Importance of timing and training to implement awake prone positioning in patients with COVID-19: a single-center prospective observational study.

Background: Awake prone positioning (APP) is broadly implemented in patients with severe acute respiratory syndrome coronavirus 2 related disease [coronavirus disease 2019 (COVID-19)] admitted to hospital with severe respiratory distress syndrome. This prospective observational study aimed to explore the factors influencing the implementation of APP in patients with acute respiratory failure due to COVID-19. Methods: Patients with COVID-19, all hospitalized with positive X-ray findings and oxygen supplementation requirement, in the Respiratory Step-Down Unit of the Peking University Third Hospital between January 6th, 2023, and January 20th, 2023, were included in this study. Data regarding basic information, activities of daily living (ADLs) scores, oxygen therapy, vital signs, and duration of APP were collected to investigate the factors influencing prone positioning. Results: Among the 134 patients included, 55.2% showed an improvement in oxygen saturation 1 hour after APP. Logistic regression revealed that the pre-APP heart rate (HR) [odds ratio (OR) =1.032; P=0.046] and peripheral oxygen saturation (SpO2) (OR =0.720; P<0.001) were the associated factors of the improvement in SpO2 after treatment. Multiple linear regression revealed that the ADL scores and pre-APP respiratory rate (RR) were the associated factors of the duration of prone positioning (P<0.01). The APP technical steering group effectively improved duration of APP. Conclusions: Patients with low SpO2 and increased HR before treatment showed greater improvement in oxygen saturation. Patients with lower tolerance to ADL but lower RRs were those to demonstrate a longer duration of prone positioning. This is pointing towards establishing the most favorable time window for APP during the course of COVID-19: after the ADLs have already decreased, but before significant tachypnea has appeared.

Discovery and Characterization of the Naturally Occurring Inhibitors Against Human Pancreatic Lipase in Ampelopsis grossedentata.

Pancreatic lipase (PL) inhibitor therapy has been validated as an efficacious way for preventing and treating obesity and overweight. In the past few decades, porcine PL (pPL) is widely used as the enzyme source for screening the PL inhibitors, which generates a wide range of pPL inhibitors. By contrast, the efficacious inhibitors against human PL (hPL) are rarely reported. This study aims to discover the naturally occurring hPL inhibitors from edible herbal medicines (HMs) and to characterize the inhibitory mechanisms of the newly identified hPL inhibitors. Following the screening of the inhibition potentials of more than 100 HMs against hPL, Ampelopsis grossedentata extract (AGE) displayed the most potent hPL inhibition activity. After that, the major constituents in AGE were identified and purified, while their anti-hPL effects were assayed in vitro. The results clearly showed that two abundant constituents in AGE (dihydromyricetin and iso-dihydromyricetin) were moderate hPL inhibitors, while myricetin and quercetin were strong hPL inhibitors [half-maximal inhibitory concentration (IC 50) values were around 1.5 µM]. Inhibition kinetic analyses demonstrated that myricetin and quercetin potently inhibited hPL-catalyzed near-infrared fluorogenic substrate of human pancreatic lipase (DDAO-ol) hydrolysis in a non-competitive inhibition manner, with K i values of 2.04 and 2.33 µM, respectively. Molecular dynamics simulations indicated that myricetin and quercetin could stably bind on an allosteric site of hPL. Collectively, this study reveals the key anti-obesity constituents in AGE and elucidates their inhibitory mechanisms against hPL, which offers convincing evidence to support the anti-obesity and lipid-lowering effects of this edible herb.

Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications.

Tyrosinase (TYR, E.C. 1.14.18.1), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the ortho-hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR activity and their biomedical applications. The design strategies of various TYR substrates, alongside with several lists of all reported biochemical assays for sensing TYR including analytical conditions and kinetic parameters, are presented for the first time. Additionally, the biomedical applications and future perspectives of these optical assays are also highlighted. The information and knowledge presented in this review offer a group of practical and reliable assays and imaging tools for sensing TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases.

Clinical Efficacy of Corticosteroids in the Early Stages of Deterioration in COVID-19 Pneumonia.

