Neuron-specific enolase as a prognostic biomarker in acute ischemic stroke patients treated with reperfusion therapies.

Introduction: Ischemic stroke is a significant global health concern, with reperfusion therapies playing a vital role in patient management. Neuron-specific enolase (NSE) has been suggested as a potential biomarker for assessing stroke severity and prognosis, however, the role of NSE in predicting long-term outcomes in patients undergoing reperfusion therapies is still scarce. Aim: To investigate the association between serum NSE levels at admission and 48 h after reperfusion therapies, and functional outcomes at 90 days in ischemic stroke patients. Methods: This study conducted a prospective cross-sectional analysis on consecutive acute ischemic stroke patients undergoing intravenous fibrinolysis and/or endovascular thrombectomy. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days post-stroke and two groups were defined according to having unfavorable (mRS3-6) or favorable (mRS0-2) outcome. Demographic, clinical, radiological, and laboratory data were collected, including NSE levels at admission and 48 h. Spearman's coefficient evaluated the correlation between analyzed variables. Logistic regression analysis was performed to verify which variables were independently associated with unfavorable outcome. Two ROC curves determined the cut-off points for NSE at admission and 48 h, being compared by Delong test. Results: Analysis of 79 patients undergoing reperfusion treatment following acute stroke revealed that patients with mRS 3-6 had higher NIHSS at admission (p < 0.0001), higher NIHSS at 24 h (p < 0.0001), and higher NSE levels at 48 h (p = 0.008) when compared to those with mRS 0-2. Optimal cut-off values for NSE0 (>14.2 ng/mL) and NSE48h (>26.3 ng/mL) were identified, showing associations with worse clinical outcomes. Adjusted analyses demonstrated that patients with NSE48h > 26.3 ng/mL had a 13.5 times higher risk of unfavorable outcome, while each unit increase in NIHSS24h score was associated with a 22% increase in unfavorable outcome. Receiver operating characteristic analysis indicated similar predictive abilities of NSE levels at admission and 48 h (p = 0.298). Additionally, a strong positive correlation was observed between NSE48h levels and mRS at 90 days (r = 0.400 and p < 0.0001), suggesting that higher NSE levels indicate worse neurological disability post-stroke. Conclusion: Serum NSE levels at 48 h post-reperfusion therapies are associated with functional outcomes in ischemic stroke patients, serving as potential tool for patient long-term prognosis.

Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation.

Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.

Safety and efficacy of reperfusion therapies in acute ischemic stroke related to left ventricular thrombus: A retrospective cohort study.

BACKGROUND: Left ventricular thrombus (LVT) is a source of cardiogenic embolic stroke. Conflicting data exist in the literature regarding the utilization of intravenous thrombolysis (IVT) at the acute phase of stroke in presence of LVT. We sought to assess the efficacy and safety of reperfusion therapies (IVT and/or thrombectomy) in patients with LVT. METHODS: We retrospectively analyzed patients with acute ischemic stroke and proven LVT and divided them in two groups: an intervention group with patients treated by reperfusion therapies and a control group with untreated patients. RESULTS: Between 2009 and 2021, 3890 patients were treated by reperfusion therapies in the Lyon stroke center, 33 of whom (0.9%) had LVT. We identified 27 control patients. There were more embolic recurrences at six months in the intervention group than in the control group (nine recurrences versus three, P=0.03, OR=13.56, 95% CI [1.5;195]). Only two early embolic recurrences (< 24h) occurred, both in the IVT group. There was a 4.8-fold decrease in the median NIHSS score between baseline and 24h follow-up in the intervention group (P<0.0001), and the two groups exhibited similar six-month mortality. At stroke onset, cardiopathy was known in 70% of patients, while LVT was known in 30%. CONCLUSION: Acute reperfusion therapies seem to be effective in the context of stroke in patients with LVT. However, further studies are needed to support the hypothesis that stroke recurrence might be related to the use of IVT.

Implementation of a retinal stroke-code protocol results in visual recovery in patients receiving reperfusion therapies.

INTRODUCTION: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment. PATIENTS AND METHODS: Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week. RESULTS: Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations. CONCLUSION: A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies.

Acute Dysphagia Following Reperfusion Therapies: A Prospective Pilot Cohort Study.

Dysphagia is a well-documented sequela of stroke. Recent advancements in medical treatments for stroke include reperfusion therapies (endovascular thrombectomy (EVT) and thrombolysis). As outcomes following reperfusion therapies are typically measured via general functional scales, the pattern and progression of acute dysphagia following reperfusion therapies is less known. To determine the progression of acute dysphagia (0-72 h) following reperfusion therapies and relationships between various stroke parameters and dysphagia, twenty-six patients were prospectively recruited across two EVT and thrombolysis centres in Brisbane, Australia. Dysphagia was screened via the Gugging Swallowing Screen (GUSS) at the bedside at three timepoints: 0-24 h, 24-48 h, and 48-72 h post-reperfusion therapies. Across three groups (EVT only, thrombolysis only, or both), the incidence of any dysphagia within the first 24 h of reperfusion therapy was 92.31% (n = 24/26), 91.30% (n = 21/23) by 48 h, and 90.91% (n = 20/22) by 72 h. Fifteen patients presented with severe dysphagia at 0-24 h, 10 at 24-48 h, and 10 at 48-72 h. Whilst dysphagia was not significantly correlated to infarct penumbra/core size, dysphagia severity was significantly related to the number of passes required during EVT (p = 0.009).Dysphagia continues to persist in the acute stroke population despite recent advancements in technology aimed to reduce morbidity and mortality post-stroke. Further research is required to establish protocols for management of dysphagia post-reperfusion therapies.

