Publications by authors named "Stephan Meckel"

56 Publications

Dural Arteriovenous Fistula Formation Secondary to Cerebral Venous Thrombosis: Longitudinal Magnetic Resonance Imaging Assessment Using 4D-Combo-MR-Venography.

Thromb Haemost 2021 Mar 3. Epub 2021 Mar 3.

Department of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background And Purpose:  Dural arteriovenous fistulae (DAVFs) can develop secondary to cerebral venous thrombosis (CVT). The incidence of DAVF has not yet been investigated prospectively.

Methods:  Between July 2012 and January 2018, combined static and dynamic 4D MR venography (4D-combo-MRV) was performed in 24 consecutive patients at diagnosis of CVT and after 6 months. 3 Tesla magnetic resonance imaging with time of flight and contrast-enhanced magnetization-prepared rapid acquisition with gradient echo were performed at baseline to evaluate the extent of thrombosis and affected vessel segments. Baseline and follow-up 4D-combo-MRV were assessed for signs of DAVF. Interrater reliability of DAVF detection and the extent of recanalization were analyzed with kappa statistics.

Results:  DAVFs were detected in 4/30 CVT patients (13.3%, 95% confidence interval [CI] 3.3-26.7). Two of 24 patients (8.3%, 95% CI: 0-20.8) had coincidental DAVF with CVT on admission. At follow-up, de novo formation of DAVF following CVT was seen in 2/24 patients (8.3%, 95% CI: 0-20.8). Both de novo DAVFs were low grade and benign fistulae (Cognard type 1, 2a), which had developed at previously thrombosed segments. Endovascular treatment was required in two high degree lesions (Cognard 2a + b) detected at baseline and in one de novo DAVF (Cognard 1) because of debilitating headache and tinnitus. Thrombus load, vessel recanalization, and frequency of cerebral lesions (hemorrhage, ischemia) were not associated with DAVF occurrence.

Conclusion:  This exploratory study showed that de novo DAVF formation occurs more frequently than previously described. Although de novo DAVFs were benign, 75% of all detected DAVFs required endovascular treatment. Therefore, screening for DAVF by dynamic MRV, such as 4D-combo-MRV, seems worthwhile in CVT patients.
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http://dx.doi.org/10.1055/s-0041-1723991DOI Listing
March 2021

Derivo embolization device in the treatment of unruptured intracranial aneurysms: a prospective multicenter study.

J Neurointerv Surg 2020 Sep 8. Epub 2020 Sep 8.

Department of Intracranial Endovascular Therapy, Alfried Krupp Krankenhaus Essen, Essen, Germany.

Background: Flow diverters (FD) are used regularly for the endovascular treatment of unruptured intracranial aneurysms. We aimed to assess the safety and effectiveness of the Derivo embolization device (DED) with respect to long-term clinical and angiographic outcomes.

Methods: A prospective multicenter trial was conducted at 12 centers. Patients presenting with modified Rankin Score (mRS) of 0-1, treated for unruptured intracranial aneurysms with DED were eligible. Primary endpoint was the mRS assessed at 18 months with major morbidity defined as mRS 3-5. Satisfactory angiographic occlusion was defined as 3+4 on the Kamran scale.

Results: Between July 2014 and February 2018, 119 patients were enrolled. Twenty-three patients were excluded. Ninety-six patients, 71 (74%) female, mean age 54±12.0 years, were included in the analysis. Mean aneurysm size was 14.2±16.9 mm. The mean number of devices implanted per patient was 1.2 (range 1-3). Clinical follow-up at 18 months was available in 90 (94%) patients, resulting in a mean follow-up period of 14.8±5.2 months. At last available follow-up of 96 enrolled patients, 91 (95%) remained mRS 0-1. The major morbidity rate (mRS 3-5) was 3.1% (3/96), major stroke rate was 4.2% (4/96), and mortality was 0%. Follow-up angiographies were available in 89 (93%) patients at a median of 12.4±5.84 months with a core laboratory adjudicated satisfactory aneurysm occlusion in 89% (79/89).

Conclusion: Our results suggest that DED is a safe and effective treatment for unruptured aneurysms with high rates of satisfactory occlusion and comparably low rates of permanent neurological morbidity and mortality.

Trial Registration: DRKS00006103.
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http://dx.doi.org/10.1136/neurintsurg-2020-016303DOI Listing
September 2020

Selective Brain Hypothermia for Ischemic MCA-M1 Stroke: Influence of Cerebral Arterial Circulation in a 3D Brain Temperature Model.

IEEE Trans Biomed Eng 2021 Feb 20;68(2):404-415. Epub 2021 Jan 20.

Acute ischemic stroke is a major health problem with a high mortality rate and a high risk for permanent disabilities. Selective brain hypothermia has the neuroprotective potential to possibly lower cerebral harm. A recently developed catheter system enables to combine endovascular blood cooling and thrombectomy using the same endovascular access. By using the penumbral perfusion via leptomeningeal collaterals, the catheter aims at enabling a cold reperfusion, which mitigates the risk of a reperfusion injury. However, cerebral circulation is highly patient-specific and can vary greatly. Since direct measurement of remaining perfusion and temperature decrease induced by the catheter is not possible without additional harm to the patient, computational modeling provides an alternative to gain knowledge about resulting cerebral temperature decrease. In this work, we present a brain temperature model with a realistic division into gray and white matter and consideration of spatially resolved perfusion. Furthermore, it includes detailed anatomy of cerebral circulation with possibility of personalizing on base of real patient anatomy. For evaluation of catheter performance in terms of cold reperfusion and to analyze its general performance, we calculated the decrease in brain temperature in case of a large vessel occlusion in the middle cerebral artery (MCA) for different scenarios of cerebral arterial anatomy. Congenital arterial variations in the circle of Willis had a distinct influence on the cooling effect and the resulting spatial temperature distribution before vessel recanalization. Independent of the branching configurations, the model predicted a cold reperfusion due to a strong temperature decrease after recanalization (1.4-2.2  C after 25 min of cooling, recanalization after 20 min of cooling). Our model illustrates the effectiveness of endovascular cooling in combination with mechanical thrombectomy and its results serve as an adequate substitute for temperature measurement in a clinical setting in the absence of direct intraparenchymal temperature probes.
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http://dx.doi.org/10.1109/TBME.2020.3000521DOI Listing
February 2021

Quality and validity of large animal experiments in stroke: A systematic review.

