Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

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Bacterial wilt disease is a devastating disease of crops, which leads to huge economic loss worldwide. It is hypothesized that the occurrence of bacterial wilt may be related to changes in soil chemical properties and microbial interactions. In this study, we compared the soil chemical properties and microbial network structures of a healthy soil (HS) and a bacterial wilt-susceptible soil (BWS). The contents of available nitrogen, potassium, and phosphorus and the soil pH in the BWS were significantly lower than those in the HS. BWS showed nutrient deficiency and acidification in comparison with the HS. The structure and composition of the BWS network were quite different from those of the HS network. The BWS network had fewer modules and edges and lower connectivity than the HS network. The HS network contained more interacting species, more key microorganisms, and better high-order organization and thus was more complex and stable than the BWS network. Most nodes and module memberships were unshared by the two networks, while the ones that were shared showed different topological roles. Some generalists in the HS network became specialists in the BWS network, indicating that the topological roles of microbes were changed and key microorganisms were shifted in the BWS. In summary, the composition and structure of the microbial network of the BWS were different from that of the HS. Many microbial network connections were missing in the BWS, which most likely provided conditions leading to higher rates of bacterial wilt disease. IMPORTANCE Bacterial wilt disease is caused by the pathogen Ralstonia solanacearum and is a widespread devastating soilborne disease leading to huge economic losses worldwide. The soil microbial community is crucial to the capacity of soils to suppress soilborne diseases through complex interactions. Network analysis can effectively explore these complex interactions. In this study, we used a random matrix theory (RMT)-based network approach to investigate the changes in microbial network and associated microbial interactions in a bacterial wilt-susceptible soil (BWS) in comparison to a healthy soil (HS). We found that the structure and composition of the microbial network in BWSs were quite different from those of the HS. The BWS network had fewer modules, edges, and key microorganisms and lower connectivity than the HS network. In the BWSs, apparently the topological role of microbes was changed and key microorganisms were shifted to specialists.

Background and Purpose: Acute ischemic stroke (AIS) is a serious threat to the life and health of middle-aged and elderly people. Mechanical thrombectomy offers the advantages of rapid recanalization, but the response of patients to this treatment varies greatly. This study investigated the risk factors for futile recanalization in AIS patients after thrombectomy through multivariate analyses.Methods: A retrospective study was conducted in AIS patients with anterior circulation occlusion from a derivation cohort and a validation cohort who underwent thrombectomy and reperfusion defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b/3. Using the modified Rankin Scale (mRS) at 90 days after the operation, the patients were divided into two groups, the meaningful recanalization group (mRS ≤ 2), and the futile recanalization group (mRS &gt; 2). Multivariate logistic regression analyses were performed, and the receiver operating characteristic (ROC) curve was used to construct a risk prediction model for futile recanalization. The performance of prediction model was evaluated on the validation cohort.Results: A total of 140 patients in the derivation cohort were enrolled, 46 patients in the meaningful recanalization group and 94 patients in the futile recanalization group. The two groups were significantly different in age, preoperative National Institute of Health Stroke Scale (NIHSS) score, and collateral circulation ASITN/SIR grade (P &lt; 0.05). In multivariate regression analyses, patients' age ≥ 71, NIHSS ≥ 12, and ASITN/SIR ≤ 3 were risk factors for futile recanalization. Hence, an ANA (Age-NIHSS-ASITN/SIR) score scale consisting of age, NIHSS score, and ASITN/SIR grade factors can effectively predict the risk for futile recanalization (area under curve 0.75, 95% CI 0.67–0.83, specificity 67.4%, and sensitivity 73.4%). The proportion of patients with futile recanalization in ANA groups 0, 1, 2, and 3 were 21.05, 56.76, 79.03, and 90.91%, respectively. Furthermore, ANA score scale had also a good performance for predicting futile recanalization on the validation cohort.Conclusions: Old age, high baseline NIHSS, and poor collateral circulation are risk factors for futile recanalization in AIS patients treated with thrombectomy. An ANA score that considers age, NIHSS, and collateral ASITN/SIR can effectively predict the risk for futile recanalization. Further studies with a larger sample size are needed to validate the prognostic value of this combined score for futile recanalization.