Highly Selective Electrochemical Baeyer-Villiger Oxidation through Oxygen Atom Transfer from Water.

The Baeyer-Villiger oxidation of ketones is a crucial oxygen atom transfer (OAT) process used for ester production. Traditionally, Baeyer-Villiger oxidation is accomplished by thermally oxidizing the OAT from stoichiometric peroxides, which are often difficult to handle. Electrochemical methods hold promise for breaking the limitation of using water as the oxygen atom source. Nevertheless, existing demonstrations of electrochemical Baeyer-Villiger oxidation face the challenges of low selectivity. We report in this study a strategy to overcome this challenge. By employing a well-known water oxidation catalyst, Fe2O3, we achieved nearly perfect selectivity for the electrochemical Baeyer-Villiger oxidation of cyclohexanone. Mechanistic studies suggest that it is essential to produce surface hydroperoxo intermediates (M-OOH, where M represents a metal center) that promote the nucleophilic attack on ketone substrates. By confining the reactions to the catalyst surfaces, competing reactions (e.g., dehydrogenation, carboxylic acid cation rearrangements, and hydroxylation) are greatly limited, thereby offering high selectivity. The surface-initiated nature of the reaction is confirmed by kinetic studies and spectroelectrochemical characterizations. This discovery adds nucleophilic oxidation to the toolbox of electrochemical organic synthesis.

Coronavirus disease 2019 infection and cerebrovascular diseases: an update on the pathophysiology and management.

PURPOSE OF REVIEW: COVID-19 is an ongoing global pandemic since it was first discovered in 2020. Cerebral vascular disease and stroke are among the most common and devastating neurological manifestations of COVID-19. This review offers an up-to-date information on the possible underlying mechanism of COVID-19-related stroke, its diagnosis, and management. RECENT FINDINGS: The thromboembolism associated with COVID-19 infection is likely related to the cytokine storm with innate immune activation, pulmonary disease leading to hypoxia-induced ischemia, thrombotic microangiopathy, endothelial damage and multifactorial activation of the coagulation cascade. Currently, there is no clear guidelines on the use of antithrombotics for the prevention and treatment of this phenomenon. SUMMARY: COVID-19 infection can directly cause a stroke or facilitate the formation of thromboembolism in the presence of other medical conditions. Physicians treating patients with COVID-19 should stay vigilant about the signs and symptoms of stroke, detect and treat early.

Low Catalyst Loading Enhances Charge Accumulation for Photoelectrochemical Water Splitting.

Solar water oxidation is a critical step in artificial photosynthesis. Successful completion of the process requires four holes and releases four protons. It depends on the consecutive accumulation of charges at the active site. While recent research has shown an obvious dependence of the reaction kinetics on the hole concentrations on the surface of heterogeneous (photo)electrodes, little is known about how the catalyst density impacts the reaction rate. Using atomically dispersed Ir catalysts on hematite, we report a study on how the interplay between the catalyst density and the surface hole concentration influences the reaction kinetics. At low photon flux, where surface hole concentrations are low, faster charge transfer was observed on photoelectrodes with low catalyst density compared to high catalyst density; at high photon flux and high applied potentials, where surface hole concentrations are moderate or high, slower surface charge recombination was afforded by low-density catalysts. The results support that charge transfer between the light absorber and the catalyst is reversible; they reveal the unexpected benefits of low-density catalyst loading in facilitating forward charge transfer for desired chemical reactions. It is implied that for practical solar water splitting devices, a suitable catalyst loading is important for maximized performance.

Bell inequalities for entangled qubits: quantitative tests of quantum character and nonlocality on quantum computers.

