2,312 results match your criteria Annual Review of Medicine[Journal]


Broadly Neutralizing Antibodies for HIV Prevention.

Annu Rev Med 2020 01;71:329-346

HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; email:

In the last decade, over a dozen potent broadly neutralizing antibodies (bnAbs) to several HIV envelope protein epitopes have been identified, and their in vitro neutralization profiles have been defined. Many have demonstrated prevention efficacy in preclinical trials and favorable safety and pharmacokinetic profiles in early human clinical trials. The first human prevention efficacy trials using 10 sequential, every-two-month administrations of a single anti-HIV bnAb are anticipated to conclude in 2020. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-110118-045506DOI Listing
January 2020

Contemporary Application of Cardiovascular Magnetic Resonance Imaging.

Annu Rev Med 2020 01;71:221-234

Departments of Medicine (Cardiovascular Division) and Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Cardiovascular magnetic resonance imaging (CMR) is a comprehensive and versatile diagnostic and prognostic imaging modality that plays an increasingly important role in management of patients with cardiovascular disease. In this review, we discuss CMR applications in nonischemic cardiomyopathy, ischemic heart disease, arrhythmias, right ventricular diseases, and valvular heart disease. We emphasize the quantitative nature of CMR in current practice, from volumes, function, myocardial strain analysis, and late gadolinium enhancement to parametric mapping, including T1, T2, and T2 relaxation times and extracellular volume fraction assessment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041818-015923DOI Listing
January 2020

Atherosclerosis: Making a U Turn.

Annu Rev Med 2020 01;71:191-201

Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA; email:

The development of potent cholesterol-reducing medications in the last decade of the twentieth century has altered the approach to prevention and treatment of cardiovascular disease (CVD). Initial experience with statins, and more recently with the addition of PCSK9 inhibitors, has proven that human CVD, like that in animal models, can be halted and regressed. Available clinical data show that the lower the achieved level of low-density lipoprotein cholesterol, the greater the regression of disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-042418-011108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112505PMC
January 2020

Cardiac Amyloidosis: Overlooked, Underappreciated, and Treatable.

Annu Rev Med 2020 01;71:203-219

Clinical Cardiovascular Research Laboratory for the Elderly, Columbia University Irving Medical Center, Allen Hospital of NewYork-Presbyterian Hospital, New York, NY 10032, USA; email:

Cardiac amyloidosis (CA) is an infiltrative and restrictive cardiomyopathy that leads to heart failure, reduced quality of life, and death. The disease has two main subtypes, transthyretin cardiac amyloidosis (ATTR-CA) and immunoglobulin light chain cardiac amyloidosis (AL-CA), characterized by the nature of the infiltrating protein. ATTR-CA is further subdivided into wild-type (ATTRwt-CA) and variant (ATTRv-CA) based on the presence or absence of a mutation in the transthyretin gene. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-052918-020140DOI Listing
January 2020

Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation.

Annu Rev Med 2020 01;71:263-276

Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, 169857 Singapore, Singapore; email:

Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases-myofibroblast activation, parenchymal cell dysfunction, and inflammation-while also inhibiting tissue regeneration. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041818-011649DOI Listing
January 2020

Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.

Annu Rev Med 2020 01;71:137-148

Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-052918-122440DOI Listing
January 2020

Low-FODMAP Diet for Irritable Bowel Syndrome: What We Know and What We Have Yet to Learn.

Annu Rev Med 2020 01;71:303-314

Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Irritable bowel syndrome (IBS) is the most prevalent of gastrointestinal (GI) conditions, affecting millions of people worldwide. Given that most IBS patients associate their GI symptoms with eating food, specific dietary manipulation has become an attractive treatment strategy. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) has generated the greatest level of scientific and clinical interest. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-050218-013625DOI Listing
January 2020

Precision Management of Advanced Non-Small Cell Lung Cancer.

Annu Rev Med 2020 01;71:117-136

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; email:

The rapid evolution of treatment for advanced lung cancer is a story of how scientists have struggled to move from nonselective cytotoxic chemotherapy to personalized precision medicine. In this century, extraordinary advances have been made in the management of advanced and metastatic non-small cell lung cancer, especially in the development of small molecules targeting specific tyrosine kinase receptors and immune checkpoint inhibitors. These developments have led to a significant improvement in survival for lung cancer patients with metastatic disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-051718-013524DOI Listing
January 2020

Bariatric Surgery as a Long-Term Treatment for Type 2 Diabetes/Metabolic Syndrome.

Annu Rev Med 2020 01;71:1-15

Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA; email:

Metabolic surgery is increasingly becoming recognized as a more effective treatment for patients with type 2 diabetes (T2D) and obesity as compared to lifestyle modification and medical management alone. Both observational studies and clinical trials have shown metabolic surgery to result in sustained weight loss (20-30%), T2D remission rates ranging from 23% to 60%, and improvement in cardiovascular risk factors such as hypertension and dyslipidemia. Metabolic surgery is cost-effective and relatively safe, with perioperative risks and mortality comparable to low-risk procedures such as cholecystectomy, hysterectomy, and appendectomy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-053117-123246DOI Listing
January 2020

Omics and Cardiometabolic Disease Risk Prediction.

Annu Rev Med 2020 01;71:163-175

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA; email:

Risk assessments are integral for the prevention and management of cardiometabolic disease (CMD). However, individuals may develop CMD without traditional risk factors, necessitating the development of novel biomarkers to aid risk prediction. The emergence of omic technologies, including genomics, proteomics, and metabolomics, has allowed for assessment of orthogonal measures of cardiometabolic risk, potentially improving the ability for novel biomarkers to refine disease risk assessments. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-042418-010924DOI Listing
January 2020

Transcatheter Mitral Valve Replacement: Rationale and Current Status.

Annu Rev Med 2020 01;71:249-261

Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Mitral regurgitation (MR) is the most prevalent form of moderate or severe valve disease in the developed world. MR can result from impairment of any part of the mitral valve apparatus and is classified as primary (disease of the leaflets) or secondary (functional). The presence of at least moderate MR is associated with increased morbidity and mortality. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-051418-060028DOI Listing
January 2020

Current Approaches to Germline Cancer Genetic Testing.

Annu Rev Med 2020 01 22;71:85-102. Epub 2019 Nov 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; email:

The prevalence of genetic predisposition to cancer is greater than initially appreciated, yet most affected individuals remain undiagnosed. Deleterious germline variants in cancer predisposition genes are implicated in 1 in 10 cases of advanced cancer. Next-generation sequencing technologies have made germline and tumor DNA sequencing more accessible and less expensive. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-052318-101009DOI Listing
January 2020

Ablation Therapy for Refractory Ventricular Arrhythmias.

Annu Rev Med 2020 01 20;71:177-190. Epub 2019 Nov 20.

Cardiac Electrophysiology Section, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Recurrent ventricular arrhythmias (VAs) are a leading cause of cardiovascular morbidity and mortality. In the last three decades, important advancements have occurred in the understanding of the mechanisms of recurrent VAs, their prognostic implications in different clinical contexts, and their treatment options. VAs occur in structurally normal hearts as well as in patients with underlying heart disease, but the latter group has a particularly high risk of recurrent VAs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041818-020033DOI Listing
January 2020

New Therapies for Emerging Endotypes of Asthma.

Annu Rev Med 2020 01 5;71:289-302. Epub 2019 Nov 5.

Division of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA; email:

The presentation, pathobiology, and prognosis of asthma are highly heterogeneous and challenging for clinicians to diagnose and treat. In addition to the adaptive immune response that underlies allergic inflammation, innate immune mechanisms are increasingly recognized to be critical mediators of the eosinophilic airway inflammation present in most patients with asthma. Efforts to classify patients by severity and immune response have identified a number of different clinical and immune phenotypes, indicating that the innate and adaptive immune responses are differentially active among patients with the disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041818-020630DOI Listing
January 2020

Prevention of HIV Transmission and the HPTN 052 Study.

