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    2251 results match your criteria Annual Review of Medicine[Journal]

    1 OF 46

    New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance.
    Annu Rev Med 2018 Jan;69:379-394
    Division of Infectious Diseases & International Health, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710.
    Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. Host-focused diagnostics have recently emerged and are based on detecting the activation of biological pathways that are highly specific to the type of infecting pathogen (e. Read More

    Risk Stratification for Sudden Cardiac Death After Myocardial Infarction.
    Annu Rev Med 2018 Jan;69:147-164
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
    Sudden cardiac death (SCD) accounts for ∼50% of mortality after myocardial infarction (MI). Most SCDs result from ventricular tachyarrhythmias, and the tachycardias that precipitate cardiac arrest result from multiple mechanisms. As a result, it is highly unlikely that any single test will identify all patients at risk for SCD. Read More

    Measuring Patient-Reported Outcomes: Key Metrics in Reconstructive Surgery.
    Annu Rev Med 2018 Jan;69:467-479
    Plastic and Reconstructive Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; email: ,
    Satisfaction and improved quality of life are among the most important outcomes for patients undergoing plastic and reconstructive surgery for a variety of diseases and conditions. Patient-reported outcome measures (PROMs) are essential tools for evaluating the benefits of newly developed surgical techniques. Modern PROMs are being developed with new psychometric approaches, such as Rasch Measurement Theory, and their measurement properties (validity, reliability, responsiveness) are rigorously tested. Read More

    Antibody-Drug Conjugates for Cancer Treatment.
    Annu Rev Med 2018 Jan;69:191-207
    ImmunoGen, Inc., Waltham, Massachusetts 02451; email: ,
    The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer. All three parts of an antibody-drug conjugate (ADC)-the antibody, the cytotoxic payload, and the linker chemistry that joins them together-as well as the biologic properties of the cell-surface target antigen are important in designing an effective anticancer agent. The approval of brentuximab vedotin in 2011 for treating relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, and the approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive metastatic breast cancer, have sparked vigorous research in the field, with >65 ADCs currently in clinical evaluation. Read More

    The Affordable Care Act: What's Next?
    Annu Rev Med 2018 Jan;69:41-52
    Duke-Margolis Center for Health Policy, Duke University, Durham, North Carolina 27708; email: ,
    The postelection efforts to repeal, replace, or modify the Affordable Care Act (ACA) suggest that the debate over healthcare coverage will remain contentious, particularly because of the high and rising cost of health care. Feasible, potentially bipartisan approaches to improving access to coverage should emphasize reforming health care to achieve higher quality at a lower cost. In the individual market, where many enrollees face limited options and rising premiums, a combination of high-risk pools, reinsurance, and risk adjustment could improve coverage options while encouraging innovations in care for the highest-risk patients. Read More

    Computed Tomography Scanning for Early Detection of Lung Cancer.
    Annu Rev Med 2018 Jan;69:235-245
    Departments of Radiology and Thoracic Surgery, Brigham and Women's Hospital, Boston, MA 02115; email: ,
    Parallel and often unrelated developments in health care and technology have all been necessary to bring about early detection of lung cancer and the opportunity to decrease mortality from lung cancer through early detection of the disease by computed tomography. Lung cancer screening programs provide education for patients and clinicians, support smoking cessation as primary prevention for lung cancer, and facilitate health care for tobacco-associated diseases, including cardiovascular and chronic lung diseases. Guidelines for lung cancer screening will need to continue to evolve as additional risk factors and screening tests are developed. Read More

    CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions.
    Annu Rev Med 2018 Jan;69:301-318
    Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA; email: , , , ,
    Antigen-specific CD8 T cells are central to the control of chronic infections and cancer, but persistent antigen stimulation results in T cell exhaustion. Exhausted CD8 T cells have decreased effector function and proliferative capacity, partly caused by overexpression of inhibitory receptors such as programmed cell death (PD)-1. Blockade of the PD-1 pathway has opened a new therapeutic avenue for reinvigorating T cell responses, with positive outcomes especially for patients with cancer. Read More

    Common Cardiovascular Complications of Cancer Therapy: Epidemiology, Risk Prediction, and Prevention.
    Annu Rev Med 2018 Jan;69:97-111
    Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
    There is growing awareness of the overlap between oncologic and cardiovascular (CV) diseases, including a wide range of CV effects of anticancer therapies. As novel anticancer therapeutics become available and cancer survival outcomes improve, the CV implications of cancer therapy become increasingly important. In addition to outlining the CV effects of commonly used cancer therapies and their consequences for long-term survivorship, this review highlights the recent efforts to improve the risk prediction and prevention of CV toxicity through the evaluation of sensitive measures for early toxicity detection and the implementation of cardioprotective strategies. Read More

    New Therapeutic Approaches for Familial Hypercholesterolemia.
    Annu Rev Med 2018 Jan;69:113-131
    Departments of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email: ,
    Familial hypercholesterolemia (FH) is a common genetic condition characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease, and considerable unmet medical need with conventional LDL-C-lowering therapies. Between 2012 and 2015, the US Food and Drug Administration approved four novel LDL-C-lowering agents for use in patients with FH based on the pronounced LDL-C-lowering efficacy of these medicines. We review the four novel approved agents, as well as promising LDL-C-lowering agents in clinical development, with a focus on their mechanism of action, efficacy in FH cohorts, and safety. Read More

    Updated Recommendations for Athletes with Heart Disease.
    Annu Rev Med 2018 Jan;69:177-189
    Krannert Institute of Cardiology, School of Medicine, Indiana University, Indianapolis, Indiana 46202; email:
    Professional society recommendations to decrease sudden cardiac death in athletes, including eligibility requirements with disqualification for athletes with diagnosed disease as well as preparticipation screening and emergency preparedness, were updated in 2015. The update includes new sections on aortic disease, channelopathies, and sickle cell trait, as well as a change in format from the previous binary yes/no format to the more nuanced and contemporary "class and level of evidence" format. Eighty-four of the 246 recommendations now carry Class II designation-"reasonable," or "may be considered. Read More

    Impact of the SPRINT Trial on Hypertension Management.
    Annu Rev Med 2018 Jan;69:81-95
    Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294; email:
    The Systolic Blood Pressure Intervention Trial is the first large prospective randomized controlled trial to demonstrate the benefit of an intensive systolic blood pressure (SBP) treatment target (<120 mm Hg) compared to a standard target (<140 mm Hg) in reducing cardiovascular morbidity and mortality and all-cause mortality in high-risk hypertensive patients. The impact of SPRINT on hypertension treatment has been large, but major questions remain about the feasibility of achieving the SPRINT intensive SBP target in routine practice, the generalizability of the SPRINT findings to hypertensive populations that were excluded from the trial, and the cost effectiveness of adopting the SPRINT intensive treatment goal. In this review, we discuss the generalizability of SPRINT data to the general population of adults with hypertension and with various comorbidities, the cost effectiveness of intensive SBP-lowering therapy, and the implications of SPRINT for future hypertension guideline development and clinical practice. Read More

    What Metrics Accurately Reflect Surgical Quality?
    Annu Rev Med 2018 Jan;69:481-491
    Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, Michigan 48105; email:
    Surgeons are increasingly under pressure to measure and improve their quality. While there is broad consensus that we ought to track surgical quality, there is far less agreement about which metrics matter most. This article reviews the important statistical concepts of case mix and chance as they apply to understanding the observed wide variation in surgical quality. Read More

    Recombinant Poliovirus for Cancer Immunotherapy.
    Annu Rev Med 2018 Jan;69:289-299
    Department of Surgery.
    Mechanisms to elicit antiviral immunity, a natural host response to viral pathogen challenge, are of eminent relevance to cancer immunotherapy. "Oncolytic" viruses, naturally existing or genetically engineered viral agents with cell type-specific propagation in malignant cells, were ostensibly conceived for their tumor cytotoxic properties. Yet, their true therapeutic value may rest in their ability to provoke antiviral signals that engage antitumor immune responses within the immunosuppressive tumor microenvironment. Read More

    Heart Failure with Preserved Ejection Fraction.
    Annu Rev Med 2018 Jan;69:65-79
    Department of Cardiovascular Disease, Division of Circulatory Failure, Mayo Clinic, Rochester, Minnesota 55905; email: , ,
    Heart failure (HF) is a clinical syndrome of diverse etiologies and can be associated with preserved, reduced, or mid-range ejection fraction (EF). In the community, heart failure with preserved ejection fraction (HFpEF) is emerging as the most common form of HF. There remains considerable uncertainty regarding its pathogenesis, diagnosis, and optimal therapeutic approach. Read More

