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1.
J Pediatr Hematol Oncol ; 46(5): 272-274, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857164

RESUMO

APML, a subtype of acute myeloid leukemia, is highly curable, with cure rates over 90%. Despite its therapeutic success, APML poses elevated bleeding risks due to frequent prior disseminated intravascular coagulation. Less commonly recognized but critical is the thrombotic risk. We document a unique pediatric case: a 13-year-old with trisomy 21 diagnosed with APML had an asymptomatic aortic valve thrombus leading to thromboembolic arterial ischemic stroke. Through endovascular thrombectomy, cerebral circulation was re-established, extracting a fibrin thrombus with APML cells. Neurological recovery was swift. This report underscores the importance of vigilance for thrombotic complications in APML, highlighting the potential severity of overlooked risks.


Assuntos
Síndrome de Down , Trombectomia , Trombose , Humanos , Síndrome de Down/complicações , Adolescente , Trombectomia/métodos , Trombose/etiologia , Trombose/patologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Valva Aórtica/cirurgia , Valva Aórtica/patologia , Masculino , Procedimentos Endovasculares/métodos , Feminino
2.
Int J Mol Sci ; 25(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38791256

RESUMO

Interrupted blood flow in the brain due to ischemic injuries such as ischemic stroke or traumatic brain injury results in irreversible brain damage, leading to cognitive impairment associated with inflammation, disruption of the blood-brain barrier (BBB), and cell death. Since the BBB only allows entry to a small class of drugs, many drugs used to treat ischemia in other tissues have failed in brain-related disorders. The administration of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) has shown promise in improving the functional recovery of the brain following cerebral ischemia by inducing blood vessel formation. To facilitate such a treatment approach, it is necessary to develop bioprocesses that can produce therapeutically relevant MSC-EVs in a reproducible and scalable manner. This study evaluated the feasibility of using stirred suspension bioreactors (SSBs) to scale-up the serum-free production of pro-angiogenic MSC-EVs under clinically relevant physioxic conditions. It was found that MSCs grown in SSBs generated EVs that stimulated angiogenesis in cerebral microvascular endothelial cells, supporting the use of SSBs to produce MSC-EVs for application in cerebral ischemia. These properties were impaired at higher cell confluency, outlining the importance of considering the time of harvest when developing bioprocesses to manufacture EV populations.


Assuntos
Reatores Biológicos , Células Endoteliais , Vesículas Extracelulares , Células-Tronco Mesenquimais , Neovascularização Fisiológica , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Encéfalo/metabolismo , Encéfalo/irrigação sanguínea , Células Cultivadas , Barreira Hematoencefálica/metabolismo , Angiogênese
3.
Bioessays ; 43(2): e2000215, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33191529

RESUMO

Mesenchymal stem cells (MSCs) are present in fat tissues throughout the body, yet little is known regarding their biological role within epidural fat. We hypothesize that debridement of epidural fat and/or subsequent loss of MSCs within this tissue, disrupts homeostasis in the vertebral environment resulting in increased inflammation, fibrosis, and decreased neovascularization leading to poorer functional outcomes post-injury/operatively. Clinically, epidural fat is commonly considered a space-filling tissue with limited functionality and therefore typically discarded during surgery. However, the presence of MSCs within epidural fat suggests that itis more biologically active than historically believed and may contribute to the regulation of homeostasis and regeneration in the dural environment. While the current literature supports our hypothesis, it will require additional experimentation to determine if epidural fat is an endogenous driver of repair and regeneration and if so, this tissue should be minimally perturbed from its original location in the spinal canal. Also see the video abstract here https://youtu.be/MIol_IWK1os.


Assuntos
Células-Tronco Mesenquimais , Tecido Adiposo , Homeostase , Humanos , Inflamação
4.
Cell Tissue Res ; 389(3): 483-499, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35704103

