Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856). RESULTS: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets. CONCLUSIONS: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets.

Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels.

Myocardial infarction (MI) results in prolonged ischemia and the subsequent cell death leads to heart failure which is linked to increased deaths or hospitalizations. New therapeutic targets are urgently needed to prevent cell death and reduce infarct size among patients with MI. Runt-related transcription factor-1 (RUNX1) is a master-regulator transcription factor intensively studied in the hematopoietic field. Recent evidence showed that RUNX1 has a critical role in cardiomyocytes post-MI. The increased RUNX1 expression in the border zone of the infarct heart contributes to decreased cardiac contractile function and can be therapeutically targeted to protect against adverse cardiac remodelling. This study sought to investigate whether pharmacological inhibition of RUNX1 function has an impact on infarct size following MI. In this work we demonstrate that inhibiting RUNX1 with a small molecule inhibitor (Ro5-3335) reduces infarct size in an in vivo rat model of acute MI. Proteomics study using data-independent acquisition method identified increased cathepsin levels in the border zone myocardium following MI, whereas heart samples treated by RUNX1 inhibitor present decreased cathepsin levels. Cathepsins are lysosomal proteases which have been shown to orchestrate multiple cell death pathways. Our data illustrate that inhibition of RUNX1 leads to reduced infarct size which is associated with the suppression of cathepsin expression. This study demonstrates that pharmacologically antagonizing RUNX1 reduces infarct size in a rat model of acute MI and unveils a link between RUNX1 and cathepsin-mediated cell death, suggesting that RUNX1 is a novel therapeutic target that could be exploited clinically to limit infarct size after an acute MI.

Prognostic value of day-of-event serum calcium and magnesium for predicting 1-year prognosis after intracerebral hemorrhage.

AIM: To investigate whether serum calcium and magnesium on the day of symptom onset contribute to prognosis at 1 year after intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled patients admitted < 24 h after symptom onset of primary ICH to West China Hospital between January 2012 and October 2014. Blood samples were collected at admission to determine the concentration of serum calcium and magnesium. We analyzed associations of the serum concentration of calcium and magnesium with unfavorable outcome (defined as modified Rankin scale, mRS ≥ 3) at 1 year. RESULTS: We included 874 patients (mean age 59.1 ± 13.5 years, 67.6% males), of whom 470 patients had mRS ≥ 3 and 284 patients died at 1 year. Compared to patients with the highest tertile level of calcium concentration (≥ 2.29 mmol/L), patients in the lowest tertile (≤ 2.15 mmol/L) had higher odds of unfavorable outcome (odds ratio, OR 1.61, 95% confidence interval [CI] 1.04-2.50, P = 0.034). The Kaplan-Meier survival curve revealed a significant difference of cumulative survival rate across calcium tertiles (log-rank P value = 0.038). There was no significant association between serum concentration of magnesium and functional outcome at 1 year. CONCLUSION: A reduced serum concentration of calcium on the day-of-event was associated with unfavorable outcome at 1 year after ICH. Future studies are needed to illustrate the pathophysiological mechanism of calcium and whether calcium could be a treatment target for improving outcomes after ICH.

Tuning oxygen vacancies in epitaxial LaInO3 films for ultraviolet photodetection.

LaInO3 (LIO) represents a new, to the best of knowledge, type of perovskite oxides for deep-ultraviolet (DUV) photodetection owing to the wide bandgap nature (∼5.0 eV) and the higher tolerance of defect engineering for tunable carrier transport. Here we fabricate fast-response DUV photodetectors based on epitaxial LIO thin films and demonstrate an effective strategy for balancing the photodetector performance using the oxygen growth pressure as a simple control parameter. Increasing the oxygen pressure is effective to suppress the oxygen vacancy formation in LIO, which is beneficial to suppress the dark current and enhance the response speed. The optimized LIO photodetector achieves a fast rise/fall time of 20 ms/73 ms, a low dark current of 2.0 × 10-12 A, a photo-to-dark current ratio of 1.2 × 103, and a detectivity of 6 × 1012 Jones.

