Advanced cerebrovascular β-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2*-weighted MRI and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On co-registered PET and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p=0.002) and declined with increasing distance from the microbleed (p<0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition.Cerebrovascular deposition of β-amyloid (cerebral amyloid angiopathy, CAA) is most commonly recognized during life as a cause of brain hemorrhage. Hemorrhages associated with CAA can be large, symptomatic strokes or small, typically asymptomatic cerebral microbleeds (CMB). CMB are sensitively imaged by T2*-weighted MRI and have been implicated as markers of, and possible contributors to, small vessel-related brain injury.1Although the link between CAA and CMB is well established,1 the precise mechanism by which vascular amyloid leads to microhemorrhage remains incompletely understood. It is unknown, for example, whether CMB occur preferentially at sites of greatest amyloid deposition. Circumstantial evidence supports this possibility, as both CAA pathology2 and CAA-related CMB3 tend to favor occipital cortex. Further, a recent study suggested that brains with many CAA-related CMB have greater thickness of vascular amyloid than brains with few CMB. METHODS Image Acquisition and AnalysisWe performed T2*-weighted MR and PiB-PET imaging on 16 CAA patients (Table 1) recruited at Massachusetts General Hospital.3 All subjects were diagnosed as probable CAA based on the Boston criteria (7 with supporting pathology, 9 by multiple lobar hemorrhages/ CMB),7 were nondemented, and free of symptoms suggestive of new stroke for 1 year prior to PiB-PET. PiB was prepared and PET acquisition performed using methods previously described.5 PET data were reconstructed and expressed as a distribution volume ratio (DVR) with cerebellum as reference tissue. Each subject also underwent research T2*-weighted MRI for detection of CMB.Full details of MRI acquisition, processing, identification of CMB, co-registration of T2*-weighted and PET images (Figures. 1A and B), and scoring of PiB values are provided in the Supplemental Methods. MR imaging was performed at 1.5 Tesla using protocols for gradient-echo (GRE) or susceptibility-weighted imaging (SWI) as described.8 PiB-PET values within a CMB were measured and averaged to provide mean DVR per voxel for each microbleed. PiB-PET values were also measured in five concentric "shells," each 2 mm in thickness, surrounding each CMB ( Figure 1C). To provide an appropriate control comparison for the observed CMB, 200 "simulated" CMB lesions were distributed thr...
Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.
BACKGROUND AND PURPOSE:Leukoaraiosis is a common finding among patients with ischemic stroke and has been associated with poor stroke outcomes. Our aim was to ascertain whether the severity of pre-existing leukoaraiosis is associated with outcome in patients with acute ischemic stroke who are treated with endovascular stroke therapy.
Interferon alpha for chronic hepatitis D.
To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged.
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