2,286 results match your criteria Annual Review of Medicine[Journal]


Prostate Magnetic Resonance Imaging: Lesion Detection and Local Staging.

Annu Rev Med 2019 01;70:451-459

Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; email:

Dramatic changes in the use of prostate magnetic resonance imaging (MRI) have occurred in the last decade. The recognition that MRI detects and localizes cancers with reasonable accuracy led to the development of directed biopsies. These image-guided biopsies have a higher sensitivity for clinically significant cancers and a lower sensitivity for indolent disease. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-053117
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http://dx.doi.org/10.1146/annurev-med-053117-123215DOI Listing
January 2019
15 Reads

Harnessing Tumor Mutations for Truly Individualized Cancer Vaccines.

Annu Rev Med 2019 01;70:395-407

Biopharmaceutical New Technologies (BioNTech) Corporation, 55131 Mainz, Germany; email: ,

T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex-bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell-mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-042617
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http://dx.doi.org/10.1146/annurev-med-042617-101816DOI Listing
January 2019
11 Reads

Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications.

Annu Rev Med 2019 01;70:461-477

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; email: ,

In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease. Read More

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http://dx.doi.org/10.1146/annurev-med-062117-073027DOI Listing
January 2019
13 Reads

Postpartum Depression: Pathophysiology, Treatment, and Emerging Therapeutics.

Annu Rev Med 2019 01;70:183-196

Department of Psychiatry, University of Toronto, Toronto, Ontario M5G 2C4, Canada; email:

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is vital to identify best treatments for optimal maternal, infant, and family outcomes. Read More

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http://dx.doi.org/10.1146/annurev-med-041217-011106DOI Listing
January 2019
3 Reads

Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis.

Annu Rev Med 2019 01;70:211-224

Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA; email: ,

This is a time of substantial progress in the evaluation and care of patients with idiopathic pulmonary fibrosis (IPF). In addition to the approval and widespread availability of the first IPF-specific therapies, there have been improvements in imaging interpretation and lung biopsy methods to enable more expeditious and more accurate diagnosis. Recent advances in identifying genetic factors that underlie susceptibility to IPF and affect prognosis have raised the possibility of personalized therapeutic approaches in the future. Read More

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http://dx.doi.org/10.1146/annurev-med-041317-102715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378692PMC
January 2019
1 Read

Abbreviated Magnetic Resonance Imaging (MRI) for Breast Cancer Screening: Rationale, Concept, and Transfer to Clinical Practice.

Annu Rev Med 2019 01;70:501-519

Department of Diagnostic and Interventional Radiology, RWTH Aachen University, 52074 Aachen, Germany; email:

Given the increasing understanding of cancer as a heterogeneous group of diseases, detection methods should offer a sensitivity profile that ensures perfect sensitivity for biologically important cancers while screening out self-limiting pseudocancers. However, mammographic screening is biased toward detection of ductal carcinoma in situ and slowly growing cancers-and thus frequently fails to detect biologically aggressive cancers. This explains the persistently high rates of interval cancers and high rates of breast cancer mortality observed in spite of decades of mammographic screening. Read More

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http://dx.doi.org/10.1146/annurev-med-121417-100403DOI Listing
January 2019
1 Read

New Drugs in Multiple Myeloma.

Annu Rev Med 2019 01;70:521-547

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; email:

Multiple myeloma is diagnosed in over 100,000 patients each year worldwide, has an increasing incidence and prevalence in many regions, and follows a relapsing course, making it a significant and growing healthcare challenge. Recent basic, translational, and clinical studies have expanded our therapeutic armamentarium, which now consists of alkylating agents, corticosteroids, deacetylase inhibitors, immunomodulatory agents, monoclonal antibodies, and proteasome inhibitors. New drugs in these categories, and additional agents, including both small and large molecules, as well as cellular therapies, are under development that promise to further expand our capabilities and bring us closer to the cure of this plasma cell dyscrasia. Read More

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http://dx.doi.org/10.1146/annurev-med-112017-091045DOI Listing
January 2019
1 Read

DNA Methylation and Susceptibility to Autism Spectrum Disorder.

Annu Rev Med 2019 01;70:151-166

Program in Genetics and Genomics, Duke University, Durham, North Carolina 27710, USA.

