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

Changes in obesity-related diseases and biochemical variables after laparoscopic sleeve gastrectomy: a two-year follow-up study

Background: To evaluate changes in obesity-related diseases and micronutrients after laparoscopic sleeve gastrectomy (LSG). Methods: We started the procedure in May 2007, and by December 2011, 117 patients could be evaluated for a two year follow-up. Comparisons of preoperative status with 12 and 24 months postoperative status were made for body mass index (BMI), obesity-related diseases and micronutrients. Results: Major complications included bleeding requiring transfusion at 5.1%, leak at 1.7% and abscess without a visible leak at 0.9%. Mean BMI was reduced from 46.6 (standard deviation (SD) 6.0) kg/m2 to 30.6 (SD 5.6) kg/m2 at two years, and resolution occurred for 80.7% of patients with type 2 diabetes, 63.9% with hypertension, 75.8% with hyperlipidemia, 93.0% with sleep apnea, 31.4% with musculoskeletal pain, 85.4% with snoring and 73.3% with urinary incontinence. Amenorrhea resolved in all premenopausal females. The proportion of patients with symptomatic gastroesophageal reflux disease increased from 12.8% to 27.4%. The prevalence of patients with low ferritin-levels increased, while 25-hydroxyvitamin D (25(OH)D) deficiency decreased postoperatively. Conclusions: LSG is an effective procedure for morbid obesity and obesity-related diseases, but the technique should be further explored particularly to avoid gastroesophageal reflux

Complications Associated with Cerebral Aneurysm Morphology in Balloon-Assisted Coil Embolization of Ruptured and Unruptured Aneurysms-a Single-Center Analysis of 116 Consecutive Cases

BACKGROUND: We investigated the complication rates of balloon-assisted coil embolization of ruptured and unruptured cerebral aneurysms dependent on their morphologic characteristics in angiography. METHODS: The study was a single-center retrospective analysis of all consecutive endovascular balloon-assisted coiling interventions performed between April 2008 and December 2013. Data were extracted from a prospective database on an intention-to-treat basis. We described the clinical (Hunt & Hess score, modified Rankin scale) and technical results (Raymond Roy aneurysm occlusion scale) and analyzed the rate of periprocedural complications with regard to aneurysm subgroups of bifurcation aneurysms versus sidewall aneurysms. RESULTS: There were 116 interventions performed on 108 patients (mean age: 51.7 +/- 11.1 years), with 70/116 emergency procedures (60%), 36/116 elective procedures (31%), and 10/116 elective procedures on recurrent aneurysms (9%). The balloon was used in 108/116 cases (93%). Among the cases, 76/116 were bifurcation aneurysms and 40/116 were sidewall aneurysms. Periprocedural complications, such as rerupture, thrombus formation, distal embolism, coil-loop protrusion, and coil migration, occurred in 26/116 cases (22%). Complications occurred significantly more often in ruptured than unruptured bifurcation aneurysms (23 vs. 3 events, P < 0.05). There was a significantly higher rate of complications in bifurcation aneurysms compared with sidewall aneurysms (17% vs. 3%, P = 0.03). Six periprocedural complications were associated with a permanent neurologic deficit (6% of cases), all of which occurred in the subgroup of acutely ruptured aneurysms. CONCLUSION: The risk of periprocedural complications in balloon-assisted coil embolization of ruptured and unruptured cerebral aneurysms is linked to the morphologic presentation of the aneurysm; the complication rate was significantly higher in bifurcation aneurysms

Carotid Artery Stenosis Contralateral to Intracranial Large Vessel Occlusion: An Independent Predictor of Unfavorable Clinical Outcome After Mechanical Thrombectomy

Background: Clinical outcome in patients undergoing mechanical thrombectomy (MT) due to intracranial large vessel occlusion (LVO) in the anterior circulation is influenced by several factors. The impact of a concomitant extracranial carotid artery stenosis (CCAS) contralateral to the intracranial lesion remains unclear. Methods: Retrospective analysis of 392 consecutive patients treated with MT due to intracranial LVO in the anterior circulation in two comprehensive stroke centers between 2014 and 2017. Clinical (including demographics and NIHSS), imaging (including angiographic evaluation of CCAS via NASCET criteria), and procedural data were evaluated. Primary endpoint was an unfavorable clinical outcome defined as modified Rankin Scale 3-6 at 90 days. Results: In 27/392 patients (7%) pre-interventional imaging exhibited a CCAS (>50%) contralateral to the intracranial lesion compared to 365 patients without relevant stenosis. Median baseline NIHSS, procedural timings, and reperfusion success did not differ between groups. Median volume of the final infarct core was larger in CCAS patients (176 cm(3), IQR 32-213 vs. 11 cm(3), 1-65; p 50% is a predictor of unfavorable clinical outcome at 90 days

