Successful Management of COVID-19 Infection in 2 Early Post-Liver Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital. CASE DESCRIPTIONS: Two patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery. CONCLUSION: The management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.

Leukoaraiosis and acute ischemic stroke: 90-day clinical outcome following endovascular recanalization, with proposed "L-ASPECTS".

BACKGROUND: To assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score. METHODS: A retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS ("L-ASPECTS") was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients. RESULTS: 174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (P<0.0001 and AUC=0.7 for L-ASPECTS; P=0.04 and AUC=0.59 for ASPECTS). In the validation cohort, the AUC for L-ASPECTS was 0.79 while the AUC for ASPECTS was 0.70. Of patients that had successful reperfusion (mTICI 2b/3), the AUC for traditional ASPECTS in predicting good functional outcome was 0.80: AUC for L-ASPECTS was 0.89. CONCLUSIONS: Leukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.

Donepezil in the treatment of ischemic stroke: Review and future perspective.

Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT) drastically changed the care of patients with ischemic stroke due to large vessel occlusion. Nevertheless, despite revascularization, many patients do not achieve a good functional outcome. Moreover, not all patients with ischemic stroke are eligible for EVT. During ischemia, a cascade of ischemic and inflammatory changes lead to permanent damage. As such, adjunct therapies that can protect neurons during acute ischemic phase prior to revascularization have the potential of enhancing functional recovery. Donepezil, an acetylcholinesterase inhibitor, improves cognition and global function in patients with Alzheimer's and Vascular dementia via modulation of acetylcholine receptors and downstream inflammatory response. Preclinical studies demonstrated the potential neuroprotective effects of donepezil in ischemic stroke. However, only a handful of clinical studies investigated this drug's safety and efficacy in stroke patients. In this review, we summarize the current evidence for the utility, or lack thereof, donepezil in treating and rehabilitating patients with ischemic stroke.

Association of local anesthesia versus conscious sedation with functional outcome of acute ischemic stroke patients undergoing embolectomy.

PURPOSE: Compare functional outcomes of acute ischemic stroke patients undergoing embolectomy with either local anesthesia or conscious sedation. Secondarily, identify differences in hemodynamic parameters and complication rates between groups. MATERIALS AND METHODS: Single institution, retrospective review of all acute ischemic stroke patients undergoing embolectomy between January 2014 and July 2018 (n = 185). Patients receiving general anesthesia (n = 27) were excluded. One-hundred and eleven of 158 (70.3%) composed the local anesthesia group, and 47 (29.7%) composed the conscious sedation group. Median age was 71 years (interquartile range 59-79). Seventy-eight (49.4%) were male. The median National Institute of Health stroke scale score was 17.5 (interquartile range 11-21). Hemodynamic, medication, complication, and functional outcome data were collected from the anesthesia protocol and medical records. Good functional outcome was defined as a three-month modified Rankin Scale < 2. A multivariate analysis was performed to estimate the association of anesthesia type on three-month modified Rankin Scale score. RESULTS: Three-month modified Rankin Scale score <2 was similar between groups (p = 0.5). Patients receiving conscious sedation were on average younger than patients receiving local anesthesia (p = 0.01). Conscious sedation patients were more likely to receive intravenous thrombolytic prior to embolectomy (p = 0.025). The complication rate and hemodynamic parameters were similar between groups. CONCLUSION: Functional outcome of acute ischemic stroke patients undergoing embolectomy appears to be similar for patients receiving local anesthesia and conscious sedation. This similarity may be beneficial to a future study comparing general anesthesia to local anesthesia and conscious sedation. The use of local anesthesia or conscious sedation does not significantly impact hemodynamic status.

Per-region interobserver agreement of Alberta Stroke Program Early CT Scores (ASPECTS).

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a commonly used scoring system to select patients with stroke for endovascular treatment (EVT). However, the inter- and intra-reader variability is high. OBJECTIVE: To determine whether the inter- and intra-reader variability is different for various regions of the ASPECTS scoring system by evaluating the interobserver variability of ASPECTS between different readers in a per-region analysis. MATERIALS AND METHODS: All patients with acute ischemic stroke who proceeded to EVT in our institutions over a 4-year period were retrospectively identified from a prospectively maintained database. Images were reviewed by two experienced neuroradiologists, who recalculated the ASPECTS independently. We examined each region of the ASPECTS system to evaluate agreement between the raters in each area. RESULTS: 375 patients were included. The median total ASPECTS was 9 (IQR 8-9). The most common region showing ischemic change was the insula, with the M6 region being least commonly affected. Overall interobserver agreement for ASPECTS using Cohen's κ was 0.56 (95% CI 0.51 to 0.61). The region with the highest agreement was the insula (κ=0.56; 0.48 to 0.64). The region with the lowest agreement was M3 (κ=0.34; 0.12 to 0.56). Agreement was relatively good when ASPECTS were dichotomized into 0-5 versus 6-10 (κ=0.66; 0.49 to 0.84). CONCLUSIONS: Substantial interobserver variability is found when calculating ASPECTS. This variability is region dependent, and practitioners should take this into account when using ASPECTS for treatment decisions in patients with acute stroke.