The prevalence of autism spectrum disorder (ASD) has been increasing steadily over the last 20 years; however, the molecular basis for the majority of ASD cases remains unknown. Recent advances in next-generation sequencing and detection of DNA modifications have made methylation-dependent regulation of transcription an attractive hypothesis for being a causative factor in ASD etiology. Evidence for abnormal DNA methylation in ASD can be seen on multiple levels, from genetic mutations in epigenetic machinery to loci-specific and genome-wide changes in DNA methylation. Read More

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http://dx.doi.org/10.1146/annurev-med-120417-091431DOI Listing
January 2019

Therapeutic Antisense Oligonucleotides Are Coming of Age.

Authors:
C Frank Bennett

Annu Rev Med 2019 01;70:307-321

Ionis Pharmaceuticals, Carlsbad, California 92010, USA; email:

The first published description of therapeutic applications of antisense oligonucleotide (ASO) technology occurred in the late 1970s and was followed by the founding of commercial companies focused on developing antisense therapeutics in the late 1980s. Since the late 1980s, there has been steady progress in improving the technology platform, taking advantage of advances in oligonucleotide chemistry and formulations as well as increased understanding of the distribution and safety of ASOs. There are several approved ASO drugs and a broad pipeline in development. Read More

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http://dx.doi.org/10.1146/annurev-med-041217-010829DOI Listing
January 2019

Ethics of Human Genome Editing.

Authors:
Barry S Coller

Annu Rev Med 2019 01;70:289-305

Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY 10065, USA; email:

Advances in human genome editing, in particular the development of the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 method, have led to increasing concerns about the ethics of editing the human genome. In response, the US National Academy of Sciences and the National Academy of Medicine constituted a multidisciplinary, international committee to review the current status and make recommendations. I was a member of that committee, and the core of this review reflects the committee's conclusions. Read More

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http://dx.doi.org/10.1146/annurev-med-112717-094629DOI Listing
January 2019
1 Read

Treatment of Advanced Prostate Cancer.

Annu Rev Med 2019 01;70:479-499

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; email:

The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed. Read More

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http://dx.doi.org/10.1146/annurev-med-051517-011947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441973PMC
January 2019
17 Reads

Structure-Based Vaccine Antigen Design.

Annu Rev Med 2019 01;70:91-104

Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA; email:

Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens, particularly difficult targets that have resisted prior vaccine development efforts. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-121217
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http://dx.doi.org/10.1146/annurev-med-121217-094234DOI Listing
January 2019
9 Reads

Entering the Modern Era of Gene Therapy.

Annu Rev Med 2019 01 26;70:273-288. Epub 2018 Nov 26.

Spark Therapeutics, Inc., Philadelphia, Pennsylvania 19104, USA; email: ,

Gene therapies are gaining momentum as promising early successes in clinical studies accumulate and examples of regulatory approval for licensing increase. Investigators are advancing with cautious optimism that effective, durable, and safe therapies will provide benefit to patients-not only those with single-gene disorders but those with complex acquired diseases as well. While the strategies being translated from the lab to the clinic are numerous, this review focuses on the clinical research that has forged the gene therapy field as it currently stands. Read More

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http://dx.doi.org/10.1146/annurev-med-012017-043332DOI Listing
January 2019
1 Read

Non-Vitamin K Antagonist Oral Anticoagulants in the Treatment of Atrial Fibrillation.

Annu Rev Med 2019 01 26;70:61-75. Epub 2018 Nov 26.

Division of Cardiology and Duke Clinical Research Institute, Duke University, Durham, North Carolina 27710, USA; email:

Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke. Read More

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http://dx.doi.org/10.1146/annurev-med-042617-092334DOI Listing
January 2019
2 Reads

The Global Landscape of Tuberculosis Therapeutics.

Annu Rev Med 2019 01 7;70:105-120. Epub 2018 Nov 7.

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; email:

Tuberculosis (TB) is one of the oldest infections afflicting humans yet remains the number one infectious disease killer worldwide. Despite decades of experience treating this disease, TB regimens require months of multidrug therapy, even for latent infections. There have been important recent advances in treatment options across the spectrum of TB, from latent infection to extensively drug-resistant (XDR) TB disease. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-040717
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http://dx.doi.org/10.1146/annurev-med-040717-051150DOI Listing
January 2019
14 Reads

Clinical Application and Potential of Fecal Microbiota Transplantation.

