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Browsing by Author "Barnard, John"
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Item Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease(Elsevier, 2022) Hemnes, Anna R.; Leopold, Jane A.; Radeva, Milena K.; Beck, Gerald J.; Abidov, Aiden; Aldred, Micheala A.; Barnard, John; Rosenzweig, Erika B.; Borlaug, Barry A.; Chung, Wendy K.; Comhair, Suzy A. A.; Desai, Ankit A.; Dubrock, Hilary M.; Erzurum, Serpil C.; Finet, J. Emanuel; Frantz, Robert P.; Garcia, Joe G. N.; Geraci, Mark W.; Gray, Michael P.; Grunig, Gabriele; Hassoun, Paul M.; Highland, Kristin B.; Hill, Nicholas S.; Hu, Bo; Kwon, Deborah H.; Jacob, Miriam S.; Jellis, Christine L.; Larive, A. Brett; Lempel, Jason K.; Maron, Bradley A.; Mathai, Stephen C.; McCarthy, Kevin; Mehra, Reena; Nawabit, Rawan; Newman, John H.; Olman, Mitchell A.; Park, Margaret M.; Ramos, Jose A.; Renapurkar, Rahul D.; Rischard, Franz P.; Sherer, Susan G.; Tang, W. H. Wilson; Thomas, James D.; Vanderpool, Rebecca R.; Waxman, Aaron B.; Wilcox, Jennifer D.; Yuan, Jason X-J; Horn, Evelyn M.; PVDOMICS Study Group; Medicine, School of MedicineBackground: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification. Objectives: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort. Methods: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death. Results: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH. Conclusions: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification.Item NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review(Elsevier, 2021) Oldham, William M.; Hemnes, Anna R.; Aldred, Micheala A.; Barnard, John; Brittain, Evan L.; Chan, Stephen Y.; Cheng, Feixiong; Cho, Michael H.; Desai, Ankit A.; Garcia, Joe G.N.; Geraci, Mark W.; Ghiassian, Susan D.; Hall, Kathryn T.; Horn, Evelyn M.; Jain, Mohit; Kelly, Rachel S.; Leopold, Jane A.; Lindstrom, Sara; Modena, Brian D.; Nichols, William C.; Rhodes, Christopher J.; Sun, Wei; Sweatt, Andrew J.; Vanderpool, Rebecca R.; Wilkins, Martin R.; Wilmot, Beth; Zamanian, Roham T.; Fessel, Joshua P.; Aggarwal, Neil R.; Loscalzo, Joseph; Xiao, Lei; Medicine, School of MedicineThe National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.Item Relationship of Auditory Electrophysiological Responses to Magnetic Resonance Spectroscopy Metabolites in Early Phase Psychosis(Elsevier, 2019) Bartolomeo, Lisa A.; Wright, Andrew M.; Ma, Ruoyun E.; Hummer, Tom A.; Francis, Michael M.; Visco, Andrew C.; Mehdiyoun, Nicole F.; Bolbecker, Amanda R.; Hetrick, William P.; Dydak, Ulrike; Barnard, John; O'Donnell, Brian F.; Breier, Alan; Psychiatry, School of MedicineBoth auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.