Reperfusion Therapies in Acute Ischemic Stroke Beyond the Conventional Time Window: A Narrative Review.

Stroke is the second most common cause of death worldwide, with 50% of survivors experiencing long-term disability. For more than two decades, treatment with intravenous thrombolysis (IVT) and mechanical endovascular thrombectomy (MET), the only approved stroke reperfusion therapies, was restricted to patients within the 4.5-6 hour time window, respectively. Therefore, patients who presented with acute ischemic stroke (AIS) beyond the conventional time window were excluded from reperfusion treatment. This narrative review aims to review the scientific literature on the possibilities of reperfusion therapies for patients who present with an unknown time of stroke onset, and those with stroke onset beyond the conventional 4.5-6 hour time window. Beyond the conventional time window, the eligibility of patients for IVT or MET, the two main therapeutic procedures, is decided based on the concept of penumbral imaging. Penumbral imaging identifies patients with hypoperfused but viable brain tissue, who could benefit from reperfusion. On the other hand, clock-based DWI-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can detect stroke that has occurred within 4.5 hours in patients with an unknown time of onset, including patients who awaken with stroke. The introduction of penumbral imaging and MRI-based tissue clocking as imaging biomarkers for stroke has revolutionized stroke therapy, potentially allowing for personalized treatment of eligible stroke patients.

Automated advanced imaging in acute ischemic stroke. Certainties and uncertainties.

The purpose of this is study was to review pearls and pitfalls of advanced imaging, such as computed tomography perfusion and diffusion-weighed imaging and perfusion-weighted imaging in the selection of acute ischemic stroke (AIS) patients suitable for endovascular treatment (EVT) in the late time window (6-24 h from symptom onset). Advanced imaging can quantify infarct core and ischemic penumbra using specific threshold values and provides optimal selection parameters, collectively called target mismatch. More precisely, target mismatch criteria consist of core volume and/or penumbra volume and mismatch ratio (the ratio between total hypoperfusion and core volumes) with precise cut-off values. The parameters of target mismatch are automatically calculated with dedicated software packages that allow a quick and standardized interpretation of advanced imaging. However, this approach has several limitations leading to a misclassification of core and penumbra volumes. In fact, automatic software platforms are affected by technical artifacts and are not interchangeable due to a remarkable vendor-dependent variability, resulting in different estimate of target mismatch parameters. In addition, advanced imaging is not completely accurate in detecting infarct core, that can be under- or overestimated. Finally, the selection of candidates for EVT remains currently suboptimal due to the high rates of futile reperfusion and overselection caused by the use of very stringent inclusion criteria. For these reasons, some investigators recently proposed to replace advanced with conventional imaging in the selection for EVT, after the demonstration that non-contrast CT ASPECTS and computed tomography angiography collateral evaluation are not inferior to advanced images in predicting outcome in AIS patients treated with EVT. However, other authors confirmed that CTP and PWI/DWI postprocessed images are superior to conventional imaging in establishing the eligibility of patients for EVT. Therefore, the routine application of automatic assessment of advanced imaging remains a matter of debate. Recent findings suggest that the combination of conventional and advanced imaging might improving our selection criteria.

Pivotal role of multiphase computed tomography angiography for collateral assessment in patients with acute ischemic stroke.

The cerebral collateral circulation is the main compensatory mechanism that maintains the ischemic penumbra viable, the tissue at risk for infarction that can be saved if blood flow is restored by reperfusion therapies. In clinical practice, the extent of collateral vessels recruited after vessel occlusion can be easily assessed with computed tomography angiography (CTA) using two different techniques: single-phase CTA (sCTA) and multi-phase CTA (mCTA). Both these methodologies have demonstrated a high prognostic predictive value for prognosis due to the strong association between the presence of good collaterals and favorable radiological and clinical outcomes in patients with acute ischemic stroke (AIS). However, mCTA seems to be superior to sCTA in the evaluation of collaterals and a promising tool for identifying AIS patients who can benefit from reperfusion therapies. In particular, it has recently been proposed the use of mCTA eligibility criteria has been recently proposed for the selection of AIS patients suitable for endovascular treatment instead of the current accepted criteria based on CT perfusion. In this review, we analyzed the characteristics, advantages and disadvantages of sCTA and mCTA to better understand their fields of application and the potential of mCTA in becoming the method of choice to assess collateral extent in AIS patients.

Mechanical Complication of Acute Myocardial Infarction Secondary to COVID-19 Disease.

The aggressive inflammatory response to COVID-19 can result in airway damage, respiratory failure, cardiac injury, and multiorgan failure, which lead to death in susceptible patients. Cardiac injury and acute myocardial infarction (AMI) secondary to COVID-19 disease can lead to hospitalization, heart failure, and sudden cardiac death. When serious collateral damage from tissue necrosis or bleeding occurs, mechanical complications of myocardial infarction and cardiogenic shock can ensue. While prompt reperfusion therapies have decreased the incidence of these serious complications, patients who present late following the initial infarct are at increased for mechanical complications, cardiogenic shock, and death. The health outcomes for patients with mechanical complications are dismal if not recognized and treated promptly. Even if they survive serious pump failure, their CICU stay is often prolonged, and their index hospitalization and follow-up visits may consume significant resources and impact the health care system.