This work provides quantitative tests of the extent of violation of two inequalities applicable to qubits coupled into Bell states, using IBM's publicly accessible quantum computers. Violations of the inequalities are well established. Our purpose is not to test the inequalities, but rather to determine how well quantum mechanical predictions can be reproduced on quantum computers, given their current fault rates. We present results for the spin projections of two entangled qubits, along three axes A, B, and C, with a fixed angle θ between A and B and a range of angles θ' between B and C. For any classical object that can be characterized by three observables with two possible values, inequalities govern relationships among the probabilities of outcomes for the observables, taken pairwise. From set theory, these inequalities must be satisfied by all such classical objects; but quantum systems may violate the inequalities. We have detected clear-cut violations of one inequality in runs on IBM's publicly accessible quantum computers. The Clauser-Horne-Shimony-Holt (CHSH) inequality governs a linear combination S of expectation values of products of spin projections, taken pairwise. Finding S > 2 rules out local, hidden variable theories for entangled quantum systems. We obtained values of S greater than 2 in our runs prior to error mitigation. To reduce the quantitative errors, we used a modification of the error-mitigation procedure in the IBM documentation. We prepared a pair of qubits in the state |00〉, found the probabilities to observe the states |00〉, |01〉, |10〉, and |11〉 in multiple runs, and used that information to construct the first column of an error matrix M. We repeated this procedure for states prepared as |01〉, |10〉, and |11〉 to construct the full matrix M, whose inverse is the filtering matrix. After applying filtering matrices to our averaged outcomes, we have found good quantitative agreement between the quantum computer output and the quantum mechanical predictions for the extent of violation of both inequalities as functions of θ'.

Exosomes Treatment Mitigates Ischemic Brain Damage but Does Not Improve Post-Stroke Neurological Outcome.

BACKGROUND/AIMS: Recent studies demonstrated that the treatment with mesenchymal stem cells (MSCs) obtained from the human umbilical cord blood improved survival, reduced brain damage, prevented apoptosis, suppressed inflammatory responses, downregulated the DNA damage-inducing genes, upregulated the DNA repair genes, and facilitated neurological recovery in stroke-induced animals. Emerging stroke literature supports the concept that the exosomes released from MSCs are the primary biological principles underlying the post-stroke neuroprotection offered by MSCs treatment. METHODS: Because the treatment with exosomes has a great potential to overcome the limitations associated with cell-based therapies, we tested the efficacy of exosomes secreted from HUCB-MSCs under standard culture conditions on post-stroke brain damage and neurological outcome in a rat model of ischemic stroke by performing TTC staining as well as the modified neurological severity scores, modified adhesive removal, beam-walking, and accelerating Rotarod performance tests before ischemia and at regular intervals until seven days reperfusion. RESULTS: Exosomes treatment attenuated the infarct size. Treatment with exosomes did not affect the post-stroke survival rate and body weight changes, but exacerbated the somatosensory and motor dysfunction and adversely affected the natural recovery that occurs without any treatment. CONCLUSION: Treatment with exosomes secreted from HUCB-MSCs under standard culture conditions attenuates the ischemic brain damage but does not improve the post-stroke neurological outcome.

Impact of Stroke Call on the Stroke Neurology Workforce in the United States: Possible Challenges and Opportunities.

BACKGROUND: The Stroke & Vascular Neurology Section of the American Academy of Neurology was charged to identify challenges to the recruitment and retention of stroke neurologists and to make recommendations to address any identified problems. The Section initiated this effort by determining the impact of stroke on-call requirements as a barrier to the recruitment and retention of vascular neurologists. METHODS: This is a cross-sectional survey of a sample of US Neurologists providing acute stroke care. RESULTS: Of the 900 neurologists who were sent surveys, 313 (35%) responded. Of respondents from institutions providing stroke coverage, 71% indicated that general neurologists and 45% indicated that vascular neurologists provided that service. Of those taking stroke call, 36% agreed with the statement, "I spent too much time on stroke call," a perception that was less common among those who took less than 12-hour shifts (P < .0001); 21% who participated in stroke call were dissatisfied with their current job. Forty-six percent indicated that their stroke call duties contributed to their personal feeling of "burnout." CONCLUSIONS: Although the reasons are likely multifactorial, our survey of neurologists providing stroke care suggests that over-burdensome on-call responsibilities may be contributing to the vascular neurology workforce burnout and could be affecting recruitment and retention of vascular neurologists. Strategies to reduce the lifestyle impact of stroke call may help address this problem.

Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases.

BACKGROUND/AIMS: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. METHODS: To test our hypothesis, we administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. RESULTS: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. CONCLUSION: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation.

