Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Thrombectomy in ischemic stroke patients with alberta stroke program early computed tomography score 4-5 and 0-3: Factors associated with favorable outcome.

OBJECTIVES: Recently published results of the ANGEL-ASPECT and SELECT2 trials suggest that stroke patients presenting with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) benefit from mechanical thrombectomy. Purpose of this retrospective study was to identify factors that are associated with a favorable outcome in patients with low ASPECTS of 4-5 and 0-3 undergoing mechanical thrombectomy. MATERIAL AND METHODS: All patients reported in the quality registry of the German Society for Neuroradiology that were treated between 2018 and 2020 were analyzed. Favorable outcome was defined as a National Institute of Health Stroke Scale (NIHSS) score of less than 9 at dismissal. Successful recanalization was defined as Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b. Multivariable logistic regression analyses were performed to assess the association of baseline and treatment variables with favorable outcome. RESULTS: 621 patients were included in the analysis, thereof 495 with ASPECTS 4-5 and 126 with ASPECTS 0-3. In patients with ASPECTS 4-5patients with favorable outcome had less severe neurological symptoms at admission with median NIHSS of 15 vs. 18 (p<0.001), had less often wake-up strokes (44% vs. 81%, p<0.001), received more often iv-lysis (37% vs. 30%, p<0.001), had more often conscious sedation (29% vs. 16%, p<0.001), had a higher rate of successful recanalization (94% vs. 66% and lower times from groin puncture to recanalization. In multivariate regression analysis lower NIHSS at admission (aOR 0.87, CI 0.89-0.91) and successful recanalization (aOR 3.96, CI 2-8.56) were associated with favorable outcome. For ASPECTS 0-3, patients with favorable outcome had lower median NIHSS at admission (16 vs. 18 (p<0.001), lower number of passes (1 vs. 3, p=0.003) and a higher rate of successful recanalization (94% vs. 66%, p<0.001) and lower times from groin puncture to recanalization. In multivariate regression analysis lower NIHSS at admission (aOR 0.87, CI 0.81-0.94) and successful recanalization, (aOR 11.19, CI 3.19-55.53), were associated with favorable outcome. CONCLUSION: Full recanalization with low groin punction to recanalization times and low number of passes were associated with favorable outcome in patients with low ASPECTS.

Expression of the zinc importer protein ZIP9/SLC39A9 in glioblastoma cells affects phosphorylation states of p53 and GSK-3ß and causes increased cell migration.

Zinc importer proteins (ZIPs) have been proven as important molecular regulators in different cancers. As a member of the solute carrier family, ZIP9/SLC39A9 is overexpressed in prostate and breast cancer and affects B-cell receptor signaling. Here, we present data indicating that changes in intracellular zinc levels in glioblastoma cells can cause enhanced cell survival and cell migration, both hallmarks of the disease process. In particular, treatment of human glioblastoma cells with sublethal doses of cell-permeable heavy metal (Zn2+ > Fe2+ > Mn2+) chelator (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN)) induced ZIP9 expression. Either TPEN treatment or expression of ZIP9 cDNA causes enhanced migration behavior of glioblastoma cells. Compared to untreated glioblastoma cells TPEN treatment or expression of ZIP9 results in activation of the tumor suppressor p53 by phosphorylation at serine residue 46 (Ser46) and in inactivation of the migration relevant glycogen synthase kinase 3 beta (GSK-3ß) by phosphorylation at serine residue 9 (Ser9). Whilst p53 activation affects cell survival in response to TPEN, GSK-3ß inactivation directly affects glioblastoma cell migration. Therefore, ZIP9 expression could regulate the migratory behavior of glioblastoma cells, so that ZIP9 may be of biological, but not of clinical relevance for glioblastomas, since in GBM tumor tissues, ZIP9 expression is not significantly increased compared to normal brain.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Outcome prediction prior to thrombectomy of the posterior circulation with machine learning.

PURPOSE: Various studies have identified prognostic factors for a favorable outcome of endovascular treatment in posterior circulation. We evaluated various machine learning algorithms in their ability to classify between patients with favorable (defined as 0-2 points on the modified Rankin scale [mRS]), unfavorable (mRS 3-6), poor (mRS 5-6), and nonpoor (mRS 0-4) outcomes at dismissal. METHODS: We retrospectively analyzed data from 415 patients that were treated between 2018 and 2021 from the multicentric DGNR registry. Five models (random forest, support vector machine, k-nearest neighbor, neural network [NN], and generalized linear model [GLM]) were trained with clinical input variables and evaluated with a test dataset of 82 patients. The model with the highest accuracy on the training dataset was defined as the best model. RESULTS: A total of 132 patients showed poor and 162 patients showed favorable outcome. All baseline variables except sex were highly significantly different between patients with favorable and unfavorable outcomes. The variables NIHSS, the presence of wake-up stroke, the administration of IV-thrombolysis and mRS pretreatment were significantly different between patients with poor and nonpoor outcomes. The best-performing NN achieved a sensitivity of 0.56, a specificity of 0.86 and an area under the curve (AUC) of 0.77 on the test dataset in the classification analysis between favorable and unfavorable outcomes. The best-performing GLM achieved a sensitivity of 0.65, a specificity of 0.91 and an AUC of 0.81 in the classification analysis between poor and nonpoor outcomes. CONCLUSION: Short-term favorable and poor outcomes in patients with acute ischemic stroke of the posterior circulation can be predicted prior to thrombectomy with moderate sensitivity and high specificity with machine learning models.