EDTA-Na2 as a recoverable draw solute for water extraction in forward osmosis.

Regeneration and reuse of draw solute (DS) is a key challenge in the application of forward osmosis (FO) technologies. Herein, EDTA-Na2 was studied as a recoverable DS for water extraction by taking advantages of its pH-responsive property. The FO system using EDTA DS achieved a higher water flux of 2.22 ± 0.06 L m-2 h-1 and a significantly lower reverse salt flux (RSF) of 0.06 ± 0.01 g m-2 h-1, compared to that with NaCl DS having either the same DS concentration or the same Na+ concentration. The suitable pH range for the application of EDTA DS was between 4.0 and 10.5. A simple recovery method via combined pH adjustment and microfiltration was employed to recover EDTA DS and could achieve the recovery efficiency (at pH 2) of 96.26 ± 0.48%, 97.13 ± 1.03% and 98.56 ± 1.40% by using H2SO4, H3PO4 and HCl, respectively. The lowest acid cost for DS recovery was estimated from 0.0012 ± 0.0001 to 0.0162 ± 0.0003 $ g-1 by using H2SO4. The recovered EDTA DS could be reused in the subsequent FO operation and the overall recovery efficiency was 94.4% for four reuse cycles. These results have demonstrated the feasible of EDTA-Na2 DS and a potentially cost-effective recovery approach, and encouraged further exploration of using EDTA-based compounds as a draw solute for FO applications.

Post stroke intervention trial in fatigue (POSITIF): Randomised multicentre feasibility trial.

OBJECTIVE: To test the feasibility of a telephone delivered intervention, informed by cognitive behavioural principles, for post-stroke fatigue, and estimated its effect on fatigue and other outcomes. DESIGN: Randomised controlled parallel group trial. SETTING: Three Scottish stroke services. SUBJECTS: Stroke survivors with fatigue three months to two years post-stroke onset. INTERVENTIONS: Seven telephone calls (fortnightly then a 'booster session' at 16 weeks) of a manualised intervention, plus information about fatigue, versus information only. MAIN MEASURES: Feasibility of trial methods, and collected outcome measures (fatigue, mood, anxiety, social participation, quality of life, return to work) just before randomisation, at the end of treatment (four months after randomisation) and at six months after randomisation. RESULTS: Between October 2018 and January 2020, we invited 886 stroke survivors to participate in postal screening: 188/886 (21%) returned questionnaires and consented, of whom 76/188 (40%) were eligible and returned baseline forms; 64/76 (84%) returned six month follow-up questionnaires. Of the 39 allocated the intervention, 23 (59%) attended at least four sessions. At six months, there were no significant differences between the groups (adjusted mean differences in Fatigue Assessment Scale -0.619 (95% CI -4.9631, 3.694; p = 0.768), the Generalised Anxiety Disorder 7 -0.178 (95% CI -3.823, 3.467, p = 0.92), and the Patient Health Questionnaire -0.247 (95% CI -2.935, 2.442, p = 0.851). There were no between-group differences in quality of life, social participation or return to work. CONCLUSION: Patients can be recruited to a trial of this design. These data will inform the design of further trials in post-stroke fatigue.

Early Prediction of Malignant Edema After Successful Recanalization in Patients with Acute Ischemic Stroke.

