Aims: The purpose of this study was to determine the most appropriate prognostic endpoint for myocardial (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with chronic heart failure (CHF) based on aggregate results from multiple studies published in the past decade.
Methods And Results: Original individual late (3-5 h) heart/mediastinum (H/M) ratio data of 636 CHF patients were retrieved from six studies from Europe and the USA. All-cause mortality, cardiac mortality, arrhythmic events, and heart transplantation were investigated to determine which provided the strongest prognostic significance for the MIBG imaging data. The majority of patients was male (78%), had a decreased left ventricular ejection fraction (31.1 ± 12.5%), and a mean late H/M of 1.67 ± 0.47. During follow-up (mean 36.9 ± 20.1 months), there were 83 deaths, 67 cardiac deaths, 33 arrhythmic events, and 56 heart transplants. In univariate regression analysis, late H/M was a significant predictor of all event categories, but lowest hazard ratios (HRs) were for the composite endpoint of any event (HR = 0.30, 95% CI 0.19-0.46), all-cause (HR = 0.29, 95% CI 0.16-0.53), and cardiac mortality (HR = 0.28, 95% CI 0.14-0.55). In multivariate analysis, late H/M was an independent predictor for all event categories, except for arrhythmias.
Conclusions: This pooled individual patient data meta-analysis showed that, in CHF patients, the late H/M ratio is not only useful as a dichotomous predictor of events (high vs. low risk), but also has prognostic implication over the full range of the outcome value for all event categories except arrhythmias.
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http://dx.doi.org/10.1093/ehjci/jeu044 | DOI Listing |
Circ Arrhythm Electrophysiol
December 2024
Heart and Lung Center (P.P., J.L., D.V., H.M., P.S., H.-K.N., M.K.).
Background: Cardiac sarcoidosis involves a significant but difficult-to-define risk of sudden cardiac death (SCD). Current guidelines recommend consideration of an implantable cardioverter defibrillator for patients with extensive or significant myocardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. However, extensive/significant LGE is not defined.
View Article and Find Full Text PDFN Engl J Med
November 2024
From Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden (O.A.C.L., B.M.D.F-.F., J.P.R.K., G.V.T.R., J.J.J., S.C.C.-M., F.J.A.G., H.M.B.-R., E.I., E.C., E.W., E.L.H., R.M., C.J.J., M.R.), and the Department of Medical Microbiology, Radboud University Medical Center, Nijmegen (G.-J.G., M.V.-B., W.G., T.R.S., B.G.M., T.B., M.B.B.M.) - both in the Netherlands.
Background: Currently licensed and approved malaria subunit vaccines provide modest, short-lived protection against malaria. Immunization with live-attenuated malaria parasites is an alternative vaccination strategy that has potential to improve protection.
Methods: We conducted a double-blind, controlled clinical trial to evaluate the safety, side-effect profile, and efficacy of immunization, by means of mosquito bites, with a second-generation genetically attenuated parasite (GA2) - a single knockout NF54 parasite (sporozoite form) with extended development into the liver stage.
Neurology
December 2024
From the Department of Neurology (A.L.C.S.); Department of Biostatistics, Epidemiology, and Informatics, (A.L.C.S.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Department of Radiation Medicine and Applied Sciences (A.R.), University of California, San Diego; Memory Impairment and Neurodegenerative Dementia (MIND) Center (J.A.H., T.H.M., M.G.), University of Mississippi Medical Center, Jackson; Department of Psychiatry and Behavioral Sciences (V.K.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Biostatistics and Bioinformatics (L.W.), Duke University, Durham, NC; Department of Population Health (J.R.P., J.C.), New York University Grossman School of Medicine, New York; Department of Epidemiology (A.G.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; National Institute on Aging Intramural Program (K.W.), Baltimore, MD; Department of Epidemiology (A.K.-N.), University of North Carolina at Chapel Hill; and National Institute of Neurologic Disorders and Stroke Intramural Research Program (R.F.G.), Bethesda, MD.
Background And Objectives: Race and ethnicity are proxy measures of sociocultural factors that influence cognitive test performance. Our objective was to compare different regression-based cognitive normative models adjusting for demographics and different combinations of easily accessible/commonly used social determinants of health (SDoH) factors, which may help describe cognitive performance variability historically captured by ethnoracial differences.
Methods: We performed cross-sectional analyses on data from Black and White participants without mild cognitive impairment/dementia in the Atherosclerosis Risk in Communities Study who attended visit 5 in 2011-2013.
Cell
November 2024
Denali Therapeutics Inc., South San Francisco, CA, USA. Electronic address:
While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation.
View Article and Find Full Text PDFTransl Vis Sci Technol
November 2024
Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
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