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1.
Metallomics ; 15(8)2023 08 01.
Article in English | MEDLINE | ID: mdl-37336558

ABSTRACT

Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity. In the current study, we employed genome-wide functional screening to help understand biological effects of exposure to Yb(III) and Lu(III), which were selected as representatives of the late lanthanides. As a model organism, we used Saccharomyces cerevisiae, since it shares many biological functions with humans. Analysis of the functional screening results indicated toxicity of late lanthanides is consistent with disruption of vesicle-mediated transport, and further supported a role for calcium transport processes and mitophagy in mitigating toxicity. Unexpectedly, our analysis suggested that late lanthanides target proteins with SH3 domains, which may underlie the observed toxicity. This study provides fundamental insights into the unique biological chemistry of late lanthanides, which may help devise new avenues toward the development of decorporation strategies and bio-inspired separation processes.


Subject(s)
Lanthanoid Series Elements , Saccharomyces cerevisiae , Humans , Lanthanoid Series Elements/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism
2.
Eur Stroke J ; 7(4): 376-383, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36478752

ABSTRACT

Background and purpose: First pass effect (FPE), the occurrence of complete reperfusion after one pass with no rescue attempt during endovascular therapy (EVT), is associated with the best clinical outcome after an acute ischemic stroke (AIS). Previous studies evaluating FPE occurrence according to EVT technical strategies, occlusion locations, or thrombus composition have provided controversial results. Here, we performed a correlation analysis between FPE occurrence and AIS thrombus cellular composition, as assessed using quantitative biochemical assays. Patients and methods: Homogenates of AIS thrombi from 250 patients were prepared by mechanical grinding. Platelet, red blood cell (RBC), and leukocyte contents of AIS thrombi were respectively estimated by quantification of GP (glycoprotein) VI, heme, and DNA in thrombus homogenates. FPE was defined as a modified Thrombolysis in Cerebral Infraction (mTICI) score of 2C or 3 after a single EVT device pass. Results: AIS thrombi successfully removed after a single pass were poorer in GPVI (0.098 ± 0.023 vs 0.111 ± 0.024 ng/mg, p < 0.001) compared to those whose removal had required several passes. GPVI content was also significantly associated with a higher number of device passes and a longer procedure time. No such significant correlation was found with DNA and heme content. Discussion and conclusion: Thrombus platelet content may hamper thrombus removal by EVT. This result suggests that adjunctive therapies or functionalization of retrieval devices targeting platelets may improve EVT efficacy.

3.
ACS Omega ; 7(38): 34412-34419, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36188298

ABSTRACT

Lanthanides are a series of elements essential to a wide range of applications, from clean energy production to healthcare. Despite their presence in multiple products and technologies, their toxicological characteristics have been only partly studied. Recently, our group has employed a genomic approach to extensively characterize the toxicity mechanisms of lanthanides. Even though we identified substantially different behaviors for mid and late lanthanides, the toxicological profiles of early lanthanides remained elusive. Here, we overcome this gap by describing a multidimensional genome-wide toxicogenomic study for two early lanthanides, namely, lanthanum and praseodymium. We used Saccharomyces cerevisiae as a model system since its genome shares many biological pathways with humans. By performing functional analysis and protein-protein interaction network analysis, we identified the main genes and proteins that participate in the yeast response to counter metal harmful effects. Moreover, our analysis also highlighted key enzymes that are dysregulated by early lanthanides, inducing cytotoxicity. Several of these genes and proteins have human orthologues, indicating that they may also participate in the human response against the metals. By highlighting the key genes and proteins in lanthanide-induced toxicity, this work may contribute to the development of new prophylactic and therapeutic strategies against lanthanide harmful exposures.