Annu Rev Med 2020 01 25;71:347-360. Epub 2019 Oct 25.

Science Facilitation Department, HIV Prevention Trials Network (HPTN) Leadership and Operations Center, FHI 360, Durham, North Carolina 27701, USA; email:

The HIV Prevention Trials Network 052 study (HPTN 052) was a clinical trial designed to determine whether early treatment for HIV infection prevented transmission of the virus in couples where one partner was infected with HIV and the other was not, referred to as HIV serodiscordant or serodifferent couples. The study enrolled 1,763 couples at 13 sites in 9 countries in Asia, Africa, and the Americas. HPTN 052 demonstrated a minimum of 96% reduction of HIV in heterosexual couples ascribed to antiretroviral treatment; early treatment of HIV significantly reduced other infections in the HIV-infected subjects. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-110918-034551DOI Listing
January 2020

Topical Microbicides in HIV Prevention: State of the Promise.

Annu Rev Med 2020 01 15;71:361-377. Epub 2019 Oct 15.

Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA; email:

HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum have the potential to prevent the sexual acquisition of HIV in women and men. Topical microbicides may meet the prevention needs of individuals and groups for whom oral daily forms of pre-exposure prophylaxis (PrEP) have not been acceptable. Microbicides can provide personal control over HIV prevention and offer the possibility of discreet use, qualities that may be particularly important for receptive partners in sexual relationships such as women and transgender women and men, who together account for the clear majority of new HIV infections worldwide. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-090518-093731DOI Listing
January 2020

Sex Hormones and Prostate Cancer.

Annu Rev Med 2020 01 15;71:33-45. Epub 2019 Oct 15.

Genitourinary Malignancies Research Center, Lerner Research Institute, Glickman Urological and Kidney Institute, and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA; email:

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-051418-060357DOI Listing
January 2020
1 Read

Is a Universal Influenza Virus Vaccine Possible?

Annu Rev Med 2020 01 10;71:315-327. Epub 2019 Oct 10.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; email:

Influenza viruses remain a severe burden to human health because of their contribution to overall morbidity and mortality. Current seasonal influenza virus vaccines do not provide sufficient protection to alleviate the annual impact of influenza and cannot confer protection against potentially pandemic influenza viruses. The lack of protection is due to rapid changes of the viral epitopes targeted by the vaccine and the often suboptimal immunogenicity of current immunization strategies. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-120617-041310DOI Listing
January 2020

Male Hormonal Contraception.

Annu Rev Med 2020 01 19;71:17-31. Epub 2019 Sep 19.

Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington 98195, USA; email:

The economic and public health burdens of unplanned pregnancies are evident globally. Since the introduction of the condom >300 years ago, assumptions about male willingness to participate in contraception, as well as concerns about failure rates and side effects, have stagnated the development of additional reversible male contraceptives. However, changing attitudes and recent research advances have generated renewed interest in developing reversible male contraceptives. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-042418-010947DOI Listing
January 2020
1 Read

New Frontiers in Osteoporosis Therapy.

Annu Rev Med 2020 01 11;71:277-288. Epub 2019 Sep 11.

Endocrine Research Unit, Endocrine-Metabolism Section, Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, USA; email:

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone-related peptide analog abaloparatide. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-052218-020620DOI Listing
January 2020
4 Reads

A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease.

Annu Rev Med 2020 01 3;71:149-161. Epub 2019 Oct 3.

Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands; email:

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-062218-023720DOI Listing
January 2020
3 Reads

Genome Editing and Hematologic Malignancy.

Annu Rev Med 2020 01 30;71:71-83. Epub 2019 Aug 30.

Departments of Internal Medicine, Human Genetics, and Pediatrics, Life Sciences Institute, and Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

The modern genomic era has seen remarkable advancement in our understanding of the molecular basis for disease, yet translation of basic discoveries into new disease treatments has arguably lagged behind. Recently, breakthroughs in genome editing technologies have created hope for their potential to directly treat the genetic causes of disease. Like any therapeutic intervention, genome editing should be considered in light of its potential risks and benefits. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-052318-100741DOI Listing
January 2020

Fecal DNA Testing for Colorectal Cancer Screening.