BACKGROUND: The World Health Organization (WHO) strongly suggests using corticosteroids in patients with severe coronavirus disease 2019 (COVID-19). Similarly, a large randomized controlled clinical trial (RCT) in the UK found that dexamethasone effectively reduced the mortality rate in severe COVID-19 patients. However, the safety profile of corticosteroids has been a controversial area of study. CASE DESCRIPTION: A case of a COVID-19 patient is described and the clinical characteristics are observed as the mildly symptomatic patient progresses into a critically ill patient and during their dramatic improvement with corticosteroid therapy in the early stage of the deterioration process with COVID-19 pneumonia. CONCLUSION: The most suitable timing and dosage for the use of corticosteroids to maximize its effect during the worsening of COVID-19 pneumonia are discussed. One of the main pathophysiological hypotheses for severe COVID-19 patients is related to cytokine storm and virus load, which can be effectively treated with corticosteroid therapy.

Discovery and characterization of flavonoids in vine tea as catechol-O-methyltransferase inhibitors.

Vine tea has been used as a traditionally functional herbal tea in China for centuries, which exhibits paramount potential for chronic metabolic diseases. Herein, the inhibitory potential of vine tea toward human catechol-O-methyltransferase (hCOMT) was investigated. A practical bioactivity-guided fractionation combined with chemical profiling strategy was developed to identify the naturally occurring hCOMT inhibitors. Five flavonoids in vine tea displayed moderate to strong inhibition on hCOMT with IC50 values ranging from 0.96 µM to 42.47 µM, in which myricetin was the critically potent constituent against hCOMT. Inhibition kinetics assays and molecular docking simulations showed that myricetin could bind to the active site of COMT and inhibited COMT-catalyzed 3-BTD methylation in a mixed manner. Collectively, our findings not only suggested that the strong hCOMT inhibition of vine tea has guiding significance in the drug exposure of catechol drugs, but also identified a promising lead compound for developing more efficacious hCOMT inhibitors.

Inhibition of catechol-O-methyltransferase by natural pentacyclic triterpenes: structure-activity relationships and kinetic mechanism.

Inhibitors of COMT are clinically used for the treatment of Parkinson's disease. Here, we report the first natural pentacyclic triterpenoid-type COMT inhibitors and their structure-activity relationships and inhibition mechanism. The most potent compounds were found to be oleanic acid, betulinic acid and celastrol with IC50 values of 3.89-5.07 µM, that acted as mixed (uncompetitive plus non-competitive) inhibitors of COMT, representing a new skeleton of COMT inhibitor. Molecular docking suggested that they can specifically recognise and bind with the unique hydrophobic residues surrounding the catechol pocket. Furthermore, oleanic acid and betulinic acid proved to be less disruptive of mitochondrial membrane potential (MMP) compared to tolcapone, thus reducing the risk of liver toxicity. These findings could be used to produce an ideal lead compound and to guide synthetic efforts in generating related derivatives for further preclinical testing.

Analytical methodologies for sensing catechol-O-methyltransferase activity and their applications.

Mammalian catechol-O-methyltransferases (COMT) are an important class of conjugative enzymes, which play a key role in the metabolism and inactivation of catechol neurotransmitters, catechol estrogens and a wide range of endobiotics and xenobiotics that bear the catechol group. Currently, COMT inhibitors are used in combination with levodopa for the treatment of Parkinson's disease in clinical practice. The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples, as well as for rapid screening and characterization of COMT inhibitors as drug candidates. This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications. Several lists of biochemical assays for measuring COMT activity, including the probe substrates, along with their analytical conditions and kinetic parameters, are presented. Finally, the challenges and future perspectives in the field, such as visualization of COMT activity in vivo and in situ, are highlighted. Collectively, this review article overviews the practical assays for measuring COMT activities in complex biological samples, which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.

Discovery and characterization of naturally occurring potent inhibitors of catechol-O-methyltransferase from herbal medicines.

