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 133

Publication Record

Connections

Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients.
Lewis JP, Backman JD, Reny JL, Bergmeijer TO, Mitchell BD, Ritchie MD, Déry JP, Pakyz RE, Gong L, Ryan K, Kim EY, Aradi D, Fernandez-Cadenas I, Lee MTM, Whaley RM, Montaner J, Gensini GF, Cleator JH, Chang K, Holmvang L, Hochholzer W, Roden DM, Winter S, Altman RB, Alexopoulos D, Kim HS, Gawaz M, Bliden KP, Valgimigli M, Marcucci R, Campo G, Schaeffeler E, Dridi NP, Wen MS, Shin JG, Fontana P, Giusti B, Geisler T, Kubo M, Trenk D, Siller-Matula JM, Ten Berg JM, Gurbel PA, Schwab M, Klein TE, Shuldiner AR, ICPC Investigators
(2020) Eur Heart J Cardiovasc Pharmacother 6: 203-210
MeSH Terms: Aged, Brain Ischemia, Clopidogrel, Coronary Artery Disease, Coronary Thrombosis, Decision Support Techniques, Europe, Female, Humans, Male, Middle Aged, Myocardial Infarction, Percutaneous Coronary Intervention, Pharmacogenomic Variants, Platelet Aggregation, Platelet Aggregation Inhibitors, Polymorphism, Single Nucleotide, Predictive Value of Tests, Risk Assessment, Risk Factors, Stents, Stroke, Treatment Outcome
Show Abstract · Added March 24, 2020
AIMS - Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial.
METHODS AND RESULTS - We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles.
CONCLUSION - Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
23 MeSH Terms
The role of coagulation and platelets in colon cancer-associated thrombosis.
Mitrugno A, Tassi Yunga S, Sylman JL, Zilberman-Rudenko J, Shirai T, Hebert JF, Kayton R, Zhang Y, Nan X, Shatzel JJ, Esener S, Duvernay MT, Hamm HE, Gruber A, Williams CD, Takata Y, Armstrong R, Morgan TK, McCarty OJT
(2019) Am J Physiol Cell Physiol 316: C264-C273
MeSH Terms: Blood Coagulation, Blood Platelets, Cell Line, Tumor, Colonic Neoplasms, Cross-Sectional Studies, Humans, Retrospective Studies, Thrombosis
Show Abstract · Added March 24, 2020
Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy.
0 Communities
1 Members
0 Resources
MeSH Terms
Angiographic Efficacy of the Atriclip Left Atrial Appendage Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach.
Ellis CR, Aznaurov SG, Patel NJ, Williams JR, Sandler KL, Hoff SJ, Ball SK, Whalen SP, Carr JJ
(2017) JACC Clin Electrophysiol 3: 1356-1365
MeSH Terms: Aged, Atrial Appendage, Atrial Fibrillation, Cardiac Surgical Procedures, Computed Tomography Angiography, Echocardiography, Transesophageal, Female, Humans, Intracranial Embolism, Male, Middle Aged, Minimally Invasive Surgical Procedures, Retrospective Studies, Surgical Instruments, Therapeutic Occlusion, Thoracoscopy, Thrombosis, Treatment Outcome, Wound Closure Techniques
Show Abstract · Added January 10, 2020
OBJECTIVES - This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography.
BACKGROUND - LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%.
METHODS - Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015.
RESULTS - Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident).
CONCLUSIONS - Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation.
Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity.
Lee Y, Le Thi P, Seon GM, Ryu SB, Brophy CM, Kim Y, Park JC, Park KD, Cheung-Flynn J, Sung HJ
(2017) J Control Release 266: 321-330
MeSH Terms: Animals, Anticoagulants, Cell Movement, Cell Proliferation, Heparin, Humans, Myocytes, Smooth Muscle, Neointima, Peptides, Platelet Adhesiveness, Polyesters, Rats, Sprague-Dawley, Saphenous Vein, Thrombosis
Show Abstract · Added May 22, 2018
The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92-272μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.
Copyright © 2017 Elsevier B.V. All rights reserved.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Clinical Risk Assessment in the Antiphospholipid Syndrome: Current Landscape and Emerging Biomarkers.
Chaturvedi S, McCrae KR
(2017) Curr Rheumatol Rep 19: 43
MeSH Terms: Antibodies, Antiphospholipid, Antiphospholipid Syndrome, Autoantibodies, Biomarkers, Humans, Risk Assessment, Risk Factors, Thrombosis
Show Abstract · Added July 17, 2017
PURPOSE OF REVIEW - Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-β2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors.
RECENT FINDINGS - Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-βGPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance. Clinical risk scores may also have value in predicting clinical events. Biomarkers that predict thrombosis risk in patients with antiphospholipid antibodies have been long sought, and several biomarkers have been proposed. Ultimately, integration of biomarkers with established assays and clinical characteristics may offer the best chance of identifying patients at highest risk of APS-related complications.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Cardiovascular and Thrombotic Complications of Novel Multiple Myeloma Therapies: A Review.
Li W, Garcia D, Cornell RF, Gailani D, Laubach J, Maglio ME, Richardson PG, Moslehi J
(2017) JAMA Oncol 3: 980-988
MeSH Terms: Antineoplastic Agents, Cardiovascular Diseases, Humans, Immunologic Factors, Lenalidomide, Multiple Myeloma, Proteasome Inhibitors, Risk Factors, Thalidomide, Thromboembolism, Thrombosis
Show Abstract · Added March 26, 2017
Importance - Multiple myeloma (MM) is the second most common hematological malignant abnormality. The introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has greatly improved the overall survival of patients with MM. Prevention and treatment of cardiovascular and thrombotic issues associated with novel MM therapies have emerged as important aspects of supportive care in patients with MM.
Observations - We searched PubMed and the Cochrance database for studies published from March 2001 to January 2016. Emerging evidence suggests that both IMiDs and PIs can have cardiovascular (CV) sequelae, which include thromboembolic complications, cardiac, and vascular toxic effects. These complications occur against the backdrop of a high prevalence of CV disease in the MM population as well as the adverse cardiac and vascular effects of MM itself.
Conclusions and Relevance - This review provides an overview of the incidences, clinical presentations, and mechanisms of CV complications in the MM population. We conclude that more research is needed for better screening and preventive strategies to abrogate these toxic effects and improve patient care.
0 Communities
1 Members
0 Resources
11 MeSH Terms
First Implantation of Silicon Nanopore Membrane Hemofilters.
Kensinger C, Karp S, Kant R, Chui BW, Goldman K, Yeager T, Gould ER, Buck A, Laneve DC, Groszek JJ, Roy S, Fissell WH
(2016) ASAIO J 62: 491-5
MeSH Terms: Animals, Dogs, Hemofiltration, Humans, Membranes, Artificial, Nanopores, Pilot Projects, Silicon, Thrombosis
Show Abstract · Added April 11, 2016
An implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3-8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5-8 nm × 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics models of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20-50 ml of transudative (albumin sieving coefficient θalb ~ 0.5 - 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3-4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (θalb ~ 0.2 - 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood-material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.
0 Communities
2 Members
0 Resources
9 MeSH Terms
At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases.
Barnado A, Crofford LJ, Oates JC
(2016) J Leukoc Biol 99: 265-78
MeSH Terms: Acetylcysteine, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Monoclonal, Antimalarials, Apoptosis, Atherosclerosis, Autoantigens, Autoimmune Diseases, Biomarkers, Deoxyribonuclease I, Extracellular Traps, Female, Humans, Hydrolases, Immunosuppressive Agents, Interferon-alpha, Lupus Erythematosus, Systemic, Molecular Targeted Therapy, Neutrophils, Pregnancy, Pregnancy Complications, Protein Processing, Post-Translational, Protein-Arginine Deiminase Type 4, Protein-Arginine Deiminases, Thrombophilia, Thrombosis, Translational Medical Research, Vitamin D
Show Abstract · Added March 25, 2020
Neutrophil extracellular traps are associated with a unique form of cell death distinct from apoptosis or necrosis, whereby invading microbes are trapped and killed. Neutrophil extracellular traps can contribute to autoimmunity by exposing autoantigens, inducing IFN-α production, and activating the complement system. The association of neutrophil extracellular traps with autoimmune diseases, particularly systemic lupus erythematosus, will be reviewed. Increased neutrophil extracellular trap formation is seen in psoriasis, antineutrophil cytoplasmic antibody-associated vasculitis, antiphospholipid antibody syndrome rheumatoid arthritis, and systemic lupus erythematosus. Neutrophil extracellular traps may promote thrombus formation in antineutrophil cytoplasmic antibody-associated vasculitis and antiphospholipid antibody syndrome. In systemic lupus erythematosus, increased neutrophil extracellular trap formation is associated with increased disease activity and renal disease, suggesting that neutrophil extracellular traps could be a disease activity marker. Neutrophil extracellular traps can damage and kill endothelial cells and promote inflammation in atherosclerotic plaques, which may contribute to accelerated atherosclerosis in systemic lupus erythematosus. As neutrophil extracellular traps induce IFN-α production, measuring neutrophil extracellular traps may estimate IFN-α levels and identify which systemic lupus erythematosus patients have elevated levels and may be more likely to respond to emerging anti-IFN-α therapies. In addition to anti-IFN-α therapies, other novel agents, such as N-acetyl-cysteine, DNase I, and peptidylarginine deiminase inhibitor 4, target neutrophil extracellular traps. Neutrophil extracellular traps offer insight into the pathogenesis of autoimmune diseases and provide promise in developing disease markers and novel therapeutic agents in systemic lupus erythematosus. Priority areas for basic research based on clinical research insights will be identified, specifically the potential role of neutrophil extracellular traps as a biomarker and therapeutic target in systemic lupus erythematosus.
© Society for Leukocyte Biology.
0 Communities
1 Members
0 Resources
MeSH Terms
The antiphospholipid syndrome: still an enigma.
Chaturvedi S, McCrae KR
(2015) Hematology Am Soc Hematol Educ Program 2015: 53-60
MeSH Terms: Administration, Oral, Antibodies, Antiphospholipid, Anticoagulants, Antiphospholipid Syndrome, Female, Heparin, Low-Molecular-Weight, Humans, Hydroxychloroquine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Immune System, Inflammation, Lupus Coagulation Inhibitor, Pregnancy, Pregnancy Complications, Cardiovascular, Protein Binding, Protein Structure, Tertiary, Risk, Thrombosis, Treatment Outcome, beta 2-Glycoprotein I
Show Abstract · Added December 16, 2015
Antiphospholipid syndrome (APS) is defined by clinical manifestations that include thrombosis and/or fetal loss or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). Antiphospholipid antibodies are among the most common causes of acquired thrombophilia, but unlike most of the genetic thrombophilias are associated with both venous and arterial thrombosis. Despite an abundance of clinical and basic research on aPL, a unified mechanism that explains their prothrombotic activity has not been defined; this may reflect the heterogeneity of aPL and/or the fact that they may influence multiple pro- and/or antithrombotic pathways. Antiphospholipid antibodies are directed primarily toward phospholipid binding proteins rather than phospholipid per se, with the most common antigenic target being β2-glycoprotein 1 (β2GPI) although antibodies against other targets such as prothrombin are well described. Laboratory diagnosis of aPL depends upon the detection of a lupus anticoagulant (LA), which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin and anti-β2-glycoprotein 1 antibodies. Indefinite anticoagulation remains the mainstay of therapy for thrombotic APS, although new strategies that may improve outcomes are emerging. Preliminary reports suggest caution in the use of direct oral anticoagulants in patients with APS-associated thrombosis. Based on somewhat limited evidence, aspirin and low molecular weight heparin are recommended for obstetrical APS. There remains a pressing need for better understanding of the pathogenesis of APS in humans, for identification of clinical and laboratory parameters that define patients at greatest risk for APS-related events, and for targeted treatment of this common yet enigmatic disorder.
© 2015 by The American Society of Hematology. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans.
Joy NG, Tate DB, Younk LM, Davis SN
(2015) Diabetes 64: 2571-80
MeSH Terms: Adult, Biomarkers, Blood Glucose, Endothelium, Vascular, Female, Fibrinolysis, Humans, Hypoglycemia, Inflammation, Male, Platelet Activation, Thrombosis
Show Abstract · Added July 30, 2015
The aim of this study was to determine the effects of single and repeated episodes of clamped hypoglycemia on fibrinolytic balance, proinflammatory biomarkers, proatherothrombotic mechanisms, and endothelial function. Twenty healthy individuals (12 male and 8 female) were studied during separate 2-day randomized protocols. Day 1 consisted of either two 2-h hyperinsulinemic (812 ± 50 pmol/L)-euglycemic (5 ± 0.1 mmol/L) or hyperinsulinemic (812 ± 50 pmol/L)-hypoglycemic (2.9 ± 0.1 mmol/L) clamps. Day 2 consisted of a single 2-h hyperinsulinemic-hypoglycemic clamp. Two-dimensional Doppler ultrasound was used to determine brachial arterial endothelial function. Plasminogen activator inhibitor 1, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, E-selectin, P-selectin, TAT (thrombin/antithrombin complex), tumor necrosis factor-α, and interleukin-6 responses were increased (P < 0.05) during single or repeated hypoglycemia compared with euglycemia. Endogenous and exogenous nitric oxide (NO)-mediated vasodilation were both impaired by repeated hypoglycemia. Neuroendocrine and autonomic nervous system (ANS) responses were also blunted by repeated hypoglycemia (P < 0.05). In summary, acute moderate hypoglycemia impairs fibrinolytic balance; increases proinflammatory responses, platelet activation, and coagulation biomarkers; and reduces NO-mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impair vascular function by additionally reducing exogenously NO-mediated endothelial function and increasing coagulation biomarkers. We conclude that despite reduced neuroendocrine and ANS responses, antecedent hypoglycemia results in greater endothelial dysfunction and an increased proatherothrombotic state compared with a single acute episode of hypoglycemia.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
0 Communities
0 Members
2 Resources
12 MeSH Terms