Rationale: More patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes than of respiratory causes, and patients with COPD have increased morbidity and mortality from stroke and coronary heart disease. Arterial stiffness independently predicts cardiovascular risk, is associated with atheromatous plaque burden, and is increased in patients with COPD compared with control subjects matched for cardiovascular risk factors. Elastin fragmentation and changes in collagen are found in the connective tissue of both emphysematous lungs and stiff arteries, but it is not known whether the severity of arterial stiffness in patients with COPD is associated with the severity of emphysema. Objectives: To identify whether the extent of arterial stiffness is associated with emphysema severity. Methods: We performed a cross-sectional study in 157 patients with COPD. Measurements and Main Results: We measured pulse wave velocity (a validated measure of arterial stiffness), blood pressure, smoking pack-years, glucose, cholesterol, and C-reactive protein in 157 patients with COPD. We assessed emphysema using quantitative computed tomography scanning in a subgroup of 73 patients. We found that emphysema severity was associated with arterial stiffness (r 5 0.471, P , 0.001). The association was independent of smoking, age, sex, FEV 1 % predicted, highly sensitive C-reactive protein and glucose concentrations, cholesterol-high-density lipoprotein ratio, and pulse oximetry oxygen saturations. Conclusions: Emphysema severity is associated with arterial stiffness in patients with COPD. Similar pathophysiological processes may be involved in both lung and arterial tissue and further studies are now required to identify the mechanism underlying this newly described association.

Introduction Advanced machine learning methods might help to identify dementia risk from neuroimaging, but their accuracy to date is unclear. Methods We systematically reviewed the literature, 2006 to late 2016, for machine learning studies differentiating healthy aging from dementia of various types, assessing study quality, and comparing accuracy at different disease boundaries. Results Of 111 relevant studies, most assessed Alzheimer's disease versus healthy controls, using AD Neuroimaging Initiative data, support vector machines, and only T1-weighted sequences. Accuracy was highest for differentiating Alzheimer's disease from healthy controls and poor for differentiating healthy controls versus mild cognitive impairment versus Alzheimer's disease or mild cognitive impairment converters versus nonconverters. Accuracy increased using combined data types, but not by data source, sample size, or machine learning method. Discussion Machine learning does not differentiate clinically relevant disease categories yet. More diverse data sets, combinations of different types of data, and close clinical integration of machine learning would help to advance the field.

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.

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N oncontrast computed tomography (CT) remains the primary imaging modality for hyperacute assessment of stroke in most centers.1 Identifying features of acute ischemic stroke on CT, therefore, remains important for routine practice. Hyperattenuation of a cerebral artery on noncontrast CT in acute ischemic stroke is thought to represent acute thrombus or embolus; the presence of the Hyperdense Artery Sign (HAS), therefore, is a surrogate of arterial obstruction and may provide useful confirmation of the diagnosis of acute ischemic stroke. The sign has been defined as any artery that subjectively appears transiently denser than adjacent or equivalent contralateral vessels 2,3 although objective measures have also been applied. 4 When compared with angiography, previous studies have shown that the HAS is a specific (although false-positives are described) 5 but not sensitive indicator of arterial obstruction. 6,7 To our knowledge, no systematic review and meta-analysis of HAS sensitivity and specificity have been published. The Third International Stroke Trial (IST-3) was a multicenter, randomized controlled trial, which tested intravenous thrombolysis (Alteplase) given within 6 hours of ischemic stroke.8 Baseline (prerandomization) and follow-up (within 48 hours) brain imaging (predominantly noncontrast CT) was performed for all . In some centers, CT or MR angiography (CTA and MRA, respectively) were also routinely obtained prerandomization as part of their local stroke imaging protocol. 9 In a prespecified analysis, we investigated the diagnostic accuracy of HAS for arterial obstruction detected with CTA or MRA and assessed if characteristics of the noncontrast CT scan (slice-thickness), the corresponding angiographic Background and Purpose-In acute ischemic stroke, the hyperdense artery sign (HAS) on noncontrast computed tomography (CT) is thought to represent intraluminal thrombus and, therefore, is a surrogate of arterial obstruction. We sought to assess the accuracy of HAS as a marker of arterial obstruction by thrombus. Methods-The Third International Stroke Trial (IST-3) was a randomized controlled trial testing the use of intravenous thrombolysis for acute ischemic stroke in patients who did not clearly meet the prevailing license criteria. Some participating IST-3 centers routinely performed CT or MR angiography at baseline. One reader assessed all relevant scans independently, blinded to all other data; we checked observer reliability. We combined IST-3 data with a systematic review and meta-analysis of all studies that assessed the accuracy of HAS using angiography (any modality). Results-IST-3 had 273 patients with baseline CT or MR angiography and was the largest study of HAS accuracy. The meta-analysis (n=902+273=1175, including IST-3) found sensitivity and specificity of HAS for arterial obstruction on angiography to be 52% and 95%, respectively. HAS was more commonly identified in proximal than distal arteries (47% versus 37%; P=0.015), and its sensitivity increased with thinner CT slices (r=−0...

The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.

Background and Purpose— Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results— Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45–110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98–3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01–0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions— Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN26986053.