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1.
Stroke ; 53(3): 913-920, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34753303

RESUMEN

BACKGROUND AND PURPOSE: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. METHODS: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. RESULTS: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63-79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2-4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6-9] versus 6 [4-9]), similar favorable thrombus permeability (residual flow grades I-II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11-13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26-60.13]) were associated with successful recanalization among mild patients. CONCLUSIONS: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.


Asunto(s)
Encéfalo/diagnóstico por imagen , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Angiografía Cerebral , Angiografía por Tomografía Computarizada , Femenino , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
2.
Stroke ; 52(8): 2562-2570, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34078107

RESUMEN

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20­1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01­1.03]) and MT (odds ratio, 1.08 [95% CI,1.05­1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time. Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.


Asunto(s)
Fibrinolíticos/uso terapéutico , Disparidades en Atención de Salud/tendencias , Racismo/tendencias , Accidente Cerebrovascular/terapia , Trombectomía/tendencias , Activador de Tejido Plasminógeno/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Estados Unidos/epidemiología , Adulto Joven
3.
Stroke ; 52(6): 1967-1973, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33910367

RESUMEN

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.


Asunto(s)
Accidente Cerebrovascular Embólico/cirugía , Procedimientos Endovasculares , Arteriosclerosis Intracraneal/cirugía , Trombolisis Mecánica , Anciano , Accidente Cerebrovascular Embólico/diagnóstico por imagen , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos
4.
Neuroradiology ; 63(1): 111-116, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32748080

RESUMEN

PURPOSE: Mechanical thrombectomy (MT) in posterior circulation large vessel occlusion (LVO), including posterior cerebral artery (PCA), has not been validated since all five major MT trials excluded such patients. To evaluate the feasibility and preliminary safety and efficacy of MT in isolated PCA occlusion stroke patients with new-generation MT devices. METHODS: Endovascularly treated acute ischemic stroke (AIS) patients were identified from a prospectively collected database and their baseline characteristics were noted. Clinical outcomes were angiographic recanalization, a favorable clinical outcome at 3 months on modified Rankin Scale (mRS) and visual field (VF) deficit improvement on confrontation test, rate of intracranial hemorrhage (ICH), and mortality at 3 months. RESULTS: A total of 355 AIS patients underwent MT from January 2018 to December 2019. Isolated PCA MT was performed in 15 consecutive patients. The mean age was 64 ± 17 years, and 9(60%) were women. Median presentation NIHSS was 9 (interquartile range 5-15). MT devices used were stent retrievers in 6 patients and combined aspiration and stent retriever in 9 patients. Complete revascularization (TICI 2c or 3) was achieved in 12/15 patients. 3-month VF normalization was seen in 7/12 of the patients. Post-procedure symptomatic ICH occurred in 1/15 of patients. mRS score of 0-2 was achieved in 9/15 of patients but one patient was dead at 3 months post procedure. CONCLUSION: MT is feasible and can achieve successful reperfusion in isolated PCA occlusions and resulted in favorable motor and visual outcomes in this small series of ischemic stroke patients.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Femenino , Humanos , Recién Nacido , Arteria Cerebral Posterior , Estudios Retrospectivos , Stents , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del Tratamiento
5.
Br J Neurosurg ; : 1-4, 2021 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-34553660

RESUMEN

BACKGROUND AND IMPORTANCE: One of the most feared and devastating complications of carotid revascularization procedures is hyperperfusion hemorrhage. The acute onset of an ipsilateral mydriatic pupil following carotid endarterectomy (CEA) or carotid artery stenting (CAS) should prompt immediate neurosurgical evaluation to rule out hyperperfusion injury. CLINICAL PRESENTATION: We describe a case of benign, transient ipsilateral mydriasis following CAS. After undergoing right common and internal carotid artery (ICA) angioplasty and stenting with distal embolic protection, the patient developed anisocoria with a right-sided 5 mm minimally reactive pupil. Imaging demonstrated no acute pathology, and the mydriasis resolved spontaneously within 48 hours. We hypothesise that the pathophysiologic mechanism is secondary to transient ischemia of parasympathetic structures within the petrous/cavernous ICA from arterial ostium occlusion that occurred during device placement. Alternatively, sympathetic stimulation during angioplasty is also plausible. CONCLUSIONS: Although an ipsilateral mydriatic pupil following carotid revascularization necessitates evaluation, it may represent a self-limiting process especially in the absence of other focal neurologic deficits.