Pathogenic Heterogeneity of Distal Single Small Subcortical Lenticulostriate Infarctions Based on Lesion Size.

BACKGROUND: Single small subcortical infarctions (SSSIs) in the lenticulostriate artery territory can be classified as proximal single small subcortical infarction (pSSSI) or distal single small subcortical infarction (dSSSI) lesions depending on the involvement of the lowest part of the basal ganglia. It was reported that pSSSI lesions have more characteristics of large artery atherosclerosis, whereas dSSSI lesions are more characteristic of small vessel disease. Because infarction of small vessels is more likely to be distal and may result in small lesions, we hypothesized that the clinical features of dSSSI lesions might be heterogeneous and classified based on lesion size. METHODS: Lenticulostriate SSSI patients admitted within 72 hours of stroke onset were included from a prospectively registered hospital-based stroke database. We determined the location (lowest slice [LS] involved) and size (total number of slices [TNS] involved) of SSSIs on magnetic resonance imagings. Based on lesion location, SSSIs were divided into pSSSI (LS ≤ 2) and dSSSI (LS > 2); the latter were further subdivided into distal and small SSSI (ds-SSSI, TNS ≤ 2) or distal and large SSSI (dl-SSSI, TNS > 2). The clinical characteristics were compared between different groups. RESULTS: A total of 204 patients were included out of 1158 patients registered in the database. We found that ds-SSSI was most often associated with severe white matter hyperintensities. However, patients with dl-SSSI most often had a higher rate of additional concurrent atherosclerotic disease as coronary heart disease, compared to patients with ds-SSSI. CONCLUSIONS: The pathogenesis of dSSSI may be heterogeneous depending on lesion size.

Matrix Metalloproteinase-12 Induces Blood-Brain Barrier Damage After Focal Cerebral Ischemia.

BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis. RESULTS: MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage. CONCLUSIONS: These results demonstrate the adverse role of MMP-12 in acute brain damage that occurs after ischemic stroke and, thereby, suggesting that MMP-12 suppression could be a promising therapeutic target for cerebral ischemia.

The Development of Cortical Microinfarcts Is Associated with Intracranial Atherosclerosis: Data from the Chinese Intracranial Atherosclerosis Study.

BACKGROUND: Little is known about the association between the cortical microinfarcts (CMIs) and intracranial atherosclerosis (ICAS) in Chinese patients with ischemic stroke. This study was designed to analyze the association and evaluate the role of CMIs in clinical outcomes. METHODS: We evaluated 1421 consecutive patients who had experienced an acute cerebral ischemia within 7 days after symptom onset and evaluated the presence of CMIs and ICAS based on patients' 3.0-T magnetic resonance imaging and magnetic resonance angiography scans. Baseline characteristics, patient risk factors, and clinical outcomes were analyzed to investigate the different outcomes between the CMIs (n = 209) group and non-CMIs (n = 1212) group. RESULTS: CMIs were present in 14.7% persons. The following parameters were associated with risk of CMIs: advanced age, National Institutes of Health Stroke Scale score on admission, lower level of systemic blood pressure, lower triglycerides level, ICAS, and cerebral microbleeds (CMBs). On multivariate logistic regression analysis, ICAS remained an independent risk factor for the development of CMIs (adjusted odds ratio, 1.493; 95% confidence interval, 1.022-2.182; P = .038). At the time point of 1 year after stroke, the rates of poor outcome (modified Rankin Scale, 3-6) in CMIs group (33.5%) were statistically significantly different from the non-CMIs group (22.6%; P = .001). In addition, patients in CMIs group had a significantly higher stroke recurrence rate than patients in the non-CMIs group (6.7% versus 4%; P = .085). CONCLUSIONS: The development of CMIs is strongly associated with ICAS. CMIs are independent predictors of poor prognosis in patients with ischemic stroke.

Standard-dose intravenous tissue-type plasminogen activator for stroke is better than low doses.