BACKGROUND: Postinterventional cerebral hyperdensities are common on non-contrast-enhanced computed tomography (CT) after endovascular thrombectomy in patients with acute ischemic stroke, which may reflect blood-brain barrier damage. The disruption of the blood-brain barrier may lead to malignant brain edema. The relationship between the extent of postinterventional cerebral hyperdensities and malignant brain edema is unclear. METHODS: Patients with middle cerebral artery territory infarction and successful recanalization were consecutively enrolled. Postinterventional non-contrast-enhanced CT was performed to evaluate postinterventional cerebral hyperdensities within 24 h after endovascular thrombectomy. On the basis of the areas of the Alberta Stroke Program Early CT Score, we devised the Hyperdensity on CT Score to evaluate the extent of postinterventional cerebral hyperdensities. The primary outcome was malignant brain edema, defined as the development of clinical signs of herniation (including a decrease in consciousness and/or anisocoria), accompanied by imaging evidence of brain swelling. The component of postinterventional cerebral hyperdensities was divided into contrast staining and hemorrhage on the basis of persistency. RESULTS: Three hundred sixty patients were included (50.6% male, mean age 67.9 years), of whom 247 (68.6%) developed postinterventional cerebral hyperdensities and 66 (18.3%) developed malignant brain edema. After adjustment for confounders, including the component of postinterventional cerebral hyperdensities, the extent of postinterventional cerebral hyperdensities assessed by the Hyperdensity on CT Score was significantly associated with malignant brain edema (odds ratio 1.46, 95% confidence interval 1.20-1.77, p < 0.001). A Hyperdensity on CT Score greater than 3 had a sensitivity of 0.73 and a specificity of 0.87 for predicting malignant brain edema. CONCLUSIONS: The extent of postinterventional cerebral hyperdensities on postinterventional non-contrast-enhanced CT was associated with malignant brain edema. The Hyperdensity on CT Score could be used to predict malignant brain edema regardless of the component of postinterventional cerebral hyperdensities.

Advances in Understanding the Pathogenesis of Lacunar Stroke: From Pathology and Pathophysiology to Neuroimaging.

Lacunar stroke (LS) accounts for about one-quarter of all acute ischemic strokes, represents an important marker of cerebral small vessel disease (CSVD), and has prognostic significance in terms of recurrent vascular events and vascular cognitive impairment. Our understanding of the etiology and pathogenesis of LS is largely based on the meticulous postmortem work of C. Miller Fisher in the late 1960s, with scarce subsequent pathological analysis of the "lacunar hypothesis" and no reliable approaches for direct in vivo imaging of the small intracranial vessels. The recent development of high-resolution MRI, which allows both large-vessel wall and perforating arteries to be imaged in one setting, provides the opportunity to advance understandings of the clinical mechanisms, imaging characteristics, and pathogenesis of LS. Given accumulating evidence of endothelial dysfunction and blood-brain-barrier disruption as early features of CSVD-related LS, advanced imaging may allow various underlying pathogenetic mechanisms to be defined and for better targeting of therapeutic approaches in LS. In this review, progress in understanding the pathogenesis of LS is outlined, covering pathology, pathophysiology, and imaging characteristics, with a focus toward future directions in the complex entity of LS.

Association between serum NLRP3 and malignant brain edema in patients with acute ischemic stroke.

BACKGROUND: We aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke. METHODS: We prospectively enrolled patients with acute ischemic stroke admitted < 24 h from onset of symptoms. Brain CT was performed on admission and blood samples were collected. Repeated brain CT/MRI was performed < 7 days of admission to identify the presence of MBE, defined as neurological deterioration with imaging signs of midline shift or compressed basal cisterns. Logistic regression analysis was performed to assess the association between inflammatory biomarkers and MBE, adjusted for age and National Institutes of Health Stroke Scale (NIHSS). RESULTS: 200 patients (69.3 ± 14.3 years; male 55 %) were included for analysis, of whom 26 patients developed MBE (median time from stroke onset to MBE 32.5 h). Compared with patients without MBE, those with MBE had higher level of serum concentration of NLRP3 (median time from onset to blood collection 3 h, 1.85 ng/ml vs. 1.11 ng/ml, P = 0.026). NLRP3 level was positively correlated with NIHSS on admission (Spearman ρ = 0.18, P = 0.01) and the association between NLRP3 and MBE was attenuated (OR 1.47, 95 % CI 0.88-2.46, P = 0.138) after adjusting for age and NIHSS. There was no significant difference in other biomarkers between MBE and non-MBE groups. CONCLUSIONS: There was a trend of association between a higher level of serum concentration of NLRP3 and an increased risk of MBE after ischemic stroke, possibly confounded by the severity of stroke, which is worth further validation in large cohort studies.

Early amantadine treatment reduces the risk of death in patients with large hemisphere infarctions:a Chinese hospital-based study.