Human catechol-O-methyltransferase (hCOMT) is considered a therapeutic target due to its crucial roles in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs. There are nevertheless few safe and effective COMT inhibitors and there lacks a diversity in structure. To discover novel safe and effective hCOMT inhibitors from herbal products, in this study, 53 herbal products were collected and their inhibitory effects against hCOMT were investigated. Among them, Scutellariae radix (SR) displayed the most potent inhibitory effect on hCOMT with an IC50 value of 0.75 µg mL-1. To further determine specific chemicals as COMT inhibitors, an affinity ultrafiltration coupled with liquid chromatography-mass spectrometry method was developed and successfully applied to identify COMT inhibitors from SR extract. The results demonstrated that scutellarein 2, baicalein 9 and oroxylin A 12 were potent COMT inhibitors, showing a high binding index (>3) and very low IC50 values (32.9 ± 3.43 nM, 37.3 ± 4.32 nM and 18.3 ± 2.96 nM). The results of inhibition kinetics assays and docking simulations showed that compounds 2, 9 and 12 were potent competitive inhibitors against COMT-mediated 3-BTD methylation, and they could stably bind to the active site of COMT. These findings suggested that affinity ultrafiltration allows a rapid identification of natural COMT inhibitors from a complex plant extract matrix. Furthermore, scutellarein 2, baicalein 9 and oroxylin A 12 are potent inhibitors of hCOMT in SR, which could be used as promising lead compounds to develop more efficacious non-nitrocatechol COMT inhibitors for biomedical applications.

Repair of Less Than Severe Tricuspid Regurgitation During Left-Sided Valve Surgery: A Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis was undertaken to investigate the short- and long-term clinical outcomes of concurrent repair of mild or moderate tricuspid regurgitation (TR) during left-sided valve surgery. METHODS: Medline, PubMed, EMBASE, and Cochrane Libraries were searched, and 12 studies were identified, comprising 1373 patients who underwent TR repair during left-sided valve surgery and 1553 patients who did not. Of these studies, 6 were classified as having a low risk of bias (randomized controlled trials or propensity-matched studies), and 6 were considered as having a high risk of bias (nonmatched observational studies). The primary analysis included only studies with a low risk of bias (399 repair and 426 nonrepair). RESULTS: Primary analysis of studies at low risk of bias demonstrated that the addition of TR repair compared with nonrepair was associated with reduced risks of cardiovascular mortality, all-cause mortality, and progression of TR over a median of 5.3 years of follow-up (cardiovascular mortality: relative risk [RR], 0.46; 95% confidence interval [CI], 0.28 to 0.75; P = .002; all-cause mortality: RR, 0.68; 95% CI, 0.49 to 0.96; P = .03; and TR progression: RR, 0.26; 95% CI, 0.12 to 0.56; P < .001). Cardiopulmonary bypass time was significantly shorter in the nonrepair group (mean weighted difference, 18 minutes; 95% CI, 6 to 30; P = .003), although the risk of perioperative mortality was comparable between the 2 groups (RR, 0.72; 95% CI, 0.27 to 1.97; P > .05). CONCLUSIONS: Concurrent repair of mild or moderate TR during left-sided valve surgery is associated with improved long-term clinical outcomes without adversely affecting early survival. Should these results be validated by ongoing trials, there should be a revision of current guidelines to recommend a more aggressive approach toward TR repair.

The expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer.

The aim of this study was to analyze the expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer (NSCLC). Seventy patients with NSCLC who underwent surgical resection or biopsy between January 2016 and February 2018 were enrolled. Among them, 30 were cases of paracancerous tissues and were assigned to the control group (CON). These cases were analyzed using immunochemical methods. Of the 70 cases, 48 were of adenocarcinoma, 19 were of squamous cell carcinoma, and 3 were of adenosquamous carcinoma. The expression rates of B7-H3 and CTLA-4 in the observation group (OBS) were 64.2% and 57.1% respectively, and those in the CON group were 6.7% and 0%, respectively (χ2=27.988, 28.571, P<0.001). The expression levels of B7-H3 and CTLA-4 in patients with poor differentiation, in stages III-IV, or with lymph node metastasis were significantly higher than those in patients with good-to-moderate differentiation, in stages I-II, and without lymph node metastasis (P<0.05). There was a positive correlation between the expressions of B7-H3 and CTLA-4 in the OBS group (r=0.74, P<0.05). B7-H3 and CTLA-4 are highly expressed and positively correlated with each other in NSCLC patients and are also closely related to clinical stages.