BACKGROUND AND PURPOSE: It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. METHODS: We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed. RESULTS: A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.7 to 0.85 mg/kg, 678 had 0.85 to 0.95 mg/kg, and 26 had ≥0.95 mg/kg. Because of sample sizes, only 0.5 to 0.7, 0.7 to 0.85, and 0.85 to 0.95 mg/kg groups were compared. Median tPA doses were 0.64, 0.79, and 0.90 mg, respectively. After adjustment for the baseline variables, there were no significant differences in mortality(5.41% versus 8.66% versus 7.36%; P=0.695) and symptomatic intracranial hemorrhage (0% versus 3.82% versus 1.46%; P=0.106). The 0.5 to 0.7 mg/kg group had less excellent recovery outcome (modified Rankin scale, 0-1) than 0.85 to 0.95 mg/kg group (41.89% versus 53.83%; odds ratio=0.58; P=0.031) at 90 days. The 0.70 to 0.85 mg/kg group had less functional independence outcome (modified Rankin scale, 0-2) than 0.85 to 0.95 mg/kg group (54.33% versus 64.51%; odds ratio=0.66; P=0.036) at 90 days. CONCLUSIONS: Our study suggests that standard-dose intravenous tPA for stroke had more favorable outcome without increasing the risk of symptomatic intracranial hemorrhage than low-dose tPA. For Asian people, 0.9 mg/kg should be the optimal dose of tPA to treat acute ischemic stroke.

Stem cell treatment after cerebral ischemia regulates the gene expression of apoptotic molecules.

Evidence suggests that apoptosis contributes significantly to cell death after cerebral ischemia. Our recent studies that utilized human umbilical cord blood-derived mesenchymal stem cells (hUCBSCs) demonstrated the potential of hUCBSCs to inhibit neuronal apoptosis in a rat model of CNS injury. Therefore, we hypothesize that intravenous administration of hUCBSCs after focal cerebral ischemia would reduce brain damage by inhibiting apoptosis and downregulating the upregulated apoptotic pathway molecules. Male Sprague-Dawley rats were obtained and randomly assigned to various groups. After the animals reached a desired weight, they were subjected to a 2 h middle cerebral artery occlusion (MCAO) procedure followed by 7 days of reperfusion. The hUCBSCs were obtained, cultured, and intravenously injected (0.25 × 10(6) cells or 1 × 10(6) cells) via the tail vein to separate groups of animals 24 h post-MCAO procedure. We performed various techniques including PCR microarray, hematoxylin and eosin, and TUNEL staining in addition to immunoblot and immunofluorescence analysis in order to investigate the effect of our treatment on regulation of apoptosis after focal cerebral ischemia. Most of the apoptotic pathway molecules which were upregulated after focal cerebral ischemia were downregulated after hUCBSCs treatment. Further, the staining techniques revealed a prominent reduction in brain damage and the extent of apoptosis at even the lowest dose of hUCBSCs tested in the present study. In conclusion, our treatment with hUCBSCs after cerebral ischemia in the rodent reduces brain damage by inhibiting apoptosis and downregulating the apoptotic pathway molecules.

Significant underuse of warfarin in patients with nonvalvular atrial fibrillation: results from the China national stroke registry.

BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation (AF) but is often underused in clinical practice. We aimed to examine the current state of warfarin use in nonvalvular atrial fibrillation (NVAF) patients with first-ever ischemic stroke (IS) or transient ischemic attack (TIA) in China and to analysis factors causing such underuse. METHODS: By accessing the China National Stroke Registry, data on consecutive patients with known NVAF who developed first-ever IS or TIA were studied. Proportion of warfarin use was estimated in those patients with known NVAF who should be eligible for anticoagulation therapy. Factors associated with warfarin underuse were identified by multivariate logistic regression. RESULTS: Of 11,080 patients with first-ever IS or TIA, 996 (9.7%) had NVAF and no contraindications to anticoagulation therapy and 592 of them had history of AF. Among these patients, only 96 (16.2%) were on warfarin and 496 (83.8%) were not. In those patients on warfarin, only 1 of his international normalized ratios on admission was in the therapeutic range of 2.0-3.0. Based on the CHADS2 scores, about 20.2% low-risk AF patients took warfarin; however, only 15.2% moderate and 16.4% high-risk patients were on warfarin. Older patients and patients with history of coronary heart disease (CHD) were less likely to be given warfarin, whereas patients with history of prestroke antiplatelet use were more likely to take warfarin. CONCLUSIONS: We found that warfarin was significantly underused in patients with known NVAF in China. Age and CHD and prestroke antiplatelet therapy were related factors.

Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates. METHODS: Members of the writing committee were appointed by the American Stroke Association Stroke Council's Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council's Level of Evidence grading algorithm. RESULTS: The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation. CONCLUSIONS: Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke remains urgently needed.

Tree-based logistic regression approach for work zone casualty risk assessment.

This study presents a tree-based logistic regression approach to assessing work zone casualty risk, which is defined as the probability of a vehicle occupant being killed or injured in a work zone crash. First, a decision tree approach is employed to determine the tree structure and interacting factors. Based on the Michigan M-94\I-94\I-94BL\I-94BR highway work zone crash data, an optimal tree comprising four leaf nodes is first determined and the interacting factors are found to be airbag, occupant identity (i.e., driver, passenger), and gender. The data are then split into four groups according to the tree structure. Finally, the logistic regression analysis is separately conducted for each group. The results show that the proposed approach outperforms the pure decision tree model because the former has the capability of examining the marginal effects of risk factors. Compared with the pure logistic regression method, the proposed approach avoids the variable interaction effects so that it significantly improves the prediction accuracy.

Atomically dispersed Ir catalysts exhibit support-dependent water oxidation kinetics during photocatalysis.

Heterogeneous water oxidation catalysis is central to the development of renewable energy technologies. Recent research has suggested that the reaction mechanisms are sensitive to the hole density at the active sites. However, these previous results were obtained on catalysts of different materials featuring distinct active sites, making it difficult to discriminate between competing explanations. Here, a comparison study based on heterogenized dinuclear Ir catalysts (Ir-DHC), which feature the same type of active site on different supports, is reported. The prototypical reaction was water oxidation triggered by pulsed irradiation of suspensions containing a light sensitizer, Ru(bpy)32+, and a sacrificial electron scavenger, S2O82-. It was found that at relatively low temperatures (288-298 K), the water oxidation activities of Ir-DHC on indium tin oxide (ITO) and CeO2 supports were comparable within the studied range of fluences (62-151 mW cm-2). By contrast, at higher temperatures (310-323 K), Ir-DHC on ITO exhibited a ca. 100% higher water oxidation activity than on CeO2. The divergent activities were attributed to the distinct abilities of the supporting substrates in redistributing holes. The differences were only apparent at relatively high temperatures when hole redistribution to the active site became a limiting factor. These findings highlight the critical role of the supporting substrate in determining the turnover at active sites of heterogeneous catalysts.

Effect of the Shanghai Stroke Service System (4S) on the quality of stroke care and outcomes: A prospective quality improvement project.

BACKGROUND: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. AIM: The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. METHODS: The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. RESULTS: The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p < 0.001; all-or-none measure 49.2% vs 44.8% patients; absolute difference 3.5%, 95% CI = [2.7%, 4.2%], p < 0.001). Further analysis of individual KPIs showed an absolute increase in six KPIs ranging from 3.4% to 8.9% (p < 0.001 for all comparisons). Compared with 2015-2017, hospital length of stay was shorter (10.95 vs 11.90 days; absolute difference -1.08, 95% CI = [-1.18, -0.99], p < 0.001), and in-hospital mortality was significantly reduced (risk ratio (RR) = 0.88, 95% CI = [0.79, 0.98], p = 0.01) in 2018-2020. CONCLUSION: The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02735226.

Using recombinant tissue plasminogen activator to treat acute ischemic stroke in China: analysis of the results from the Chinese National Stroke Registry (CNSR).