RESUMO

Mesenchymal progenitor cells (MPCs) have been recently identified in human and murine epidural fat and have been hypothesized to contribute to the maintenance/repair/regeneration of the dura mater. MPCs can secrete proteoglycan 4 (PRG4/lubricin), and this protein can regulate tissue homeostasis through bio-lubrication and immunomodulatory functions. MPC lineage tracing reporter mice (Hic1) and human epidural fat MPCs were used to determine if PRG4 is expressed by these cells in vivo. PRG4 expression co-localized with Hic1+ MPCs in the dura throughout skeletal maturity and was localized adjacent to sites of dural injury. When Hic1+ MPCs were ablated, PRG4 expression was retained in the dura, yet when Prx1+ MPCs were ablated, PRG4 expression was completely lost. A number of cellular processes were impacted in human epidural fat MPCs treated with rhPRG4, and human MPCs contributed to the formation of epidural fat, and dura tissues were xenotransplanted into mouse dural injuries. We have shown that human and mouse MPCs in the epidural/dura microenvironment produce PRG4 and can contribute to dura homeostasis/repair/regeneration. Overall, these results suggest that these MPCs have biological significance within the dural microenvironment and that the role of PRG4 needs to be further elucidated.


Assuntos
Dura-Máter/metabolismo , Células-Tronco Mesenquimais , Proteoglicanas/metabolismo , Animais , Dura-Máter/citologia , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos
5.
Neuroradiology ; 63(1): 117-123, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32740709

RESUMO

PURPOSE: Deciding about whether an unruptured intracranial aneurysm (UIA) should be treated or not is challenging because robust data on rupture risks, endovascular treatment complication rates, and treatment success rates are limited. We aimed to investigate how neurointerventionalists conceptually approach endovascular treatment decision-making in UIAs. METHODS: In a web-based international multidisciplinary case-based survey among neurointerventionalists, participants provided their demographics and UIA treatment-volumes, estimated 5-year rupture rates, endovascular treatment complication and success rates and gave their endovascular treatment decision for 15 pre-specified UIA case-scenarios. Differences in estimated 5-year rupture rates, endovascular treatment complication and success rates based on physician and hospital characteristics were evaluated with the Kruskal-Wallis test. Multivariable logistic regression analysis was used to derive adjusted effect size estimates for predictors of endovascular treatment decision. RESULTS: Two hundred-thirty-three neurointerventionalists from 38 countries participated in the survey (median age 47 years [IQR: 41-55], 25/233 [10.7%] females). The ranges of estimates for 5-year rupture risks, endovascular treatment complication rates, and particularly endovascular treatment success rates were wide, especially for UIAs in the posterior circulation. Estimated 5-year rupture risks, endovascular treatment complication and success rates differed significantly based on personal and institutional endovascular UIA treatment volume, and all three estimates were significantly associated with physicians' endovascular treatment decision. CONCLUSION: Although several predictors of endovascular treatment decision were identified, there seems to be a high degree of uncertainty when estimating rupture risks, treatment complications, and treatment success for endovascular UIA treatment. More data on the clinical course of UIAs with and without endovascular treatment is needed.


Assuntos
Procedimentos Endovasculares , Aneurisma Intracraniano , Médicos , Adulto , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento
6.
Can J Neurol Sci ; 48(6): 807-816, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33472716

RESUMO

BACKGROUND: Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to "self-fulfilling prophecy," where withdrawal of life-sustaining measures (WLSM) is invariably followed by death. METHODS: We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM. RESULTS: Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02). CONCLUSIONS: We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from "self-fulfilling prophecy." Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.


Assuntos
Hemorragia Subaracnóidea , Estudos de Coortes , Escala de Coma de Glasgow , Humanos , Prognóstico , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento
7.
J Neurol Neurosurg Psychiatry ; 91(9): 985-990, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32723730

RESUMO

BACKGROUND AND PURPOSE: We previously reported a single-centre study demonstrating that smoking confers a six-fold increased risk for having an unruptured intracranial aneurysm (UIA) in women aged between 30 and 60 years and this risk was higher if the patient had chronic hypertension. There are no data with greater generalisability evaluating this association. We aimed to validate our previous findings in women from a multicentre study. METHODS: A multicentre case-control study on women aged between 30 and 60 years, that had magnetic resonance angiography (MRA) during the period 2016-2018. Cases were those with an incidental UIA, and these were matched to controls based on age and ethnicity. A multivariable conditional logistic regression was conducted to evaluate smoking status and hypertension differences between cases and controls. RESULTS: From 545 eligible patients, 113 aneurysm patients were matched to 113 controls. The most common reason for imaging was due to chronic headaches in 62.5% of cases and 44.3% of controls. A positive smoking history was encountered in 57.5% of cases and in 37.2% of controls. A multivariable analysis demonstrated a significant association between positive smoking history (OR 3.7, 95%CI 1.61 to 8.50), hypertension (OR 3.16, 95% CI 1.17 to 8.52) and both factors combined with a diagnosis of an incidental UIA (OR 6.9, 95% CI 2.49 to 19.24). CONCLUSIONS: Women aged between 30 and 60 years with a positive smoking history have a four-fold increased risk for having an UIA, and a seven-fold increased risk if they have underlying chronic hypertension. These findings indicate that women aged between 30 and 60 years with a positive smoking history might benefit from a screening recommendation.