Association between pain control and patient satisfaction outcomes in the emergency department setting.

OBJECTIVE: Pain management and patient satisfaction are key markers for health systems performance. There is a lack of consensus on the role of analgesia, its adequacy, and its links to patient satisfaction in the ED. The present study aimed to assess the relationship between adequacy of analgesia and patient satisfaction in the ED setting. METHODS: Consenting adult patients (n = 115) presenting to the ED with pain were enrolled, and their pain tracked throughout admission with 11 point numerical pain scores. Eleven point numerical scores were also utilised to measure satisfaction and compassion at the end of each ED stay. The primary outcome was patient satisfaction score ≥7. RESULTS: Of 115 enrolled patients, 94 (81.7%) were eligible for analysis. Median time to physician evaluation was 54.0 min (inter-quartile range [IQR] 35.0-98.0) and median ED length of stay was 205 min (IQR 129.0-280.0). Fifty-four patients (57.5%) received analgesia during their stay, of whom 36 (38.3%) had a significant response to analgesia (≥2 change in pain score). Median time to analgesia was 87.5 min (IQR 66.1-108.9). Patient satisfaction was inversely associated with male sex, and positively correlated (Spearman's rank correlation P < 0.05) with increasing age, significant change in pain score (±2) and compassion scores. CONCLUSION: In the present study of patients presenting to the ED with pain, oligoanalgesia remains a significant issue. Male sex was inversely associated with satisfaction, whereas compassion, and significant change in pain score were associated with improved patient satisfaction. Of the factors analysed, staff compassion demonstrated the strongest correlation with satisfaction.

Serratia oryzae sp. nov., isolated from rice stems.

A novel endophytic bacterium, strain J11-6T, was isolated from rice stems. Its taxonomic position was investigated using a polyphasic approach. The novel strain was Gram-staining-negative, facultatively anaerobic, motile and rod-shaped. Although the results of phylogenetic analysis based on 16S rRNA gene sequences indicated that J11-6T represented a member of the genus Rahnella, multilocus sequence analysis (MLSA) on the basis of concatenated partial atpD, gyrB, rpoB and infB gene sequences showed a clear distinction of J11-6T from the type strains of species of the genus Rahnella but indicated that it lay within the clade of the genus Serratia. The phylogenetically closest species were Serratia fonticola and Serratia aquatilis on the basis of the results of the MLSA phylogenetic analysis. The predominant cellular fatty acids were C16 : 1ω7c (38.7 %) and C16 : 0 (25.0 %). The DNA G+C content was 53.2 mol%. The DNA-DNA relatedness was 17.4 % between J11-6T and Rahnella aquatilis CIP 78.65T, and 29.2 % between J11-6T and S. fonticola LMG 7882T which indicates that this strain represents a novel species of the genus Serratia. Characterization by genotypic and phenotypic analysis indicated that J11-6T (=ACCC 19934T=KCTC 52529T) represents a novel species of the genus Serratia, for which the name Serratia oryzae sp. nov. is proposed.

Long-term prognosis and cost-effectiveness of left ventricular assist device as bridge to transplantation: A systematic review.