J Cereb Blood Flow Metab 2020 11 23;40(11):2152-2164. Epub 2020 Jun 23.

School of Life Sciences, University of Warwick, Coventry, UK.

An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models.
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http://dx.doi.org/10.1177/0271678X20931062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585919PMC
November 2020

Bioresorbable zinc stent with ultra-thin center struts attenuates stent jail in porcine femoral artery bifurcations.

Minim Invasive Ther Allied Technol 2020 Jun 13:1-8. Epub 2020 Jun 13.

Optimed GmbH, Ettlingen, Germany.

Introduction: An ultra-thin, fracture-resistant and bioresorbable stent may be advantageous for provisional stenting in vessel bifurcations, if catheter passage and side-branch post-dilatation is facilitated to prevent a 'stent jail' by struts obstructing the orifice of a major side branch.

Material And Methods: We studied a highly radiopaque, slowly bioresorbable zinc alloy stent characterized by a novel design of a radiopaque-marked region of ultra-thin struts in the center of the stent. The stent is characterized by an extended range flexibility and high fracture resistance. Zn-stents and Zn-drug eluting stents (DES) were implanted opposite to rigid Nitinol stents into both femoral artery bifurcations of 21 juvenile pigs, followed for one and three months and studied by angiography and histomorphometry. : Bare Zn-stents with thinner stent struts showed less neointimal hyperplasia compared to Zn-stents with thicker struts. Neointimal formation was further reduced by 12% in Zn-alloy DES. Both, bare Zn-stents and Zn-DES, can be precisely positioned into the femoral artery bifurcation, allowing easy balloon catheter passage through the very thin strut mesh. Side branch orifices remained open after Zn-stent deployment without stent jailing. No stent fractures or particles emboli occurred after the deployment. A Zn-stent with ultra-thin center struts may be useful for provisional stenting in vessel bifurcations.
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http://dx.doi.org/10.1080/13645706.2020.1770797DOI Listing
June 2020

Correction to: Endovascular stroke treatment's impact on malignant type of edema (ESTIMATE).

J Neurol 2020 08;267(8):2481

Department of Neurology, University Hospital Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.

The original keywords were not sufficiently precise in describing the article content. Therefore, the key words were amended to include hemicraniectomy and malignant edema.
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http://dx.doi.org/10.1007/s00415-020-09828-xDOI Listing
August 2020

Modeling selective therapeutic hypothermia in case of acute ischemic stroke using a 1D hemodynamics model and a simplified brain geometry.

Math Biosci Eng 2019 11;17(2):1147-1167

Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.

Therapeutic hypothermia (TH) is an approved neuroproctetive treatment to reduce neurological morbidity and mortality after hypoxic-ischemic damage related to cardiac arrest and neonatal asphyxia. Also in the treatment of acute ischemic stroke (AIS), which in Western countries still shows a very high mortality rate of about 25 %, selective mild TH by means of Targeted Temperature Management (TTM) could potentially decrease final infarct volume. In this respect, a novel intracarotid blood cooling catheter system has recently been developed, which allows for combined carotid blood cooling and mechanical thrombectomy (MT) and aims at selective mild TH in the affected ischemic brain (core and penumbra). Unfortunately, so far direct measurement and control of cooled cerebral temperature requires invasive or elaborate MRI-assisted measurements. Computational modeling provides unique opportunities to predict the resulting cerebral temperatures on the other hand. In this work, a simplified 3D brain model was generated and coupled with a 1D hemodynamics model to predict spatio-temporal cerebral temperature profiles using finite element modeling. Cerebral blood and tissue temperatures as well as the systemic temperature were analyzed for physiological conditions as well as for a middle cerebral artery (MCA) M1 occlusion. Furthermore, vessel recanalization and its effect on cerebral temperature was analyzed. The results show a significant influence of collateral flow on the cooling effect and are in accordance with experimental data in animals. Our model predicted a possible neuroprotective temperature decrease of 2.5 ℃ for the territory of MCA perfusion after 60 min of blood cooling, which underlines the potential of the new device and the use of TTM in case of AIS.
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http://dx.doi.org/10.3934/mbe.2020060DOI Listing
November 2019

Evaluation of a biocompatible sealant for on-demand repair of vascular defects-a chronic study in a large animal model.

Interact Cardiovasc Thorac Surg 2020 05;30(5):715-723

Department of Congenital Heart Defects and Pediatric Cardiology, University Heart Center Freiburg-Bad Krozingen, University of Freiburg, Freiburg, Germany.

Objectives: Existing surgical sealants fail to combine design requirements, such as sealing performance, on-demand activation and biocompatibility. The aim of this study was to compare the effectiveness and safety of the SETALIUM™ Vascular Sealant (SVS), a novel, on-demand activatable sealant, with the commercial sealant, BioGlue®, for the repair of vascular defects.

Methods: In an in vivo porcine model, the use of SVS was compared with BioGlue, for sealing 2-mm defects of the carotid artery and jugular vein. Animals were followed for 7 days and 5 weeks (each time point and per experimental group, n = 4), respectively. The degree of stenosis and flow velocity was determined, and the local tissue response was evaluated.

