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Annual Review of Medicine

Ephraim L Tsalik, Robert A Bonomo, Vance G Fowler
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.g., viral, bacterial, protozoan, fungal). Although this progress is encouraging, it is unlikely that any single diagnostic platform will fully address the clinician's need for actionable data with short turnaround times in all settings...
January 29, 2018: Annual Review of Medicine
Jonathan W Waks, Alfred E Buxton
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. Current guidelines for use of implantable cardioverter-defibrillators (ICDs) to prevent SCD are based primarily on measurement of left ventricular ejection fraction (LVEF). Although reduced LVEF is associated with increased total cardiac mortality after MI, the focus of current guidelines on LVEF omits ∼50% of patients who die suddenly...
January 29, 2018: Annual Review of Medicine
Sophocles H Voineskos, Jonas A Nelson, Anne F Klassen, Andrea L Pusic
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. These advances have resulted in the availability of PROMs that provide clinically meaningful data and effectively measure functional as well as psychosocial outcomes...
January 29, 2018: Annual Review of Medicine
John M Lambert, Anna Berkenblit
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...
January 29, 2018: Annual Review of Medicine
Mark McClellan, Mark Japinga
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...
January 29, 2018: Annual Review of Medicine
Francine L Jacobson, Michael T Jaklitsch
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...
January 29, 2018: Annual Review of Medicine
Masao Hashimoto, Alice O Kamphorst, Se Jin Im, Haydn T Kissick, Rathi N Pillai, Suresh S Ramalingam, Koichi Araki, Rafi Ahmed
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. Other strategies to restore function in exhausted CD8 T cells are currently under evaluation-many in combination with PD-1-targeted therapy...
January 29, 2018: Annual Review of Medicine
Vivek Narayan, Bonnie Ky
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...
January 29, 2018: Annual Review of Medicine
Ezim Ajufo, Daniel J Rader
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...
January 29, 2018: Annual Review of Medicine
Rachel Lampert, Douglas P Zipes
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...
January 29, 2018: Annual Review of Medicine
Lama Ghazi, Suzanne Oparil
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...
January 29, 2018: Annual Review of Medicine
Andrew M Ibrahim, Justin B Dimick
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. We then discuss the benefits and drawbacks of current measurement strategies through the framework of structure, process, and outcomes approaches...
January 29, 2018: Annual Review of Medicine
Matthias Gromeier, Smita K Nair
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...
January 29, 2018: Annual Review of Medicine
James D Gladden, Antoine H Chaanine, Margaret M Redfield
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. Hypotheses have been advanced to explain the underlying pathophysiology responsible for HFpEF, but to date, no specific therapy based on these hypotheses has been proven to improve outcomes in HFpEF...
January 29, 2018: Annual Review of Medicine
Julie A Bradley, Nancy P Mendenhall
During the early decades of radiation therapy for breast cancer, local control of disease was documented consistently but, enigmatically, an anticipated impact on breast cancer survival was not observed, leading to confusion in our understanding of the natural history of breast cancer and radiation effects. Now, almost 90 years after its first use in breast cancer, technology developments in diagnostic imaging and radiation therapy have elucidated parts of this enigma. The data now available demonstrate a significant impact of radiation therapy on survival as well as disease control and treatment-related mortality, opening a doorway to understanding the powerful impact of radiation therapy on both breast cancer and critical organs...
January 29, 2018: Annual Review of Medicine
Thomas Caskey
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. These technologies are discussed and placed in clinical context for the medical specialties of internal medicine, pediatrics, obstetrics, and gynecology. Publications in these fields support the concept of a higher level of precision in identifying disease risk...
December 20, 2017: Annual Review of Medicine
Mamta Parikh, Primo N Lara
In the last 30 years, there have been many advances in the treatment of metastatic renal cell carcinoma of the clear cell type. Renal cell carcinoma has long been understood to have a component of immune mediation and has been responsive to immune-based therapies; in addition to early cytokine therapy, newer checkpoint inhibition therapies have also demonstrated activity. Molecular characterization of the genome of clear cell renal cell carcinoma enabled identification of the roles of angiogenesis and hypoxic stress...
November 16, 2017: Annual Review of Medicine
Jessica J Tao, Alison M Schram, David M Hyman
Understanding a tumor's detailed molecular profile has become increasingly necessary to deliver the standard of care for patients with advanced cancer. Innovations in both tumor genomic sequencing technology and the development of drugs that target molecular alterations have fueled recent gains in genome-driven oncology care. "Basket studies," or histology-agnostic clinical trials in genomically selected patients, represent one important research tool to continue making progress in this field. We review key aspects of genome-driven oncology care, including the purpose and utility of basket studies, biostatistical considerations in trial design, genomic knowledge-base development, and patient matching and enrollment models, which are critical for translating our genomic knowledge into clinically meaningful outcomes...
November 8, 2017: Annual Review of Medicine
Larisa I Labzin, Michael T Heneka, Eicke Latz
The innate immune system plays diverse roles in health and disease. It represents the first line of defense against infection and is involved in tissue repair, wound healing, and clearance of apoptotic cells and cellular debris. Excessive or nonresolving innate immune activation can lead to systemic or local inflammatory complications and cause or contribute to the development of inflammatory diseases. In the brain, microglia represent the key innate immune cells, which are involved in brain development, brain maturation, and homeostasis...
November 6, 2017: Annual Review of Medicine
Barry I Hudson, Marc E Lippman
The receptor for advanced glycation end-products (RAGE) is a multiligand pattern recognition receptor implicated in diverse chronic inflammatory states. RAGE binds and mediates the cellular response to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA. RAGE can also act as an innate immune sensor of microbial pathogen-associated molecular pattern molecules (PAMPs) including bacterial endotoxin, respiratory viruses, and microbial DNA. RAGE is expressed at low levels under normal physiology, but it is highly upregulated under chronic inflammation because of the accumulation of various RAGE ligands...
November 6, 2017: Annual Review of Medicine
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