Leukoaraiosis and collateral blood flow in stroke patients with anterior circulation large vessel occlusion.

BACKGROUND: Leukoaraiosis and collateral blood flow are processes that involve small vessels, the former related to flow within the deep perforating arterioles and the latter involving the small, cortical pial-pial connections, both of which are independently used to predict cerebrovascular events and treatment outcomes. The aim of this study was to investigate their relationship to each other. METHODS: We retrospectively reviewed patients who underwent mechanical thrombectomy for stroke with pre-procedural CT imaging within 24 hours of the onset of symptoms. Leukoaraiosis was graded by the total Fazekas score on non-contrast CT, periventricular white matter (PVWM) and deep white matter (DWM) scores, both ranging from 0 to 3. Collateral cerebral blood flow was measured by the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) collateral scale. RESULTS: 178 patients were included with a mean age of 67.6±14.8 years. We found an inverse relationship between total Fazekas score and collateral flow (p<0.0001). Among patients with good collaterals, 75.1% had total Fazekas scores of 0-2, compared with 36.6% of patients with moderate collaterals and 32.7% of patients with poor collaterals with total Fazekas scores of 0-2. Mean Fazekas scores were 1.6±1.5, 3.1±1.5 and 3.4±1.6 for good, moderate and poor collaterals, respectively (p<0.0001). On multivariate analysis, total Fazekas score was the only variable independently associated with collateral status (p<0.0001). CONCLUSIONS: Increasing severity of leukoaraiosis is associated with poor collateral grade among ischemic stroke patients with anterior circulation large vessel occlusion. These findings suggest that leukoaraiosis may be a marker for global cerebrovascular dysfunction.

Selective brain hypothermia: feasibility and safety study of a novel method in five patients.

BACKGROUND/OBJECTIVE: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. METHODS: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. RESULTS: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. CONCLUSION: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body-brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.

Region-specific agreement in ASPECTS estimation between neuroradiologists and e-ASPECTS software.

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a widely used measure of ischemic change on non-contrast CT. Although predictive of long-term outcome, ASPECTS is limited by its modest interobserver agreement. One potential solution to this is the use of machine learning strategies, such as e-ASPECTS, to detect ischemia. Here, we compared e-ASPECTS with manual scoring by experienced neuroradiologists for all 10 individual ASPECTS regions. MATERIALS AND METHODS: We retrospectively reviewed 178 baseline non-contrast CT scans from patients with acute ischemic stroke undergoing endovascular thrombectomy. All scans were reviewed by two independent neuroradiologists with a third reader arbitrating disagreements for a consensus read. Each ASPECTS region was scored individually. All scans were then evaluated using a machine learning-based software package (e-ASPECTS, Brainomix). Interobserver agreement between readers and the software for each region was calculated with a kappa statistic. RESULTS: The median ASPECTS was 9 for manual scoring and 8.5 for e-ASPECTS, with an overall agreement of κ=0.248. Regional agreement varied from κ=0.094 (M1) to κ=0.555 (lentiform), with better performance in subcortical regions. When corrected for the low number of infarcts in any given region, prevalence-adjusted bias-adjusted kappa ranged from 0.483 (insula) to 0.888 (M3), with greater agreement for cortical areas. Intraclass correlation coefficients were between 0.09 (M1) and 0.556 (lentiform). CONCLUSION: Manual scoring and e-ASPECTS had fair agreement in our dataset on a per-region basis. This warrants further investigation using follow-up scans or MRI as the gold standard measure of true ASPECTS.

Submaximal angioplasty in the treatment of patients with symptomatic ICAD: a systematic review and meta-analysis.

INTRODUCTION: Management approaches for intracranial atherosclerosis include medical, surgical, or endovascular treatment. Among endovascular treatments, recent studies have stated that submaximal angioplasty (SA) may offer considerable benefits and be a promising alternative to aggressive medical therapyand/or stenting in the treatment of intracranial atherosclerotic disease (ICAD). OBJECTIVE: To investigate the rates of periprocedural and long-term cerebrovascular accidents, mortality, and restenosis in patients with symptomatic ICAD who were treated with SA. METHODS: An electronic database search was performed for relevant studies that reported clinical outcomes of patients with ICAD following SA. Outcomes of interest were incidence of transient ischemic attack, intracerebral hemorrhage, stroke, and mortality in the periprocedural period and at 1 year. The periprocedural period was defined as the time from SA until 30 days after the procedure. Technical success and restenosis rates after the procedure were also analyzed. RESULTS: A total of 19 studies with 777 patients were identified. The technical success rate was 93% (95% CI 85% to 98%). The incidence of 30-day and 1-year stroke (all types) was 3% (95% CI 1% to 5%) and 5% (95% CI 4% to 8%), respectively. Thirty-day and 1-year mortality was found to be 1% (95% CI 0% to 2%) and 2% (95% CI 0% to 4%), respectively. The combined incidence of stroke or death was 5% (95% CI 3% to 8%) at 30 days, and 9% (95% CI 7% to 12%) at 1 year. CONCLUSION: The findings suggest that SA might be a promising alternative treatment in the treatment of symptomatic ICAD due to its favorable technical profile, periprocedural safety, and long-term efficacy. A randomized clinical trial is warranted to compare the safety and efficacy of SA with 'gold standard' medical treatment.