Results: In vivo incision closure succeeded in all cases, and SVS was superior in clinical usability, enabled by its on-demand activation. Unlike BioGlue, SVS use did not induce stenosis and was associated with physiological blood flow in all cases. Moreover, closure with SVS was associated with a low inflammatory reaction and no thrombus formation or intima proliferation, in contrast to BioGlue.

Conclusions: SVS demonstrated effective and rapid sealing of 2-mm vascular defects, with favourable biocompatibility compared to BioGlue. Thus, SVS seems to be an effective and safe vascular sealant.
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http://dx.doi.org/10.1093/icvts/ivaa012DOI Listing
May 2020

Review of selective brain hypothermia in acute ischemic stroke therapy using an intracarotid, closed-loop cooling catheter.

Brain Circ 2019 Oct-Dec;5(4):211-217. Epub 2019 Dec 27.

Department of Neuroradiology, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany.

In acute ischemic stroke patients, selective brain hypothermia is a promising concept aiming at a fast decrease of brain temperature and thus neuroprotection in the acute phase of ischemia. At the same time, the emergence of mechanical thrombectomy (MT) as an effective treatment in large-vessel occlusion opens the door for a combination of neuroprotective approaches in the frame of a neurovascular, catheter-based intervention. In this regard, intracarotid cooling is a very effective energetic approach, using the blood supply to the penumbra as a fast transport vector for heat exchange in affected brain regions. We review the state of development of a novel closed-loop cooling catheter, describing design-related as well as procedural aspects and presenting results from different theoretical and experimental studies. Finally, we compare the concept with two alternative methods: cold saline infusion and extracorporeal blood cooling. We focus on the combination with MT, considering the effect of different and variable perfusion rates on the final goal of a "cold reperfusion" at the time of blood flow restoration.
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http://dx.doi.org/10.4103/bc.bc_54_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950513PMC
December 2019

Cerebral amyloid angiopathy-related intracerebral hemorrhage: Feasibility and safety of bedside catheter hematoma evacuation with urokinase.

Clin Neurol Neurosurg 2020 03 30;190:105655. Epub 2019 Dec 30.

Neurological Department, University of Freiburg, Breisacher Strasse 64, 79106, Freiburg, Germany.

Objective: Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage (ICH). However, data on surgical intervention in CAA-related ICH is very limited. In this retrospective study we assessed safety and efficacy of free-hand catheter aspiration followed by local thrombolysis in CAA-related large ICH.

Patients And Methods: Patients with CAA-related lobar ICH>30 ml that were treated with this catheter technique were identified from our prospective database. The catheter was inserted at the bedside in the core of the hematoma and urokinase (5000IE) was administered every 6 h for a maximum of 4 days. Evolution of hematoma volume, perihemorrhagic edema (PHE) and midline-shift (MLS) as well as adverse events and functional outcome were analyzed.

Results: Twenty-one patients (median age 79 years) were treated between 2013-2018. Hematoma volume decreased from 70 ml at admission (IQR 49-98 ml) to 52 ml (IQR 35-76 ml, p < 0.001) immediately after catheter aspiration, and to 23.5 ml (IQR 17-47 ml, p < 0.001) at the end of urokinase treatment. At day 4, PHE volume (from 45 ml [IQR 33-71 ml] to 36 ml [IQR 22-50 ml]; p = 0.001) and MLS (from 5 mm [IQR 3.5-7 mm] to 1 mm [IQR 0.5-3 mm]; p < 0.001) were reduced significantly. No infection was observed, rebleeding after administration of 4 × 5000IE urokinase occurred in one patient (5 %). At discharge, modified Rankin Scale was 3 in 33 %, 4 in 24 %, and 5 in 43 % of patients, and had further improved after rehabilitation to an mRS of 2 in 10 %, 3 in 38 %, 4 in 19 %, and 5 in 33 % (median 9 weeks after ictus). There were no patient deaths during this time.

Conclusions: Bedside catheter hematoma evacuation in large CAA-related ICH seemed feasible and safe and could immediately decrease mass effect. Further studies assessing functional outcome are warranted.
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http://dx.doi.org/10.1016/j.clineuro.2019.105655DOI Listing
March 2020

Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study.

Crit Care Med 2020 03;48(3):e241-e248

Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome.

Design: Preclinical, randomized controlled animal study.

Setting: Animal research facility.

Subjects: Nineteen German landrace hybrid pigs.

Intervention: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid.

Measurements And Main Results: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated PaO2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable PaCO2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 µm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039).

Conclusions: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.
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http://dx.doi.org/10.1097/CCM.0000000000004209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017946PMC
March 2020

High-resolution Compressed-sensing T1 Black-blood MRI : A New Multipurpose Sequence in Vascular Neuroimaging?

Clin Neuroradiol 2021 Mar 18;31(1):207-216. Epub 2019 Dec 18.

Department of Neuroradiology, Medical Center-University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

Background And Purpose: In vasculopathies of the central nervous system, reliable and timely diagnosis is important against the background of significant morbidity and sequelae in cases of incorrect diagnosis or delayed treatment. Magnetic resonance imaging (MRI) plays a major role in the detection and monitoring of intracranial and extracranial vascular pathologies of different etiologies, in particular for evaluation of the vessel wall in addition to luminal information, thus allowing differentiation between various vasculopathies. Compressed-sensing black-blood MRI combines high image quality with relatively short acquisition time and offers promising potential in the context of neurovascular vessel wall imaging in clinical routine. This case review gives an overview of its application in the diagnosis of various intracranial and extracranial entities.

Methods: An optimized high-resolution compressed-sensing black-blood 3D T1-weighted fast (turbo) spin echo technique (T1 CS-SPACE prototype) precontrast and postcontrast application at 3T was used for the evaluation of various vascular conditions in neuroradiology.