6.
J Stroke Cerebrovasc Dis ; 30(4): 105599, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33545519

RESUMEN

BACKGROUND: Large vessel occlusion (LVO) strokes can in part be prevented with better atrial fibrillation (AF) stroke prevention strategies; thus we evaluated the rate of AF in patients presenting with acute LVO strokes undergoing mechanical thrombectomy (MT) and assessed patterns of oral anticoagulant (OAC) use prior to the index stroke. METHODS AND RESULTS: We identified 347 MT cases from February 2015 to September 2018. A retrospective chart review was conducted to identify patient sociodemographics, presence of AF, use of anticoagulation, stroke severity, CHA2DS2-VASc scores, and functional outcomes. AF was present in 161 (46%) cases. Patients with AF were older (mean 76 ± 11 years vs. 66 ± 15 years) and more likely to be female (56% vs. 46%) with higher rates of hypertension, dyslipidemia, heart failure and smoking. Of the 100 patients with known AF, 59 were not on anticoagulation prior to the index stroke. Of 39 patients with known AF on OAC, 57% were not therapeutic on warfarin and 20% were not taking prescribed direct OACs. A total of 72 (21%) thrombectomy cases were performed on patients with known AF who were not effectively anticoagulated. After multivariate adjustments, there was no significant difference in modified Rankin Scale score at discharge, in-hospital mortality, or symptomatic intracranial hemorrhage between the AF and non-AF groups. CONCLUSION: In our study, 21% of patients with LVO stroke had known AF and were not effectively anticoagulated. Improved stroke preventive measures could potentially reduce the occurrence of stroke and avoid unnecessary procedures for patients with AF.


Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Trombectomía , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Hemorragias Intracraneales/inducido químicamente , Masculino , Persona de Mediana Edad , Prevención Primaria , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Prevención Secundaria , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Trombectomía/efectos adversos , Trombectomía/mortalidad , Factores de Tiempo , Resultado del Tratamiento
7.
J Stroke Cerebrovasc Dis ; 30(8): 105806, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34058701

RESUMEN

BACKGROUND: The COVID-19 pandemic has strained the healthcare systems across the world but its impact on acute stroke care is just being elucidated. We hypothesized a major global impact of COVID-19 not only on stroke volumes but also on various aspects of thrombectomy systems. AIMS: We conducted a convenience electronic survey with a 21-item questionnaire aimed to identify the changes in stroke admission volumes and thrombectomy treatment practices seen during a specified time period of the COVID-19 pandemic. METHODS: The survey was designed using Qualtrics software and sent to stroke and neuro-interventional physicians around the world who are part of the Global Executive Committee (GEC) of Mission Thrombectomy 2020, a global coalition under the aegis of Society of Vascular and Interventional Neurology, between April 5th and May 15th, 2020. RESULTS: There were 113 responses to the survey across 25 countries with a response rate of 31% among the GEC members. Globally there was a median 33% decrease in stroke admissions and a 25% decrease in mechanical thrombectomy (MT) procedures during the COVID-19 pandemic period until May 15th, 2020 compared to pre-pandemic months. The intubation policy for MT procedures during the pandemic was highly variable across participating centers: 44% preferred intubating all patients, including 25% of centers that changed their policy to preferred-intubation (PI) from preferred non-intubation (PNI). On the other hand, 56% centers preferred not intubating patients undergoing MT, which included 27% centers that changed their policy from PI to PNI. There was no significant difference in rate of COVID-19 infection between PI versus PNI centers (p=0.60) or if intubation policy was changed in either direction (p=1.00). Low-volume (<10 stroke/month) compared with high-volume stroke centers (>20 strokes/month) were less likely to have neurointerventional suite specific written personal protective equipment protocols (74% vs 88%) and if present, these centers were more likely to report them to be inadequate (58% vs 92%). CONCLUSION: Our data provides a comprehensive snapshot of the impact on acute stroke care observed worldwide during the pandemic. Overall, respondents reported decreased stroke admissions as well as decreased cases of MT with no clear preponderance in intubation policy during MT. DATA ACCESS STATEMENT: The corresponding author will consider requests for sharing survey data. The study was exempt from institutional review board approval as it did not involve patient level data.