4.
Mol Omics ; 18(3): 237-248, 2022 03 28.
Article in English | MEDLINE | ID: mdl-35040455

ABSTRACT

Gadolinium is a metal used in contrast agents for magnetic resonance imaging. Although gadolinium is widely used in clinical settings, many concerns regarding its toxicity and bioaccumulation after gadolinium-based contrast agent administration have been raised and published over the last decade. To date, most toxicological studies have focused on identifying acute effects following gadolinium exposure, rather than investigating associated toxicity mechanisms. In this study, we employ functional toxicogenomics to assess mechanistic interactions of gadolinium with Saccharomyces cerevisiae. Furthermore, we determine which mechanisms are conserved in humans, and their implications for diseases related to the use of gadolinium-based contrast agents in medicine. A homozygous deletion pool of 4291 strains were screened to identify biological functions and pathways disturbed by the metal. Gene ontology and pathway enrichment analyses showed endocytosis and vesicle-mediated transport as the main yeast response to gadolinium, while certain metabolic processes, such as glycosylation, were the primary disrupted functions after the metal treatments. Cluster and protein-protein interaction network analyses identified proteins mediating vesicle-mediated transport through the Golgi apparatus and the vacuole, and vesicle cargo exocytosis as key components to reduce the metal toxicity. Moreover, the metal seemed to induce cytotoxicity by disrupting the function of enzymes (e.g. transferases and proteases) and chaperones involved in metabolic processes. Several of the genes and proteins associated with gadolinium toxicity are conserved in humans, suggesting that they may participate in pathologies linked to gadolinium-based contrast agent exposures. We thereby discuss the potential role of these conserved genes and gene products in gadolinium-induced nephrogenic systemic fibrosis, and propose potential prophylactic strategies to prevent its adverse health effects.


Subject(s)
Contrast Media , Gadolinium , Contrast Media/toxicity , Gadolinium/toxicity , Homozygote , Humans , Magnetic Resonance Imaging/adverse effects , Magnetic Resonance Imaging/methods , Saccharomyces cerevisiae/genetics , Sequence Deletion , Toxicogenetics
5.
Platelets ; 33(2): 285-290, 2022 Feb 17.
Article in English | MEDLINE | ID: mdl-33840346

ABSTRACT

Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro, the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization (p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.


Subject(s)
Abciximab/therapeutic use , Administration, Intravenous/methods , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Platelet Aggregation Inhibitors/therapeutic use , Thrombectomy/methods , Abciximab/pharmacology , Acute Disease , Aged , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacology
6.
J Neurointerv Surg ; 14(10): 957-961, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34611032

ABSTRACT

BACKGROUND: The concept of intra-aneurysmal flow disruption has emerged as a new paradigm for the treatment of primarily bifurcation aneurysms. The purpose of this study was to determine the clinical and angiographic outcomes of patients treated with the new ARTISSE intrasaccular device (ISD). METHODS: Selected patients with bifurcation aneurysms that matched the indications of the ARTISSE ISD defined by the manufacturer were treated in a single center. Clinical and angiographic follow-up was conducted at 6 and 36 months. Aneurysm occlusion was assessed using the Raymond-Roy classification scale. RESULTS: Nine subjects with nine unruptured bifurcation aneurysms were enrolled. Mean aneurysm size was 7.2±1.2 mm (range 5.5-9.7 mm). An adequate aneurysm occlusion (defined as a complete occlusion or a neck remnant) was achieved in 6/9 patients (66.7%) at 6 months and 4/7 patients (57.1%) at 36 months follow-up. Two of the nine subjects experienced a major stroke (22.2%), including one on postoperative day 1 due to a procedure-related parent vessel occlusion and subsequent ischemic stroke. The other major stroke occurred within the 36-month follow-up period during treatment of a separate aneurysm with coils, leading to perforation with hemorrhagic stroke causing a permanent neurological deficit. CONCLUSION: The ARTISSE ISD was successfully deployed in all nine cases. There were, however, several procedure-related complications and results in terms of angiographic aneurysm occlusion were modest.