Results: In this article seven cases of intracranial and extracranial arterial and venous vasculopathies with representative imaging findings in high-resolution compressed-sensing black-blood MRI are presented.

Conclusion: High-resolution 3D T1 CS-SPACE black-blood MRI is capable of imaging various vascular entities in high detail with whole head coverage and low susceptibility for motion artifacts and within acceptable scan times. It represents a highly versatile, non-invasive technique for the visualization and differentiation of a wide variety of neurovascular arterial and venous disorders.
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http://dx.doi.org/10.1007/s00062-019-00867-0DOI Listing
March 2021

Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program.

Cell 2019 12;179(7):1609-1622.e16

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signaling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany; Center for NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.
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http://dx.doi.org/10.1016/j.cell.2019.11.010DOI Listing
December 2019

Long-term outcome changes after mechanical thrombectomy for anterior circulation acute ischemic stroke.

J Neurol 2020 Apr 13;267(4):1026-1034. Epub 2019 Dec 13.

Department of Neuroradiology, Medical Center, University Hospital Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.

Background And Purpose: Mechanical thrombectomy (MT) improves early clinical outcome in patients with acute ischemic stroke but insights on determinants of long-term outcome after MT treatment are scarce.

Methods: Data from stroke patients with anterior circulation large vessel occlusion of a prospective MT registry (01/2014-06/2017) of a large comprehensive stroke center were analyzed regarding clinical outcome between short- (3 months) and long-term (12 months) assessment reflected by a change of modified Rankin scores (∆mRS). Secondary endpoints included favorable long-term outcome (mRS 0-2). Multi-variable regression analysis was performed to identify determinants of outcome changes and favorable outcome at long term.

Results: Of 264 patients included, 42.0% showed a favorable long-term outcome. Longitudinal analysis found that some individuals still improved, but no overall mRS difference between short and long-term follow-up was detected [∆mRS - 0.004 (95% CI - 0.020; 0.013); p = 0.672]. Right hemispheric stroke [∆mRS 0.286 (0.011; 0.561); p = 0.043] and high NIHSS at discharge [∆mRS, 0.039 (0.004; 0.074); p = 0.029] were associated with a longitudinal mRS decline. Favorable long-term outcome was associated with successful recanalization (p < 0.0001).

Conclusions: A significant number of patients with MT experience a favorable long-term outcome. Outcomes remained stable between short- and long-term follow-up, but some individuals may still show improvement beyond short-term rehabilitation. Right hemispheric stroke and clinical stroke severity at hospital discharge may be frail predictors for delayed decline of functional status, whereas successful recanalization remains a positive outcome predictor. Death rarely occurs beyond 3 months after MT treatment.
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http://dx.doi.org/10.1007/s00415-019-09670-wDOI Listing
April 2020

Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

Front Neurol 2019 14;10:1113. Epub 2019 Nov 14.

Department of Neurosurgery, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.

Temporary middle cerebral artery occlusion (MCAO) in sheep allows modeling of acute large vessel occlusion stroke and subsequent vessel recanalization. However, rapid and precise imaging-based assessment of vessel occlusion and the resulting perfusion deficit during MCAO still represents an experimental challenge. Here, we tested feasibility and suitability of a strategy for MCAO verification and perfusion deficit assessment. We also compared the extent of the initial perfusion deficit and subsequent lesion size for different MCAO durations. The rete mirabile prevents reliable vascular imaging investigation of middle cerebral artery filling status. Hence, computed tomography perfusion imaging was chosen for indirect confirmation of MCAO. Follow-up infarct size evaluation by diffusion-weighted magnetic resonance imaging revealed fluctuating results, with no apparent relationship of lesion size with MCAO at occlusion times below 4 h, potentially related to the variable collateralization of the MCA territory. This underlines the need for intra-ischemic perfusion assessment and future studies focusing on the correlation between perfusion deficit, MCAO duration, and final infarct volume. Temporary MCAO and intra-ischemic perfusion imaging nevertheless has the potential to be applied for the simulation of novel recanalization therapies, particularly those that aim for a fast reperfusion effect in combination with mechanical thrombectomy in a clinically realistic scenario.
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http://dx.doi.org/10.3389/fneur.2019.01113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868089PMC
November 2019

Emergency Free-Hand Bedside Catheter Evacuation of Large Intracerebral Hematomas Following Thrombolysis for Ischemic Stroke: A Case Series.

Neurocrit Care 2020 08;33(1):207-217

Department of Neurology, University of Freiburg Medical School, Breisacher Str. 64, 79106, Freiburg, Germany.

Introduction: Symptomatic intracerebral hemorrhage (sICH) following systemic thrombolysis for ischemic stroke is often devastating, and open surgical evacuation is considered dangerous due to the increased risk of perioperative bleeding, and stereotactic placement of a catheter is too time-consuming. We therefore evaluated the feasibility of a free-hand bedside catheter technique for emergency hematoma evacuation.

Methods: Patients who had a supratentorial sICH after thrombolysis, a hematoma volume > 30 ml, and an ensuing reduction in vigilance were consecutively treated with acute minimally invasive catheter hematoma evacuation. Catheter insertion and trajectory were planned via 3D-reconstructed computed tomography (CT) scan, and free-hand insertion of an external ventricular catheter into the core of the hematoma was performed bedside, followed by careful blood aspiration. Cranial CT was used to verify catheter position and residual hematoma volume. In cases, where the residual volume exceeded 15 ml, urokinase (5000 IE) was administered into the clot every 6 h until the volume decreased to < 15 ml.