Assuntos
Fumar Cigarros/epidemiologia , Hipertensão/epidemiologia , Aneurisma Intracraniano/epidemiologia , Adulto , Canadá/epidemiologia , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
8.
N Engl J Med ; 372(11): 1019-30, 2015 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-25671798

RESUMO

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).


Assuntos
Procedimentos Endovasculares , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Hemorragia Cerebral/induzido quimicamente , Terapia Combinada , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Reperfusão , Método Simples-Cego , Stents , Acidente Vascular Cerebral/mortalidade , Trombectomia/instrumentação , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X
9.
Neuroradiology ; 59(4): 361-365, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28265722

RESUMO

PURPOSE: We propose a magnetic resonance (MR) imaging protocol for the characterization of carotid web morphology, composition, and vessel wall dynamics. The purpose of this case series was to determine the feasibility of imaging carotid webs with MR imaging. METHODS: Five patients diagnosed with carotid web on CT angiography were recruited to undergo a 30-min MR imaging session. MR angiography (MRA) images of the carotid artery bifurcation were acquired. Multi-contrast fast spin echo (FSE) images were acquired axially about the level of the carotid web. Two types of cardiac phase resolved sequences (cineFSE and cine phase contrast) were acquired to visualize the elasticity of the vessel wall affected by the web. RESULTS: Carotid webs were identified on MRA in 5/5 (100%) patients. Multi-contrast FSE revealed vessel wall thickening and cineFSE demonstrated regional changes in distensibility surrounding the webs in these patients. CONCLUSION: Our MR imaging protocol enables an in-depth evaluation of patients with carotid webs: morphology (by MRA), composition (by multi-contrast FSE), and wall dynamics (by cineFSE).


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Angiografia por Tomografia Computadorizada , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Prospectivos
10.
Heart Lung Circ ; 24(8): 824-30, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25804624

RESUMO

BACKGROUND: Delayed ipsilateral intraparenchymal haemorrhage is a recently recognised complication after endovascular flow diversion for intracranial aneurysms. Although the mechanism of this phenomenon is not understood, one proposed explanation (the windkessel hypothesis) is that removal of aneurysmal compliance increases distal pulse pressure. METHODS: We present a case of delayed haemorrhage after placement of a Pipeline stent, discuss the proposed mechanisms, and describe a novel electrical analogue model that was used to evaluate the likely haemodynamic effect of stent placement. RESULTS: Model-based analysis suggests that stenting is not likely to produce a significant change in distal pulse pressure. Moreover, basic fluid dynamics principles suggest that a local reduction in disturbed flow in the region of the aneurysm could produce only a minor increase in distal pressure (a few mmHg), which is unlikely to be the main cause of the observed haemorrhage. CONCLUSION: The windkessel hypothesis is unlikely to explain the occurrence of delayed ipsilateral intraparenchymal haemorrhage after flow diversion; however, other mechanisms involving altered haemodynamics distal to the treated aneurysm may play a role. Further studies involving the assessment of haemodynamic changes after flow diversion would be useful to understand, and eventually mitigate, this currently unpredictable risk.


Assuntos
Circulação Cerebrovascular , Procedimentos Endovasculares/efeitos adversos , Aneurisma Intracraniano , Modelos Cardiovasculares , Complicações Pós-Operatórias , Stents , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/cirurgia , Feminino , Humanos , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/fisiopatologia , Aneurisma Intracraniano/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia
11.
J Neurointerv Surg ; 16(3): 296-301, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-37188503

