ERASER.

Background and Purpose- Using a novel study design with virtual comparators based on predictive modeling, we investigated whether next-generation mechanical thrombectomy devices improve outcomes in patients with ischemic stroke. We hypothesized that this new study design shows that a next-generation mechanical thrombectomy system is superior to intravenous tPA (tissue-type plasminogen activator) therapy (IVT) alone. Methods- ERASER (Eric Acute Stroke Recanalization) was an investigator-initiated, prospective, multicenter, single-arm (virtual 2-arm) study that evaluated the effectiveness of a new recanalization device together with a specific intermediate catheter (Embolus Retriever with Interlinked Cages/SOFIA, Microvention) in stroke patients with internal carotid artery or middle cerebral artery occlusions. The primary end point was the volume of saved tissue. Volume of saved tissue was defined as the difference of actual infarct volume and brain volume predicted to develop infarction using a machine learning model based on data from intravenous tPA therapy patients. Results- Eighty-one patients were enrolled. The median patient age was 71 years (interquartile range, 61-77). National Institutes of Health Stroke Scale score was 14 (interquartile range, 12-18). The actual infarct volume was smaller than predicted by the intravenous tPA therapy model, with a median volume of saved tissue of 50 mL (interquartile range, 19-103; P<0.0001). Good clinical outcome (modified Rankin Scale, 0-2 at 90 days) was observed in 48 out of 69 (70%). The recanalization rate (Thrombolysis in Cerebral Infarction 2b/3) was 95%. Conclusions- ERASER is the first mechanical thrombectomy study with a primary end point based on predictive analytics enabling intraindividual virtual comparisons. The next-generation mechanical thrombectomy method resulted in smaller infarcts than predicted after intravenous tPA therapy alone and showed a high rate of good clinical outcome. The novel study design with virtual comparisons is promising for further application and testing in the neurovascular arena. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02534701.

Recanalization Rate per Retrieval Attempt in Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Purpose- In acute ischemic stroke, mechanical thrombectomy allows flow restoration in the majority of cases. In case of an unsuccessful retrieval, little is known about how many retrieval attempts should be performed before stopping the procedure. This study assessed the recanalization rate and clinical outcome per retrieval maneuver. Methods- In this analysis, 330 patients with acute large vessel occlusion treated exclusively with stentrieval devices were included. Successful recanalization was defined as Thrombolysis in Cerebral Infarction 2b-3, a good clinical outcome was defined as modified Rankin Scale at 90 days of ≤2. Results- The median number of retrieval attempts was 1 (interquartile range, 1-2, maximum 8). Recanalization rates per retrieval attempt were highest for the first retrieval (46.8%) and lowest for the fifth retrieval (22.7%). After 3 retrieval attempts, 67.9% of patients were successfully recanalized. Patients with 1 to 3 retrieval attempts had higher rates of good clinical outcome (28.9% versus 7.4%; P=0.018). The number of passes was an independent negative predictor of good clinical outcome (adjusted odds ratio, 0.65; 95% CI, 0.435-0.970; P=0.035). Conclusions- Two-thirds of occlusions were successfully recanalized with up to 3 retrieval attempts. Further attempts had good recanalization rates, but the rate of favorable clinical outcome did not improve.

Central nervous system complications after liver transplantation: common but mostly transient phenomena.

Although central nervous system complications (CNSCs) are common after orthotopic liver transplantation (OLT), standardized prospective studies are still lacking. This prospective study was aimed at determining the incidence of CNSCs, describing their clinical presentations, and establishing predicting factors. One hundred thirty-six adult patients who underwent OLT at Hannover Medical School between December 2008 and June 2011 were included. Weekly examinations were performed by a neurologist during the hospital stay after OLT. Patient data, donor data, and operative and postoperative variables were collected. Patients with cerebral dysfunction after OLT underwent a diagnostic work-up, which included brain imaging and, if necessary, cerebrospinal fluid analysis. Patients with central nervous system (CNS) symptoms but negative imaging and cerebrospinal fluid results and patients with pontine myelinolysis or posterior reversible encephalopathy syndrome were placed in a metabolic-toxic CNSC group, and patients with strokes, intracranial hemorrhaging, or CNS infections were placed in a nonmetabolic CNSC group. Multiple regression analysis was used to identify independent risk factors for the development of metabolic-toxic CNSCs. After excluding two patients that died after OLT without regaining consciousness, forty-four (32.8%) patients developed CNSCs: 37 of these patients (27.6%) had metabolic-toxic CNSCs, and 7 (5.2%) had nonmetabolic CNSCs. Acute-on-chronic liver failure, the number of subsequent surgeries, and primary sclerosing cholangitis were identified as independent predictors for the development of metabolic-toxic CNSCs. Metabolic-toxic CNSCs were associated with prolonged hospital stays, and nonmetabolic CNSCs were associated with higher mortality. In conclusion, CNSCs are common and relevant complications after OLT. Patients after OLT, especially with risk factors, should undergo a regular standardized neurological examination that would allow early detection of these complications.

Reasons for failed endovascular recanalization attempts in stroke patients.

PURPOSE: Mechanical thrombectomy (MT) is a highly effective therapy in patients with acute ischemic stroke due to large vessel occlusion (LVO). However, complete recanalization of the occluded vessel cannot be achieved in all patients, leading to poor clinical outcome. We analyzed the reasons for failed recanalization to help direct future improvements in therapy. METHODS: 648 consecutive stroke patients with LVO and an MT attempt were retrospectively analyzed for none or minimal recanalization, assessed according to the Thrombolysis in Cerebral Infarction (TICI) score (0/1). Procedural parameters were evaluated in a standardized approach. Among other variables, number of retrieval attempts, devices, duration of the intervention, and rescue methods were analyzed. RESULTS: TICI 0/1 was observed in 72/648 patients (11%). In these patients, the thrombus could not be reached in 21% (n=15/72), was reached but not passed in 21% (n=15/72), and was reached and passed in 58% (n=42/72). Only a minor degree of initial recanalization was achieved in 19% (n=8/42) of patients with a reached occlusion during the course of the intervention. Furthermore, a higher number of passes with a single retriever device led to significant prolongation of the intervention. Therefore, major reasons for failed endovascular recanalization were difficult anatomical access and hard or resistant occlusions that might reflect hard thrombi or pre-existing atherosclerotic stenosis. Procedural complications such as dissection or perforation played a minor role. CONCLUSION: In stroke patients with failed MT attempts, approximately 60% of occlusions can be passed. In such cases, rescue therapy might be considered to improve recanalization and clinical outcome. Further development of access devices might help in the remaining cases where the microcatheter could not be manipulated to or through the occlusion.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.