA was selected as the manufacturing cell line for this project. In order to understand the molecular mechanism causing the high NGNA content in cell line A, we initiated comprehensive genetic gap analyses using next-generation sequencing technologies and determined the differences in genomic, transcriptomic, and miRnomic profiles of the two cell lines. The results indicate spontaneous upregulation of CMAH mRNA expression, at least 10 fold higher in cell line A compared to cell line B. In this talk we will summarize the results of our studies of this unusual sialylation behavior in CHO cells

Association of the 24‐Hour National Institutes of Health Stroke Scale After Mechanical Thrombectomy With Early and Long‐Term Survival

Background The National Institutes of Health Stroke Scale (NIHSS) obtained 24 hours after ischemic stroke is a good indicator for functional outcome and early mortality, but the correlation with long‐term survival is less clear. We analyzed the correlation of the NIHSS after 24 hours (24h NIHSS) and early clinical neurological development after mechanical thrombectomy with early and long‐term survival as well as its predictive power on survival. Methods We reviewed a prospective observational registry for all patients undergoing mechanical thrombectomy between January 2010 and December 2018. Vital status was extracted from the Swiss Population Registry. Adjusted hazard ratio (aHR) and crude hazard ratios were calculated using Cox regression. To assess predictive power of the 24h NIHSS, different Random Survival Forest models were evaluated. Results We included 957 patients (median follow‐up 1376 days). Patients with lower 24h NIHSS and major early neurological improvement had substantially better survival rates. We observed significantly higher aHR for death in patients with 24h NIHSS 12 to 15 (aHR, 1.78; 95% CI, 1.1–2.89), with 24h NIHSS 16 to 21 (aHR, 2.54, 95% CI, 1.59–4.06), and with 24h NIHSS >21 (aHR, 5.74; 95% CI, 3.47–9.5). The 24h NIHSS showed the best performance predicting mortality (receiver operating characteristic area under the curve at 3 months [0.85±0.034], at 1 year [0.82±0.029], at 2 years [0.82±0.031], and at 5 years [0.83±0.035]), followed by NIHSS change. Conclusions Patients with acute ischemic stroke achieving a low 24h NIHSS or major early neurological improvement after mechanical thrombectomy had markedly lower long‐term mortality. Furthermore, 24h NIHSS had the best predictive power for early and long‐term survival in our machine learning–based prediction

Long‐Term Outcome and Quality of Life in Patients With Stroke Presenting With Extensive Early Infarction

Background The benefit of mechanical thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for short‐term outcomes is debatable and long‐term outcomes remain unknown. This retrospective, monocentric cohort study aimed to assess the association between reperfusion grade and the long‐term functional outcome measured with modified Rankin scale as well as the long‐term health‐related quality of life recorded at the last follow‐up in patients according to baseline ASPECTS (0–5 versus 6–10). Methods Deceased patients were identified from the Swiss population register and follow‐up telephone interviews were conducted with all surviving patients with stroke treated with mechanical thrombectomy between January 1, 2010, and December 31, 2018. Favorable outcome was defined as modified Rankin scale 0 to 3; health‐related quality of life was assessed using the 3‐level version of the EuroQol 5‐dimensional questionnaire. The EuroQol 5‐dimension utility index was calculated for statistical analyses. The reperfusion grade was core laboratory adjudicated using the expanded treatment in cerebral ischemia score. Adjusted odds ratios for the association between the reperfusion grade assessed by expanded treatment in cerebral ischemia and outcomes were calculated from multivariable logistic regression. Results Of the 1114 patients with available long‐term follow‐up records (median follow‐up, 3.67 years), 997 were included in the final analysis. Respectively, patients with low ASPECTS more often had complaints regarding mobility (67.1% versus 42.1%, P<0.001), self‐care (53.4% versus 31.2%, P<0.001), and usual activities (65.8% versus 41.4%, P<0.001) than patients with high ASPECTS, whereas reported pain/discomfort (65.7% versus 69.9%, P=0.49) and anxiety/depression (71.2% versus 78.9%, P=0.17) did not differ. In patients with low ASPECTS, increasing reperfusion grade was associated with a higher likelihood of long‐term favorable functional outcome (adjusted odds ratio, 1.43; 95% CI, 1.09–1.88 [P=0.01]) and health‐related quality of life (adjusted linear correlation coefficient, 0.05; 95% CI, 0.02–0.08) despite early extensive infarction. Conclusion Despite low baseline ASPECTS, a higher reperfusion grade results in better functional outcomes and may improve health‐related quality of life in the long term

Designing Multispecies Worlds for Robots, Cats, and Humans

We reflect on the design of a multispecies world centred around a bespoke enclosure in which three cats and a robot arm coexist for six hours a day during a twelve-day installation as part of an artist-led project. In this paper, we present the project’s design process, encompassing various interconnected components, including the cats, the robot and its autonomous systems, the custom end-effectors and robot attachments, the diverse roles of the humans-in-the-loop, and the custom-designed enclosure. Subsequently, we provide a detailed account of key moments during the deployment and discuss the design implications for future multispecies systems. Specifically, we argue that designing the technology and its interactions is not sufficient, but that it is equally important to consider the design of the ‘world’ in which the technology operates. Finally, we highlight the necessity of human involvement in areas such as breakdown recovery, animal welfare, and their role as audience

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable