Pyridones

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  Subject Areas on Research

  • A 2-pyridone-amide inhibitor targets the glucose metabolism pathway of Chlamydia trachomatis. 
  • A Randomized Dose-Escalation Study of the Safety and Anti-Inflammatory Activity of the p38 Mitogen-Activated Protein Kinase Inhibitor Dilmapimod in Severe Trauma Subjects at Risk for Acute Respiratory Distress Syndrome. 
  • A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. 
  • A kinetic study of the hydrogen-bond dimerization of 2-pyridone. 
  • A mathematical model for analysis of pharmacologically induced changes in the kinetics of cardiac muscle. 
  • A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE. 
  • A review of global health technology assessments of non-VKA oral anticoagulants in non-valvular atrial fibrillation. 
  • A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra. 
  • ACP Journal Club. Apixaban reduced stroke or systemic embolism in AF more than warfarin regardless of type or duration of AF. 
  • ALSUntangled 48: Perampanel (Fycompa). 
  • Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale. 
  • Alternatives to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a look back at the state of the field in 2012. 
  • Amiodarone, anticoagulation, and clinical events in patients with atrial fibrillation: insights from the ARISTOTLE trial. 
  • An open-Label, 2 × 2 factorial, randomized controlled trial to evaluate the safety of apixaban vs. vitamin K antagonist and aspirin vs. placebo in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention: Rationale and design of the AUGUSTUS trial. 
  • Andexanet Alfa Use in Cardiac Surgical Patients: A Xa Inhibitor and Heparin Reversal Agent. 
  • Andexanet Alfa Use in Patients Requiring Cardiopulmonary Bypass: Quo Vadis? 
  • Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. 
  • Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage. 
  • Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 
  • Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation. 
  • Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial. 
  • Anticoagulation in atrial fibrillation. 
  • Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial. 
  • Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. 
  • Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial. 
  • Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial. 
  • Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial. 
  • Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease. 
  • Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Left Ventricular Hypertrophy: Insights From the ARISTOTLE Trial. 
  • Apixaban after acute coronary syndrome. 
  • Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. 
  • Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial. 
  • Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. 
  • Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. 
  • Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation. 
  • Apixaban in patients with atrial fibrillation and prior coronary artery disease: insights from the ARISTOTLE trial. 
  • Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial. 
  • Apixaban to prevent stroke in patients with atrial fibrillation: a review. 
  • Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. 
  • Apixaban versus warfarin in patients with atrial fibrillation. 
  • Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. 
  • Apixaban with antiplatelet therapy after acute coronary syndrome. 
  • Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. 
  • Apixaban: an emerging oral factor Xa inhibitor. 
  • Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy. 
  • Atrial fibrillation: a spectrum of risk with a uniform treatment effect of novel anticoagulants? 
  • Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. 
  • Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. 
  • C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates. 
  • Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin? 
  • Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome. 
  • Characteristics and Outcomes of Atrial Fibrillation in Patients With Thyroid Disease (from the ARISTOTLE Trial). 
  • Chlorpyrifos accumulation patterns for child-accessible surfaces and objects and urinary metabolite excretion by children for 2 weeks after crack-and-crevice application. 
  • Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor. 
  • Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial. 
  • Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial. 
  • Clinical and Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients With Coronary Artery Disease and/or Peripheral Artery Disease. 
  • Clinical and Pharmacological Effects of Apixaban Dose Adjustment in the ARISTOTLE Trial. 
  • Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: Insights from the APPRAISE-2 trial. 
  • Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 
  • Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. 
  • Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial. 
  • Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban: results from the ARISTOTLE trial. 
  • Computational Immune Monitoring Reveals Abnormal Double-Negative T Cells Present across Human Tumor Types. 
  • Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone. 
  • Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors 
  • D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation--observations from the ARISTOTLE trial. 
  • Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. 
  • Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system. 
  • Direct oral anticoagulant- versus vitamin K antagonist-related gastrointestinal bleeding: Insights from a nationwide cohort. 
  • Discontinuation and Management of Direct-Acting Anticoagulants for Emergency Procedures. 
  • Documentation of study medication dispensing in a prospective large randomized clinical trial: experiences from the ARISTOTLE Trial. 
  • Doses of apixaban and rivaroxaban prescribed in real-world United States cardiology practices compared to registration trials. 
  • Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. 
  • Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin. 
  • Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial. 
  • Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a Meta-Analysis Based on Imputed Placebo Effect. 
  • Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation. 
  • Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome. 
  • Effect of extended-duration thromboprophylaxis on venous thromboembolism and major bleeding among acutely ill hospitalized medical patients: a bivariate analysis. 
  • Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease. 
  • Effects of apixaban compared with warfarin as gain in event-free time - a novel assessment of the results of the ARISTOTLE trial. 
  • Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial. 
  • Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial. 
  • Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight. 
  • Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial Fibrillation and a History of Cancer: Insights from the ARISTOTLE Trial. 
  • Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants After Cardioversion for Nonvalvular Atrial Fibrillation. 
  • Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. 
  • Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. 
  • Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. 
  • Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. 
  • Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). 
  • Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial. 
  • Efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a meta-analysis of randomized controlled trials. 
  • Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. 
  • Evaluation of the Age, Biomarkers, and Clinical History-Bleeding Risk Score in Patients With Atrial Fibrillation With Combined Aspirin and Anticoagulation Therapy Enrolled in the ARISTOTLE and RE-LY Trials. 
  • Factors associated with non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with new-onset atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II). 
  • Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 
  • Genomic Status of MET Potentiates Sensitivity to MET and MEK Inhibition in NF1-Related Malignant Peripheral Nerve Sheath Tumors. 
  • Gestational exposure to chlorpyrifos: comparative distribution of trichloropyridinol in the fetus and dam. 
  • Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 
  • High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. 
  • High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin. 
  • History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. 
  • Hospitalization Among Patients With Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention Treated With Apixaban or Aspirin: Insights From the AUGUSTUS Trial. 
  • Impact of prior oral anticoagulant use and outcomes on patients from secondary analysis in the AUGUSTUS trial. 
  • Integrase inhibitors in late pregnancy and rapid HIV viral load reduction. 
  • Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial. 
  • Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy. 
  • Intrapulmonary Milrinone for Cardiac Surgery Provides Insight Into Precision Delivery of Aerosolized Vasodilators. 
  • Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non-Vitamin K Antagonist Oral Anticoagulants Preceding Stroke. 
  • Iron overload and allogeneic hematopoietic stem-cell transplantation. 
  • Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. 
  • MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer. 
  • Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. 
  • Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. 
  • Management of Idiopathic Pulmonary Fibrosis. 
  • Managing new oral anticoagulants in the perioperative and intensive care unit setting. 
  • Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC-Driven Evolutionary Convergence. 
  • N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation). 
  • Non-Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation. 
  • Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. 
  • Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF. 
  • Novel oral anticoagulants in gastroenterology practice. 
  • Oral factor Xa inhibitors for the prevention of stroke in atrial fibrillation. 
  • Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease. 
  • Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial. 
  • Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. 
  • Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial. 
  • Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial. 
  • Periprocedural antithrombotic and bridging therapy: recommendations for standardized reporting in patients with arterial indications for chronic oral anticoagulant therapy. 
  • Pharmacodynamics and pharmacokinetics of milrinone administration to increase oxygen delivery in critically ill patients. 
  • Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery. 
  • Pharmacology and safety of new oral anticoagulants: the challenge of bleeding persists. 
  • Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia. 
  • Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial. 
  • Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. 
  • Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation. 
  • Prevention of chronic cerebral vasospasm in dogs with milrinone. 
  • Protein synthesis-dependent potentiation by thyroxine of antiviral activity of interferon-gamma. 
  • Rationale and design for the study Apixaban versus ClopidoGRel on a background of aspirin in patient undergoing InfraPoPliteal angioplasty for critical limb ischemia: AGRIPPA trial. 
  • Rationale and design of AXAFA-AFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation. 
  • Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve. 
  • Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial. 
  • Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial. 
  • Reply: Specifics of Dose Modification in ARISTOTLE. 
  • Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome Trial: Results With Integrated Collection. 
  • Response to letter regarding article, "Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation". 
  • Risk/Benefit Tradeoff of Antithrombotic Therapy in Patients With Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From AUGUSTUS. 
  • Safe and Effective Anticoagulation: What Does Drug Concentration Add? 
  • Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. 
  • Screening of Multiple Biomarkers Associated With Ischemic Stroke in Atrial Fibrillation. 
  • Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials. 
  • Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non-vitamin K antagonist oral anticoagulant dose adjustment. 
  • Stent Thrombosis in Patients With Atrial Fibrillation Undergoing Coronary Stenting in the AUGUSTUS Trial. 
  • Stroke prevention in atrial fibrillation: Closing the gap. 
  • Substituted 1,3-Dihydro-2H-pyrrolo-[2,3-b]pyridin-2-ones as Potential Antiinflammatory Agents 
  • Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina. 
  • Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation. 
  • That Was Then, This Is Now: A Fresh Look at Idiopathic Pulmonary Fibrosis Biomarkers in the Antifibrotic Era. 
  • The 'obesity paradox' in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. 
  • The effect of milrinone on hemodynamics and left ventricular function after emergence from cardiopulmonary bypass. 
  • The effects of milrinone on platelets in patients undergoing cardiac surgery. 
  • The in vitro effects of phosphodiesterase inhibitors on the human internal mammary artery. 
  • The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies. 
  • The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. 
  • The oral iron chelator deferiprone protects against iron overload-induced retinal degeneration. 
  • The oral iron chelator deferiprone protects against systemic iron overload-induced retinal degeneration in hepcidin knockout mice. 
  • The safety and efficacy of apixaban : where do we stand in 2013? 
  • Trametinib (GSK1120212) in the treatment of melanoma. 
  • Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. 
  • Uninterrupted apixaban for atrial fibrillation ablation is a reasonable alternative, but what is the significance of silent cerebral infarctions? 
  • Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants. 
  • Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. 
  • Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non-Vitamin K Antagonist Oral Anticoagulants Before Stroke. 
  • Widespread Repression of Gene Expression in Cancer by a Wnt/β-Catenin/MAPK Pathway. 
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  Keywords of People

  • Alexander, John Hunter Peel, Professor of Medicine, Medicine, Cardiology
  • Levy, Jerrold Henry, Professor of Anesthesiology, Anesthesiology, Cardiothoracic