Thrombectomy of Mild Stroke : An Analysis of the Nationwide Registry of the German Society for Neuroradiology.

PURPOSE: Whether patients presenting with mild stroke (NIHSS at admission < 6) should be treated with mechanical thrombectomy (MT) is the subject of an ongoing debate. This retrospective study based on large-scale clinical data aims to identify factors associated with favorable outcome (FO) in patients with mild stroke. METHODS: A total of 761 patients with mild stroke enrolled between 1 January 2020 and 31 December 2020 in the Quality Registry of the German Society for Neuroradiology were analyzed. The FO was defined as stable or improved NIHSS at discharge vs. admission. Descriptive statistics and multivariable logistic regression analyses were performed to identify factors associated with FO. Furthermore, a subgroup analysis of mild stroke based on distal vessel occlusion was conducted. RESULTS: In this study 610 patients had FO with a median NIHSS at discharge of 1 (interquartile range, IQR, 0-2) and 151 had an unfavorable outcome (UO) with median NIHSS at discharge of 10 (IQR 13). Patients with FO had a slightly higher NIHSS at admission (4 vs. 3, p < 0.001), lower mTICI 0 (2.7% vs. 14.2%, p < 0.001), higher mTICI 3 (61.3% vs. 34.5%, p < 0.001) and a lower number of passes (1 vs. 2, p < 0.001). No statistically significant difference was observed for MT-related adverse events. Multivariable logistic regression suggested that NIHSS at admission (adjusted odds ratio (aOR) = 1.28, 95% confidence interval (CI) = 1.10-1.48), mTICI 2b (aOR = 5.44, CI = 2.06-15.03), mTICI 2c (aOR = 10.81, CI = 3.65-34.07) and mTICI 3 (aOR = 11.56, CI = 4.49-31.10) as well as number of passes (aOR 0.76, CI = 0.66-0.88) were significantly associated with FO. No MT-related adverse events were observed for distal vessel occlusions. CONCLUSION: The FO in patients with mild stroke undergoing MT was associated with successful recanalization. No significant differences between patients with FO and UO were found for MT-related adverse events, suggesting that MT complications have no significant effects on the outcome of these patients. MT might improve the prognosis also in patients with mild stroke based on distal vessel occlusions without significantly increasing the risk of adverse events.

[Artificial intelligence in orthopaedic and trauma surgery imaging]. / Künstliche Intelligenz in der orthopädisch-unfallchirurgischen Radiologie.

Artificial intelligence (AI) is playing an increasing role in radiological imaging in orthopaedics and trauma surgery. The algorithms available to date are predominantly used in the detection of (occult) fractures and in length and angle measurements in conventional X­ray images. However, current AI solutions also enable the analysis and pattern recognition of CT datasets, e.g. in the detection of rib or vertebral body fractures. A special application is EOS™ (ATEC Spine Group, Paris, France), which enables a 3­D simulation of the axial skeleton and semi-automatic length and angle calculations based on a digital 2­D X­ray image. In this paper, the current spectrum of AI applications for orthopaedics and trauma surgery is presented and discussed.

Predictors of Successful First-Pass Thrombectomy with a Balloon Guide Catheter: Results of a Decision Tree Analysis.

Complete recanalization after a single retrieval maneuver is an interventional goal in acute ischemic stroke and an independent factor for good clinical outcome. Anatomical biomarkers for predicting clot removal difficulties have not been comprehensively analyzed and await unused. We retrospectively evaluated 200 consecutive patients who suffered acute stroke and occlusion of the anterior circulation and were treated with mechanical thrombectomy through a balloon guide catheter (BGC). The primary objective was to evaluate the influence of carotid tortuosity and BGC positioning on the one-pass Modified Thrombolysis in Cerebral Infarction Scale (mTICI) 3 rate, and secondarily, the influence of communicating arteries on the angiographic results. After the first-pass mTICI 3, recanalization fell from 51 to 13%. The regression models and decision tree (supervised machine learning) results concurred: carotid tortuosity was the main constraint on efficacy, reducing the likelihood of mTICI 3 after one pass to 30%. BGC positioning was relevant only in carotid arteries without elongation: BGCs located in the distal internal carotid artery (ICA) had a 70% probability of complete recanalization after one pass, dropping to 43% if located in the proximal ICA. These findings demonstrate that first-pass mTICI 3 is influenced by anatomical and interventional factors capable of being anticipated, enabling the BGC technique to be adapted to patient's anatomy to enhance effectivity.