Background-A blood-based biomarker of Alzheimer disease (AD) would be superior to CSF and neuroimaging measures in terms of cost, invasiveness and feasibility for repeated measures. We previously reported blood ceramides varied in relation to timing of memory impairment in a population-based study. The present objective was to examine whether plasma ceramides varied by AD severity in a well-characterized clinic sample and were associated with cognitive decline and hippocampal volume loss over one year.Methods-Participants included 25 normal controls (NC), 17 amnestic Mild Cognitive Impairment (MCI), and 21 early probable AD. A thorough neuropsychological battery and neuroimaging with hippocampal volume determination were conducted at baseline and one year later. Plasma ceramides were assayed at baseline using HPLC-coupled electrospray ionization tandem mass spectrometry. : 443-326-5174, Fax: 410-550-1407, mmielke1@jhmi.edu. Disclosure: All authors report no conflicts of interest. The corresponding author had full access to all the data in the study and had final responsibility of the decision to submit for publication.Disclosure Statement: While funding for the neuroimaging and participant follow-up was partially obtained through a grant from GlaxoSmithKline, the authors had access to the data at all times and retain the data. Funding for the plasma lipids were obtained from NIH grants. All authors report no conflicts of interests with regards to GlaxoSmithKline or any other organization. All participants provided informed consent and the study was approved by the Johns Hopkins University Institutional Review Board.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-While all saturated ceramides were lower in MCI compared to AD at baseline, Ceramides C22:0 and C24:0 were significantly lower in the MCI group compared to both NC and AD groups (p<0.01). Ceramide levels did not differ (p>0.05) in AD versus NC. There were no cross-sectional associations between ceramides C22:0 and C24:0 and either cognitive performance or hippocampal volume among any group. However, among the MCI group, higher baseline ceramide C22:0 and C24:0 levels were predictive of cognitive decline and hippocampal volume loss one year later. NIH Public AccessAuthor Manuscript Alzheimers Dement. Author manuscript; available in PMC 2011 September 1. Conclusion-Resultssuggest that very long-chain plasma ceramides C22:0 and C24:0 are altered in MCI and predict memory loss and right hippocampal volume loss among subjects with MCI. These plasma ceramides may be early indicators of AD progression.

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Background More than 500 000 sudden cardiac arrests (SCAs) occur annually in the United States. Clinical predictive models (CPMs) may be helpful tools to differentiate between patients who are likely to survive or have good neurologic recovery and those who are not. However, which CPMs are most reliable for discriminating between outcomes in SCA is not known. Methods and Results We performed a systematic review of the literature using the Tufts PACE (Predictive Analytics and Comparative Effectiveness) CPM Registry through February 1, 2020, and identified 81 unique CPMs of SCA and 62 subsequent external validation studies. Initial cardiac rhythm, age, and duration of cardiopulmonary resuscitation were the 3 most commonly used predictive variables. Only 33 of the 81 novel SCA CPMs (41%) were validated at least once. Of 81 novel SCA CPMs, 56 (69%) and 61 of 62 validation studies (98%) reported discrimination, with median c‐statistics of 0.84 and 0.81, respectively. Calibration was reported in only 29 of 62 validation studies (41.9%). For those novel models that both reported discrimination and were validated (26 models), the median percentage change in discrimination was −1.6%. We identified 3 CPMs that had undergone at least 3 external validation studies: the out‐of‐hospital cardiac arrest score (9 validations; median c‐statistic, 0.79), the cardiac arrest hospital prognosis score (6 validations; median c‐statistic, 0.83), and the good outcome following attempted resuscitation score (6 validations; median c‐statistic, 0.76). Conclusions Although only a small number of SCA CPMs have been rigorously validated, the ones that have been demonstrate good discrimination.

Background We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc., Maple Grove, Minnesota) implantation using a finite element (FE) model of the left ventricle (LV). Chronic ischemic mitral regurgitation (CIMR) is due to LV remodeling after postero-lateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases CIMR. Methods FE models of the LV were based on magnetic resonance images (MRI) obtained before (PRE-OP) and after (POST-OP) CABG + Coapsys in a single patient. To determine the effect of Coapsys and LV pre-stress, virtual Coapsys (VIRTUAL-COAPSYS) was performed on the PRE-OP model. Diastolic and systolic material parameters in the PRE-OP, POST-OP and VIRTUAL-COAPSYS were adjusted so that model LV volume agreed with MRI data. CIMR was abolished in the post-op models. In each case, myofiber stress and pump function were calculated. Results Both POST-OP and VIRTUAL-COAPSYS shifted end-systolic (ES) and end diastolic (ED) pressure volume relationships (PVR) to the left. As a consequence and because CIMR was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at ED and ES in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV pre-stress was necessary for accurate calculation of LV myofiber stress especially in the remote zone. Conclusions Coapsys decreases myofiber stress at ED and ES. The improvement in myofiber stress may contribute to the long term effect of Coapsys on LV remodeling.