BACKGROUND: Amantadine hydrochloride is one of the most frequently prescribed drugs for patients with severe traumatic brain injury in restoring consciousness and accelerating the pace of functional recovery. However, there is a paucity of studies on the effectiveness of amantadine in patients with severe stroke especially large hemisphere infarction (LHI). The present study aimed to investigate whether amantadine treatment is associated with better clinical outcomes in conservatively treated LHI patients. METHODS: We retrospectively collected conservatively treated LHI patients according to inclusion/exclusion criteria. The patients were divided into two groups based on the treatment regimen, whether they did receive amantadine hydrochloride in addition to standard therapy (ST) or not. The primary outcomes were in-hospital death, 3-month mortality, and unfavorable outcome (defined as modified Rankin Scale score of 4 to 6). All outcomes were compared between the two groups before and after propensity score matching (PSM). Multivariate logistic regression was performed to identify the association between early amantadine hydrochloride treatment and clinical outcomes in LHI patients. RESULTS: Thirty-one LHI patients treated with amantadine combined with ST and 127 patients treated with ST were enrolled. Amantadine group had a shorter prehospital delay (median: 2 vs. 10 h), a higher baseline NIHSS score (21.71 ± 4.76 vs. 17.49 ± 5.84), and a higher rate of dominant hemisphere involvement (67.74% vs. 45.67%). After PSM, amantadine treatment significantly reduced the risk of in-hospital death (7.41% vs. 31.11%, p=0.019) and 3-month mortality (25.93% vs. 55.56%, p=0.008). Amantadine treatment yielded a significant decrease in death in-hospital (before PSM: OR 0.143, 95% CI 0.034 to 0.605; after PSM: OR 0.113, 95% CI 0.020 to 0.635) and 3-month mortality (before PSM: OR 0.214, 95% CI 0.077 to 0.598; after PSM: OR 0.176, 95% CI 0.053 to 0.586) in unmatched and matched multivariate analyses. CONCLUSION: The results of our study provide initial evidence that early amantadine treatment was associated with a decrease in death in conservatively treated LHI patients. Considering the limitations of observational study, randomized controlled trials with a large sample size may help provide a clearer picture of the utility of amantadine in LHI patients.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta-analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre-specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow-up. Thirty-eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD -0.0; 95% CI -0.05 to 0.05; 5 studies, 5436 participants, high-quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high-quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high-quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high-quality evidence). Cognition was slightly better in the control group (MD -1.22, 95% CI -2.37 to -0.07; 4 studies, 5373 participants, moderate-quality evidence). Only one study (n = 30) reported neurological deficit score (SMD -0.39, 95% CI -1.12 to 0.33; low-quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, -0.02 to 0.08; 6 studies, 5518 participants, moderate-quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high-quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate-quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high-quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD -0.06; 95% CI -1.24 to 1.11; 4 studies, 5524 participants, moderate-quality of evidence), nor in quality of life (MD 0.00; 95% CI -0.02 to 0.02, 3 studies, 5482 participants, high-quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta-analysis of outcomes at end of follow-up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

External Validation and Modification of the EDEMA Score for Predicting Malignant Brain Edema After Acute Ischemic Stroke.

