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His fame bolstered after helping to rebuild Gotham City after an earthquake, billionaire Lex Luthor decides to run for the highest office in the land, the American presidency.

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18–83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8–20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24–48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55–2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc.

Human stroke serum (HSS) has been shown to impair cerebrovascular function, likely by factors released into the circulation after ischemia. 20 nm gold nanoparticles (GNPs) have demonstrated anti‐inflammatory properties, with evidence that they decrease pathologic markers of ischemic severity. Whether GNPs affect cerebrovascular function, and potentially protect against the damaging effects of HSS on the cerebral circulation remains unclear. HSS obtained 24 h poststroke was perfused through the lumen of isolated and pressurized third‐order posterior cerebral arteries (PCAs) from male Wistar rats with and without GNPs (~2 × 109 GNP/ml), or GNPs in vehicle, in an arteriograph chamber (n = 8/group). All vessels were myogenically reactive ≥60 mmHg intravascular pressure; however, vessels containing GNPs had significantly less myogenic tone. GNPs increased vasoreactivity to small and intermediate conductance calcium activated potassium channel activation via NS309; however, reduced vasoconstriction to nitric oxide synthase inhibition. Hydraulic conductivity and transvascular filtration, were decreased by GNPs, suggesting a protective effect on the blood–brain barrier. The stress–strain curves of PCAs exposed to GNPs were shifted leftward, indicating increased vessel stiffness. This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications.

In this long-term follow-up of a randomized trial comparing endarterectomy with stenting for carotid-artery stenosis, the risks of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke did not differ between groups over a 10-year period. We previously reported the outcomes up to 4 years in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). 1 No significant difference was shown between patients assigned to stenting and those assigned to endarterectomy with respect to the composite primary end point of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. At baseline, the mean age of the patients was 69 years, and at that age the average life expectancy is 15 years for men and 17 years for women. 2 As such, long-term treatment differences should be central to treatment decisions. We now report whether the outcomes after stenting . . .

Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12–95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment—12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38–0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42–0·83). Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. NoNO Inc and Arbor Vita Corp.

In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively; P=0.51). Stroke was more common with carotid-artery stenting than carotid endarterectomy; myocardial infarction was more common with carotid endarterectomy. The 4-year rate of stroke or death was 6.4% for carotid-artery stenting and 4.7% for carotid endarterectomy (P=0.03). In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively). Carotid-artery atherosclerosis is an important cause of ischemic stroke. 1 Carotid endarterectomy has been established as effective treatment for both symptomatic patients and asymptomatic patients. 2 – 4 Carotid-artery stenting is another option for treatment. The results of randomized trials comparing carotid-artery stenting and carotid endarterectomy for use in symptomatic patients are conflicting. 5 – 7 The primary aim of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis. Methods Study Design CREST is a randomized, controlled trial with blinded end-point adjudication. Ethics review . . .

While endovascular thrombectomy (EVT) has become standard of care for patients’ acute ischemic stroke (AIS) due to large vessel occlusion (LVO), many patients still suffer profound neurological disability, also termed futile recanalization (FR). The BAND score, which incorporates baseline disability, age, stroke severity, and treatment time window, is derived as a simple tool for upfront prediction of FR prior to EVT. This study aims to externally validate the BAND score and to incorporate upfront imaging biomarkers into the prediction tool. Consecutive stroke thrombectomy patients with anterior circulation LVO who achieved successful recanalization (mTICI 2b or greater) were retrospectively identified at a single institution from 2019 to 2023. Clinical information, procedural details, and 90-day outcomes were recorded. The performance of the BAND score in predicting FR (90-day modified Rankin scale [mRS] >3) and loss of complete independence (LCID, 90-day mRS>2) was assessed. Then, Alberta stroke programme early CT score (ASPECTS) was added to create the PANDA score (pre-stroke disability, age, NIH stroke scale, delay from last known normal, and ASPECTS). The performance of PANDA to predict FR was assessed and compared with the original BAND score and also the widely validated THRIVE score. 296 patients were included; 36.5 % experienced FR. BAND had areas under the receiver-operating curve (AUCs) of 0.72 and 0.74 for predicting FR and LCID, respectively (both p < 0.001). The new PANDA score had AUCs of 0.76 and 0.78 for predicting FR and LCID, respectively (both p < 0.001), and it outperformed both BAND and THRIVE (all p < 0.05). Of the 30 patients (11.2 %) with high PANDA scores (≥7), 24 patients (80.0 %) suffered FR and 26 (86.7 %) suffered LCID. This external validation study confirmed the adequate performance of BAND in predicting FR. The improved PANDA score performed better than the original BAND score and the widely validated THRIVE score. •Futile endovascular recanalization is a common and challenging phenomenon.•There is a lack of accurate tools to navigate complex acute stroke patients.•The PANDA score’s simplicity and accuracy make it a valuable tool for clinicians.•The PANDA score further refines the previously published BAND score.•PANDA outperformed the previously validated THRIVE score.

Tenecteplase for thrombolysis in a 4.5-to-24-hour window did not improve disability outcomes at 90 days in patients with ischemic stroke who had been chosen on the basis of imaging. Most patients had endovascular thrombectomy.

BackgroundRandomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints.MethodsAll randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h.ResultsThree trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02).ConclusionsOur meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

Background General anesthesia (GA) for acute stroke interventions may be associated with inferior functional outcomes. Our goal was to identify physiologic parameters that mediate this association. Methods Consecutive patients treated at our institution between August 2007 and December 2010 were identified from a prospective database. Clinical data were then extracted by retrospective chart review. Variables significantly associated with outcome in univariate analysis were also examined in multivariate analysis, controlling for well-established prespecified predictors of functional outcome. Results Of the 106 patients identified, 20 were excluded (17 due to the absence of 90-day mRS and 3 due to insufficient anesthetic records). Blood pressure (BP) decreased significantly after induction of GA, but there was no association between BP and outcome. End tidal carbon dioxide values (ETCO2) at 60 and 90 min, however, were significantly associated with outcomes in both univariate and multivariate analyses. Mean ETCO2 in patients with favorable outcomes (modified Rankin Scale (mRS) 0–3) was higher than in those with unfavorable outcomes (mRS 4–6): 35.2 mmHg versus 32.2 ( p  = 0.03) at 60 min and 34.9 versus 31.9 ( p  = 0.04) at 90 min. The adjusted odds ratios for poor outcomes for each 1 mmHg decrease in ETCO2 were the same: 0.76 (95 % CI 0.65–0.92; p  = 0.004) at 60 min and 0.76 (95 % CI 0.61–0.93; p  = 0.01) at 90 min. Conclusions While BP decreased significantly in patients undergoing GA for acute stroke intervention, it did not correlate with patient outcome. Decreases in ETCO2 at 30 and 60 min, however, were associated with 90-day mRS.