Memantine for the treatment of ischemic stroke: experimental benefits and clinical lack of studies.

Stroke is an important cause of mortality and disability worldwide. Immediately after stroke onset, the ischemic cascade initiates and deleteriously affects neural cells. Time to reperfusion therapy is a critical determinant of functional recovery in stroke patients. Although recent trials have shown the significant efficacy of endovascular thrombectomy, either alone or with intravenous tissue plasminogen activator, in improving the functional outcomes of stroke patients with large vessel occlusion, hours can pass before patients receive reperfusion therapy. Moreover, many patients do not meet the eligibility criteria to receive reperfusion treatments. Therefore, an adjunct and alternative agent that can protect ischemic neuronal tissue during the hyperacute phase until reperfusion therapy can be administered may prevent further brain damage and enhance functional recovery. Memantine is a US Food and Drug Administration approved drug for the treatment of Alzheimer's disease. Memantine blocks overstimulated N-methyl-d-aspartate receptors and prevents neurotoxicity caused by massive glutamate release. Preclinical studies show that memantine decreases infarction volume and improves neurologic outcomes. However, few clinical studies have evaluated the safety and efficacy of memantine in stroke patients. This review article summarizes the current evidence for the role of memantine in the treatment of ischemic stroke and highlights areas for future research.

Redefining 'success': a systematic review and meta-analysis comparing outcomes between incomplete and complete revascularization.

BACKGROUND: Conventionally, 'successful' endovascular thrombectomy (EVT) had been defined as achieving revascularization of thrombolysis in cerebral infarction (TICI)-2B or greater, rather than as 'complete' (TICI-3) versus 'incomplete' (TICI-2B) revascularization. PURPOSE: We performed a systematic review and meta-analysis of studies comparing clinical outcomes between patients with TICI-2B and TICI-3 revascularization. METHODS: Multiple databases were searched for relevant publications between January 2003 and March 2018. Studies comparing outcomes between the TICI-2B and the TICI-3 group of acute ischemic stroke (AIS) patients treated with EVT were included. Random effects meta-analysis was performed to evaluate outcomes among TICI-2B and TICI-3 groups. The following outcomes were assessed: good neurologic outcome (modified Rankin Scale (mRS)≤2 at day 90), mortality, and intracerebral hemorrhage (ICH). RESULTS: Twenty-one studies comprising 2747 patients were identified. Patients with TICI-2B revascularization had mRS≤2 at day 90 rates of 46% (391/847) compared with 66% (522/791) for TICI-3 patients (OR 0.46, 95% CI 0.37 to 0.57). Mortality rates were significantly higher in the TICI-2B group (78/570, 14%) than in the TICI-3 group (55/709, 8%) (OR 2.00, 95% CI 1.38 to 2.91). The ICH rates were also significantly higher in the TICI-2B group as compared with the TICI-3 group (31% [134/439] vs. 22% [108/490]; OR 2.20, 95% CI 1.47 to 3.30). CONCLUSIONS: Differences in all major outcome measures were markedly better in patients with complete versus incomplete but still 'successful' revascularization using prior thresholds, with ORs in the order of those seen in recent definitive trials comparing EVT to an intravenous tissue plasminogen activator.

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5-24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36-0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46-11·60; p<0·0001), antiplatelet use (1·68, 1·06-2·66; p=0·026), and anticoagulant use (3·48, 1·96-6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75-0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95-6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03-0·07). INTERPRETATION: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. FUNDING: UK Medical Research Council and British Heart Foundation.

Awareness toward stroke in a population-based sample of Iranian adults.

Background: Stroke is the leading cause of death and functional disability. While there have been major advances regarding the management of stroke, a significant proportion of people are still unaware of stroke-related symptoms and risk factors. This study was performed to assess the awareness of stroke's warning signs and risk factors among a sample of Iranian population. Methods: A total of 649 participants were randomly selected using systematic randomization from the list of telephone numbers obtained from the telephone directory. Demographic characteristics were recorded. Participants were asked to answer questions regarding the awareness about stroke, its warning signs and risk factors. Results: Patients' mean age was 32.0 ± 12.2 years old, and 56.4% were women. Hypertension and history of stroke were major risk factors, and loss of consciousness, vertigo and ataxia were major warning signs of stroke correctly identified by respondents. Multiple linear regressions showed that age (ß = 0.277, P < 0.001), academic level of education (ß = 6.41, P = 0.01), housewifery (ß = 8.9, P < 0.001), jobs related to medical care (ß = 13.17, P = 0.016) and previous information about stroke (ß = 18.71, P < 0.001) were significant predictors of the overall awareness about stroke. Conclusion: The awareness of people about stroke, its risk factors and warning signs were good in this study. The awareness toward stroke can be associated with factors such as age, academic level of education, job and previous information about stroke. Further studies are recommended to program public multimedia and health education in academies and colleges.