Subject(s)
Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Stroke , Cerebral Angiography/methods , Embolization, Therapeutic/methods , Endovascular Procedures/methods , Follow-Up Studies , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Stroke/therapy , Treatment Outcome
7.
Metallomics ; 13(12)2021 12 06.
Article in English | MEDLINE | ID: mdl-34694395

ABSTRACT

Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans. By using a multidimensional approach and functional and network analyses, we have identified a group of genes and proteins associated with the yeast responses to ameliorate metal toxicity, which include metal discharge paths through vesicle-mediated transport, paths to regulate biologically relevant cations, and processes to reduce metal-induced stress. Furthermore, the analyses indicated that europium promotes yeast toxicity by disrupting the function of chaperones and cochaperones, which have metal-binding sites. Several of the genes and proteins highlighted in our study have human orthologues, suggesting they may participate in europium-induced toxicity in humans. By identifying the endogenous targets of europium as well as the already existing paths that can decrease its toxicity, we can determine specific genes and proteins that may help to develop future therapeutic strategies.


Subject(s)
Europium/toxicity , Genome, Fungal , Saccharomyces cerevisiae/drug effects , Europium/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Toxicogenetics
8.
Stroke ; 52(9): 2964-2967, 2021 08.
Article in English | MEDLINE | ID: mdl-34134507

ABSTRACT

BACKGROUND AND PURPOSE: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency. METHODS: We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Patients were included if they had middle cerebral artery occlusions. Primary outcome was favorable FO, defined by a modified Rankin Scale scores between 0 and 2 at 3 months. RESULTS: One hundred forty-eight patients with middle cerebral artery occlusion were included. In patients with no PComA, an increase in minimum mean arterial pressure was positively associated with favorable FO (odds ratio per 10 mm Hg increase, 1.59 [95%CI, 1.11-2.25]; P=0.010), whereas no association was found in patients with a PComA (odds ratio, 0.77 [95% CI, 0.54-1.08]; P=0.12). Patients with no PComA and longer cumulative time with mean arterial pressure <90 mm Hg or systolic blood pressure <140 mm Hg had significantly lower rates of favorable FO, with an odds ratio per 10-minute increase of 0.75 (95% CI, 0.59-0.94; P=0.010) and 0.74 (95% CI, 0.60-0.91; P=0.003), but not in patients with a PComA. CONCLUSIONS: Hypotension during endovascular therapy for middle cerebral artery occlusion is consistently associated with worse FO in patients with no PComA but not in those with a PComA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02523261.


Subject(s)
Brain Ischemia/surgery , Hypotension/surgery , Ischemic Stroke/surgery , Stroke/surgery , Thrombectomy , Blood Pressure/physiology , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Humans , Thrombectomy/adverse effects , Treatment Outcome
9.
Proc Natl Acad Sci U S A ; 118(18)2021 05 04.
Article in English | MEDLINE | ID: mdl-33903247

ABSTRACT

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group. In the current study, we assessed potential toxicity mechanisms in the lanthanide series using a functional toxicogenomics approach in baker's yeast, which shares many cellular pathways and functions with humans. We screened the homozygous deletion pool of 4,291 Saccharomyces cerevisiae strains with the lanthanides and identified both common and unique functional effects of these metals. Three very different trends were observed within the lanthanide series, where deletions of certain proteins on membranes and organelles had no effect on the cellular response to early lanthanides while inducing yeast sensitivity and resistance to middle and late lanthanides, respectively. Vesicle-mediated transport (primarily endocytosis) was highlighted by both gene ontology and pathway enrichment analyses as one of the main functions disturbed by the majority of the metals. Protein-protein network analysis indicated that yeast response to lanthanides relied on proteins that participate in regulatory paths used for calcium (and other biologically relevant cations), and lanthanide toxicity included disruption of biosynthetic pathways by enzyme inhibition. Last, multiple genes and proteins identified in the network analysis have human orthologs, suggesting that those may also be targeted by lanthanides in humans.