BACKGROUND: Accurate prediction of malignant brain edema (MBE) after stroke is paramount to facilitate close monitoring and timely surgical intervention. The Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score was useful to predict potentially lethal malignant edema in Western populations. We aimed to validate and modify it to achieve a better predictive value for MBE in Chinese patients. METHODS: Of ischemic stroke patients consecutively admitted in the Department of Neurology, West China Hospital between January 2010 and December 2017, we included patients with anterior circulation stroke, early signs of brain edema on computed tomography within 24 h of onset, and admission National Institutes of Health Stroke Scale (NIHSS) score ≥ 8. MBE was defined as the development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift ≥ 5 mm on follow-up imaging. The EDEMA score consisted of five parameters: glucose, stroke history, reperfusion therapy, midline shift, and cistern effacement. We created a modified score by adding admission NIHSS score to the original EDEMA score. The discrimination of the score was assessed by the area under the receiver operating characteristics curve (AUC). Calibration was assessed by Hosmer-Lemeshow test and calibration plot. We compared the discrimination of the original and modified score by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Clinical usefulness of the two scores was compared by plotting net benefits at different threshold probabilities in the decision curve analysis. RESULTS: Of the 478 eligible patients (mean age 67.3 years; median NIHSS score 16), 93 (19%) developed MBE. The EDEMA score showed moderate discrimination (AUC 0.72, 95% confidence interval [CI] 0.67-0.76) and good calibration (Hosmer-Lemeshow test, P = 0.77). The modified score showed an improved discriminative ability (AUC 0.80, 95% CI 0.76-0.84, P < 0.001; NRI 0.67, 95% CI 0.55-0.78, P < 0.001; IDI 0.07, 95% CI 0.06-0.09, P < 0.001). Decision curves showed that the modified score had a higher net benefit than the original score in a range of threshold probabilities lower than 60%. CONCLUSIONS: The original EDEMA score showed an acceptable predictive value for MBE in Chinese patients. By adding the admission NIHSS score, the modified score allowed for a more accurate prediction and clinical usefulness. Further validation in large cohorts of different ethnicities is needed to confirm our findings.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. MAIN RESULTS: We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. AUTHORS' CONCLUSIONS: We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.

Heavy metal leaching and distribution in glass products from the co-melting treatment of electroplating sludge and MSWI fly ash.

Melting is a common solidification treatment that concentrates and encapsulates heavy metals into a glass matrix for waste containing heavy metals (Chae et al., 2016). To control the risk of heavy metal leaching into the glass product, a reduction in the amount of heavy metal was achieved in a pilot-scale furnace by co-melting electroplating sludge (EPS) and municipal solid waste incineration fly ash (MSWI FA). Through the melting process, the chloride from MSWI FA led to heavy metals volatilization in the form of chlorine salts. The fly ash additionally increased heavy metals volatilization by 4%-91%. The highest volatilization ratios of Zn, Pb, Cu, Cd, Cr and Ni were 33%, 96%, 33%, 79%, 81% and 31%, respectively. The concentrations of Pb and Zn in the secondary fly ash were close to the Pb and Zn concentrations in lead-zinc ore that are required in smelting industry. Moreover, glass sand was produced after the melting treatment. With an increase in the fly ash mixing ratio, the leaching concentration of Zn and Cu decreased to 3.8 mg/L and 2.1 mg/L. The leaching concentrations of other heavy metals stayed below 1 mg/L in all cases. When the ratio of MSWI FA reached 10%, the glass sand contained the least amount of impurities and a large amount of phosphate and silicate, which were probably responsible for the stability of the heavy metals. Therefore, our results provided a promising approach to the stability of the waste by the recovery of heavy metals in the co-treatment of heavy metal-bearing wastes.

Early Prediction of Malignant Brain Edema After Ischemic Stroke.

Background and Purpose- Malignant brain edema after ischemic stroke has high mortality but limited treatment. Therefore, early prediction is important, and we systematically reviewed predictors and predictive models to identify reliable markers for the development of malignant edema. Methods- We searched Medline and Embase from inception to March 2018 and included studies assessing predictors or predictive models for malignant brain edema after ischemic stroke. Study quality was assessed by a 17-item tool. Odds ratios, mean differences, or standardized mean differences were pooled in random-effects modeling. Predictive models were descriptively analyzed. Results- We included 38 studies (3278 patients) with 24 clinical factors, 7 domains of imaging markers, 13 serum biomarkers, and 4 models. Generally, the included studies were small and showed potential publication bias. Malignant edema was associated with younger age (n=2075; mean difference, -4.42; 95% CI, -6.63 to -2.22), higher admission National Institutes of Health Stroke Scale scores (n=807, median 17-20 versus 5.5-15), and parenchymal hypoattenuation >50% of the middle cerebral artery territory on initial computed tomography (n=420; odds ratio, 5.33; 95% CI, 2.93-9.68). Revascularization (n=1600, odds ratio, 0.37; 95% CI, 0.24-0.57) were associated with a lower risk for malignant edema. Four predictive models all showed an overall C statistic >0.70, with a risk of overfitting. Conclusions- Younger age, higher National Institutes of Health Stroke Scale, and larger parenchymal hypoattenuation on computed tomography are reliable early predictors for malignant edema. Revascularization reduces the risk of malignant edema. Future studies with robust design are needed to explore optimal cutoff age and National Institutes of Health Stroke Scale scores and to validate and improve existing models.

