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Annual Review of Medicine

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https://www.readbyqxmd.com/read/27860545/mechanisms-and-medicines-for-remyelination
#1
Mark Bothwell
Demyelination of central nervous system axons, associated with traumatic injury and demyelinating diseases such as multiple sclerosis, causes impaired neural transmission and ultimately axon degeneration. Consequently, extensive research has focused on signaling systems that promote myelinating activity of oligodendrocytes or promote production of new oligodendrocytes from oligodendrocyte progenitor cells. Many receptor systems, notably including growth factor receptors and G protein-coupled receptors, control myelination...
November 17, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27860544/car-t-cell-therapy-for-solid-tumors
#2
Kheng Newick, Shaun O'Brien, Edmund Moon, Steven M Albelda
The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematologic malignancies (e.g., CD19 CARs in leukemias). However, this success has yet to be extrapolated to solid tumors, and the reasons for this are being actively investigated...
November 17, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27860546/transcatheter-aortic-valve-replacement-state-of-the-art-and-future-directions
#3
Mackram F Eleid, David R Holmes
Transcatheter aortic valve replacement (TAVR) is a transformational and rapidly evolving treatment for patients with aortic stenosis who require valve replacement. Novel technological advancements have made this percutaneous minimally invasive therapy a first-line treatment for many patients at extreme risk for conventional cardiac surgery. New devices and improvements in existing devices have reduced procedural complications, and scientific trials are investigating the role of TAVR in lower-risk aortic stenosis populations, in patients with aortic regurgitation, and in patients with bicuspid aortic valve disease...
November 14, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27813876/next-generation-sequencing-and-result-interpretation-in-clinical-oncology-challenges-of-personalized-cancer-therapy
#4
Yekaterina B Khotskaya, Kenna R Mills Shaw, Gordon B Mills
The tools of next-generation sequencing (NGS) technology, such as targeted sequencing of candidate cancer genes and whole-exome and -genome sequencing, coupled with encouraging clinical results based on the use of targeted therapeutics and biomarker-guided clinical trials, are fueling further technological advancements of NGS technology. However, NGS data interpretation is associated with challenges that must be overcome to promote the techniques' effective integration into clinical oncology practice. Specifically, sequencing of a patient's tumor yields 30-65 somatic variants, but most of these variants are "passenger" mutations that are phenotypically neutral and thus not targetable...
November 2, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27813875/the-type-i-interferonopathies
#5
Min Ae Lee-Kirsch
Type I interferons (IFNs) play a central role in the immune defense against viral infections. Type I IFN activation is induced by pattern-recognition receptors of the innate immune system that sense pathogen-derived nucleic acids. Cellular responses to type I IFN signaling are orchestrated by a complex network of regulatory pathways that involve both the innate and adaptive immune system. The genetic and molecular dissection of rare Mendelian disorders associated with constitutive overproduction of type I IFN has provided unique insight into cell-intrinsic disease mechanisms that initiate and sustain autoinflammation and autoimmunity and that are caused by disturbances in the intracellular nucleic acid metabolism or in cytosolic nucleic acid-sensing pathways...
November 2, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27813877/biosimilars-the-us-regulatory-framework
#6
Leah A Christl, Janet Woodcock, Steven Kozlowski
With the passage of the Biologics Price Competition and Innovation Act of 2009, the US Food and Drug Administration established an abbreviated pathway for developing and licensing biosimilar and interchangeable biological products. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a "totality of the evidence" that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance...
October 28, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27813879/ebola-anatomy-of-an-epidemic
#7
Terrence Q Lo, Barbara J Marston, Benjamin A Dahl, Kevin M De Cock
As of the end of March 2016, the West Africa epidemic of Ebola virus disease (Ebola) had resulted in a total of 28,646 cases, 11,323 of them fatal, reported to the World Health Organization. Guinea, Liberia, and Sierra Leone were most heavily affected, but Ebola cases were exported to several other African and European countries as well as the United States, with limited further transmission, including to healthcare workers. We review the descriptive epidemiology of the outbreak, novel aspects and insights concerning the unprecedented response, scientific observations, and public health implications...
October 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27813878/antimalarial-drugs-as-immune-modulators-new-mechanisms-for-old-drugs
#8
Jie An, Mark Minie, Tomikazu Sasaki, Joshua J Woodward, Keith B Elkon
The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during WorldWar II. In this review, we discuss the chemistry of AMDs and their mechanisms of action, emphasizing how they may impact multiple pathways of innate immunity...