Results: In all six patients, catheter aspiration immediately reduced hematoma volume by 77%, from 73 ± 20 ml to 17 ± 16 ml (p = 0.028). In four patients, the hematoma was almost completely removed (< 10 ml) by singular aspiration. In the remaining two patients with a residual hematoma size > 15 ml, consecutive urokinase application resulted in a further reduction to 1 ml and 15 ml, respectively, after 30 h. The median National Institues of Health Stroke Scale/Score after sICH was 19.5 points, rapidly decreasing to 11 after catheter aspiration (p = 0.027), and further improving to 4 at discharge. No procedure-related complications were observed.

Conclusions: Emergency free-hand bedside catheter aspiration is a reasonable option for hematoma evacuation in large thrombolysis-associated sICH when performed by experienced neurosurgeons. Larger studies would help in determining the generalizability of our findings to other centers and assessing their impact on functional outcome.
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http://dx.doi.org/10.1007/s12028-019-00887-1DOI Listing
August 2020

Combined local hypothermia and recanalization therapy for acute ischemic stroke: Estimation of brain and systemic temperature using an energetic numerical model.

J Therm Biol 2019 Aug 4;84:316-322. Epub 2019 Jul 4.

Adceris GmbH & Co KG, Pforzheim, Germany.

Local brain hypothermia is an attractive method for providing cerebral neuroprotection for ischemic stroke patients and at the same time reducing systemic side effects of cooling. In acute ischemic stroke patients with large vessel occlusion, combination with endovascular mechanical recanalization treatment could potentially allow for an alleviation of inflammatory and apoptotic pathways in the critical phase of reperfusion. The direct cooling of arterial blood by means of an intra-carotid heat exchange catheter compatible with recanalization systems is a novel promising approach. Focusing on the concept of "cold reperfusion", we developed an energetic model to calculate the rate of temperature decrease during intra-carotid cooling in case of physiological as well as decreased perfusion. Additionally, we discussed and considered the effect and biological significance of temperature decrease on resulting brain perfusion. Our model predicted a 2 °C brain temperature decrease in 8.3, 11.8 and 26.2 min at perfusion rates of 50, 30 and 10ml100g⋅min, respectively. The systemic temperature decrease - caused by the venous blood return to the main circulation - was limited to 0.5 °C in 60 min. Our results underline the potential of catheter-assisted, intracarotid blood cooling to provide a fast and selective brain temperature decrease in the phase of vessel recanalization. This method can potentially allow for a tissue hypothermia during the restoration of the physiological flow and thus a "cold reperfusion" in the setting of mechanical recanalization.
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http://dx.doi.org/10.1016/j.jtherbio.2019.06.011DOI Listing
August 2019

Real-time magnetic resonance imaging - guided coronary intervention in a porcine model.

Sci Rep 2019 06 17;9(1):8663. Epub 2019 Jun 17.

Cardiology and Angiology I, Heart Center Freiburg University and Faculty of Medicine, Freiburg, Germany.

X-ray fluoroscopy is the gold standard for coronary diagnostics and intervention. Magnetic resonance imaging is a radiation-free alternative to x-ray with excellent soft tissue contrast in arbitrary slice orientation. Here, we assessed real-time MRI-guided coronary interventions from femoral access using newly designed MRI technologies. Six Goettingen minipigs were used to investigate coronary intervention using real-time MRI. Catheters were custom-designed and equipped with an active receive tip-coil to improve visibility and navigation capabilities. Using modified standard clinical 5 F catheters, intubation of the left coronary ostium was successful in all animals. For the purpose of MR-guided coronary interventions, a custom-designed 8 F catheter was used. In spite of the large catheter size, and therefore limited steerability, intubation of the left coronary ostium was successful in 3 of 6 animals within seconds. Thereafter, real-time guided implantation of a non-metallic vascular scaffold into coronary arteries was possible. This study demonstrates that real-time MRI-guided coronary catheterization and intervention via femoral access is possible without the use of any contrast agents or radiation, including placement of non-metallic vascular scaffolds into coronary arteries. Further development, especially in catheter and guidewire technology, will be required to drive forward routine MR-guided coronary interventions as an alternative to x-ray fluoroscopy.
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http://dx.doi.org/10.1038/s41598-019-45154-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572773PMC
June 2019

High-resolution contrast-enhanced vessel wall imaging in patients with suspected cerebral vasculitis: Prospective comparison of whole-brain 3D T1 SPACE versus 2D T1 black blood MRI at 3 Tesla.

PLoS One 2019 8;14(3):e0213514. Epub 2019 Mar 8.

Department of Neuroradiology, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany.

Purpose: Vessel wall imaging (VWI) using T1 dark blood MRI can depict inflammation of intracranial arteries in patients with cerebral vasculitis. Recently, 3D VWI sequences were introduced at 3 Tesla. We aimed to compare 2D and 3D VWI for detection of intracranial vessel wall enhancement (VWE) in patients suspected of cerebral vasculitis.

Methods: 44 MRI scans of 39 patients were assessed that included bi-planar 2D T1 and whole-brain 3D T1 SPACE dark blood VWI pre and post contrast. Visibility and VWE were analyzed in 31 pre-specified intracranial artery segments. Additionally, leptomeningeal and parenchymal contrast enhancement was assessed.

Results: Overall, more arterial segments were visualized with 3D VWI (p<0.0001). Detection of VWE showed fair agreement between 2D and 3D VWI (κ = 0.583). On segmental level, more VWE was detected in intradural ICA by 2D VWI (p<0.001) and in VA V4 segment by 3D VWI (p<0.05). 3D VWI showed more leptomeningeal (p<0.05) and parenchymal (p<0.01) contrast enhancement. In patients with positive diagnosis of cerebral vasculitis, sensitivity was of 67% (2D and 3D VWI) and specificity was 44% (2D VWI) and 48% (3D VWI); more VWE was seen in arteries distal to VA and ICA compared to non-vasculitic patients.

