Comparing the Impact of Stenting vs. Medical Therapy for Intracranial Arterial Stenosis : A Systematic Review and One-stage and Two-stage Meta-Analysis of Randomized Clinical Trials.

PURPOSE: In the treatment of intracranial arterial stenosis (ICAS), controversies remain regarding the optimal treatment strategy. Our study aims to conduct an individual patient-level data meta-analysis of existing RCTs comparing PTAS versus best medical therapy and to identify differences in outcomes such as incidence of ischemic stroke or death. METHODS: Randomised controlled trials comparing the outcomes of stenting versus best medical therapy for patients who had symptomatic ICAS of >50%. Excluded studies included case reports, case series, reviews, observational studies,  letters or studies evaluating isolated angioplasty techniques without stenting. Data was extracted in accordance with PRISMA guidelines. RESULTS: 7 studies involving 1425 participants were included. There was an increased risk in the incidence of stroke and death within the first 30 days post-procedure for patients treated with PTAS over best medical therapy (RR = 2.22 [1.28-3.86], I²â€¯= 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41-66.45], I²â€¯= 0%) and death (RR = 5.41 [1.20-24.28], I²â€¯= 0%).Under the shared frailty model, stenting when compared to medical therapy has a HR of 1.81 (95% CI:1.25-2.6) of stroke or death across 1 year. Under the parametric Royston-Parmar model, stenting has a significant decrease in the RMST(-0.83 months; 95% CI: -1.30-0.37). Stenting continued to show worse outcomes up to the 3 year mark with a HR of 1.60 (95% CI: 1.11-2.32). CONCLUSIONS AND RELEVANCE: There is an increased risk of peri- and post-procedural stroke and death over best medical therapy in patients with symptomatic ICAS who undergo PTAS. Further work is required to refine patient selection and mitigate peri-procedural risks.

Revolutionizing the Management of Large-Core Ischaemic Strokes: Decoding the Success of Endovascular Therapy in the Recent Stroke Trials.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic-RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

Safety and clinical outcomes in endovascular treatment for symptomatic cerebral venous thrombosis: a single-center experience with meta-analysis.

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world.

Impact of atrial fibrillation on the treatment effect of bridging thrombolysis in ischemic stroke patients undergoing endovascular thrombectomy: a multicenter international cohort study.

BACKGROUND: The role of bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS) remains debatable. Atrial fibrillation (AF) associated strokes may be associated with reduced treatment effect from IVT. This study compares the effect of bridging IVT in AF and non-AF patients. METHODS: This retrospective cohort study comprised anterior circulation large vessel occlusion (LVO) AIS patients receiving EVT alone or bridging IVT plus EVT within 6 hours of symptom onset. Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0-2 at 90 days. Secondary outcomes were successful reperfusion defined as expanded Thrombolysis In Cerebral Infarction (eTICI) grading ≥2b flow, symptomatic intracerebral hemorrhage (sICH), and in-hospital mortality. RESULTS: We included 705 patients (314 AF and 391 non-AF patients). The mean age was 68.6 years and 53.9% were male. The odds of good functional outcomes with bridging IVT was higher in the non-AF (adjusted odds ratio (aOR) 2.28, 95% CI 1.06 to 4.91, P=0.035) compared with the AF subgroups (aOR 1.89, 95% CI 0.89 to 4.01, P=0.097). However, this did not constitute a significant effect modification by the presence of AF on bridging IVT (interaction aOR 0.12, 95% CI -1.94 to 2.18, P=0.455). The rate of successful reperfusion, sICH, and mortality were similar between bridging IVT and EVT for both AF and non-AF patients. CONCLUSION: The presence of AF did not modify the treatment effect of bridging IVT. Further individual patient data meta-analysis of randomized trials may shed light on the comparative efficacy of bridging IVT in AF versus non-AF LVO strokes.

Preprocedural Imaging : A Review of Different Radiological Factors Affecting the Outcome of Thrombectomy.

BACKGROUND: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.

Evidence-Based Updates to Thrombectomy: Targets, New Techniques, and Devices.

Endovascular thrombectomy (EVT) has been validated in several randomized controlled trials in recent years for its efficacy in the treatment of acute ischemic strokes (AIS) and is now the standard of care according to international guidelines. However, in about 20% of EVT procedures, recanalization is not achieved, and over 50% of patients who undergo EVT still do not have good functional outcome. In this article, we provide an extensive review of the latest evidence and developments in the field of EVT, with particular focus on the factors that improve patient outcomes. These factors include new and adjunctive techniques such as combination of direct aspiration and stent retriever, intra-arterial urokinase or 2b/3a inhibitors, rescue stenting, as well as novel devices including balloon guide catheters and the newer generations of aspiration catheters and stent retrievers. We also examined the latest notion of using first-pass effect (FPE) as the target to achieve during EVT, which has been associated with an improved functional outcome. While the field of EVT has been rapidly evolving, further research is required in specific AIS patient populations such as those with large ischemic core, late presentation beyond 24 h, posterior circulation strokes, and with distal medium vessel occlusion or tandem lesions to better assess its efficacy and safety.

Asian-Pacific perspective on the psychological well-being of healthcare workers during the evolution of the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers. AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes. METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country. RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries. CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

An unusual presentation of Idiopathic hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a rare but life-threatening multi-organ disease which can be complicated by stroke, with devastating outcomes. Eosinophils can accumulate in multiple organs, most commonly involving the heart, skin, lungs, spleen, and liver. Neurological end-organ complications in hypereosinophilic syndrome are unusual and have been established to be of three types: brain infarction, encephalopathy and sensory polyneuropathy. We present a case where acute ischaemic stroke and encephalopathy are early manifestations of Idiopathic HES. It is important to consider HES as an aetiology for stroke and a high eosinophil count is an initial diagnostic clue. Early initiation of steroid therapy can potentially prevent disease progression.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Comparison of Long-Term Mortality of Patients Aged ≤40 Versus >40 Years With Acute Myocardial Infarction.

Young patients with acute myocardial infarction (MI) have a more favorable prognosis than older patients with MI. However, there are limited data comparing the prognosis of young patients with MI with young population controls. Comparison with an age-matched background population could unmask residual mortality risk in young patients with MI that would otherwise not be apparent when merely comparing the mortality risk of young and older patients with MI. We studied 15,151 patients with AMI from 2000 to 2005, of which 601 patients were ≤40 years (young MI). The relative survival ratio (RSR) was calculated as the ratio of the observed survival of patients with MI divided by the expected survival, estimated from the background population (n = 3,771,700) matched for age, gender, and follow-up year. An RSR of <1.0 or >1.0 indicates poorer or better survival, respectively, than the background population. The 12-year all-cause and cardiovascular mortality of young versus older patients was 12.8% versus 50.7% (p <0.001) and 9.2% versus 34.5% (p <0.001), respectively. The adjusted hazard ratio (95% confidence interval) for all-cause and cardiovascular mortality comparing young with older patients was 0.20 (0.16 to 0.27) and 0.27 (0.20 to 0.36), respectively. The RSR (95% confidence interval) of young and older patients was, respectively, 0.969 (0.950 to 0.980) and 0.804 (0.797 to 0.811) at 1 year, 0.942 (0.918 to 0.960) and 0.716 (0.707 to 0.726) at 5 years, and 0.908 (0.878 to 0.938) and 0.638 (0.620 to 0.654) at 9 years. In conclusion, despite a fivefold lower long-term mortality than older patients with MI, young patients with MI remain at significantly greater risk of long-term mortality than an age-matched background population.