Authors:
John M Carethers

Annu Rev Med 2020 01 26;71:59-69. Epub 2019 Aug 26.

Division of Gastroenterology and Hepatology, Department of Internal Medicine and Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-103018-123125DOI Listing
January 2020

The Clinical Spectrum of Mutations.

Annu Rev Med 2020 01 21;71:103-116. Epub 2019 Aug 21.

Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA; email:

is a tumor suppressor gene that classically dampens the PI3K/AKT/mTOR growth-promoting signaling cascade. dysfunction causes dysregulation of this and other pathways, resulting in overgrowth. Cowden syndrome, a hereditary cancer predisposition and overgrowth disorder, was the first Mendelian condition associated with germline mutations. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-052218
Publisher Site
http://dx.doi.org/10.1146/annurev-med-052218-125823DOI Listing
January 2020
9 Reads

Postural Orthostatic Tachycardia Syndrome: Mechanisms and New Therapies.

Annu Rev Med 2020 01 14;71:235-248. Epub 2019 Aug 14.

Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada; email:

Postural orthostatic tachycardia syndrome (POTS) is a clinically heterogeneous disorder with multiple contributing pathophysiologic mechanisms manifesting as symptoms of orthostatic intolerance in the setting of orthostatic tachycardia (increase in heart rate by at least 30 beats per minute upon assuming an upright position) without orthostatic hypotension. The three major pathophysiologic mechanisms include partial autonomic neuropathy, hypovolemia, and hyperadrenergic state. Patients often will exhibit overlapping characteristics from more than one of these mechanisms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041818-011630DOI Listing
January 2020
1 Read

CD40 Agonist Antibodies in Cancer Immunotherapy.

Annu Rev Med 2020 01 14;71:47-58. Epub 2019 Aug 14.

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic and found to be tolerable and feasible. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-062518-045435DOI Listing
January 2020
1 Read

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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-053117
Publisher Site
http://dx.doi.org/10.1146/annurev-med-053117-123215DOI Listing
January 2019
54 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-042617
Publisher Site
http://dx.doi.org/10.1146/annurev-med-042617-101816DOI Listing
January 2019
12 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-062117-073027DOI Listing
January 2019
40 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041217-011106DOI Listing
January 2019
11 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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-121417-100403DOI Listing
January 2019
9 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-112017-091045DOI Listing
January 2019
6 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-120417-091431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597259PMC
January 2019
1 Read

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

View Article

Download full-text PDF

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

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-112717-094629DOI Listing
January 2019
3 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-051517-011947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441973PMC
January 2019
36 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-121217
Publisher Site
http://dx.doi.org/10.1146/annurev-med-121217-094234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936610PMC
January 2019
33 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-012017-043332DOI Listing
January 2019
2 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-042617-092334DOI Listing
January 2019
3 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-040717
Publisher Site
http://dx.doi.org/10.1146/annurev-med-040717-051150DOI Listing
January 2019
28 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-111717
Publisher Site
http://dx.doi.org/10.1146/annurev-med-111717-122956DOI Listing
January 2019
30 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-040717
Publisher Site
http://dx.doi.org/10.1146/annurev-med-040717-051127DOI Listing
January 2019
38 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-062617-035821DOI Listing
January 2019
2 Reads

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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-081117-010451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415693PMC
January 2019
4 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-050217-121900DOI Listing
January 2019
6 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-081117
Publisher Site
http://dx.doi.org/10.1146/annurev-med-081117-041238DOI Listing
January 2019
35 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-120617-041210DOI Listing
January 2019
3 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-041217-013717DOI Listing
January 2019
3 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

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-med-081117
Publisher Site
http://dx.doi.org/10.1146/annurev-med-081117-043436DOI Listing
January 2019
31 Reads