Asunto(s)
COVID-19 , Salud Global/tendencias , Disparidades en Atención de Salud/tendencias , Pautas de la Práctica en Medicina/tendencias , Accidente Cerebrovascular/terapia , Trombectomía/tendencias , Estudios Transversales , Encuestas de Atención de la Salud , Hospitales de Alto Volumen/tendencias , Hospitales de Bajo Volumen/tendencias , Humanos , Control de Infecciones/tendencias , Intubación Intratraqueal/tendencias , Admisión del Paciente/tendencias , Accidente Cerebrovascular/diagnóstico , Factores de Tiempo
8.
Mol Cell Biochem ; 474(1-2): 95-112, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32705629

RESUMEN

The Nm23 metastasis suppressor family is involved in a variety of physiological and pathological processes including cell proliferation, differentiation, tumorigenesis, and metastasis. Given that Nm23 proteins may function as hexamers composed of different members of the family, especially Nm23-H1 and H2 isoforms, it is pertinent to assess the importance of interface and surface residues in defining the functional characteristics of Nm23 proteins. Using molecular modeling to identify clusters of residues that may affect dimer formation and isoform specificity, mutants of Nm23-H1 were constructed and assayed for their ability to modulate cell migration. Mutations of dimer interface residues Gly22 and Lys39 affected the expression level of Nm23-H1, without altering the transcript level. The reduced protein expression was not due to increased protein degradation or altered subcellular distribution. Substitution of the surface residues of Nm23-H1 with Nm23-H2-specific Ser131 and/or Lys124/135 affected the electrophoretic mobility of the protein. Moreover, in cell migration assays, several mutants with altered surface residues exhibited impaired ability to suppress the mobility of MDA-MB-231 cells. Collectively, the study suggests that disrupting the dimer interface may affect the expression of Nm23-H1, while the residues at α-helix and ß-sheet on the surface of Nm23-H1 may contribute to its metastasis suppressive function.


Asunto(s)
Neoplasias de la Mama/patología , Movimiento Celular , Proliferación Celular , Mutación , Nucleósido Difosfato Quinasas NM23/metabolismo , Secuencia de Aminoácidos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Modelos Moleculares , Nucleósido Difosfato Quinasas NM23/química , Nucleósido Difosfato Quinasas NM23/genética , Metástasis de la Neoplasia , Multimerización de Proteína , Células Tumorales Cultivadas
9.
Curr Neurol Neurosci Rep ; 19(11): 91, 2019 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-31768660

RESUMEN

PURPOSE OF REVIEW: We aim to evaluate the epidemiology, racial and gender disparity, etiology, and treatment of stroke in the younger population. RECENT FINDINGS: The younger age group without vascular risk factors exhibits an increased prevalence of cardio-embolism in context of patent foramen ovale/atrial septal aneurysm strokes, from other determined etiology of non-atherosclerotic vasculopathy including dissection, inherited or acquired thrombophilia, and other unusual causes of stroke. Ethnic disparities also exist in certain populations. The prevalence of stroke in the young is increasing due to several factors. Since stroke is often disabling, this trend poses an enormous threat to socioeconomic stability especially in developing countries. In young patients with an absence of conventional vascular risk factors and negative preliminary stroke work-up, clinicians must consider less common causes of stroke in this population. There is prime opportunity for future investigations as there is currently a lack of evidence-based management guidelines for these uncommon etiologies based on research completed to date.