Annu Rev Med 2019 01 7;70:335-351. Epub 2018 Nov 7.

Department of Gastroenterology and Hepatology and Centralized Biobanking Facility, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-111717
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http://dx.doi.org/10.1146/annurev-med-111717-122956DOI Listing
January 2019
13 Reads

Zika Virus Vaccine Development: Progress in the Face of New Challenges.

Annu Rev Med 2019 01 2;70:121-135. Epub 2018 Nov 2.

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA; email:

Zika virus (ZIKV) emerged at a global level when it spread to the Americas and began causing congenital malformations and microcephaly in 2015. A rapid response by academia, government, public health infrastructure, and industry has enabled the expedited development and testing of a suite of vaccine platforms aiming to control and eliminate ZIKV-induced disease. Analysis of key immunization and pathogenesis studies in multiple animal models, including during pregnancy, has begun to define immune correlates of protection. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-040717
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http://dx.doi.org/10.1146/annurev-med-040717-051127DOI Listing
January 2019
20 Reads

Redirected T Cell Cytotoxicity in Cancer Therapy.

Annu Rev Med 2019 01 31;70:437-450. Epub 2018 Oct 31.

Xencor, Inc., Monrovia, California 91016, USA; email: ,

Bispecific antibodies that recruit and redirect T cells to attack tumor cells have tremendous potential for the treatment of various malignancies. In general, this class of therapeutics, known as CD3 bispecifics, promotes tumor cell killing by cross-linking a CD3 component of the T cell receptor complex with a tumor-associated antigen on the surface of the target cell. Importantly, this mechanism does not rely on a cognate interaction between the T cell receptor and a peptide:HLA complex, thereby circumventing HLA (human leukocyte antigen) restriction. Read More

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http://dx.doi.org/10.1146/annurev-med-062617-035821DOI Listing
January 2019
1 Read

CRISPR Correction of Duchenne Muscular Dystrophy.

Annu Rev Med 2019 01 31;70:239-255. Epub 2018 Oct 31.

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, and Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; email:

The ability to efficiently modify the genome using CRISPR technology has rapidly revolutionized biology and genetics and will soon transform medicine. Duchenne muscular dystrophy (DMD) represents one of the first monogenic disorders that has been investigated with respect to CRISPR-mediated correction of causal genetic mutations. DMD results from mutations in the gene encoding dystrophin, a scaffolding protein that maintains the integrity of striated muscles. Read More

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http://dx.doi.org/10.1146/annurev-med-081117-010451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415693PMC
January 2019
2 Reads
12.928 Impact Factor

New Hope for Therapeutic Cancer Vaccines in the Era of Immune Checkpoint Modulation.

Annu Rev Med 2019 01 31;70:409-424. Epub 2018 Oct 31.

Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

The driver and passenger mutations accumulated in the process of malignant transformation offer an adequate spectrum of immune visible alterations to the cellular proteome and resulting peptidome to render these cancers targetable-and, in theory, rejectable-by the host T cell immune response. In addition, cancers often overexpress tissue-specific and developmental antigens to which immune tolerance is incomplete. Sometimes, virally transferred oncogenes drive malignant transformation and remain expressed throughout the cancer. Read More

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http://dx.doi.org/10.1146/annurev-med-050217-121900DOI Listing
January 2019
4 Reads

Metformin for Treatment of Fragile X Syndrome and Other Neurological Disorders.

Annu Rev Med 2019 01 26;70:167-181. Epub 2018 Oct 26.

Department of Biochemistry, McGill University, Montréal H3A 2T5, Québec, Canada; email: , ,

Fragile X syndrome (FXS) is the most frequent inherited form of intellectual disability and autism spectrum disorder. Loss of the fragile X mental retardation protein, FMRP, engenders molecular, behavioral, and cognitive deficits in FXS patients. Experiments using different animal models advanced our knowledge of the pathophysiology of FXS and led to the discovery of many targets for drug treatments. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-081117
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http://dx.doi.org/10.1146/annurev-med-081117-041238DOI Listing
January 2019
17 Reads

Expanding Therapeutic Opportunities for Hematopoietic Stem Cell Transplantation: T Cell Depletion as a Model for the Targeted Allograft.