Conclusion: 2D and 3D VWI differed in the ability to detect VWE. Whole brain coverage with better evaluability of VAs and distal intracranial artery segments, and depiction of more parenchymal and leptomeningeal enhancement make 3D VWI more favorable. As VWE in arteries distal to VA and ICA may be used for discrimination of vasculitic and non-vasculitic patients, future increase in spatial resolution of 3D VWI sequences may be beneficial.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213514PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407784PMC
December 2019

Large animals in neurointerventional research: A systematic review on models, techniques and their application in endovascular procedures for stroke, aneurysms and vascular malformations.

J Cereb Blood Flow Metab 2019 03 7;39(3):375-394. Epub 2019 Feb 7.

5 School of Life Sciences, University of Warwick, UK.

Neuroendovascular procedures have led to breakthroughs in the treatment of ischemic stroke, intracranial aneurysms, and intracranial arteriovenous malformations. Due to these substantial successes, there is continuous development of novel and refined therapeutic approaches. Large animal models feature various conceptual advantages in translational research, which makes them appealing for the development of novel endovascular treatments. However, the availability and role of large animal models have not been systematically described so far. Based on comprehensive research in two databases, this systematic review describes current large animal models in neuroendovascular research including their primary use. It may therefore serve as a compact compendium for researchers entering the field or looking for opportunities to refine study concepts. It also describes particular applications for ischemic stroke and aneurysm therapy, as well as for the treatment of arteriovenous malformations. It focuses on most promising study designs and readout parameters, as well as on important pitfalls in endovascular translational research including ways to circumvent them.
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http://dx.doi.org/10.1177/0271678X19827446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421248PMC
March 2019

Endovascular stroke treatment's impact on malignant type of edema (ESTIMATE).

J Neurol 2019 Jan 23;266(1):223-231. Epub 2018 Nov 23.

Department of Neurology, University Hospital Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.

Background And Purpose: In patients with acute ischemic stroke and large vessel occlusion, the prognosis has improved tremendously since the implementation of endovascular thrombectomy (EVT). The effect of EVT on the incidence of malignant middle cerebral artery infarctions (MMI) has not been studied before.

Methods: ESTIMATE, a multicenter retrospective study, evaluates data of ischemic stroke patients with occlusion in the anterior circulation in the years of 2007-2015 comparing three treatment options (no therapy; IV-TPA; IV-TPA plus EVT or EVT only). Primary endpoint of the study was the incidence of MMI on follow-up imaging and mortality rates. Secondary endpoints were functional outcome, further clinical and imaging data. Logistic and Cox-regression models with a propensity score weighting approach were applied to evaluate differences between treatment groups.

Results: In 2161 patients over 9 years, EVT reduced the MMI rates significantly: patients without acute stroke treatment had increased odds for MMI of 1.57 [95% confidence interval (CI) 1.49-1.65]. In contrast, after treatment with IV-TPA, only we observed an OR of 0.88 (95% CI 0.83-0.94, p < 0.001), and after EVT an OR of 0.80 (95% CI 0.76-0.85, p < 0.001). This was more pronounced in larger pretreatment infarctions (ASPECTS < 5, p < 0.01). IV-TPA also lowers the MMI rates but not to the same extent. EVT-treated patients had increased survival rates (p < 0.05) and the best functional outcome at discharge.

Conclusions: The findings of this study illustrate that occurrence of MMI and mortality rates was significantly reduced in patients treated with EVT.
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http://dx.doi.org/10.1007/s00415-018-9127-xDOI Listing
January 2019

Improved lung recruitment and oxygenation during mandatory ventilation with a new expiratory ventilation assistance device: A controlled interventional trial in healthy pigs.

Eur J Anaesthesiol 2018 10;35(10):736-744

From the Department of Anesthesiology and Critical Care (JS, CW, MM, SS, HCS, SB, ZL, SW, HB, SS), Experimental Surgery, Centre for Experimental Models and Transgenic Service (JH) and Department of Neuroradiology (SM, SE), Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: In contrast to conventional mandatory ventilation, a new ventilation mode, expiratory ventilation assistance (EVA), linearises the expiratory tracheal pressure decline.

Objective: We hypothesised that due to a recruiting effect, linearised expiration oxygenates better than volume controlled ventilation (VCV). We compared the EVA with VCV mode with regard to gas exchange, ventilation volumes and pressures and lung aeration in a model of peri-operative mandatory ventilation in healthy pigs.

Design: Controlled interventional trial.

Setting: Animal operating facility at a university medical centre.

Animals: A total of 16 German Landrace hybrid pigs.

Intervention: The lungs of anaesthetised pigs were ventilated with the EVA mode (n=9) or VCV (control, n=7) for 5 h with positive end-expiratory pressure of 5 cmH2O and tidal volume of 8 ml kg. The respiratory rate was adjusted for a target end-tidal CO2 of 4.7 to 6 kPa.

Main Outcome Measures: Tracheal pressure, minute volume and arterial blood gases were recorded repeatedly. Computed thoracic tomography was performed to quantify the percentages of normally and poorly aerated lung tissue.

Results: Two animals in the EVA group were excluded due to unstable ventilation (n=1) or unstable FiO2 delivery (n=1). Mean tracheal pressure and PaO2 were higher in the EVA group compared with control (mean tracheal pressure: 11.6 ± 0.4 versus 9.0 ± 0.3 cmH2O, P < 0.001 and PaO2: 19.2 ± 0.7 versus 17.5 ± 0.4 kPa, P = 0.002) with comparable peak inspiratory tracheal pressure (18.3 ± 0.9 versus 18.0 ± 1.2 cmH2O, P > 0.99). Minute volume was lower in the EVA group compared with control (5.5 ± 0.2 versus 7.0 ± 1.0 l min, P = 0.02) with normoventilation in both groups (PaCO2 5.4 ± 0.3 versus 5.5 ± 0.3 kPa, P > 0.99). In the EVA group, the percentage of normally aerated lung tissue was higher (81.0 ± 3.6 versus 75.8 ± 3.0%, P = 0.017) and of poorly aerated lung tissue lower (9.5 ± 3.3 versus 15.7 ± 3.5%, P = 0.002) compared with control.