BACKGROUND: This systematic review aimed to evaluate the clinical outcomes and cost-effectiveness of left ventricular assist devices (LVADs) used as bridge to transplantation (BTT), compared to orthotopic heart transplantation (OHT) without a bridge. METHOD: Systematic searches were performed in electronic databases with available data extracted from text and digitized figures. Meta-analysis of short and long-term term post-transplantation outcomes was performed with summation of cost-effectiveness analyses. RESULTS: Twenty studies reported clinical outcomes of 4575 patients (1083 LVAD BTT and 3492 OHT). Five studies reported cost-effectiveness data on 837 patients (339 VAD BTT and 498 OHT). There was no difference in long-term post-transplantation survival (HR 1.24, 95% CI 1.00-1.54), acute rejection (HR 1.10, 95% CI 0.93-1.30), or chronic rejection and cardiac allograft vasculopathy (HR 0.99, 95% CI 0.73-1.36). No differences were found in 30-day post-operative mortality (OR 0.91, 95% CI 0.42-2.00), stroke (OR 1.64, 95% CI 0.43-6.27), renal failure (OR 1.43, 95% CI 0.58-3.54), bleeding (OR 1.56, 95% CI 0.78-3.13), or infection (OR 2.44, 95% CI 0.81-7.38). Three of the five studies demonstrated incremental cost-effectiveness ratios below the acceptable maximum threshold. The total cost of VAD BTT ranged from $316,078 to $1,025,500, and OHT ranged from $179,051 to $802,200. CONCLUSION: LVADs used as BTT did not significantly alter post-transplantation long-term survival, rejection, and post-operative morbidity. LVAD BTT may be cost-effective, particularly in medium and high-risk patients with expected prolonged waiting times, renal dysfunction, and young patients.

Coronary Artery Bypass Grafting With and Without Manipulation of the Ascending Aorta: A Network Meta-Analysis.

BACKGROUND: Coronary artery bypass grafting (CABG) remains the standard of treatment for 3-vessel and left main coronary disease, but is associated with an increased risk of post-operative stroke compared to percutaneous coronary intervention. It has been suggested that CABG techniques that eliminate cardiopulmonary bypass and reduce aortic manipulation may reduce the incidence of post-operative stroke. OBJECTIVES: A network meta-analysis was performed to compare post-operative outcomes between all CABG techniques, including anaortic off-pump CABG (anOPCABG), off-pump with the clampless Heartstring device (OPCABG-HS), off-pump with a partial clamp (OPCABG-PC), and traditional on-pump CABG with aortic cross-clamping. METHODS: A systematic search of 6 electronic databases was performed to identify all publications reporting the outcomes of the included operations. Studies reporting the primary endpoint, 30-day post-operative stroke rate, were included in a Bayesian network meta-analysis. RESULTS: There were 13 included studies with 37,720 patients. At baseline, anOPCABG patients had higher previous stroke than did the OPCABG-PC (7.4% vs. 6.5%; p = 0.02) and CABG (7.4% vs. 3.2%; p = 0.001) patients. AnOPCABG was the most effective treatment for decreasing the risk of post-operative stroke (-78% vs. CABG, 95% confidence interval [CI]: 0.14 to 0.33; -66% vs. OPCABG-PC, 95% CI: 0.22 to 0.52; -52% vs. OPCABG-HS, 95% CI: 0.27 to 0.86), mortality (-50% vs. CABG, 95% CI: 0.35 to 0.70; -40% vs. OPCABG-HS, 95% CI: 0.38 to 0.94), renal failure (-53% vs. CABG, 95% CI: 0.31 to 0.68), bleeding complications (-48% vs. OPCABG-HS, 95% CI: 0.31 to 0.87; -36% vs. CABG, 95% CI: 0.42 to 0.95), atrial fibrillation (-34% vs. OPCABG-HS, 95% CI: 0.49 to 0.89; -29% vs. CABG, 95% CI: 0.55 to 0.87; -20% vs. OPCABG-PC, 95% CI: 0.68 to 0.97), and shortening the length of intensive care unit stay (-13.3 h; 95% CI: -19.32 to -7.26; p < 0.0001). CONCLUSIONS: Avoidance of aortic manipulation in anOPCABG may decrease the risk of post-operative stroke, especially in patients with higher stroke risk. In addition, the elimination of cardiopulmonary bypass may reduce the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay.