Factors associated with favourable outcome in large hemispheric infarctions.

BACKGROUND: Large hemispheric infarction (LHI) is a devastating condition with high mortality and poor functional outcome in most conservatively treated patients. The purpose of this study was to explore factors associated with favorable outcome in patients with LHI. METHODS: We prospectively enrolled consecutive patients with LHI. Favorable outcome was defined as a modified Rankin Scale (mRS) score of 0 to 3 at 90 days. Multivariate logistic regression analysis was employed to identify the independent factors associated with favorable outcome. RESULTS: Two hundred fifty-six cases with LHI were identified: 41 (16.0%) died during hospitalization, 94 (36.7%) died at 3 month, and 113 (44.1%) survived with favorable outcome at day 90. Compared with patients with unfavorable outcome, the favorable cases were younger (55.8 ± 14.7 vs. 66.2 ± 14.1), had less history of hypertension (38.9% vs. 59.3%), lower baseline NIHSS score (median NIHSS score 11 vs. 17), lower blood pressure on admission (systolic 134.7 ± 24.9 vs. 145.1 ± 26.1 mmHg; diastolic 80.2 ± 14.9 vs. 86.9 ± 16.2 mmHg; respectively), lower level of baseline serum glucose (7.2 ± 3.3 vs. 8.2 ± 3.3 mmol/L), a lower frequency of stroke-related complications (55.8% vs. 91.4%), more use of antiplatelets (93.8% vs. 57.1%) and statins (46.9% vs. 25.7%) in the acute phase of stroke, but less use of osmotic agents (69.9% vs. 89.3%), mechanical ventilation (1.8% vs. 20.0%) or decompressive hemicraniectomy (1.8% vs. 15.7%). Multivariable analysis identified the following factors associated with favorable outcome: age (odds ratio, OR 0.95, 95% confidence interval [CI] 0.92-0.98, p < 0.001), baseline NIHSS score (OR 0.90, 95% CI 0.84-0.96, p = 0.002), statins used in acute phase (OR 2.49, 95% CI 1.10-5.65, p = 0.029), brain edema (OR 0.05, 95% CI 0.01-0.21, p < 0.001) and pneumonia (OR 0.42, 95% CI 0.19-0.93, p = 0.032). CONCLUSION: More than one third of patients with LHI have relatively favorable clinical outcomes at 90 days. Younger age, lower baseline NIHSS score, absence of brain edema and pneumonia, and statins used in the acute phase were associated with favorable outcome of patients with LHI at 90 days.

The burden of non-symptomatic cerebral ischemia on MRI and its effect on clinical outcomes in patients with first-ever intracerebral hemorrhage.

PURPOSE: To compare the burden of non-symptomatic cerebral ischemia (NSCI) detected on magnetic resonance imaging (MRI) and computed tomography (CT), and assess the association of MRI-NSCI with clinical outcomes among patients with first-ever intracerebral hemorrhage (ICH). METHODS: Two thousand three hundred and five consecutive ICH patients admitted to our institution from May 2012 to October 2015 were retrospectively reviewed. Data on clinical characteristics and MRI/CT scans were collected during hospitalization. Information on clinical outcomes at three-month were also obtained. RESULTS: Three hundred and seventy-seven patients performed MRIs and 1966 had CTs during hospitalization. NSCI was detected in 152 (40.3%) patients with MRIs and in 638 (32.5%) with CTs. Comparing with CT, NSCI detected by MRI was more common (40.3% vs. 32.5%; P = 0.011), more likely to be multiple loci (93.4% vs. 79.6%; P < 0.001) and bilateral hemispheres (84.9% vs. 73.2%; P = 0.003). Furthermore, the presence of NSCI, multiple NSCI, bilateral NSCI and bilateral hematoma combined with bilateral NSCI were associated with poor outcomes (P < 0.001, P < 0.001, P < 0.001, P = 0.041, respectively) in univariate analysis. In multivariable logistic regression, bilateral hematoma combined with bilateral NSCI was still associated with poor outcomes (OR 3.983, 95% CI 1.172-13.539; P = 0.027). CONCLUSIONS: Compared with CT, NSCI on MRI tends to be multiple loci and located in bilateral hemispheres. The results of NSCI in ICH may be underestimated based on CT. In addition, the increased poor outcomes at three-month suggest that NSCI may play an important role in reducing clinical outcomes.