Subject(s)
Endocytosis/drug effects , Lanthanoid Series Elements/toxicity , Saccharomyces cerevisiae/drug effects , Toxicological Phenomena/genetics , Biosynthetic Pathways/drug effects , Genome, Fungal/drug effects , Humans , Lanthanoid Series Elements/pharmacology , Saccharomyces cerevisiae/genetics , Toxicogenetics/trends
10.
Lancet Neurol ; 20(4): 265-274, 2021 04.
Article in English | MEDLINE | ID: mdl-33647246

ABSTRACT

BACKGROUND: High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. METHODS: We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites. FINDINGS: Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. INTERPRETATION: An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. FUNDING: French Health Ministry.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Cerebral Hemorrhage/prevention & control , Endovascular Procedures/methods , Ischemic Stroke/therapy , Aged , Aged, 80 and over , Cerebral Hemorrhage/etiology , Female , Humans , Hypertension/complications , Hypertension/prevention & control , Ischemic Stroke/complications , Male , Middle Aged
12.
J Neurointerv Surg ; 13(9): 809-815, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33077577

ABSTRACT

BACKGROUND: Endovascular therapy (EVT) for acute ischemic stroke (AIS) can be challenging in older patients with supra-aortic tortuosity. Rescue carotid puncture (RCP) can be an alternative in case of supra-aortic catheterization failure by femoral access, but data regarding RCP are scarce. We sought to investigate the feasibility, effectiveness and safety of RCP for AIS treated by EVT. METHODS: Patients treated by EVT with RCP were included from January 2012 to December 2019 in the Endovascular Treatment in Ischemic Stroke (ETIS) multicentric registry. Main outcomes included reperfusion rates ( ≥ TICI2B), 3 month functional outcome (modified Rankin Scale) and 3 month mortality. We also performed an additional systematic review of the literature according to the PRISMA checklist to summarize previous studies on RCP. RESULTS: 25 patients treated by EVT with RCP were included from the ETIS registry. RCP mainly concerned elderly patients (median age 85 years, range 73-92) with supra-aortic tortuosity (n=16 (64%)). Intravenous thrombolysis (IVT) was used for nine patients (36%). Successful reperfusion was achieved in 64%, 87.5% of patients were dependent at 3 months, and 3 month mortality was 45.8%. The systematic review yielded comparable results. In pooled individual data, there was a shift toward better functional outcome in patients with successful reperfusion (median (IQR) 4 (2-6) vs 6 (4-6), p=0.011). CONCLUSION: RCP mainly concerned elderly patients admitted for AIS with anterior LVO with supra-aortic tortuosity. The procedure seemed feasible, notably for patients treated with IVT, and led to significant reperfusion rates at the end of procedure, but with pronounced unfavorable outcomes at 3 months. RCP should be performed under general anesthesia to avoid life-threatening complications and ensure airways safety. Finally, RCP led to low rates of closure complications, emphasizing that this concern should not withhold RCP, if indicated.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Aged , Aged, 80 and over , Brain Ischemia/diagnostic imaging , Brain Ischemia/therapy , Humans , Punctures , Stroke/diagnostic imaging , Stroke/therapy , Thrombectomy , Thrombolytic Therapy , Treatment Outcome
13.
Front Neurol ; 12: 815814, 2021.
Article in English | MEDLINE | ID: mdl-35153990