RESUMO

BACKGROUND: Flow-diverting stents are not currently indicated for the treatment of bifurcation aneurysms, and some case series have demonstrated low occlusion rates, possibly due to a lack in neck coverage. The ReSolv stent is a unique hybrid metal/polymer stent that can be deployed with the shelf technique in order to improve neck coverage. METHODS: A Pipeline, unshelfed ReSolv, and shelfed ReSolv stent were deployed in the left-sided branch of an idealized bifurcation aneurysm model. After determining stent porosity, high-speed digital subtraction angiography runs were acquired under pulsatile flow conditions. Time-density curves were created using two region of interest (ROI) paradigms (total aneurysm and left/right), and four parameters were extracted to characterize flow diversion performance. RESULTS: The shelfed ReSolv stent demonstrated better aneurysm outflow alterations compared to the Pipeline and unshelfed ReSolv stent when using the total aneurysm as the ROI. On the left side of the aneurysm, there was no significant difference between the shelfed ReSolv stent and the Pipeline. On the right side of the aneurysm, however, the shelfed ReSolv stent had a significantly better contrast washout profile than the unshelfed ReSolv stent and the Pipeline stent. CONCLUSIONS: The ReSolv stent with the shelf technique demonstrates the potential to improve flow diversion outcomes for bifurcation aneurysms. Further in vivo testing will help to determine whether the additional neck coverage leads to better neointimal scaffolding and long-term aneurysm occlusion.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Stents , Angiografia Digital , Resultado do Tratamento , Angiografia Cerebral
12.
Interv Neuroradiol ; : 15910199241260896, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899902

RESUMO

BACKGROUND: Bioresorbable polymer-based flow-diverting stents have potential benefits over existing metal devices. This study aimed to evaluate the safety and efficacy of the novel ReSolv device, which is a primarily polymer-based flow-diverting stent, using the in vivo rabbit sidewall saccular aneurysm model. METHODS: ReSolv stents were deployed in 14 New Zealand White rabbits that had undergone aneurysm creation procedures. Animals were allocated to follow-up time points of 1, 3, 6, 9, 12, 16, or 18 months. Angiographic images were evaluated by an independent neurointerventionalist blinded to follow-up time points for (1) in-stent stenosis, (2) parent vessel and jailed side branch patency, (3) wall apposition, and (4) aneurysm occlusion using the Raymond-Roy Occlusion Classification (RROC), O'Kelly Marotta grading scale, and the 4F flow diversion predictive score. Primary efficacy outcome was defined as RROC Class I or II. RESULTS: At a median follow-up time of 7.5 months, parent vessel (14/14) and jailed side (33/33) branches were patent in all cases. There was no development of thrombus on the stent or cases of significant in-stent stenosis, and all stents had good wall apposition. Adequate occlusion was found in 85.7% (n = 12) of animals, including an RROC Class I in 64.3% (n = 9) and RROC Class II in 21.4% (n = 3). CONCLUSIONS: The ReSolv stent shows encouraging angiographic safety and efficacy outcomes after placement in a rabbit sidewall saccular aneurysm model. Longer term studies are ongoing to determine eventual fate of the aneurysm, parent vessel, and jailed side branches after absorption of the polymer component of the stent.

13.
Interv Neuroradiol ; 29(5): 498-503, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35484816

RESUMO

BACKGROUND: Spinal catheter angiography is commonly performed in the evaluation and treatment of spinal vascular lesions. The typical approach to spinal angiography consists of access through the femoral artery with the use of suitably shaped catheters for selective catheterization of the spinal segmental vasculature. The purpose of our study was to evaluate the safety and feasibility of distal transradial access through the "anatomical snuffbox" for targeted spinal angiography, for the investigation and treatment of selected spinal lesions. METHODS: A retrospective review of patients who underwent transradial spinal angiography and embolization was performed from August 2019 to January 2022. A total of eight patients were identified, who underwent targeted spinal angiography through distal transradial access. Outcome measures were documented in a tabular manner. RESULTS: Radial access was successful in all patients. Seven patients had vascular tumors of the spinal column and underwent tumor embolization followed by segmental artery occlusion prior to surgery. One patient had a spinal dural AV fistula that could not be embolized due to feeding vessel tortuosity and eventually went on to have a laminectomy. Mean fluoroscopy time was 31.4 min. There were no access site hemorrhagic complications. One patient experienced transient mild hand numbness during the period of hemostasis with the vascular compression device that resolved completely within 24 h. CONCLUSIONS: Distal transradial access is a feasible and safe option for targeted spinal angiography and treatment in selected patients.


