Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 62

Publication Record

Connections

Platelet transfusion does not improve outcomes in patients with brain injury on antiplatelet therapy.
Holzmacher JL, Reynolds C, Patel M, Maluso P, Holland S, Gamsky N, Moore H, Acquista E, Carrick M, Amdur R, Hancock H, Metzler M, Dunn J, Sarani B
(2018) Brain Inj 32: 325-330
MeSH Terms: Aged, Aged, 80 and over, Aspirin, Brain Injuries, Clopidogrel, Female, Humans, Injury Severity Score, Length of Stay, Male, Platelet Aggregation Inhibitors, Platelet Transfusion, Statistics, Nonparametric, Treatment Outcome
Show Abstract · Added June 26, 2018
INTRODUCTION - Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.
METHODS - An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.
RESULTS - Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality.
CONCLUSION - Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
Cavallari LH, Lee CR, Beitelshees AL, Cooper-DeHoff RM, Duarte JD, Voora D, Kimmel SE, McDonough CW, Gong Y, Dave CV, Pratt VM, Alestock TD, Anderson RD, Alsip J, Ardati AK, Brott BC, Brown L, Chumnumwat S, Clare-Salzler MJ, Coons JC, Denny JC, Dillon C, Elsey AR, Hamadeh IS, Harada S, Hillegass WB, Hines L, Horenstein RB, Howell LA, Jeng LJB, Kelemen MD, Lee YM, Magvanjav O, Montasser M, Nelson DR, Nutescu EA, Nwaba DC, Pakyz RE, Palmer K, Peterson JF, Pollin TI, Quinn AH, Robinson SW, Schub J, Skaar TC, Smith DM, Sriramoju VB, Starostik P, Stys TP, Stevenson JM, Varunok N, Vesely MR, Wake DT, Weck KE, Weitzel KW, Wilke RA, Willig J, Zhao RY, Kreutz RP, Stouffer GA, Empey PE, Limdi NA, Shuldiner AR, Winterstein AG, Johnson JA, IGNITE Network
(2018) JACC Cardiovasc Interv 11: 181-191
MeSH Terms: Aged, Clinical Decision-Making, Clopidogrel, Cytochrome P-450 CYP2C19, Drug Resistance, Female, Humans, Male, Middle Aged, Patient Selection, Percutaneous Coronary Intervention, Pharmacogenetics, Pharmacogenomic Testing, Pharmacogenomic Variants, Platelet Aggregation Inhibitors, Prasugrel Hydrochloride, Predictive Value of Tests, Risk Assessment, Risk Factors, Ticagrelor, Time Factors, Treatment Outcome, United States
Show Abstract · Added March 14, 2018
OBJECTIVES - This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).
BACKGROUND - CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.
METHODS - After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.
RESULTS - Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).
CONCLUSIONS - These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Physician response to implementation of genotype-tailored antiplatelet therapy.
Peterson JF, Field JR, Unertl KM, Schildcrout JS, Johnson DC, Shi Y, Danciu I, Cleator JH, Pulley JM, McPherson JA, Denny JC, Laposata M, Roden DM, Johnson KB
(2016) Clin Pharmacol Ther 100: 67-74
MeSH Terms: Age Factors, Aged, Clinical Decision-Making, Clopidogrel, Cytochrome P-450 CYP2C19, Female, Genetic Variation, Genotype, Humans, Male, Middle Aged, Pharmacogenetics, Platelet Aggregation Inhibitors, Practice Patterns, Physicians', Precision Medicine, Prospective Studies, Stents, Ticlopidine
Show Abstract · Added March 14, 2018
Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss-of-function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision-making.
© 2015 American Society for Clinical Pharmacology and Therapeutics.
0 Communities
1 Members
0 Resources
18 MeSH Terms
CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease.
Hoh BL, Gong Y, McDonough CW, Waters MF, Royster AJ, Sheehan TO, Burkley B, Langaee TY, Mocco J, Zuckerman SL, Mummareddy N, Stephens ML, Ingram C, Shaffer CM, Denny JC, Brilliant MH, Kitchner TE, Linneman JG, Roden DM, Johnson JA
(2016) J Neurosurg 124: 1746-51
MeSH Terms: Aged, Aspirin, Carboxylic Ester Hydrolases, Clopidogrel, Cytochrome P-450 CYP2C19, Female, Gene Frequency, Genotyping Techniques, Heterozygote, Humans, Intracranial Arteriosclerosis, Ischemic Attack, Transient, Kaplan-Meier Estimate, Male, Myocardial Infarction, Platelet Aggregation Inhibitors, Polymorphism, Single Nucleotide, Prospective Studies, Stroke, Ticlopidine
Show Abstract · Added March 14, 2018
OBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, (*)3, (*)8, (*)17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03-0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08-0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06-1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05-1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.