ABSTRACT

More than 40% of endovascular therapy (EVT) fail to achieve complete reperfusion of the territory of the occluded artery in patients with acute ischemic stroke (AIS). Understanding factors influencing EVT could help overcome its limitations. Our objective was to study the impact of thrombus cell composition on EVT procedures, using a simulation system for modeling thrombus-induced large vessel occlusion (LVO) in flow conditions. In an open comparative trial, we analyzed the behavior of size-standardized platelet-rich and red blood cells (RBC)-rich thrombi during simulated stent retriever-mediated EVT procedures. Sixteen simulated EVT procedures were performed (8 RBC- vs. 8 platelet-rich thrombi). Platelet-rich thrombi were associated with a higher number of stent retriever passes (p = 0.03) and a longer procedure duration (p = 0.02) compared to RBC-rich thrombi. Conversely, RBC-rich thrombi released more embolic fragments than platelet-rich thrombi (p = 0.004). Both RBC-rich and platelet-rich thrombi underwent drastic compaction after being injected into the in vitro circulation model, and histologic analyses showed that these EVT-retrieved thrombi displayed features comparable to those previously observed in thrombi from patients with AIS patients having LVO, including a marked structural dichotomy between RBC- and platelet-rich areas. Our results show that the injection of in vitro-produced thrombi in artificial cerebrovascular arterial networks is suitable for testing recanalization efficacy and the risk of embolization of EVT devices and strategies in association with thrombus cell composition.

15.
J Stroke Cerebrovasc Dis ; 30(2): 105521, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33310073

ABSTRACT

INTRODUCTION: Guidelines for antiplatelet therapy administration, during emergent stenting for extra-cranial internal carotid artery (EC-ICA) occlusion in the setting of acute ischemic stroke (AIS) are lacking. Different antiplatelet regimen are used in association to endovascular therapy (EVT) for the treatment of EC-ICA lesions. We aimed to compare the clinical and radiological effects of three intravenous antiplatelet agents used during emergent EC-ICA stenting. MATERIAL AND METHODS: Clinical data were collected from January 2015 to December 2019 in a monocentric prospective registry of AIS patients treated by EVT. All patients who underwent emergent EC-ICA stenting were sorted regarding the intravenous antiplatelet agent used during the procedure. RESULTS: Among 218 patients treated by EVT for an EC-ICA occlusion of the anterior circulation during the study period, 70 underwent an emergent stenting of the EC-ICA. 60 were included in the present study, 9 received intravenous (IV) Cangrelor, 8 IV abciximab and 43 Aspirin. The rate of favorable neurological outcome, defined as modified Rankin Scale (mRS) ≤ 2 at three months were better in the Cangrelor and Aspirin groups (66,7% and 58,1%, respectively) than in the Abciximab group (37,5%), as well as, the rate of any intracranial ICH (22,2% and 37,2% vs 62,5%). The rate of acute stent reocclusion was similar between groups. CONCLUSION: When used as a rescue treatment during emergent stenting of EC-ICA, Cangrelor and Aspirin present a better safety profile than Abciximab, with less intracranial hemorrhages and a higher rate of good clinical outcome. Additional studies are needed to confirm these findings.


Subject(s)
Carotid Artery, Internal , Carotid Stenosis/therapy , Endovascular Procedures/instrumentation , Ischemic Stroke/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Stents , Abciximab/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Administration, Intravenous , Aged , Aspirin/administration & dosage , Carotid Artery, Internal/diagnostic imaging , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Drug Administration Schedule , Emergencies , Endovascular Procedures/adverse effects , Female , Humans , Ischemic Stroke/complications , Ischemic Stroke/diagnostic imaging , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Registries , Retrospective Studies , Time Factors , Treatment Outcome
16.
Front Neurol ; 11: 573382, 2020.
Article in English | MEDLINE | ID: mdl-33193021