Assuntos
Embolização Terapêutica , Artéria Radial , Humanos , Artéria Radial/diagnóstico por imagem , Artéria Radial/cirurgia , Angiografia , Embolização Terapêutica/métodos , Catéteres , Hemorragia , Estudos Retrospectivos
14.
Stem Cell Res Ther ; 14(1): 218, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612731

RESUMO

BACKGROUND: Following an ischemic injury to the brain, the induction of angiogenesis is critical to neurological recovery. The angiogenic benefits of mesenchymal stem cells (MSCs) have been attributed at least in part to the actions of extracellular vesicles (EVs) that they secrete. EVs are membrane-bound vesicles that contain various angiogenic biomolecules capable of eliciting therapeutic responses and are of relevance in cerebral applications due to their ability to cross the blood-brain barrier (BBB). Though MSCs are commonly cultured under oxygen levels present in injected air, when MSCs are cultured under physiologically relevant oxygen conditions (2-9% O2), they have been found to secrete higher amounts of survival and angiogenic factors. There is a need to determine the effects of MSC-EVs in models of cerebral angiogenesis and whether those from MSCs cultured under physiological oxygen provide greater functional effects. METHODS: Human adipose-derived MSCs were grown in clinically relevant serum-free medium and exposed to either headspace oxygen concentrations of 18.4% O2 (normoxic) or 3% O2 (physioxic). EVs were isolated from MSC cultures by differential ultracentrifugation and characterized by their size, concentration of EV specific markers, and their angiogenic protein content. Their functional angiogenic effects were evaluated in vitro by their induction of cerebral microvascular endothelial cell (CMEC) proliferation, tube formation, and angiogenic and tight junction gene expressions. RESULTS: Compared to normoxic conditions, culturing MSCs under physioxic conditions increased their expression of angiogenic genes SDF1 and VEGF, and subsequently elevated VEGF-A content in the EV fraction. MSC-EVs demonstrated an ability to induce CMEC angiogenesis by promoting tube formation, with the EV fraction from physioxic cultures having the greatest effect. The physioxic EV fraction further upregulated the expression of CMEC angiogenic genes FGF2, HIF1, VEGF and TGFB1, as well as genes (OCLN and TJP1) involved in BBB maintenance. CONCLUSIONS: EVs from physioxic MSC cultures hold promise in the generation of a cell-free therapy to induce angiogenesis. Their positive angiogenic effect on cerebral microvascular endothelial cells demonstrates that they may have utility in treating ischemic cerebral conditions, where the induction of angiogenesis is critical to improving recovery and neurological function.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Células Endoteliais , Fator A de Crescimento do Endotélio Vascular/genética , Encéfalo , Fatores Imunológicos
15.
Oper Neurosurg (Hagerstown) ; 24(1): 44-54, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36519878

RESUMO

BACKGROUND: Intramedullary spinal cord cavernous malformations (SCCMs) account for only 5% of overall cavernous malformations (CMs). The occurrence of recurrent or residual SCCMs has not been well discussed, nor have the technical nuances of resection. OBJECTIVE: To assess the characteristics of residual SCCMs and surgical outcomes and describe the techniques to avoid leaving lesion remnants during primary resection. METHODS: Demographic, radiologic, intraoperative findings and surgical outcomes data for a cohort of surgically managed intramedullary SCCMs were obtained from an institutional database and retrospectively analyzed. A systematic literature review was performed using PRISMA guidelines. RESULTS: Of 146 SCCM resections identified, 17 were for residual lesions (12%). Patients with residuals included 13 men and 4 women, with a mean age of 43 years (range 16-70). All patients with residual SCCMs had symptomatic presentations: sensory deficits, paraparesis, spasticity, and pain. Residuals occurred between 3 and 264 months after initial resection. Approaches for 136 cases included posterior midline myelotomy (28.7%, n = 39), pial surface entry (37.5%, n = 51), dorsal root entry zone (27.9%, n = 38), and lateral entry (5.9%, n = 8). Follow-up outcomes were similar for patients with primary and residual lesions, with the majority having no change in modified Rankin Scale score (63% [59/93] vs 75% [9/12], respectively, P = .98). CONCLUSION: SCCMs may cause significant symptoms. During primary resection, care should be taken to avoid leaving residual lesion remnants, which can lead to future hemorrhagic events and neurological morbidity. However, satisfactory results are achievable even with secondary or tertiary resections.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Procedimentos Neurocirúrgicos/métodos , Medula Espinal/diagnóstico por imagem , Medula Espinal/cirurgia
16.
J Neurosurg ; 138(4): 933-943, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36087324