Annu Rev Med 2019 01 25;70:381-393. Epub 2018 Oct 25.

Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA; email: ,

Allogeneic hematopoietic cell transplantation is a fundamental part of the treatment of hematologic malignancies and marrow failure syndromes, but complications including graft-versus-host disease, prolonged immune deficiency and infection, and organ toxicities, as well as relapse, remain obstacles to improved overall survival. As the cellular characteristics of the allograft can exert significant impact on outcomes, the development of more strategically designed grafts represents a rich area for therapeutic intervention. We describe the use of ex vivo T cell-depleted grafts as a model for the targeted graft and review evolving knowledge and approaches for further refinement of allografts to improve patient outcomes. Read More

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http://dx.doi.org/10.1146/annurev-med-120617-041210DOI Listing
January 2019
2 Reads

Long-Acting HIV Drugs for Treatment and Prevention.

Annu Rev Med 2019 01 24;70:137-150. Epub 2018 Oct 24.

Divisions of Clinical Pharmacology and Infectious Diseases, Long Acting/Extended Release Antiretroviral Resource Program, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287-5554, USA; email:

Antiretroviral drugs have revolutionized the treatment and prevention of HIV infection; however, adherence is critical for sustained efficacy. Current HIV treatment consists of three-drug regimens, and current HIV pre-exposure prophylaxis (PrEP) consists of a two-drug regimen; both generally require adherence to once-daily dosing. Long-acting formulations are useful in the treatment and prevention of other conditions (e. Read More

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http://dx.doi.org/10.1146/annurev-med-041217-013717DOI Listing
January 2019
2 Reads

Gastric Cancer Etiology and Management in Asia and the West.

Annu Rev Med 2019 01 24;70:353-367. Epub 2018 Oct 24.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; email: ,

Regional variation in treatment paradigms for gastric adenocarcinoma has attracted a great deal of interest. Between Asia and the West, major differences have been identified in tumor biology, implementation of screening programs, extent of surgical lymphadenectomy, and routine use of neoadjuvant versus adjuvant treatment strategies. Minimally invasive techniques, including both laparoscopic and robotic platforms, have been studied in both regions, with attention to safety, feasibility, and long-term oncologic outcomes. Read More

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http://dx.doi.org/10.1146/annurev-med-081117-043436DOI Listing
January 2019
15 Reads

PD-1 Blockade in Early-Stage Lung Cancer.

Annu Rev Med 2019 01 24;70:425-435. Epub 2018 Oct 24.

Upper Aerodigestive Division, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA; email: , ,

Early-stage non-small cell lung cancer is a potentially curable disease, but with relapse rates exceeding 50% with standard treatments, this is a patient population in critical need of therapy innovation. Immunotherapy with immune checkpoint blockade has revolutionized the treatment strategy for advanced lung cancer. However, the role of this therapy in earlier-stage disease is largely unknown. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-050217
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http://dx.doi.org/10.1146/annurev-med-050217-025205DOI Listing
January 2019
17 Reads

Emerging Genetic Therapy for Sickle Cell Disease.

Annu Rev Med 2019 01 24;70:257-271. Epub 2018 Oct 24.

Dana Farber/Boston Children's Cancer and Blood Disorders Center, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

The genetic basis of sickle cell disease (SCD) was elucidated >60 years ago, yet current therapy does not rely on this knowledge. Recent advances raise prospects for improved, and perhaps curative, treatment. First, transcription factors, BCL11A and LRF/ZBTB7A, that mediate silencing of the β-like fetal (γ-) globin gene after birth have been identified and demonstrated to act at the γ-globin promoters, precisely at recognition sequences disrupted in rare individuals with hereditary persistence of fetal hemoglobin. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-041817
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http://dx.doi.org/10.1146/annurev-med-041817-125507DOI Listing
January 2019
17 Reads

Capitalizing on Insights from Human Genetics to Identify Novel Therapeutic Targets for Coronary Artery Disease.

Annu Rev Med 2019 01 24;70:19-32. Epub 2018 Oct 24.

Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA; email:

Coronary artery disease (CAD) is a major cause of morbidity and mortality. Unfortunately, despite decades of research focused on disease pathogenesis, we still lack a sufficient pharmacopeia for preventing CAD. The failure of many novel cardiovascular drugs to improve clinical outcomes reflects the major substantial challenge of drug development: identifying causal mechanisms that can be therapeutically manipulated to lower disease risk. Read More

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http://dx.doi.org/10.1146/annurev-med-041717-085853DOI Listing
January 2019
1 Read

Current Status of Living Donor Liver Transplantation in the United States.

Annu Rev Med 2019 01 24;70:225-238. Epub 2018 Oct 24.

Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, USA; email:

Adult-to-adult living donor liver transplantation (LDLT) was introduced in response to the shortage of deceased donor liver grafts. The number of adult living donor transplants is increasing due to improved outcomes and increasing need. Advantages of LDLT include optimization of the timing of transplant, better organ quality, and lower rates of recipient mortality compared to staying on the wait list for deceased donor liver transplant. Read More

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http://dx.doi.org/10.1146/annurev-med-051517-125454DOI Listing
January 2019
8 Reads

Arrhythmogenic Right Ventricular Cardiomyopathy: Progress Toward Personalized Management.

Annu Rev Med 2019 01 24;70:1-18. Epub 2018 Oct 24.

Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA; email: ,

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by fibrofatty replacement of the ventricular myocardium, a high risk of ventricular arrhythmias, and progressive ventricular dysfunction. The clinical course is highly variable, and optimal approaches to management remain undefined. ARVC is associated with pathogenic variants in genes encoding the cardiac desmosome. Read More

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http://dx.doi.org/10.1146/annurev-med-041217-010932DOI Listing
January 2019
3 Reads

Cystic Fibrosis: Emerging Understanding and Therapies.

Annu Rev Med 2019 01 12;70:197-210. Epub 2018 Oct 12.

Division of Pulmonary, Allergy and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: , ,

Cystic fibrosis (CF) is the most common life-limiting genetic disease in Caucasian patients. Continued advances have led to improved survival, and adults with CF now outnumber children. As our understanding of the disease improves, new therapies have emerged that improve the basic defect, enabling patient-specific treatment and improved outcomes. Read More

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http://dx.doi.org/10.1146/annurev-med-112717-094536DOI Listing
January 2019
1 Read

Innovations in Ventricular Assist Devices for End-Stage Heart Failure.

Annu Rev Med 2019 01 8;70:33-44. Epub 2018 Oct 8.

Section of Heart Failure, Cardiac Transplant, and Mechanical Circulatory Support, and Department of Medicine, Stanford University, Stanford, California 94305, USA; email: , ,

The number of patients with end-stage heart failure (HF) continues to increase over time, but there has been little change in the availability of organs for cardiac transplantation, intensifying the demand for left ventricular assist devices (LVADs) as a bridge to transplantation. There is also a growing number of patients with end-stage HF who are not transplant candidates but may be eligible for long-term support with an LVAD, known as destination therapy. Due to this increasing demand, LVAD technology has evolved, resulting in transformative improvements in outcomes. Read More

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http://dx.doi.org/10.1146/annurev-med-041217-011015DOI Listing
January 2019
2 Reads

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors and the Treatment of Type 2 Diabetes.

Annu Rev Med 2019 01 26;70:323-334. Epub 2018 Sep 26.

Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto M5T 3L9, Canada; email:

Clinical studies evaluating the cardiovascular safety/impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors demonstrated a reduction in major adverse cardiovascular events driven primarily by a reduced cardiovascular mortality in individuals with type 2 diabetes and previous cardiovascular disease. These somewhat unexpected results are coupled with SGLT-2 inhibitors' known acute effect of improvement in glycemia, reduction in blood pressure, and weight loss. In this review, we summarize the mechanism of action of SGLT-2 inhibitors, the metabolic effects of this class of medication, and the remarkable results of cardiovascular safety trials. Read More

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http://dx.doi.org/10.1146/annurev-med-042017-094221DOI Listing
January 2019
2 Reads

Active Surveillance as First-Line Management of Papillary Microcarcinoma.