Conclusion: EVA ventilation improves lung aeration via elevated mean tracheal pressure and consequently improves arterial oxygenation at unaltered positive end-expiratory pressure (PEEP) and peak inspiratory pressure (PIP). These findings suggest the EVA mode is a new approach for protective lung ventilation.
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http://dx.doi.org/10.1097/EJA.0000000000000819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133202PMC
October 2018

Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.

Authors:
Nimitha R Mathew Francis Baumgartner Lukas Braun David O'Sullivan Simone Thomas Miguel Waterhouse Tony A Müller Kathrin Hanke Sanaz Taromi Petya Apostolova Anna L Illert Wolfgang Melchinger Sandra Duquesne Annette Schmitt-Graeff Lena Osswald Kai-Li Yan Arnim Weber Sonia Tugues Sabine Spath Dietmar Pfeifer Marie Follo Rainer Claus Michael Lübbert Christoph Rummelt Hartmut Bertz Ralph Wäsch Johanna Haag Andrea Schmidts Michael Schultheiss Dominik Bettinger Robert Thimme Evelyn Ullrich Yakup Tanriver Giang Lam Vuong Renate Arnold Philipp Hemmati Dominik Wolf Markus Ditschkowski Cordula Jilg Konrad Wilhelm Christian Leiber Sabine Gerull Jörg Halter Claudia Lengerke Thomas Pabst Thomas Schroeder Guido Kobbe Wolf Rösler Soroush Doostkam Stephan Meckel Kathleen Stabla Stephan K Metzelder Sebastian Halbach Tilman Brummer Zehan Hu Joern Dengjel Björn Hackanson Christoph Schmid Udo Holtick Christof Scheid Alexandros Spyridonidis Friedrich Stölzel Rainer Ordemann Lutz P Müller Flore Sicre-de-Fontbrune Gabriele Ihorst Jürgen Kuball Jan E Ehlert Daniel Feger Eva-Maria Wagner Jean-Yves Cahn Jacqueline Schnell Florian Kuchenbauer Donald Bunjes Ronjon Chakraverty Simon Richardson Saar Gill Nicolaus Kröger Francis Ayuk Luca Vago Fabio Ciceri Antonia M Müller Takeshi Kondo Takanori Teshima Susan Klaeger Bernhard Kuster Dennis Dong Hwan Kim Daniel Weisdorf Walter van der Velden Daniela Dörfel Wolfgang Bethge Inken Hilgendorf Andreas Hochhaus Geoffroy Andrieux Melanie Börries Hauke Busch John Magenau Pavan Reddy Myriam Labopin Joseph H Antin Andrea S Henden Geoffrey R Hill Glen A Kennedy Merav Bar Anita Sarma Donal McLornan Ghulam Mufti Betul Oran Katayoun Rezvani Omid Shah Robert S Negrin Arnon Nagler Marco Prinz Andreas Burchert Andreas Neubauer Dietrich Beelen Andreas Mackensen Nikolas von Bubnoff Wolfgang Herr Burkhard Becher Gerard Socié Michael A Caligiuri Eliana Ruggiero Chiara Bonini Georg Häcker Justus Duyster Jürgen Finke Erika Pearce Bruce R Blazar Robert Zeiser

Nat Med 2018 Apr;24(4):526

This corrects the article DOI: 10.1038/nm.4484.
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http://dx.doi.org/10.1038/nm0418-526cDOI Listing
April 2018

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.

Authors:
Nimitha R Mathew Francis Baumgartner Lukas Braun David O'Sullivan Simone Thomas Miguel Waterhouse Tony A Müller Kathrin Hanke Sanaz Taromi Petya Apostolova Anna L Illert Wolfgang Melchinger Sandra Duquesne Annette Schmitt-Graeff Lena Osswald Kai-Li Yan Arnim Weber Sonia Tugues Sabine Spath Dietmar Pfeifer Marie Follo Rainer Claus Michael Lübbert Christoph Rummelt Hartmut Bertz Ralph Wäsch Johanna Haag Andrea Schmidts Michael Schultheiss Dominik Bettinger Robert Thimme Evelyn Ullrich Yakup Tanriver Giang Lam Vuong Renate Arnold Philipp Hemmati Dominik Wolf Markus Ditschkowski Cordula Jilg Konrad Wilhelm Christian Leiber Sabine Gerull Jörg Halter Claudia Lengerke Thomas Pabst Thomas Schroeder Guido Kobbe Wolf Rösler Soroush Doostkam Stephan Meckel Kathleen Stabla Stephan K Metzelder Sebastian Halbach Tilman Brummer Zehan Hu Joern Dengjel Björn Hackanson Christoph Schmid Udo Holtick Christof Scheid Alexandros Spyridonidis Friedrich Stölzel Rainer Ordemann Lutz P Müller Flore Sicre-de-Fontbrune Gabriele Ihorst Jürgen Kuball Jan E Ehlert Daniel Feger Eva-Maria Wagner Jean-Yves Cahn Jacqueline Schnell Florian Kuchenbauer Donald Bunjes Ronjon Chakraverty Simon Richardson Saar Gill Nicolaus Kröger Francis Ayuk Luca Vago Fabio Ciceri Antonia M Müller Takeshi Kondo Takanori Teshima Susan Klaeger Bernhard Kuster Dennis Dong Hwan Kim Daniel Weisdorf Walter van der Velden Daniela Dörfel Wolfgang Bethge Inken Hilgendorf Andreas Hochhaus Geoffroy Andrieux Melanie Börries Hauke Busch John Magenau Pavan Reddy Myriam Labopin Joseph H Antin Andrea S Henden Geoffrey R Hill Glen A Kennedy Merav Bar Anita Sarma Donal McLornan Ghulam Mufti Betul Oran Katayoun Rezvani Omid Shah Robert S Negrin Arnon Nagler Marco Prinz Andreas Burchert Andreas Neubauer Dietrich Beelen Andreas Mackensen Nikolas von Bubnoff Wolfgang Herr Burkhard Becher Gerard Socié Michael A Caligiuri Eliana Ruggiero Chiara Bonini Georg Häcker Justus Duyster Jürgen Finke Erika Pearce Bruce R Blazar Robert Zeiser

Nat Med 2018 03 12;24(3):282-291. Epub 2018 Feb 12.

Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD leukemia cells. This synergized with the allogeneic CD8 T cell response, leading to long-term survival in six mouse models of FLT3-ITD AML. Sorafenib-related IL-15 production caused an increase in CD8CD107aIFN-γ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8 T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.
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http://dx.doi.org/10.1038/nm.4484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029618PMC
March 2018

Involution von Cherubismus im MRT unter Therapie mit Imatinib.

Rofo 2017 Jul 26;189(7):675-677. Epub 2017 Apr 26.

Dept. of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

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http://dx.doi.org/10.1055/s-0043-105074DOI Listing
July 2017

Acute Cerebral Venous Thrombosis: Three-Dimensional Visualization and Quantification of Hemodynamic Alterations Using 4-Dimensional Flow Magnetic Resonance Imaging.

Stroke 2017 03 8;48(3):671-677. Epub 2017 Feb 8.

From the Department of Neurology (F.S., L.S., T.W., A. Harloff) and Department of Neuroradiology (S.M.), University Medical Centre, Freiburg, Germany; Fraunhofer MEVIS, Bremen, Germany (A. Hennemuth); and Department of Radiology, Feinberg School of Medicine (M.M.) and Department of Biomedical Engineering, McCormick School of Engineering (M.M.), Northwestern University, Chicago, IL.

Background And Purpose: Cerebral venous thrombosis (CVT) affects venous hemodynamics and can provoke severe stroke and chronic intracranial hypertension. We sought to comprehensively analyze 3-dimensional blood flow and hemodynamic alterations during acute CVT including collateral recruitment and at follow-up.

Methods: Twenty-two consecutive patients with acute CVT were prospectively included and underwent routine brain magnetic resonance imaging (MRI) and 4-dimensional flow MRI at 3 T for the in vivo assessment of cerebral blood flow. Neurological and MRI follow-up at 6 months was performed in 18 patients.

Results: Three-dimensional blood flow visualization and quantification of large dural venous sinuses and deep cerebral veins was successfully performed in all patients. During acute CVT, we observed abnormal flow patterns including stagnant flow, flow acceleration in stenoses, and change of flow directions. In patients with complete recanalization, flow trajectories resembled those known from previously published 4-dimensional flow MRI data in healthy adults. There was a trend toward a relationship between occluded segments and cerebral lesions (not significant). Furthermore, patients with versus without cerebral lesions showed increased mean (0.08±0.09 versus 0.005±0.014 m/s) and peak velocities (0.18±0.21 versus 0.006±0.02 m/s) within partially thrombosed left and right transverse sinuses (<0.05) at baseline.

Conclusions: Four-dimensional flow MRI was successfully applied for the 3-dimensional visualization and quantification of venous hemodynamics in patients with CVT and provided new dynamic information regarding vessel recanalization. This technique seems promising to investigate the contribution of hemodynamic parameters and collaterals in a larger cohort to identify those at risk of stroke.
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http://dx.doi.org/10.1161/STROKEAHA.116.015102DOI Listing
March 2017

Radiologic-Histopathologic Correlation of Cerebral Microbleeds Using Pre-Mortem and Post-Mortem MRI.

PLoS One 2016 9;11(12):e0167743. Epub 2016 Dec 9.

Medical School of the University of Geneva, Geneva, Switzerland.

Introduction: Cerebral microbleeds (CMB), also known as cerebral microhemorrhages, are small areas of susceptibility on brain magnetic resonance imaging (MRI), that are increasingly detected due to the higher availability of high-field MRI systems and dedicated pulse sequences. The prevalence of CMBs increases in cases with cognitive decline. The current investigation assessed the poorly investigated radiologic-histopathologic correlation of CMBs on MRI.

Methods: The local ethical committee approved the current investigation. We retrospectively assessed a consecutive series of 1303 autopsy cases hospitalized in Geneva University Hospitals between 2000-2014. Of 112 cases with pre-mortem T2* sequences, we included 25 cases (mean age 77.3 ± 9.6, 9 females) with at least one CMB. We compared pre-mortem CMBs with targeted histopathology and post-mortem MRI.

Results: 25 cases had 31 CMB lesions detected by pre-mortem MRI. 25 additional CMB were detected on histopathology. 4 CMBs on pre-mortem MRI were false positives, resulting in a total of 52 CMBs. 27 CMBs on pre-mortem MRI were confirmed on histopathology, corresponding to a sensitivity or true positive rate of 51.9% (95% CI 37.6-66.0%). The false negative rate of pre-mortem MRI was 48.1% (95% CI 34.0-62.4%). Post-mortem MRI showed only 3 cases with additional CMBs. Overall, pre-mortem MRI significantly underestimated CMBs (p = 0.0001).

Conclusions: Routine clinical brain MRI underestimates the prevalence of CMBs by approximately 50%, and 12% of radiologic pre-mortem MRI CMBs were false positives. Post-mortem MRI confirmed that this discordance is not explained by microbleeds occurring after the pre-mortem MRI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167743PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147972PMC
July 2017