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Background:\ud \ud CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients.\ud \ud Methods:\ud \ud We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2–4) 6–60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124.\ud \ud Findings:\ud \ud 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60–82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6–8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points.\ud \ud Interpretation:\ud \ud Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients.

The significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) depicts left ventricular (LV) dimension and pathology. Native T1 quantified by CMR (T1 proton relaxation time, milliseconds) is a fundamental tissue property determined by water

Background: The pathophysiological basis of reperfusion injury in smokers is incompletely understood. Methods: Patients with acute STEMI were prospectively enrolled during emergency PCI, and categorized according to a current smoking status (yes/no). Contrast-enhanced MRI at 1.5T was acquired 2

Background: The segmental extent of late gadolinium enhancement imaged with cardiac magnetic resonance early after acute ST-segment elevation myocardial infarction (STEMI) has weak spatial correspondence with final infarct on follow-up, thus its prognostic value is uncertain. We hypothesized that

Background Infarct size assessed early after acute ST-segment elevation myocardial infarction (STEMI) can overestimate the true extent of infarction, limiting its usefulness as a prognostic biomarker. Myocardial strain derived from displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) provides information on myocardial contractility with high precision and accuracy. We hypothesised that the prognostic value of peak circumferential strain is higher than infarct size. Methods In a prospective, single centre study, participants underwent 1·5T CMR 2 days and 6 months after myocardial infarction. The 5-SD technique was used to quantify late gadolinium enhancement (LGE) as proportion of left ventricular mass. Mid-left ventricular DENSE acquisitions were analysed using postprocessing software. During longer-term follow-up, major adverse cardiac events (MACE) were independently assessed by masked cardiologists. Participants provided written informed consent and ethics approval was given (reference 10/S0703/28). This study is registered with ClinicalTrials.gov, number NCT02072850. Findings 300 patients underwent CMR (mean age 58·6 years [SD 13·2], 237 men [79%], 118 anterior myocardial infarction [39%], 30 with diabetes [10%], 284 with normal flow [Thrombolysis in Myocardial Infarction grade 3] after percutaneous coronary intervention [95%]). 259 of these patients had DENSE acquired, of whom 21 (8%) experienced a MACE at 3 years' follow-up. DENSE and baseline LGE had reasonable power for prediction of adverse events (area under the curve [AUC] DENSE 0·712, p=0·001; AUC LGE 0·644, p=0·028). For MACE (receiver operating characteristic analysis), optimal cut-offs for peak circumferential strain using DENSE was −10·51%, and LGE 24·05 g. Cox-regression analysis showed that DENSE (hazard ratio 1·175, 95% CI 0·036–1·334; p=0·012) offered an incremental prognostic benefit over LGE (1·040, 1·010–1·070; p=0·008) to predict MACE. Interpretation DENSE-derived peak circumferential strain offers an incremental prognostic benefit over infarct size revealed by LGE to predict MACE; a cut-off of −10·51% can identify STEMI patients at higher risk of events. This is the first time, to our knowledge, that CMR-derived strain has been shown to provide prognostic utility in patients with STEMI. Funding This research was supported by project grants from the Chief Scientist Office (SC01), Medical Research Scotland (343 FRG), and the British Heart Foundation (BHF-PG/14/64/31043).

Despite the success of emergency percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (STEMI), failed myocardial reperfusion (microvascular obstruction (MVO)) is common and prognostically important. Our aim was to compare coronary flow reserve (CFR), a measure of