Abnormal Blood Flow on Transcranial Duplex Sonography Predicts Poor Outcome After Stroke Thrombectomy.

Background and Purpose- Hemodynamic changes following mechanical thrombectomy for large vessel occlusion stroke could be associated with complications and might affect prognosis. We investigated postinterventional middle cerebral artery blood flow on transcranial duplex sonography (TCD) and its prognostic value for anterior large vessel occlusion stroke patients. Methods- We identified all ischemic stroke patients who had undergone mechanical thrombectomy for anterior circulation large vessel occlusion from 2010 onwards. Postinterventional middle cerebral artery flow was graded according to the sonographic Thrombolysis in Brain Ischemia score and related to patient outcome stratified by the angiographic Thrombolysis in Cerebral Infarction reperfusion status. Results- Of 215 large vessel occlusion stroke patients, 193 patients (90%) showed successful angiographic recanalization (Thrombolysis in Cerebral Infarction grade 2b-3). Of those, 69 (36%) patients had abnormal sonographic middle cerebral artery blood flow (Thrombolysis in Brain Ischemia grade 0-4) within 72 hours after mechanical thrombectomy, which was an independent predictor for poor 90-day outcome. Conclusions- TCD indicates abnormal middle cerebral artery hemodynamics in a substantial proportion of patients with angiographically defined successful mechanical thrombectomy of the anterior cerebral circulation. Such changes are associated with poor short-term outcome.

Improved cerebral vasoreactivity following percutaneous transluminal angioplasty with stenting of high-grade internal carotid artery stenosis.

BACKGROUND: The aim of this study was to assess the effects of percutaneous transluminal angioplasty with stenting on cerebral vasoreactivity in carotid stenosis (CS). METHODS: We studied the changes in the middle cerebral artery using transcranial Doppler and the breath-holding index (BHI) after hypercapnia in 33 patients with CS (15 symptomatic, 18 asymptomatic) before and 1 day and 1 month after stenting. RESULTS: One day after stenting, the BHI significantly increased (p < 0.01) on the previously stenotic side in all patients. One month after stenting, the BHI was significantly higher on the contralateral side of asymptomatic (p < 0.05) and symptomatic patients (p < 0.01). CONCLUSION: Percutaneous transluminal angioplasty with stenting results in increasing improvement close to normalization of impaired cerebral vasoreactivity in patients with symptomatic and asymptomatic high-grade CS.

Increased middle cerebral artery mean blood flow velocity index after stroke thrombectomy indicates increased risk for intracranial hemorrhage.

BACKGROUND AND PURPOSE: Cerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH. METHODS: We retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b-3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome. RESULTS: 123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome. CONCLUSIONS: A high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis.

Rapid large-scale expansion of functional mesenchymal stem cells from unmanipulated bone marrow without animal serum.

Adult mesenchymal stem cells (MSCs) are considered as valuable mediators for tissue regeneration and cellular therapy. This study was performed to develop conditions for regularly propagating a clinical quantity of > 2 x 10(8) MSCs without animal serum from small bone marrow (BM) aspiration volumes within short time. We established optimized culture conditions with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) for MSC propagation. MSC quality, identity, purity, and function were assessed accordingly. Biologic safety was determined by bacterial/fungal/mycoplasma/endotoxin testing and genomic stability by array comparative genomic hybridization (CGH). We demonstrate that unmanipulated BM can be used to efficiently initiate MSC cultures without the need for cell separation. Just diluting 1.5-5 mL heparinized BM per 500 mL minimum essential medium supplemented with L-glutamine, heparin, and 10% pHPL sufficiently supported the safe propagation of 7.8 +/- 1.5 x 10(8) MSCs within a single 11- to 16-day primary culture under defined conditions. This procedure also resulted in sustained MSC colony recovery. MSC purity, immune phenotype, and in vitro differentiation potential fully matched current criteria. Despite high proliferation rate, MSCs showed genomic stability in array CGH. This easy single-phase culture procedure can build the basis for standardized manufacturing of MSC-based therapeutics under animal serum-free conditions for dose-escalated cellular therapy and tissue engineering.

Blood monocytes mimic endothelial progenitor cells.

The generation of endothelial progenitor cells (EPCs) from blood monocytes has been propagated as a novel approach in the diagnosis and treatment of cardiovascular diseases. Low-density lipoprotein (LDL) uptake and lectin binding together with endothelial marker expression are commonly used to define these EPCs. Considerable controversy exists regarding their nature, in particular, because myelomonocytic cells share several properties with endothelial cells (ECs). This study was performed to elucidate whether the commonly used endothelial marker determination is sufficient to distinguish supposed EPCs from monocytes. We measured endothelial, hematopoietic, and progenitor cell marker expression of monocytes before and after angiogenic culture by fluorescence microscopy, flow cytometry, and real-time reverse transcription-polymerase chain reaction. The function of primary monocytes and monocyte-derived supposed EPCs was investigated during vascular network formation and EC colony-forming unit (CFU-EC) development. Monocytes cultured for 4 to 6 days under angiogenic conditions lost CD14/CD45 and displayed a commonly accepted EPC phenotype, including LDL uptake and lectin binding, CD31/CD105/CD144 reactivity, and formation of cord-like structures. Strikingly, primary monocytes already expressed most tested endothelial genes and proteins at even higher levels than their supposed EPC progeny. Neither fresh nor cultured monocytes formed vascular networks, but CFU-EC formation was strictly dependent on monocyte presence. LDL uptake, lectin binding, and CD31/CD105/CD144 expression are inherent features of monocytes, making them phenotypically indistinguishable from putative EPCs. Consequently, monocytes and their progeny can phenotypically mimic EPCs in various experimental models.