RESUMO

OBJECTIVE: Flow diverters have revolutionized the endovascular treatment of intracranial aneurysms. Here, the authors present the first large-scale North American multicenter experience using the Flow Redirection Endoluminal Device (FRED) in the treatment of cerebral aneurysms. METHODS: Consecutive cerebral aneurysms treated with FRED at 7 North American centers between June 2020 and November 2021 were included. Data collected included patient demographic characteristics, aneurysm characteristics, periprocedural and long-term complications, modified Rankin Scale (mRS) scores, and radiological follow-up. RESULTS: In total, 133 aneurysms in 116 patients were treated with 123 FRED deployment procedures and included in this study. One hundred twenty-six aneurysms (94.7%) were unruptured, 117 (88.0%) saccular, and 123 (92.5%) located in anterior circulation. The mean (range) aneurysm maximal width and neck width sizes were 7.2 (1.5-42.5) mm and 4.1 (1.0-15.1) mm, respectively. Successful FRED deployment was achieved in 122 procedures (99.2%). Adjunctive coiling was used in 4 procedures (3.3%). Radiological follow-up was available for 101 aneurysms at a median duration of 7.0 months. At last follow-up, complete occlusion was observed in 55.4% of patients, residual neck in 8.9%, and filling aneurysm in 35.6%; among cases with radiological follow-up duration > 10 months, these values were 21/43 (48.8%), 3/43 (7.0%), and 19/43 (44.2%), respectively. On multivariate regression analysis, age (OR 0.93, p = 0.001) and aneurysm neck size (OR 0.83, p = 0.048) were negatively correlated with odds of complete occlusion at latest follow-up. The retreatment rate was 6/124 (4.8%). The overall complication rate was 31/116 (26.7%). Parent vessel occlusion, covered branch occlusion, and in-stent stenosis were detected in 9/99 (9.1%), 6/63 (9.5%), and 15/99 (15.2%) cases, respectively. The FRED-related, symptomatic, thromboembolic, and hemorrhagic complication rates were 22.4%, 12.9%, 6.9%, and 0.9% respectively. The morbidity rate was 10/116 patients (8.6%). There was 1 death due to massive periprocedural internal carotid artery stroke, and 3.6% of the patients had an mRS score > 2 at the last follow-up (vs 0.9% at baseline). CONCLUSIONS: As the first large-scale North American multicenter FRED experience, this study confirmed the ease of successful FRED deployment but suggested lower efficacy and a higher rate of complications than reported by previous European and South American studies on FRED and other flow-diverting devices. The authors recommend judicious use of this device until future studies can better elucidate the long-term outcomes of FRED treatment.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Stents , Embolização Terapêutica/métodos , América do Norte/epidemiologia , Estudos Retrospectivos , Seguimentos
17.
J Neurosurg ; 139(3): 661-669, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36708530

RESUMO

OBJECTIVE: Routine antiplatelet responsiveness testing for patients undergoing carotid artery stenting procedures is not performed at most endovascular centers and remains a topic of controversy within the neurointerventional community. The objective of this study was to determine if nonresponsiveness to acetylsalicylic acid or clopidogrel was associated with the development of symptomatic thromboembolic events in patients undergoing carotid stenting procedures. METHODS: A prospective study was conducted at the Foothills Medical Centre in Calgary, Alberta, Canada, from August 2019 to July 2021. Patients undergoing carotid artery stenting procedures and who were receiving dual antiplatelet therapy were enrolled in the study. Responsiveness to the antiplatelet medications was determined through whole blood impedance aggregometry. The primary outcome was development of a symptomatic thromboembolic event within 90 days after the procedure. The treating physicians were blinded to the aggregometry results for the duration of the study. RESULTS: One hundred two procedures were performed in 100 patients. Eight thromboembolic events (8%) occurred during the study. Age (p = 0.03) and nonresponsiveness to clopidogrel (p = 0.003) were associated with the development of thromboembolic events. The multivariable model showed that clopidogrel nonresponsiveness was independently associated with the development of a thromboembolic event (adjusted OR 6.14, 95% CI 1.25-30.11, p = 0.03). CONCLUSIONS: This study demonstrated that patients who were identified as clopidogrel nonresponders, using whole blood impedance aggregometry, were at an increased risk of developing thromboembolic events. Larger studies are needed to assess the utility of routine platelet function testing prior to carotid artery stenting procedures.