Gengo F, Westphal ES, Rainka MM, Janda M, Robson MJ, Hourihane JM, Bates V
(2016) J Clin Pharmacol 56: 414-21
MeSH Terms: Aspirin, Blood Coagulation Tests, Blood Platelets, Collagen, Drug Resistance, Female, Humans, Male, Middle Aged, Platelet Aggregation, Platelet Aggregation Inhibitors, Platelet Function Tests
Show Abstract · Added August 26, 2015
This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose.
© 2015, The American College of Clinical Pharmacology.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Platelet Inhibitors Reduce Rupture in a Mouse Model of Established Abdominal Aortic Aneurysm.
Owens AP, Edwards TL, Antoniak S, Geddings JE, Jahangir E, Wei WQ, Denny JC, Boulaftali Y, Bergmeier W, Daugherty A, Sampson UKA, Mackman N
(2015) Arterioscler Thromb Vasc Biol 35: 2032-2041
MeSH Terms: Aged, Angiotensin II, Animals, Aorta, Abdominal, Aortic Aneurysm, Abdominal, Aortic Rupture, Disease Models, Animal, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Male, Mice, Mice, Inbred C57BL, Platelet Aggregation Inhibitors
Show Abstract · Added February 22, 2016
OBJECTIVE - Rupture of abdominal aortic aneurysms causes a high morbidity and mortality in the elderly population. Platelet-rich thrombi form on the surface of aneurysms and may contribute to disease progression. In this study, we used a pharmacological approach to examine a role of platelets in established aneurysms induced by angiotensin II infusion into hypercholesterolemic mice.
APPROACH AND RESULTS - Administration of the platelet inhibitors aspirin or clopidogrel bisulfate to established abdominal aortic aneurysms dramatically reduced rupture. These platelet inhibitors reduced abdominal aortic platelet and macrophage recruitment resulting in decreased active matrix metalloproteinase-2 and matrix metalloproteinase-9. Platelet inhibitors also resulted in reduced plasma concentrations of platelet factor 4, cytokines, and components of the plasminogen activation system in mice. To determine the validity of these findings in human subjects, a cohort of aneurysm patients were retrospectively analyzed using developed and validated algorithms in the electronic medical record database at Vanderbilt University. Similar to mice, administration of aspirin or P2Y12 inhibitors was associated with reduced death among patients with abdominal aortic aneurysm.
CONCLUSIONS - These results suggest that platelets contribute to abdominal aortic aneurysm progression and rupture.
© 2015 American Heart Association, Inc.
0 Communities
3 Members
0 Resources
15 MeSH Terms
2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW, American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(2014) J Am Coll Cardiol 64: e1-76
MeSH Terms: Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Autonomic Nervous System, C-Reactive Protein, Cardiac Output, Low, Catheter Ablation, Comorbidity, Defibrillators, Implantable, Echocardiography, Transesophageal, Electric Countershock, Electrocardiography, Fibrinolytic Agents, Heart Atria, Heart Conduction System, Humans, Inflammation, Natriuretic Peptide, Brain, Oxidative Stress, Pacemaker, Artificial, Platelet Aggregation Inhibitors, Renin-Angiotensin System, Risk Assessment, Risk Factors, Septal Occluder Device, Stroke, Thromboembolism, Ventricular Remodeling
Added May 27, 2014
0 Communities
1 Members
0 Resources
29 MeSH Terms
Blocking the P2X7 receptor improves outcomes after axonal fusion.
Rodriguez-Feo CL, Sexton KW, Boyer RB, Pollins AC, Cardwell NL, Nanney LB, Shack RB, Mikesh MA, McGill CH, Driscoll CW, Bittner GD, Thayer WP
(2013) J Surg Res 184: 705-13
MeSH Terms: Action Potentials, Adenosine Triphosphate, Animals, Axons, Benzenesulfonates, Coloring Agents, Drug Carriers, Male, Motor Activity, Nerve Regeneration, Neurosurgical Procedures, Platelet Aggregation Inhibitors, Polyethylene Glycols, Purinergic P2X Receptor Antagonists, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2X7, Sciatic Neuropathy, Wallerian Degeneration, Wound Healing
Show Abstract · Added July 9, 2013
BACKGROUND - Activation of the P2X7 receptor on peripheral neurons causes the formation of pannexin pores, which allows the influx of calcium across the cell membrane. Polyethylene glycol (PEG) and methylene blue have previously been shown to delay Wallerian degeneration if applied during microsuture repair of the severed nerve. Our hypothesis is that by modulating calcium influx via the P2X7 receptor pathway, we could improve PEG-based axonal repair. The P2X7 receptor can be stimulated or inhibited using bz adenosine triphosphate (bzATP) or brilliant blue (FCF), respectively.