Asunto(s)
Salud Global/tendencias , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Adulto , Factores de Edad , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Femenino , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico , Foramen Oval Permeable/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Adulto Joven
10.
J Neurol Neurosurg Psychiatry ; 87(9): 937-43, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26780938

RESUMEN

OBJECTIVES: To compare two modes of natalizumab cessation interventions: immediate versus tapered down, as measured by serial MRI and the occurrence of relapses during a 12-month period. BACKGROUND: Weighing progressive multifocal encephalopathy risk associated with ≥24 months of natalizumab therapy against the benefits of disease control, we initiated a natalizumab discontinuation study. METHODS: A phase IV, 12-month, single-blinded randomised (MRI) study. Fifty relapsing patients with multiple sclerosis (MS) who had been on natalizumab therapy ≥24 months and were contemplating natalizumab discontinuation were enrolled. Participants were randomised to either the immediate discontinuation group (IDG) or the tapered group (TG). IDG discontinued natalizumab at once and initiated another disease modifying therapy (DMT) following the last natalizumab infusion, while the TG received two more natalizumab infusions, at 6 and 8 weeks (14 weeks from study entry) before initiating another DMT. Standardised MRI was performed at baseline, 6 and 12 months from the last natalizumab infusion. RESULTS: A higher rate of relapses in the IDG (n=28) compared to the TG (n=8) over 12 months from the last infusion (p=0.007) was observed, most relapses occurred within 3 months of discontinuation (20 vs 7 relapses, p=0.012). The IDG showed a higher number of new T2 lesions within 6-12 months of discontinuation (p=0.025), a higher mean absolute T2-LV change from 0 to 12 months (1.1 vs 0.1 mL, p=0.024) and a higher number of new T1-hypointense lesions over 0-12 months (p=0.005) as well as from baseline to 6 months (p=0.026) compared to the TG. CONCLUSIONS: Natalizumab discontinuation therapy was associated with development of new disease activity. Our tapered protocol showed benefits, as patients in the TG experienced less relapses and lower accumulation of MRI lesions compared to those in the IDG.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/patología , Natalizumab , Recurrencia , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética/métodos , Masculino , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/efectos adversos , Natalizumab/uso terapéutico , Resultado del Tratamiento
11.
Mult Scler ; 22(6): 717-25, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26895718

RESUMEN

The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach.


Asunto(s)
Envejecimiento/fisiología , Progresión de la Enfermedad , Esclerosis Múltiple/fisiopatología , Envejecimiento/inmunología , Envejecimiento/patología , Humanos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología
12.
Cell Signal ; 120: 111203, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38723736

RESUMEN

Metastasis is a key determinant in cancer mortality which is often associated with decreased levels of Nm23-H1, a well-established metastasis suppressor. Despite lacking a secretion signal peptide, Nm23-H1 has been reported to be present in the extracellular space and enclosed within extracellular vesicles (EVs). While the presence of Nm23-H1 proteins in EVs released by cancer cells has been observed through proteomics profiling, the role of vesicular Nm23-H1 remains unclear. Here, we investigated the function of vesicular Nm23-H1 using MDA-MB-231 (highly metastatic, low Nm23-H1) and MCF-7 (low/non-metastatic, high Nm23-H1) breast cancer cell models. Our findings confirm that Nm23-H1 is indeed encapsulated within EVs, and its levels can be manipulated through overexpression and knockdown approaches. Functional assays revealed that EVs derived from MDA-MB-231 cells that contained high levels of Nm23-H1 exhibit impaired pro-migratory properties, suggesting that vesicular Nm23-H1 may act as a metastasis suppressor. Furthermore, EVs with increased levels of Nm23-H1 altered the transcript levels of multiple cancer-related genes in recipient cells and stimulated type I interferon signaling through STAT1 phosphorylation. These results suggest the existence of an unconventional signaling pathway mediated by the uptake of EVs enriched with Nm23-H1, which may contribute to the anti-metastatic effect of Nm23-H1 in the tumor microenvironment. Additionally, our study demonstrates that elevated Nm23-H1 levels can impact the abundance of various other proteins encapsulated within breast cancer cell-derived EVs, such as SUSD2 (Sushi Domain Containing 2) which can also modulate metastasis.


Asunto(s)
Neoplasias de la Mama , Movimiento Celular , Vesículas Extracelulares , Nucleósido Difosfato Quinasas NM23 , Humanos , Vesículas Extracelulares/metabolismo , Nucleósido Difosfato Quinasas NM23/metabolismo , Nucleósido Difosfato Quinasas NM23/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Línea Celular Tumoral , Factor de Transcripción STAT1/metabolismo , Células MCF-7
13.
World Neurosurg ; 181: e399-e404, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37852472

RESUMEN

BACKGROUND: Transradial access is an important tool for many neuroendovascular procedures. Occlusion of the radial or ulnar artery is not uncommon after transradial or transulnar access and can present a challenge for patients requiring repeat angiography. METHODS: Between March 2022 and June 2023, patients undergoing transradial or transulnar angiography who were found to have a radial artery occlusion or ulnar artery occlusion were identified. Repeat catheterization of the occluded artery was attempted using a 21-gauge single wall puncture needle and a 0.021-inch wire to traverse the occlusion and insert a 23-cm sheath into the brachial artery. RESULTS: A total of 25 patients undergoing 26 angiograms during the study period were found to have a radial artery occlusion or ulnar artery occlusion. Successful repeat catheterization of the occluded artery was achieved in 21 of 26 cases (80.7%). Outer diameter sheath size ranged from 5 Fr (0.0655 inch) to 8 Fr (0.1048 inch). No access complications were encountered. Number of prior angiograms, time since prior angiogram, and prior angiogram procedure time were associated with lower likelihood of successful access. CONCLUSIONS: Transradial or transulnar neuroangiography through an occluded radial or ulnar artery is safe and feasible by traversing the occlusion into the brachial artery with a 23-cm sheath. Repeat catheterization is most successful in patients with an arterial occlusion <6 months old. This technique is important in patients who have limited options for arterial access, avoiding access site complications inherent in transfemoral access, and in patients who specifically require radial or ulnar artery access.


Asunto(s)
Arteriopatías Oclusivas , Arteria Cubital , Humanos , Lactante , Arteria Cubital/diagnóstico por imagen , Arteria Cubital/cirugía , Arteria Braquial/cirugía , Angiografía , Arteria Radial/cirugía , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/cirugía , Arteriopatías Oclusivas/etiología , Angiografía Coronaria/métodos
14.
AME Case Rep ; 8: 17, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38234343

RESUMEN

Background: Distal cervical internal carotid artery (cICA) pseudoaneurysms are uncommon. They may lead to thromboembolic or hemorrhagic complications, especially in young adults. We report one of the first cases in the literature regarding the management via PK Papyrus (Biotronik, Lake Oswego, Oregon, USA) balloon-mounted covered stent of a 23-year-old male with an enlarging cervical carotid artery pseudoaneurysm and progressive internal carotid artery stenosis. Case Description: We report the management of a 23-year-old male with an enlarging cervical carotid artery pseudoaneurysm and progressive internal carotid artery stenosis. Based on clinical judgment and imaging analysis, the best option to seal the aneurysm was a PK Papyrus 5×26 balloon-mounted covered stent. A follow-up angiogram showed no residual filling of the pseudoaneurysm, but there was some contrast stagnation just proximal to the stent, which is consistent with a residual dissection flap. We then deployed another PK Papyrus 5×26 balloon-mounted covered stent, providing some overlap at the proximal end of the stent. An angiogram following this subsequent deployment demonstrated complete reconstruction of the cICA with no residual evidence of pseudoaneurysm or dissection flap. There were no residual in-stent stenosis or vessel stenosis. The patient was discharged the day after the procedure with no complications. Conclusions: These positive outcomes support the use of a balloon-mounted covered stent as a safe and feasible modality with high technical success for endovascular management of pseudoaneurysm.

15.
Interv Neuroradiol ; : 15910199231196451, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37593806

RESUMEN

INTRODUCTION: Endovascular mechanical thrombectomy (MT) is an established treatment for large vessel occlusion strokes with a National Institutes of Health Stroke Scale (NIHSS) score of 6 or higher. Data pertaining to minor strokes, medium, or distal vessel occlusions, and most effective MT technique is limited and controversial. METHODS: A multicenter retrospective study of all patients treated with MT presenting with NIHSS score of 5 or less at 29 comprehensive stroke centers. The cohort was dichotomized based on location of occlusion (proximal vs. distal) and divided based on MT technique (direct aspiration first-pass technique [ADAPT], stent retriever [SR], and primary combined [PC]). Outcomes at discharge and 90 days were compared between proximal and distal occlusion groups, and across MT techniques. RESULTS: The cohort included 759 patients, 34% presented with distal occlusion. Distal occlusions were more likely to present with atrial fibrillation (p = 0.008) and receive IV tPA (p = 0.001). Clinical outcomes at discharge and 90 days were comparable between proximal and distal groups. Compared to SR, patients managed with ADAPT were more likely to have a modified Rankin Scale of 0-2 at discharge and at 90 days (p = 0.024 and p = 0.013). Primary combined compared to ADAPT, prior stroke, multiple passes, older age, and longer procedure time were independently associated with worse clinical outcome, while successful recanalization was positively associated with good clinical outcomes. CONCLUSIONS: Proximal and distal occlusions with low NIHSS have comparable outcomes and safety profiles. While all MT techniques have a similar safety profile, ADAPT was associated with better clinical outcomes at discharge and 90 days.

16.
J Stroke ; 25(2): 282-290, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37282375

RESUMEN

BACKGROUND AND PURPOSE: Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). METHODS: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). RESULTS: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0-2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. CONCLUSION: In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients' age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

17.
Clin Neurol Neurosurg ; 225: 107592, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36657358

RESUMEN

OBJECTIVE: The role of endovascular mechanical thrombectomy (MT) in patients presenting with "minor" stroke is uncertain. We aimed to compare outcomes after MT for ischemic stroke patients presenting with National Institutes of Health Stroke Scale (NIHSS) 5 and - within the low NIHSS cohort - identify predictors of a favorable outcome, mortality, and symptomatic intracranial hemorrhage (ICH). METHODS: We retrospectively analyzed a prospectively maintained, international, multicenter database. RESULTS: The study cohort comprised a total of 7568 patients from 29 centers. NIHSS was low (<5) in 604 patients (8%), and > 5 in 6964 (92%). Patients with low NIHSS were younger (67 + 14.8 versus 69.6 + 14.7 years, p < 0.001), more likely to have diabetes (31.5% versus 26.9%, p = 0.016), and less likely to have atrial fibrillation (26.6% versus 37.6%, p < 0.001) compared to those with higher NIHSS. Radiographic outcomes (TICI > 2B 84.6% and 84.3%, p = 0.412) and complication rates (8.1% and 7.2%, p = 0.463) were similar between the low and high NIHSS groups, respectively. Clinical outcomes at every follow up interval, including NIHSS at 24 h and discharge, and mRS at discharge and 90 days, were better in the low NIHSS group, however patients in the low NIHSS group experienced a relative decline in NIHSS from admit to discharge. Mortality was lower in the low NIHSS group (10.4% versus 24.5%, p < 0.001). CONCLUSIONS: Relative to patients with high NIHSS, MT is safe and effective for stroke patients with low NIHSS, and it is reasonable to offer it to appropriately selected patients presenting with minor stroke symptoms. Our findings justify efforts towards a randomized trial comparing MT versus medical management for patients with low NIHSS.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Estados Unidos , Humanos , Estudios Retrospectivos , Trombectomía/efectos adversos , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/cirugía , National Institutes of Health (U.S.) , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/cirugía , Procedimientos Endovasculares/efectos adversos
18.
World Neurosurg ; 160: 16-21, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35032711

RESUMEN

BACKGROUND: Although studies have continued to demonstrate the advantages of transradial access (TRA) for neurointervention, radial artery spasm (RAS) has remained a frequent cause of TRA failure. Dotter and Judkins initially described a technique to dilate areas of peripheral vascular stenosis by advancing sequentially larger catheters across the lesion over a guidewire. We have presented our institutional experience with the use of a modified Dotter technique with long radial sheaths to dilate areas of proximal flow-limiting RAS. In the present study, we reviewed the use of the Dotter technique for alleviating RAS in patients undergoing TRA for neurointervention. METHODS: We performed a retrospective review of all patients undergoing TRA for neurointervention at our institution from 2018 to 2020 to identify patients with proximal flow-limiting RAS. For the identified patients, a modified Dotter technique had been used to dilate the stenosis. The demographic and periprocedural data were assessed to identify any adverse outcomes. RESULTS: Four patients with severe proximal flow-limiting RAS were identified. In each case, a hydrophilic long radial sheath and vascular dilator were sequentially advanced through the stenosis. In all cases, repeat angiography demonstrated improvement of the spasm, and the final radial angiograms demonstrated persistent improvement in caliber and regularity of the vessel. Each procedure was also completed via TRA with no periprocedural complications. CONCLUSIONS: Our modified Dotter technique was effective in bypassing areas of severe proximal flow-limiting RAS, obviating the need for access site conversion. Additional studies are warranted to understand the implication of the angioplasty-like effects seen within the radial artery after removal of the long radial sheaths.


Asunto(s)
Enfermedades Vasculares Periféricas , Arteria Radial , Angioplastia/efectos adversos , Humanos , Arteria Radial/cirugía , Estudios Retrospectivos , Espasmo/etiología
19.
Interv Neuroradiol ; : 15910199221127074, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36114634

RESUMEN

INTRODUCTION: The purpose of this study was to report our initial experience of using a large-bore (0.096″ inner diameter) access catheter in neurovascular interventions. METHODS: Data were retrospectively collected from 5 sites in the US for neurovascular procedures performed using a large-bore access catheter. The effectiveness outcome was technical success, defined as the access catheter's successfully reaching its target vessel without conversion to direct carotid puncture or to a smaller-bore access catheter and successfully completing the intended neurointervention. RESULTS: One hundred and thirteen procedures performed in 112 patients were included in this study. The mean age of the patients was 67.5 years (SD 16.2), and about half (49.1%) were female. The most common primary access sites were the femoral (64.6%) or radial (32.7%) artery. Challenging anatomic variations included severe vessel tortuosity (26/81, 32.1%), type II aortic arch (17/88, 19.3%), type III aortic arch (14/88, 15.9%), bovine arch (16/104, 15.4%), severe angle (<30°) between the subclavian and target vessel (11/74, 14.9%), and subclavian loop (7/79, 8.9%). The median access time to branch view was 18 min (IQR 11-28, N = 75). The technical success rate was 94.7%. Two dissections (1.8%) were related to the large-bore access catheter. Access site complications occurred in 2 patients (1.8%). Four additional symptomatic periprocedural complications not related to the large-bore access catheter occurred (7.1%). CONCLUSION: For neurovascular interventions, a 0.096″ inner diameter access catheter could be used with both femoral and radial arterial approaches, had a high technical success rate, and had a low rate of periprocedural complications.

20.
Neurosurg Clin N Am ; 33(2): 149-159, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35346447

RESUMEN

Transradial access (TRA) has gained traction in neurointerventions as studies continue to demonstrate improved access site safety and equivalent end artery effectiveness when compared with traditional transfemoral techniques. Herein, we describe the technical nuances of obtaining TRA with a focus on distal TRA, left TRA, and sheathless TRA using larger bore catheters. We also discuss various strategies to avoid access site conversion if radial artery spasm or radial anomalies are encountered and offer some solutions for forming the Simmons catheter especially when it cannot be performed in the descending aorta. Lastly, we provide some insights regarding contraindications to TRA.


Asunto(s)
Cateterismo Periférico , Arteria Radial , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/métodos , Humanos , Arteria Radial/cirugía , Resultado del Tratamiento
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