    Precision Medicine: Functional Advancements.
    Annu Rev Med 2018 Jan;69:1-18
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030; email:
    Precision medicine was conceptualized on the strength of genomic sequence analysis. High-throughput functional metrics have enhanced sequence interpretation and clinical precision. These technologies include metabolomics, magnetic resonance imaging, and I rhythm (cardiac monitoring), among others. Read More

    Novel Radiotherapy Techniques for Breast Cancer.
    Annu Rev Med 2018 Jan 1;69:277-288. Epub 2017 Dec 1.
    Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida 32206; email: ,
    During the early decades of radiation therapy for breast cancer, local control of disease was documented consistently but, enigmatically, an anticipated impact on breast cancer survival was not observed, leading to confusion in our understanding of the natural history of breast cancer and radiation effects. Now, almost 90 years after its first use in breast cancer, technology developments in diagnostic imaging and radiation therapy have elucidated parts of this enigma. The data now available demonstrate a significant impact of radiation therapy on survival as well as disease control and treatment-related mortality, opening a doorway to understanding the powerful impact of radiation therapy on both breast cancer and critical organs. Read More

    Modern Systemic Therapy for Metastatic Renal Cell Carcinoma of the Clear Cell Type.
    Annu Rev Med 2018 Jan 16;69:209-221. Epub 2017 Nov 16.
    Comprehensive Cancer Center, University of California at Davis, Sacramento, California 95819; email: ,
    In the last 30 years, there have been many advances in the treatment of metastatic renal cell carcinoma of the clear cell type. Renal cell carcinoma has long been understood to have a component of immune mediation and has been responsive to immune-based therapies; in addition to early cytokine therapy, newer checkpoint inhibition therapies have also demonstrated activity. Molecular characterization of the genome of clear cell renal cell carcinoma enabled identification of the roles of angiogenesis and hypoxic stress. Read More

    Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology.
    Annu Rev Med 2018 Jan 9;69:319-331. Epub 2017 Nov 9.
    Early Drug Development Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; email: , ,
    Understanding a tumor's detailed molecular profile has become increasingly necessary to deliver the standard of care for patients with advanced cancer. Innovations in both tumor genomic sequencing technology and the development of drugs that target molecular alterations have fueled recent gains in genome-driven oncology care. "Basket studies," or histology-agnostic clinical trials in genomically selected patients, represent one important research tool to continue making progress in this field. Read More

    Innate Immunity and Neurodegeneration.
    Annu Rev Med 2018 Jan 6;69:437-449. Epub 2017 Nov 6.
    Institute of Innate Immunity, University Hospitals Bonn, Bonn 53127, Germany; email:
    The innate immune system plays diverse roles in health and disease. It represents the first line of defense against infection and is involved in tissue repair, wound healing, and clearance of apoptotic cells and cellular debris. Excessive or nonresolving innate immune activation can lead to systemic or local inflammatory complications and cause or contribute to the development of inflammatory diseases. Read More

    Targeting RAGE Signaling in Inflammatory Disease.
    Annu Rev Med 2018 Jan 6;69:349-364. Epub 2017 Nov 6.
    University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136, USA.
    The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including bacterial endotoxin, respiratory viruses, and microbial DNA. Read More

    Novel Latency Reversal Agents for HIV-1 Cure.
    Annu Rev Med 2018 Jan 3;69:421-436. Epub 2017 Nov 3.
    Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112; email:
    Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness; however, ART is not curative owing to the persistence of replication-competent, latent proviruses in long-lived resting T cells. Strategies that target these latently infected cells and allow immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir so that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure. Read More

    Molecular and Genomic Determinants of Response to Immune Checkpoint Inhibition in Cancer.
    Annu Rev Med 2018 Jan 3;69:333-347. Epub 2017 Nov 3.
    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; email:
    Molecularly targeted therapy and immunotherapy have dramatically changed the landscape of available treatment options for patients with advanced cancer. Improved understanding of the molecular and genomic features of cancers over the last decade has led to the development of successful targeted therapies and the field of precision cancer medicine. As a result of these advances, patients whose tumors harbor select molecular alterations are eligible for treatment with targeted therapies active against the unique molecular aberration. Read More

    PCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes.
    Annu Rev Med 2018 Jan 2;69:133-145. Epub 2017 Nov 2.
    Division of Cardiology and.
    Atherosclerotic cardiovascular disease (ASCVD) is associated with significant morbidity and mortality worldwide. Increased serum levels of low-density lipoprotein cholesterol (LDL-C) are an independent risk factor for ASCVD, and clinical trial data have shown that lowering LDL-C generally reduces cardiovascular risk. Until recently, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been the main therapy for lowering LDL-C. Read More

    Use and Misuse of Opioids in Chronic Pain.
    Annu Rev Med 2018 Jan 13;69:451-465. Epub 2017 Oct 13.
    Treatment Research Institute, Philadelphia, Pennsylvania 19106; email:
    The prescribing of opioid analgesics for pain management-particularly for management of chronic noncancer pain (CNCP)-has increased more than fourfold in the United States since the mid-1990s. Yet there is mounting evidence that opioids have only limited effectiveness in the management of CNCP, and the increased availability of prescribed opioids has contributed to upsurges in opioid-related addiction cases and overdose deaths. These concerns have led to critical revisiting and modification of prior pain management practices (e. Read More

    Refinement of the Affordable Care Act: A Progressive Perspective.
    Annu Rev Med 2018 Jan 13;69:29-39. Epub 2017 Oct 13.
    Division of General Internal Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136; email: ,
    The Affordable Care Act (ACA) was the most significant expansion of health coverage since Medicare and Medicaid were enacted. The law resulted in approximately 13-20 million uninsured persons gaining coverage. Despite these gains, the ACA has numerous shortcomings. Read More

    Evidence for Genetic Risk Contributing to Long-Term Adverse Treatment Effects in Childhood Cancer Survivors.
    Annu Rev Med 2018 Jan 13;69:247-262. Epub 2017 Oct 13.
    University of Alabama, Birmingham, Alabama 35233, USA; email:
    Survivors of childhood cancer are at increased risk for therapy-related morbidities and mortality. Although the demographic and clinical factors predicting the risk for long-term effects of cancer therapy are well known, the impact of genetic risk for specific late effects is less clearly defined. Here, we review the extant literature and recent research describing genetic modifiers to risk for the more common late effects of childhood cancer therapy. Read More

    New-Generation High-Potency and Designer Antibodies: Role in HIV-1 Treatment.
    Annu Rev Med 2018 Jan 13;69:409-419. Epub 2017 Oct 13.
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; email: ,
    Broadly neutralizing antibodies (bNAbs) have been evaluated as promising agents in the fight against infectious diseases. HIV-1-specific bNAbs, in particular, have been tested in both preventive and therapeutic modalities. Multiple bNAbs have been isolated, characterized, and assessed in vitro and in vivo, but no single antibody appears to possess the breadth and potency that may be needed if it is to be used in the treatment of HIV-1 infection. Read More

    New Concepts in the Treatment of Malignant Pleural Mesothelioma.
    Annu Rev Med 2018 Jan 13;69:365-377. Epub 2017 Oct 13.
    Division of General Thoracic Surgery, Michael E. DeBakey Department of General Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
    Malignant pleural mesothelioma (MPM) is a highly aggressive and generally incurable cancer. Current anti-MPM chemotherapy-based treatments are only marginally effective, and long-term survival remains an unmet goal. Nonetheless, in selected cases, personalized surgery-based multimodality treatments (MMT) have been shown to significantly extend survival. Read More

    Lymphedema: Pathogenesis and Novel Therapies.
    Annu Rev Med 2018 Jan 6;69:263-276. Epub 2017 Sep 6.
    Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email: , , ,
    Lymphedema affects up to 1 in 6 patients who undergo treatment for a solid tumor in the United States. Its prevalence has increased as more effective oncologic therapies have improved patient survival, but there remains no definitive cure. Recent research has elucidated new details in the pathogenesis of the disease and has demonstrated that it is fundamentally an immunologic process that ultimately results in inflammation, fibroadipose deposition, impaired lymphangiogenesis, and dysfunctional lymphatic pumping. Read More

    Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases.
    Annu Rev Med 2018 Jan 28;69:395-408. Epub 2017 Aug 28.
    Institut Pasteur, Biology of Infection Unit, INSERM Unité 1117, 75006 Paris, France; email: ,
    Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Read More

    Circulating Tumor DNA: Measurement and Clinical Utility.
    Annu Rev Med 2018 Jan 28;69:223-234. Epub 2017 Aug 28.
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; email:
    Circulating tumor DNA (ctDNA) is a component of the "naked" DNA found in blood. It can be isolated from plasma and represents combined genetic material from the primary tumor and metastases. Quantitative and qualitative information about a cancer, including mutations, can be derived using digital polymerase chain reaction and other technologies. Read More

    Refinement of the Affordable Care Act.
    Annu Rev Med 2018 Jan 25;69:19-28. Epub 2017 Aug 25.
    Baker Institute for Public Policy, Rice University, Houston, Texas 77251; email:
    Regardless of what legislation the federal government adopts to address health insurance coverage for nonelderly Americans, private insurance will likely play a major role. This article begins by listing some of the major reasons critics dislike the Affordable Care Act (ACA), then discusses the validity of these concerns from an economics perspective. Criticisms of the ACA include the increased role of government in health care, the ACA's implicit income redistribution, and concern about high and rising insurance premiums. Read More

    Understanding Peripartum Cardiomyopathy.
    Annu Rev Med 2018 Jan 16;69:165-176. Epub 2017 Aug 16.
    Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
    Peripartum cardiomyopathy (PPCM) is the unexplained loss of maternal cardiac systolic function in the period surrounding parturition. PPCM affects women worldwide and is a leading cause of maternal mortality. The cause of PPCM has remained elusive until recently. Read More

    Atrial Fibrillation Ablation.
    Annu Rev Med 2018 Jan 14;69:53-63. Epub 2017 Aug 14.
    Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109; email: ,
    The prevalence of atrial fibrillation (AF) has risen significantly over the past two decades. Catheter ablation is an increasingly utilized treatment strategy and has evolved significantly over the same time period. Successful ablation improves patient symptoms, reduces stroke risk, and can preserve or improve cardiac function. Read More

    Lysosomal Proteins as a Therapeutic Target in Neurodegeneration.
    Annu Rev Med 2017 01;68:445-458
    Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-4296; email: ,
    Several proteins that are mutated in lysosomal storage diseases are linked to neurodegenerative disease. This review focuses on some of these lysosomal enzymes and transporters, as well as current therapies that have emerged from the lysosomal storage disease field. Given the deeper genetic understanding of lysosomal defects in neurodegeneration, we explore why some of these orphan disease drug candidates are also attractive targets in subpopulations of individuals with neurodegenerative disease. Read More

    Mechanisms and New Strategies for Primary Sjögren's Syndrome.
    Annu Rev Med 2017 01;68:331-343
    Department of Physiology, School of Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece; email:
    Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development. Activation of both innate and adaptive immune pathways contributes to disease pathogenesis, with prominent interferon (IFN) signatures identified in both peripheral blood and affected salivary gland tissues. Read More

    Update on Alzheimer's Disease Therapy and Prevention Strategies.
    Annu Rev Med 2017 01;68:413-430
    Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY 10065; email:
    Alzheimer's disease (AD) is the primary cause of age-related dementia. Effective strategies to prevent and treat AD remain elusive despite major efforts to understand its basic biology and clinical pathophysiology. Significant investments in therapeutic drug discovery programs over the past two decades have yielded some important insights but no blockbuster drugs to alter the course of disease. Read More

    Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models.
    Annu Rev Med 2017 01;68:51-67
    Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
    Thoracic aortic diseases, including aneurysms and dissections of the thoracic aorta, are a major cause of morbidity and mortality. Risk factors for thoracic aortic disease include increased hemodynamic forces on the ascending aorta, typically due to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease either disrupt smooth muscle cell (SMC) contraction or adherence to an impaired extracellular matrix, or decrease canonical transforming growth factor beta (TGF-β) signaling. Read More

    Controversies in the Treatment of Ductal Carcinoma in Situ.
    Annu Rev Med 2017 01;68:197-211
    Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email:
    Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. Read More

    Catastrophic Antiphospholipid Syndrome: Candidate Therapies for a Potentially Lethal Disease.
    Annu Rev Med 2017 01;68:287-296
    Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY 10021.
    Catastrophic antiphospholipid syndrome (CAPS) is a potentially lethal disease that presents with rapidly progressive multiple organ thromboses. Anticoagulation, corticosteroids, intravenous immunoglobulin, and plasma exchange are the most commonly used treatments for CAPS patients. However, the high mortality despite these medications necessitates new treatment strategies. Read More

    Lymphangioleiomyomatosis: A Monogenic Model of Malignancy.
    Annu Rev Med 2017 01;68:69-83
    Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267; email:
    Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure. Read More