BACKGROUND AND PURPOSE: Little is known about intravenous recombinant tissue plasminogen activator (rtPA) use in China. By accessing the Chinese National Stroke Registry (CNSR), the rate of intravenous rtPA use was reviewed. We specifically examined the issues of prehospital and in-emergency department delay and compared them with the published data from developed countries. METHODS: Funded by Chinese government, CNSR is the only nationwide stroke registry that includes 132 urban hospitals. All patients eligible for intravenous rtPA were included for analysis. We then compared the onset-to-needle time and door-to-needle time in the emergency department in China with those in developed countries. RESULTS: From September 2007 to August 2008, 14,702 patients with ischemic stroke were entered into CNSR. Among 11,675 patients with known time of stroke onset, 2514 (21.5%) presented to the emergency department within 3 hours, 1469 (12.6%) were eligible for thrombolytic treatment, and 284 (2.4%) were finally treated, 181 (1.6%) of them with intravenous rtPA. The median onset-to-needle time was 180 (interquartile range, 150 to 228) minutes; the median door-to-needle time was 116 (interquartile range, 70 to 150) minutes; the median imaging-to-needle time was 90 (interquartile range, 60 to 129) minutes. Patients who were younger, presented to the emergency department quicker, with higher National Institutes of Health Stroke Scale scores, having higher income, and better education had a better chance of receiving intravenous rtPA. CONCLUSIONS: Approximately 1 in 5 patients with stroke presenting within 3 hours received thrombolytic therapy. The onset-to-needle time, door-to-needle time, and especially imaging-to-needle time were significantly longer than those in developed countries. Reducing prehospital and in-emergency department response time would help increase intravenous rtPA use in China.

Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases.

BACKGROUND AND PURPOSE: Several retrospective studies suggested that contrast extravasation on CT angiography predicts hematoma expansion, poor outcome, and mortality in primary intracerebral hemorrhage. We aimed to determine the predictive value of contrast extravasation on multidetector CT angiography for clinical outcome in a prospective study. METHODS: In 160 consecutive patients with spontaneous intracerebral hemorrhage admitted within 6 hours of symptom onset, noncontrast CT and multidetector CT angiography were performed on admission. A follow-up noncontrast CT was done at 24 hours. Multidetector CT angiography images were analyzed to identify the presence of contrast extravasation. Clinical outcome was assessed by modified Rankin Scale on discharge and at 90 days. RESULTS: A total of 139 patients with primary intracerebral hemorrhage were included in the final analysis. Contrast extravasation occurred in 30 (21.6%) patients. The presence of contrast extravasation was associated with increased hematoma expansion (P<0.0001), in-hospital mortality (P=0.008), prolonged hospital stay (P=0.006), poor outcome on discharge (P=0.025), increased 3-month mortality (P=0.009), and poor clinical outcome (P<0.0001). In multivariate analysis, contrast extravasation was a promising independent predictor (OR, 10.5; 95% CI, 3.2-34.7; P<0.0001) for 90-day poor clinical outcome followed by the presence of intraventricular hemorrhage (OR, 3.4; 95% CI, 1.5-7.7; P=0.003) and initial hematoma volume (OR, 1.0; 95% CI, 1.0-1.1; P=0.013). CONCLUSIONS: The presence of contrast extravasation on multidetector CT angiography in patients with hyperacute-stage intracerebral hemorrhage is an independent and strong factor associated with poor outcome. Any patient with intracerebral hemorrhage with such sign on multidetector CT angiography should be monitored intensely and treated accordingly.

Acute Decompressive Hemicraniectomy to Control High Intracranial Pressure in Patients with Malignant MCA Ischemic Strokes.

OPINION STATEMENT: Malignant middle cerebral artery (MCA) infarction occurs in about 10% of all patients with supratentorial ischemic strokes. The infarction involves the entire MCA territory. Due to the consequences of severe brain edema, brain herniation, elevated intracranial pressure (ICP), and midline shift, these events carry a mortality rate of up to 80%. No clinical trials have been conducted to study the efficacy of the osmotic agents such as mannitol or hypertonic saline. Furthermore, aggressive use of such treatments may be detrimental. Surgical decompression has previously been proposed as a way to relieve the vicious cycle of malignant cerebral edema and reduced cerebral perfusion. Its use in relieving ICP is also controversial. Recently, a pooled analysis of three independent European trials has shown that decompressive hemicraniectomy is clearly beneficial in reducing mortality from large hemispheric infarctions. Although controversies still exist on its indications, surgical decompression can effectively reduce ICP, reduce mortality, and improve neurologic outcomes in selected patients with a malignant MCA stroke syndrome.