ABSTRACT

Background and Purpose: Optimal blood pressure (BP) targets after endovascular therapy (EVT) for acute ischemic stroke (AIS) still need to be assessed, especially according to the recanalization status. Facing the lack of randomized controlled trials addressing this question, we performed a systematic review of studies assessing the post-EVT BP impact on functional outcome and symptomatic intracranial hemorrhage (sICH). Methods: Studies published after January 1, 2012 were included in the systematic review. The PRISMA checklist and flow diagram were followed for the design and reporting of this work. Results: Five studies were included in the present analysis. Despite a significant heterogeneity among studies which precluded a meta-analysis, systolic BP (SBP) was the most frequently used parameter to describe BP. BP variability (standard deviation, successive variability) after EVT was associated with worse functional outcome, especially in studies without specific BP targets after successful EVT. Lower BP values after successful EVT were associated with lower odds of sICH. Four studies evaluated the post-EVT BP impact on recanalized patients solely, with only one specifically addressing the impact of a TICI 2B vs. 2C. Interestingly, SBP reduction was inversely associated with worse outcomes in TICI 3 patients but not in TICI 2B patients, pointing to the potential value of BP management according to the exact TICI. Conclusions: BP post-EVT seems to be associated with worse functional outcomes and sICH. However, given the important heterogeneity depicted among the included studies, no decisive conclusion can be made from this systematic review, thus underlying the urgent need of randomized controlled trials evaluating this question.

17.
J Stroke Cerebrovasc Dis ; 29(10): 105052, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32912529

ABSTRACT

BACKROUND AND PURPOSE: Role of peri-procedural heparin as an adjuvant treatment during mechanical thrombectomy (MT) for patients contra-indicated for alteplase remains a source of debate. METHODS: We included patients from the multicenter French register ETIS that underwent MT without administration of alteplase, and compared patients who received heparin during MT with patients who did not. Heparin impact on outcome were analyzed regarding final TICI score, NIHSS at day one, modified rankin scale (mRS) and intracranial hemorrhagic transformation on imaging at day one. RESULTS: Over 1031 patients, 751 were included between January 2015 and June 2018 in 6 different centers, and 223 (26.69%) received heparin. Heparin administration was associated with a significant deleterious effect on NIHSS at 24h [adjusted OR = 1.2; p = 0.02], mRS at 3 months [adjusted OR 1.58; p = 0.03], and on complete reperfusion [TICI 3 adjusted OR 0.68; p = 0.02]. Heparin administration was associated with a significant reduction of hemorrhagic transformation [adjusted OR 0.48; p = 0.00005]. CONCLUSIONS: Heparin administration during MT seems deleterious for reperfusion and functional outcome. Randomized trials are needed to identify the role of antithrombotic treatments, such as heparin, in the setting of acute ischemic stroke management.


Subject(s)
Anticoagulants/adverse effects , Brain Ischemia/therapy , Contraindications, Drug , Fibrinolytic Agents/adverse effects , Heparin/administration & dosage , Stroke/therapy , Thrombectomy , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Brain Ischemia/diagnosis , Female , France , Heparin/adverse effects , Humans , Male , Middle Aged , Registries , Retrospective Studies , Risk Factors , Stroke/diagnosis , Thrombectomy/adverse effects , Time Factors , Treatment Outcome
18.
Stroke ; 51(11): 3366-3370, 2020 11.
Article in English | MEDLINE | ID: mdl-32813602