METHODS - A single incision rat sciatic nerve injury model was used. The defect was repaired using a previously described PEG methylene blue fusion protocol. Experimental animals were treated with 100 μL of 100 μM FCF solution (n = 8) or 100 μL of a 30 μM bzATP solution (n = 6). Control animals received no FCF, bzATP, or PEG. Compound action potentials were recorded prior to transection (baseline), immediately after repair, and 21 d postoperatively. Animals underwent behavioral testing 3, 7, 14, and 21 d postoperatively. After sacrifice, nerves were fixed, sectioned, and immunostained to allow for counting of total axons.
RESULTS - Rats treated with FCF showed an improvement compared with control at all time points (n = 8) (P = 0.047, 0.044, 0.014, and 0.0059, respectively). A statistical difference was also shown between FCF and bzATP at d 7 (P < 0.05), but not shown with d 3, 14, and 21 (P > 0.05).
CONCLUSIONS - Blocking the P2X7 receptor improves functional outcomes after PEG-mediated axonal fusion.
Copyright © 2013 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
PGI₂ signaling inhibits antigen uptake and increases migration of immature dendritic cells.
Toki S, Goleniewska K, Huckabee MM, Zhou W, Newcomb DC, Fitzgerald GA, Lawson WE, Peebles RS
(2013) J Leukoc Biol 94: 77-88
MeSH Terms: Animals, Bone Marrow Cells, Cell Movement, Chemokine CCL19, Chemokine CCL21, Chemotaxis, Cytokines, Dendritic Cells, Epoprostenol, Female, Flow Cytometry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin, Platelet Aggregation Inhibitors, Receptors, CCR7, Receptors, Epoprostenol, Signal Transduction
Show Abstract · Added May 27, 2014
PGI₂ signaling through IP inhibits allergen-induced inflammatory responses in mice. We reported previously that PGI₂ analogs decreased proinflammatory cytokine and chemokine production by mature BMDCs. However, whether PGI₂ modulates the function of immature DCs has not been investigated. We hypothesized that PGI2 negatively regulates immature DC function and investigated the effect of PGI2 analogs on immature BMDC antigen uptake and migration in vitro and in vivo. Immature BMDCs were obtained from WT and IPKO mice, both on a C57BL/6 background. The PGI2 analog cicaprost decreased FITC-OVA uptake by immature BMDCs. In addition, cicaprost increased immature BMDC podosome dissolution, pro-MMP-9 production, cell surface CCR7 expression, and chemotactic migration toward CCL19 and CCL21, as well as chemokinesis, in an IP-specific fashion. These in vitro results suggested that cicaprost promotes migration of immature DCs from mucosal surface to draining LNs. This concept was supported by the finding that migration of immature GFP⁺ BMDCs to draining LNs was enhanced by pretreatment with cicaprost. Further, migration of immature lung DCs labeled with PKH26 was enhanced by intranasal cicaprost administration. Our results suggest PGI2-IP signaling increases immature DC migration to the draining LNs and may represent a novel mechanism by which this eicosanoid inhibits immune responses.
0 Communities
1 Members
0 Resources
20 MeSH Terms
A huge coronary artery aneurysm in osteogenesis imperfecta: a case report.
Hajsadeghi S, Jafarian Kerman SR, Pouraliakbar H, Mohammadi R
(2012) Acta Med Iran 50: 785-8
MeSH Terms: Adult, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Clopidogrel, Coronary Aneurysm, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Hypotension, Inferior Wall Myocardial Infarction, Osteogenesis Imperfecta, Platelet Aggregation Inhibitors, Rare Diseases, Ticlopidine, Treatment Outcome, Ultrasonography
Show Abstract · Added April 25, 2016
Osteogenesis imperfecta (OI) as an inherited connective tissue disorder can affect all tissues that contains type I collagen. Well-known cardiac complications of this disease such as aortic root dilatation, aortic regurgitation and mitral valve prolapse have been rarely reported in the literature. Coronary artery aneurysm is a rare cardiac complication in OI, as reported in a 19 year old female presenting with myocardial infarction and hypotension.
0 Communities
1 Members
0 Resources
17 MeSH Terms