    Transcatheter Aortic Valve Replacement: State of the Art and Future Directions.
    Annu Rev Med 2017 01 14;68:15-28. Epub 2016 Nov 14.
    Department of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; email:
    Transcatheter aortic valve replacement (TAVR) is a transformational and rapidly evolving treatment for patients with aortic stenosis who require valve replacement. Novel technological advancements have made this percutaneous minimally invasive therapy a first-line treatment for many patients at extreme risk for conventional cardiac surgery. New devices and improvements in existing devices have reduced procedural complications, and scientific trials are investigating the role of TAVR in lower-risk aortic stenosis populations, in patients with aortic regurgitation, and in patients with bicuspid aortic valve disease. Read More

    Mechanisms and Medicines for Remyelination.
    Annu Rev Med 2017 01 17;68:431-443. Epub 2016 Nov 17.
    Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195; email:
    Demyelination of central nervous system axons, associated with traumatic injury and demyelinating diseases such as multiple sclerosis, causes impaired neural transmission and ultimately axon degeneration. Consequently, extensive research has focused on signaling systems that promote myelinating activity of oligodendrocytes or promote production of new oligodendrocytes from oligodendrocyte progenitor cells. Many receptor systems, notably including growth factor receptors and G protein-coupled receptors, control myelination. Read More

    CAR T Cell Therapy for Solid Tumors.
    Annu Rev Med 2017 01 17;68:139-152. Epub 2016 Nov 17.
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; email:
    The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. Read More

    Ebola: Anatomy of an Epidemic.
    Annu Rev Med 2017 01 21;68:359-370. Epub 2016 Oct 21.
    Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30333; email: , , ,
    As of the end of March 2016, the West Africa epidemic of Ebola virus disease (Ebola) had resulted in a total of 28,646 cases, 11,323 of them fatal, reported to the World Health Organization. Guinea, Liberia, and Sierra Leone were most heavily affected, but Ebola cases were exported to several other African and European countries as well as the United States, with limited further transmission, including to healthcare workers. We review the descriptive epidemiology of the outbreak, novel aspects and insights concerning the unprecedented response, scientific observations, and public health implications. Read More

    Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs.
    Annu Rev Med 2017 01 21;68:317-330. Epub 2016 Oct 21.
    Division of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington 98195; email
    The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during World War II. Read More

    Biosimilars: The US Regulatory Framework.
    Annu Rev Med 2017 01 28;68:243-254. Epub 2016 Oct 28.
    US Food and Drug Administration, Silver Spring, Maryland 20993; email: , ,
    With the passage of the Biologics Price Competition and Innovation Act of 2009, the US Food and Drug Administration established an abbreviated pathway for developing and licensing biosimilar and interchangeable biological products. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a "totality of the evidence" that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. Read More

    Next-Generation Sequencing and Result Interpretation in Clinical Oncology: Challenges of Personalized Cancer Therapy.
    Annu Rev Med 2017 01 2;68:113-125. Epub 2016 Nov 2.
    Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.
    The tools of next-generation sequencing (NGS) technology, such as targeted sequencing of candidate cancer genes and whole-exome and -genome sequencing, coupled with encouraging clinical results based on the use of targeted therapeutics and biomarker-guided clinical trials, are fueling further technological advancements of NGS technology. However, NGS data interpretation is associated with challenges that must be overcome to promote the techniques' effective integration into clinical oncology practice. Specifically, sequencing of a patient's tumor often yields 30-65 somatic variants, but most of these variants are "passenger" mutations that are phenotypically neutral and thus not targetable. Read More

    The Type I Interferonopathies.
    Annu Rev Med 2017 01 2;68:297-315. Epub 2016 Nov 2.
    Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; email:
    Type I interferons (IFNs) play a central role in the immune defense against viral infections. Type I IFN activation is induced by pattern-recognition receptors of the innate immune system that sense pathogen-derived nucleic acids. Cellular responses to type I IFN signaling are orchestrated by a complex network of regulatory pathways that involve both the innate and adaptive immune system. Read More

    Obstructive Sleep Apnea: Update and Future.
    Annu Rev Med 2017 01 5;68:99-112. Epub 2016 Oct 5.
    Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
    Obstructive sleep apnea (OSA) is a worldwide disease whose prevalence is increasing as obesity rates increase. The link between obesity and OSA is likely to be the deposition of fat in the tongue, compromising upper airway size. The role of obesity varies in different ethnic groups, with Chinese being particularly sensitive to increases in weight. Read More

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