ABSTRACT

BACKGROUND AND PURPOSE: Reports are emerging regarding the association of acute ischemic strokes with large vessel occlusion and coronavirus disease 2019 (COVID-19). While a higher severity of these patients could be expected from the addition of both respiratory and neurological injury, COVID-19 patients with strokes can present with mild or none respiratory symptoms. We aimed to compare anterior circulation large vessel occlusion strokes severity between patients with and without COVID-19. METHODS: We performed a comparative cohort study between patients with COVID-19 who had anterior circulation large vessel occlusion and early brain imaging within 3 hours from onset, in our institution during the 6 first weeks of the COVID-19 outbreak and a control group admitted during the same calendar period in 2019. RESULTS: Twelve COVID-19 patients with anterior circulation large vessel occlusion and early brain imaging were included during the study period and compared with 34 control patients with anterior circulation large vessel occlusion and early brain imaging in 2019. Patients in the COVID-19 group were younger (P=0.032) and had a history of diabetes mellitus more frequently (P=0.039). Patients did not significantly differ on initial National Institutes of Health Stroke Scale nor time from onset to imaging (P=0.18 and P=0.6, respectively). Patients with COVID-19 had more severe strokes than patients without COVID-19, with a significantly lower clot burden score (median: 6.5 versus 8, P=0.016), higher rate of multivessel occlusion (50% versus 8.8%, P=0.005), lower DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores; median: 5 versus 8, P=0.006), and higher infarct core volume (median: 58 versus 6 mL, P=0.004). Successful recanalization rate was similar in both groups (P=0.767). In-hospital mortality was higher in the COVID-19 patients' group (41.7% versus 11.8%, P=0.025). CONCLUSIONS: Early brain imaging showed higher severity large vessel occlusion strokes in patients with COVID-19. Given the massive number of infected patients, concerns should be raised about the coming neurovascular impact of the pandemic worldwide.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/diagnostic imaging , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Case-Control Studies , Cerebral Angiography , Computed Tomography Angiography , Diffusion Magnetic Resonance Imaging , Female , Hospital Mortality , Humans , Infarction, Anterior Cerebral Artery/complications , Infarction, Anterior Cerebral Artery/diagnostic imaging , Infarction, Anterior Cerebral Artery/physiopathology , Infarction, Anterior Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/therapy , Infarction, Posterior Cerebral Artery/complications , Infarction, Posterior Cerebral Artery/diagnostic imaging , Infarction, Posterior Cerebral Artery/physiopathology , Infarction, Posterior Cerebral Artery/therapy , Magnetic Resonance Angiography , Male , Middle Aged , Pandemics , SARS-CoV-2 , Severity of Illness Index , Stroke/complications , Stroke/physiopathology , Stroke/therapy , Thrombectomy , Thrombolytic Therapy
19.
Expert Rev Med Devices ; 17(7): 697-706, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32552093

ABSTRACT

INTRODUCTION: Acute ischemic stroke (AIS) secondary to the occlusion of a large intracranial vessel (LVO) is a recognized public health problem. Mechanical thrombectomy (MT) has gained full acceptance: Class A, Level 1 in 2015 after the publication of numerous trials. Further meta-analyses have scrutinized extensively those results and international recommendations and guidelines have been given. Nevertheless, multiple-specific points remain to be clarified and are or will be under investigations. AREAS COVERED: This review of the most recent literature (mostly publications after 2015) will cover the actual common practice for MT, especially focusing on the devices available (and their validation), how they are commonly used, relate the most relevant results, and detail some emerging technologies. EXPERT OPINION: The authors will express their own view on the current practice and emphasize on the areas where questions remain and hypothesize what specific improvements are necessary and prone to occur.


Subject(s)
Thrombectomy/instrumentation , Thrombectomy/trends , Brain Ischemia/complications , Brain Ischemia/surgery , Catheters , Humans , Stents , Stroke/complications , Stroke/surgery , Treatment Outcome
20.
J Neurointerv Surg ; 12(11): 1099-1106, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32532857

ABSTRACT

Mechanical thrombectomy is now the standard of care for acute ischemic stroke patients with large vessel occlusions, and can be performed with several devices and techniques. One of these techniques, direct aspiration (DA), consists of navigating a large-bore catheter up to the face of the clot and initiating forceful suction. This comprehensive review has three objectives: (1) to describe the direct aspiration technique; (2) to present the available evidence regarding predictive factors of DA success and performance compared with other techniques; and (3) to discuss the forthcoming improvements in distal aspiration.


Subject(s)
Brain Ischemia/surgery , Ischemic Stroke/surgery , Thrombectomy/methods , Brain Ischemia/diagnostic imaging , Catheters , Female , Humans , Ischemic Stroke/diagnostic imaging , Male , Suction/methods , Thrombosis/diagnostic imaging , Thrombosis/surgery , Treatment Outcome
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