Prognostic Significance of Intraventricular Hemorrhage in Vascular Structural Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: The prognostic significance of intraventricular hemorrhage (IVH) in patients with vascular structural abnormality-related intracerebral hemorrhage (VSARICH) is poorly understood. METHOD: We prospectively included consecutive patients diagnosed with VSARICH. Imaging of initial brain computed tomography (CT) scans within 48 hours of symptom onset was analyzed. The presence and severity of IVH were recorded. Severity of IVH was measured using the modified Graeb (mGraeb) score. Baseline characteristics and 3-month outcomes were compared between the IVH and non-IVH groups. Multivariate logistic regression was used to examine the independent association between IVH and 3-month outcomes. RESULTS: A total of 132 VSARICH patients were included for analysis, and 71 (53.8%) of them had IVH on initial CT imaging. IVH patients had a median mGraeb score of 15 (6-21), and compared to non-IVH patients, they had shorter delay to first CT scan and higher stroke severity on admission (all P ≤ .005). At 3 months, IVH patients had higher death rates (30.3% versus 7.0%; P = .001) and poor outcome rates (48.5% versus 21.1%; P = .002) than non-IVH patients. After multivariate analysis, IVH severity was associated with 3-month death (Model 1 OR 1.112, 95% CI [1.027-1.204], P = .009; Model 2 OR 1.110, 95% CI [1.027-1.200], P = .009) and poor outcome (Model 2 OR 1.053, 95% CI [1.001-1.108], P = .047), although no independent association between IVH presence and outcomes was observed. CONCLUSION: IVH severity measured by mGraeb score independently predicts death and poor functional outcome in patients with VSARICH.

Increased Serum Alkaline Phosphatase as a Predictor of Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease.

BACKGROUND AND OBJECTIVE: Elevated alkaline phosphatase (ALP) is considered as a marker of liver function in clinical practice. Furthermore, it has been identified that liver function can contribute to hemorrhagic transformation (HT). However, whether ALP levels play a role in HT after stroke remains an open question, especially in cardioembolic stroke patients. METHODS: We prospectively and consecutively enrolled ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. Baseline data including ALP levels within 48 hours after admission were collected. ALP levels were divided into tertiles. The presence of HT, hemorrhagic infarction (HI), parenchymal hematoma (PH), and symptomatic HT was evaluated according to brain magnetic resonance imaging and European-Australasian Acute Stroke Study III definitions. We used logistic regression to examine the associations between ALP levels and risk of HT, HI, PH, and symptomatic HT. RESULTS: Of the 130 patients (56 male; mean age: 63 years) included finally, 50 (38.5%) developed HT and 13 (10.0%) developed symptomatic HT. ALP levels were not associated with risk of HT, HI, and PH. However, compared with the first ALP tertile, patients in the third tertile were 8.96 times more likely to have symptomatic HT (95% confidence interval: 1.33-60.21; P = .02) after adjusting for age, gender, alanine aminotransferase levels, aspartate aminotransferase levels, antiplatelet therapy, anticoagulation therapy, and thrombolysis therapy. CONCLUSION: Elevated ALP levels may help identify high-risk symptomatic HT in ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. However, further studies with larger cohorts are needed to identify our results.