Bioprosthetic versus mechanical prostheses for valve replacement in end-stage renal disease patients: systematic review and meta-analysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) indicated for dialysis are increasingly requiring cardiac valve surgery. The choice of bioprosthetic or mechanic valve prosthesis for such patients requires careful risk assessment. A systematic review and meta-analysis was performed to assess current evidence available. METHODS: A comprehensive search from six electronic databases was performed from their inception to February 2015. Results from patients with ESRD undergoing cardiac surgery for bioprosthetic or mechanical valve replacement were identified. RESULTS: Sixteen studies with 8,483 patients with ESRD undergoing cardiac valve replacement surgery were included. No evidence of publication bias was detected. Prior angioplasty by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery was significantly higher in the bioprosthetic group compared to the mechanical group (16.0% vs. 12.0%, P=0.04); all other preoperative baseline patient characteristics were similar. There was no significant difference in 30-day mortality or all-cause mortality between the two comparisons. Compared with the mechanical group, the frequency of bleeding (5.2% vs. 6.4%, P=0.04) and risk of thromboembolism (2.7% vs. 12.8%, P=0.02) were significantly lower in the bioprosthetic group. There were similar rates of reoperation and valve endocarditis. CONCLUSIONS: The present study demonstrated that patients with ESRD undergoing bioprosthetic or mechanical valve replacement had similar mid-long term survival. The bioprosthetic group had lower rates of bleeding and thromboembolism. Further studies are required to differentiate the impact of valve location. The presented results may be applicable for ESRD patients requiring prosthetic valve replacement.

Clinical relevance of using autofluorescence bronchoscopy and white light bronchoscopy in different types of airway lesions.

OBJECTIVES: The aim of this study was to evaluate the sensitivity and specificity of autofluorescence bronchoscopy (AFB) according to the macroscopic appearance of airway lesions under white light bronchoscopy (WLB). MATERIALS AND METHODS: The bronchoscopic findings of 708 patients, who were pathologically and clinically diagnosed with airway lesions and underwent both WLB and AFB, were analyzed. RESULTS: We recruited 708 patients for this study, of which 336 (47.5%) had benign lesions; 300 and 254 benign lesions were detected by AFB (specificity, 89.3%) and WLB (specificity, 75.6%), respectively. In 372 (52.5%) patients with bronchiogenic carcinoma, 356 and 235 lesions were identified by AFB (sensitivity, 95.7%) and WLB (sensitivity, 63.2%), respectively. The sensitivity and specificity of AFB for diagnosing lung cancer were higher than those of WLB (P < 0.05). Moreover, AFB showed high sensitivity for detecting lung cancer in cases in which WLB revealed hyperplasia, infiltration, and stenosis (P < 0.05). CONCLUSIONS: AFB combined with WLB could effectively improve the diagnosis of airway lesions.

Endovascular therapy including thrombectomy for acute ischemic stroke: A systematic review and meta-analysis with trial sequential analysis.

One of the primary strategies for the management of acute ischemic stroke is intravenous (IV) thrombolysis with tissue plasminogen activator (t-PA). Over the past decade, endovascular therapies such as the use of stent retrievers to perform mechanical thrombectomy have been found to improve functional outcomes compared to t-PA alone. We aimed to reassess the functional outcomes and complications of IV thrombolysis with and without endovascular treatment for acute ischemic stroke using conventional meta-analysis and trial sequential analysis. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated for the effect of IV thrombolysis with and without endovascular therapy on functional outcome, mortality and symptomatic intracranial hemorrhage (SICH). Trial sequential analysis was done to strengthen the meta-analysis. We analyzed six randomized controlled trials involving 1943 patients. Patients who received IV thrombolysis with endovascular treatment showed significantly higher rates of excellent functional outcomes (modified Rankin Scale [mRS] 0-1) (RR, 1.75 [95% CI, 1.29-2.39]) compared to those who received IV thrombolysis alone. A similar association was seen for good functional outcomes (mRS 0-2) (RR, 1.56 [95% CI, 1.24-1.96]). Trial sequential analysis demonstrated endovascular treatment increased the RR of a good functional outcome by at least 30% compared to IV thrombolysis alone. There was no significant difference in all-cause mortality for mechanical thrombectomy compared to IV thrombolysis alone or the incidence of SICH at 3month follow-up. Endovascular treatment is more likely to result in a better functional outcome for patients compared to IV thrombolysis alone for acute ischemic stroke.