Annu Rev Med 2019 01 19;70:369-379. Epub 2018 Sep 19.

Department of Surgery, Kuma Hospital, Kobe 650-0011, Japan; email: ,

Papillary thyroid microcarcinoma (PMC) is defined as papillary thyroid carcinoma ≤10 mm. Active surveillance of PMC without high-risk features, such as clinical node metastasis, distant metastasis, and clinical evidence of significant extrathyroid extension, was initiated in two Japanese hospitals in the mid-1990s. This strategy was incorporated into guidelines in Japan in 2010 and in the United States in 2015. Read More

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January 2019
1 Read

New and Emerging Therapies for Pulmonary Arterial Hypertension.

Annu Rev Med 2019 01 14;70:45-59. Epub 2018 Sep 14.

Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA; email: ,

Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes right ventricular dysfunction and exercise limitation and progresses to death. New findings from translational studies have suggested alternative pathways for treatment. These avenues include sex hormones, genetic abnormalities and DNA damage, elastase inhibition, metabolic dysfunction, cellular therapies, and anti-inflammatory approaches. Read More

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http://dx.doi.org/10.1146/annurev-med-041717-085955DOI Listing
January 2019
1 Read

Molecular Diagnostics for Mycobacterium tuberculosis Infection.

Annu Rev Med 2019 01 20;70:77-90. Epub 2018 Aug 20.

Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA; email: ,

Resistance to antimycobacterial drugs is a major barrier to effective treatment of Mycobacterium tuberculosis infection. Molecular diagnostic techniques based on the association between specific gene mutations and phenotypic resistance to certain drugs offer the opportunity to rapidly ascertain whether drug resistance is present and to alter treatment before further resistance develops. Current barriers to successful implementation of rapid diagnostics include imperfect knowledge regarding the full spectrum of mutations associated with resistance, limited utilization of molecular diagnostics where they are most needed, and the requirement for specialized laboratory facilities to perform molecular testing. Read More

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https://www.annualreviews.org/doi/10.1146/annurev-med-040717
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http://dx.doi.org/10.1146/annurev-med-040717-051502DOI Listing
January 2019
17 Reads

New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-052716-030320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214178PMC
January 2018
14 Reads

Risk Stratification for Sudden Cardiac Death After Myocardial Infarction.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-041316-090046DOI Listing
January 2018
10 Reads

Measuring Patient-Reported Outcomes: Key Metrics in Reconstructive Surgery.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-060116-022831DOI Listing
January 2018
9 Reads

Antibody-Drug Conjugates for Cancer Treatment.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-061516-121357DOI Listing
January 2018
10 Reads

The Affordable Care Act: What's Next?

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-061516-112359DOI Listing
January 2018
8 Reads

Computed Tomography Scanning for Early Detection of Lung Cancer.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-020917-053556DOI Listing
January 2018
7 Reads

CD8 T Cell Exhaustion in Chronic Infection and Cancer: Opportunities for Interventions.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-012017-043208DOI Listing
January 2018
11 Reads

Common Cardiovascular Complications of Cancer Therapy: Epidemiology, Risk Prediction, and Prevention.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-041316-090622DOI Listing
January 2018
6 Reads

New Therapeutic Approaches for Familial Hypercholesterolemia.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-051215-030943DOI Listing
January 2018
8 Reads

Updated Recommendations for Athletes with Heart Disease.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-041316-090402DOI Listing
January 2018
7 Reads

Impact of the SPRINT Trial on Hypertension Management.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-050416-024516DOI Listing
January 2018
7 Reads

What Metrics Accurately Reflect Surgical Quality?

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-060116-022805DOI Listing
January 2018
6 Reads

Recombinant Poliovirus for Cancer Immunotherapy.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-050715-104655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013836PMC
January 2018
7 Reads

Heart Failure with Preserved Ejection Fraction.

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-041316-090654DOI Listing
January 2018
9 Reads

Precision Medicine: Functional Advancements.

Authors:
Thomas Caskey

Annu Rev Med 2018 01;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

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http://dx.doi.org/10.1146/annurev-med-041316-090905DOI Listing
January 2018
8 Reads