Abstract Number ‐ 151: Impact of Stent‐Retriever Tip Design on Distal Embolization during Mechanical Thrombectomy

Introduction Mechanical thrombectomy (MT) is a widely performed procedure for acute ischemic stroke (AIS) due to large vessel occlusion. Repeated number of passes, clot fragmentation, and distal embolization during MT lead to worse clinical outcomes. We aim to evaluate the impact of different stent‐retriever (SR) distal tip designs on distal emboli generation during MT. Methods Fragment‐prone clot analogs (diameter = 3.53±0.14mm; length = 6.74±0.61mm) were used to create proximal middle cerebral artery (MCA‐M1) occlusions in an in vitro neurovascular model featuring a complete circle of Willis. The anatomical replica was connected to a flow loop with circulating saline at physiological flow rate and temperature; 100‐µm filters were placed at the neurovascular outflow points of the model to collect generated distal emboli. After initial embolization, experiments were randomized into one of the three treatment arms based on SR tip design: open‐end (Open‐SR: Solitaire 6.0×40mm), closed‐end (Closed‐SR: Embotrap II 5.0×33mm), and filter‐end (Filter‐SR: NeVa NET 5.5×37mm). A balloon guide catheter was inflated at the internal carotid artery C1 level immediately after SR deployment, and the SR was pulled out under continuous proximal pump aspiration. A total of 90 cases were performed (30 cases/treatment arm). A single attempt was performed per case and after each pass, distal emboli collected in the outflow filters were analyzed by an image processing algorithm. Successful first pass recanalization (FPR) was confirmed if no residual clot was observed at the initial location or in a distal branch of the model. Primary study endpoints were: FPR rate (%FPR), the size of the largest embolus (largest‐E), the total emboli count (total‐E), the total count of emboli larger than 1mm (total>1mm‐E), and the total area of the filter covered by emboli (area‐E). Results FPR was achieved in 57.8% of cases (52/90): Filter‐SR achieved a non‐significantly higher %FPR (70%) than closed‐SR (50%) and open‐SR (53.3%) (p = 0.244). In comparison to open‐ and closed‐SR, filter‐SR significantly reduced the largest‐E (open‐SR = 1.66±0.68mm vs. closed‐SR = 1.77±0.90mm vs. filter‐SR = 1.22±0.77mm; p = 0.013) as well as the total>1mm‐E (open‐SR = 2.27±2.33 vs. closed‐SR = 3.97±5.68 vs. filter‐SR = 0.93±1.28; p = 0.002), and the area‐E (open‐SR = 18.22±14.47mm2 vs. closed‐SR = 23.98±22.39mm2 vs. filter‐SR = 10.14±8.81mm2; p = 0.013). The differences between distal tip designs were not clearly evidenced in the total‐E (open‐SR = 22.7±10.75 vs. closed‐SR = 23.13±13.16 vs. filter‐SR = 20.63±12.77; p = 0.464). No significant differences were found between open‐ and closed‐SR (p>0.05 in all metrics). Conclusions When facing fragment‐prone clots with low SR engagement, the filter‐SR significantly reduces the number of large clot fragments (>1mm), the size of the largest embolus, and the overall surface area of clot fragments that embolize distally during an MT procedure

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

Maximizing First-Pass Complete Reperfusion with SAVE

Background Endovascular techniques for treatment of large vessel occlusions (LVO) in patients with acute ischemic stroke (AIS) have advanced in recent years. We report a multicenter experience using a combined aspiration and stent retriever technique for mechanical thrombectomy (MT). Methods We retrospectively analyzed 32 consecutive MT patients using a novel, combined approach of Stent retriever Assisted Vacuum-locked Extraction (SAVE) by 3 operators at 3 stroke centers. Primary endpoint was successful firstpass reperfusion with a modified Thrombolysis in Cerebral Infarction (mTICI) score of 3. Secondary endpoints were number of passes, time from groin puncture to reperfusion, embolization to new territories (ENT), postinterventional symptomatic intracranial hemorrhage (sICH) and clinical outcome at discharge. Results First-pass mTICI 3 reperfusion was achieved in 23 out of 32 patients (72%) with a mean groin puncture to reperfusion time of 36.0min +/- 15.8 and mTICI 3 was accomplished in 25 out of 32 cases (78%) with a maximum of 3 attempts. Successful reperfusion (mTICI = 2b) was achieved in all patients (100%) with a mean time from groin puncture to reperfusion of 44.5min +/- 25.8 and an average of 1.2 +/- 0.7 attempts. The rate of ENT was 0% and 1 patient with sICH after MT died on postoperative day 4. At discharge, the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (range 0-17) and favorable neurological outcome by the modified Rankin score (mRS <= 2) was achieved in 19 out of 32 patients (59%). Conclusion SAVE is fast and appears to be very effective in terms of first-pass complete reperfusion in patients with LVO

Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections.

Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained-but optionally de-activatable-expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections