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Neurotherapeutics : the Journal of the... Apr 2023Racial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to... (Review)
Review
Racial and ethnic inequities in stroke care are ubiquitous. Acute reperfusion therapies, i.e., IV thrombolysis (IVT) and mechanical thrombectomy (MT), are central to acute stroke care and are highly efficacious at preventing death and disability after stroke. Disparities in the use of IVT and MT in the USA are pervasive and contribute to worse outcomes among racial and ethnic minority individuals with ischemic stroke. A meticulous understanding of disparities and underlying root causes is necessary in order to develop targeted mitigation strategies with lasting effects. This review details racial and ethnic disparities in the use of IVT and MT after stroke and highlights inequities in the underlying process measures as well as the contributing root causes. Furthermore, this review spotlights the systemic and structural inequities that contribute to race-based differences in the use of IVT and MT, including geographic and regional differences and differences based on neighborhood, zip code, and hospital type. In addition, recent promising trends suggesting improvements in racial and ethnic IVT and MT disparities and potential approaches for future solutions to achieve equity in stroke care are briefly discussed.
Topics: Humans; Thrombectomy; Ethnicity; Brain Ischemia; Treatment Outcome; Minority Groups; Stroke; Reperfusion
PubMed: 37219714
DOI: 10.1007/s13311-023-01388-y -
Neuron May 2024Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals...
Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.
Topics: Animals; Ischemic Stroke; Mice; Collateral Circulation; Humans; Reperfusion; Meninges; Male; Cerebrovascular Circulation; Mice, Inbred C57BL; Disease Models, Animal; Brain; Thrombectomy
PubMed: 38412858
DOI: 10.1016/j.neuron.2024.01.031 -
Arquivos de Neuro-psiquiatria Dec 2023Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of... (Review)
Review
Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.
Topics: Humans; Ischemic Stroke; Brain Ischemia; Stroke; Thrombectomy; Thrombolytic Therapy; Reperfusion; Treatment Outcome
PubMed: 38157871
DOI: 10.1055/s-0043-1777721 -
CNS Neuroscience & Therapeutics Feb 2024In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete... (Review)
Review
In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.
Topics: Humans; No-Reflow Phenomenon; Microcirculation; Stroke; Thrombectomy; Reperfusion; Treatment Outcome
PubMed: 38358074
DOI: 10.1111/cns.14631 -
Journal of Cerebral Blood Flow and... May 2021While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow... (Comparative Study)
Comparative Study Review
While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia.
Topics: Brain; Cerebral Blood Volume; Cerebrovascular Circulation; Child; Combined Modality Therapy; Diffusion Magnetic Resonance Imaging; Female; Fibrinolytic Agents; Humans; Ischemic Stroke; Magnetic Resonance Angiography; Male; Mechanical Thrombolysis; Middle Aged; Reperfusion; Risk Factors; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33325765
DOI: 10.1177/0271678X20978861 -
Cells Jul 2023Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric... (Review)
Review
Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury. NO binds to soluble guanylyl cyclase (sGC) to regulate vasodilation, maintain endothelial barrier integrity, and modulate inflammation through the production of cyclic-GMP in vascular smooth muscle. Pharmacologic sGC stimulators and activators have recently been developed. In preclinical studies, sGC stimulators, which augment the reduced form of sGC, and activators, which activate the oxidized non-NO binding form of sGC, increase vasodilation and decrease cardiac, cerebral, renal, pulmonary, and hepatic injury following IR. These effects may be a result of the improved regulation of perfusion and decreased oxidative injury during IR. sGC stimulators are now used clinically to treat some chronic conditions such as heart failure and pulmonary hypertension. Clinical trials of sGC activators have been terminated secondary to adverse side effects including hypotension. Additional clinical studies to investigate the effects of sGC stimulation and activation during acute conditions, such as IR, are warranted.
Topics: Humans; Soluble Guanylyl Cyclase; Hypertension, Pulmonary; Signal Transduction; Ischemia; Reperfusion
PubMed: 37508567
DOI: 10.3390/cells12141903 -
JAMA Network Open Jun 2023Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China.
OBJECTIVE
To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China.
DESIGN, SETTING, AND PARTICIPANTS
In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020.
INTERVENTIONS
Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team.
MAIN OUTCOMES AND MEASURES
The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2.
RESULTS
All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses.
CONCLUSIONS AND RELEVANCE
In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03578107.
Topics: Humans; Male; Aged; Ischemic Stroke; Tissue Plasminogen Activator; Quality Improvement; Stroke; Reperfusion
PubMed: 37266940
DOI: 10.1001/jamanetworkopen.2023.16465 -
International Journal of Molecular... Nov 2023Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although...
Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients suffering ischemia or stroke. Our main purpose was to analyze if the transient receptor potential channel 7 (TRPM7) could contribute to retinal dysfunction in retinal pathologies associated with ischemia. By using an experimental model of acute retinal ischemia, we analyzed the changes in retinal function by electroretinography and the changes in retinal morphology by optical coherence tomography (OCT) and OCT-angiography (OCTA). Immunohistochemistry was performed to assess the pattern of TRPM7 and its expression level in the retina. Our results show that ischemia elicited a decrease in retinal responsiveness to light stimuli along with reactive gliosis and a significant increase in the expression of TRPM7 in Müller cells. TRPM7 could emerge as a new drug target to be explored in retinal pathologies associated with ischemia.
Topics: Animals; Humans; Infant, Newborn; Mice; Ischemia; Protein Serine-Threonine Kinases; Reperfusion; Retina; Retinal Diseases; Retinal Vessels; TRPM Cation Channels
PubMed: 38003256
DOI: 10.3390/ijms242216068 -
Journal of the American College of... May 2023Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related...
BACKGROUND
Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown.
OBJECTIVES
The authors sought to relate spontaneous reperfusion to the thrombotic profile.
METHODS
In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke).
RESULTS
Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029).
CONCLUSIONS
We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes.
Topics: Humans; ST Elevation Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Myocardial Infarction; Thrombosis; Biomarkers; Reperfusion; Treatment Outcome; Myocardial Reperfusion
PubMed: 37164525
DOI: 10.1016/j.jacc.2023.03.388 -
Stroke Feb 2023Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke...
BACKGROUND
Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO).
METHODS
Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography-based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining.
RESULTS
Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 (<0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls (<0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 (<0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls (<0.05).
CONCLUSIONS
DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.
Topics: Rats; Mice; Female; Animals; Male; Infarction, Middle Cerebral Artery; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Rats, Wistar; Sex Characteristics; Stroke; Reperfusion; Reperfusion Injury; Brain Injuries; Disease Models, Animal; Middle Cerebral Artery
PubMed: 36689578
DOI: 10.1161/STROKEAHA.122.040972