Assuntos
Estenose das Carótidas , Tromboembolia , Humanos , Clopidogrel/uso terapêutico , Ticlopidina/uso terapêutico , Estenose das Carótidas/complicações , Estudos Prospectivos , Stents/efeitos adversos , Tromboembolia/prevenção & controle , Tromboembolia/complicações , Artérias Carótidas
18.
Neuroradiology ; 54(11): 1261-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22552837

RESUMO

INTRODUCTION: Timely recanalization during endovascular procedures for acute ischemic stroke can be challenging in cases with large clot burden, such as those encountered in the terminal internal carotid T- or L-type occlusion. METHODS: A novel but simple technique to achieve fast reduction in clot burden in stroke patients with occlusion of the internal carotid artery termination is described where manual suction using a 60-ml syringe applied through an 8-F balloon guide catheter positioned in the cervical carotid vasculature with proximal flow arrest allows subsequent revascularization of the residual middle cerebral artery clot. RESULTS: The use of manual suction through a balloon-tipped guide catheter in internal carotid artery L- or T-type occlusion is illustrated. This resulted in a significant reduction of the clot burden and facilitated further interventions leading to full recanalization. CONCLUSION: Manual suction using a 60-ml syringe through a balloon guide catheter is a useful and feasible technique that facilitates thrombectomy of large burden cerebral clots.


Assuntos
Trombose das Artérias Carótidas/cirurgia , Artéria Carótida Interna , Trombectomia/instrumentação , Trombectomia/métodos , Trombose das Artérias Carótidas/classificação , Catéteres , Desenho de Equipamento , Humanos , Sucção/métodos , Fatores de Tempo
19.
Stem Cells Transl Med ; 11(2): 200-212, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35259263

RESUMO

Epidural fat is commonly discarded during spine surgery to increase the operational field. However, mesenchymal progenitor cells (MPCs) have now been identified in human epidural fat and within the murine dura mater. This led us to believe that epidural fat may regulate homeostasis and regeneration in the vertebral microenvironment. Using two MPC lineage tracing reporter mice (Prx1 and Hic1), not only have we found that epidural fat MPCs become incorporated in the dura mater over the course of normal skeletal maturation, but have also identified these cells as an endogenous source of repair and regeneration post-dural injury. Moreover, our results reveal a partial overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. This study effectively challenges the notion of epidural fat as an expendable tissue and mandates further research into its biological function and relevance.


Assuntos
Dura-Máter , Células-Tronco Mesenquimais , Animais , Dura-Máter/lesões , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição Kruppel-Like , Camundongos
20.
Interv Neuroradiol ; 28(6): 660-667, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34787481

RESUMO

BACKGROUND: Five to ten percent of the global population have unruptured intracranial aneurysms, and ruptured brain aneurysms cause approximately 500,000 deaths a year. Flow-diverting stent treatment is a less invasive intracranial aneurysm treatment that induces aneurysm thrombosis. The imaging characteristics of a novel primarily bioresorbable flow-diverting stent (BFDS) are assessed in comparison to the leading metal stent using fluoroscopy, CT, and MRI. METHODS: X-ray/fluoroscopic images of stents were taken using a human cadaveric skull model. CT and MRI were acquired using silicone flow models of residual aneurysms. Images were analyzed with Likert scales in anonymous surveys by neurointerventionalists. Quantitative measurements of radiographic density (CT) and artifact boundary size (CT & MRI) were also obtained. RESULTS: Visibility of the BFDS on X-ray was less than the metal stent but deemed adequate for deployment and intraprocedural assessment. The metal stent was more radiopaque than the BFDS on CT, but qualitative assessment was not significantly different for the two stents. MRI imaging was significantly better using the BFDS in terms of overall artifact and intraluminal assessment. CONCLUSIONS: The BFDS has adequate visualization on X-ray/fluoroscopy and should be clinically acceptable for fluoroscopic deployment. On MRI, there is less quantitative artifact as well as overall improved qualitative assessment that will allow for more detailed non-invasive imaging follow-up of treated aneurysms, potentially reducing the need for digital subtraction catheter angiography.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Humanos , Implantes Absorvíveis , Resultado do Tratamento , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Stents , Imageamento por Ressonância Magnética , Fluoroscopia , Tomografia Computadorizada por Raios X/métodos , Angiografia Cerebral
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