October 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27732785/noninvasive-prenatal-dna-testing-the-vanguard-of-genomic-medicine
#9
Lisa Hui, Diana W Bianchi
Noninvasive prenatal DNA testing is the vanguard of genomic medicine. In only four years, this screening test has revolutionized prenatal care globally and opened up new prospects for personalized medicine for the fetus. There are widespread implications for increasing the scope of human genetic variation that can be detected before birth, and for discovering more about materno-fetal and placental biology. These include an urgent need to develop pretest education for all pregnant women and consistent posttest management recommendations for those with discordant test results...
October 10, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27732789/obstructive-sleep-apnea-update-and-future
#10
Diane C Lim, Allan I Pack
Obstructive sleep apnea (OSA) is a worldwide disease whose prevalence is increasing as obesity rates increase. The link between obesity and OSA is likely to be the deposition of fat in the tongue, compromising upper airway size. The role of obesity varies in different ethnic groups, with Chinese being particularly sensitive to increases in weight. OSA lends itself to a personalized approach to diagnosis and therapy. For example, different clinical OSA subtypes likely benefit from therapy in different ways. Hypoglossal nerve stimulation is a useful second-line therapy in patients who cannot tolerate continous positive airway pressure (CPAP) machines or intraoral devices...
October 5, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27732787/nonalcoholic-steatohepatitis
#11
Ayako Suzuki, Anna Mae Diehl
Nonalcoholic steatohepatitis (NASH) has become a major cause of cirrhosis and liver-related deaths worldwide. NASH is strongly associated with obesity and the metabolic syndrome, conditions that cause lipid accumulation in hepatocytes (hepatic steatosis). It is not well understood why some, but not other, individuals with hepatic steatosis develop NASH. The factors that determine whether or not NASH progresses to cirrhosis are also unclear. This review summarizes key components of NASH pathogenesis and discusses how inherent and acquired variations in regulation of these processes impact the risk for NASH and NASH cirrhosis...
October 5, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27732788/tissue-engineering-toward-a-new-era-of-medicine
#12
Ashkan Shafiee, Anthony Atala
The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering...
September 30, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686016/resection-of-liver-metastases-in-colorectal-cancer-in-the-era-of-expanding-systemic-therapy
#13
Robert P Jones, Graeme J Poston
About 25% of patients with colorectal cancer develop liver metastases after resection of the primary tumor, and surgical resection of the metastases offers the only opportunity for long-term survival. However, only 20% of patients present with resectable disease. Deciding which patients should be offered surgery, and which should receive additional treatment in the form of perioperative chemotherapy, is complex. For the majority of patients who present with technically irresectable liver-limited disease, systemic downsizing chemotherapy offers the only opportunity to reach surgery and potential cure...
September 28, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686015/toward-an-effective-ebola-virus-vaccine
#14
Rohan Keshwara, Reed F Johnson, Matthias J Schnell
Long-term control of viral outbreaks requires the use of vaccines to impart acquired resistance and ensuing protection. In the wake of an epidemic, established immunity against a particular disease can limit spread and significantly decrease mortality. Creation of a safe and efficacious vaccine against Ebola virus (EBOV) has proven elusive so far, but various inventive strategies are now being employed to counteract the threat of outbreaks caused by EBOV and related filoviruses. Here, we present a current overview of progress in the field of Ebola virus vaccine development...
September 28, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686018/highly-effective-new-treatments-for-psoriasis-target-the-il-23-type-17-t-cell-autoimmune-axis
#15
Jaehwan Kim, James G Krueger
Psoriasis vulgaris, affecting the skin, is one of the most common organspecific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis...
September 23, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686017/oral-combination-therapies-for-hepatitis-c-virus-infection-successes-challenges-and-unmet-needs
#16
Susanna Naggie, Andrew J Muir
The current standard of care for the treatment of hepatitis C virus (HCV) consists of interferon-free direct-acting antiviral (DAA) regimens, including combinations of DAAs and fixed-dose combination pills. DAAs for HCV are likely to be heralded as one of medicine's greatest advancements. Viral eradication rates are pushing 100% for many HCV-infected populations, including patients with HIV/HCV coinfection, decompensated cirrhosis, liver and kidney transplants, and end-stage liver disease. We highlight the greatest successes of combination DAA therapies, discuss the ongoing challenges, and identify the remaining patient subgroups with unmet medical needs...
September 23, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686021/management-of-systemic-lupus-erythematosus-during-pregnancy
#17
Lisa R Sammaritano
Reproductive issues including contraception, fertility, and pregnancy are important components of the comprehensive care of women with systemic lupus erythematosus (SLE). SLE pregnancies are complicated due to risk for maternal disease exacerbation and potential for fetal and neonatal complications. Pre-pregnancy assessment is important to identify patients with severe disease-related damage who should avoid pregnancy, counsel patients to conceive when disease has been stable and inactive on appropriate medications, and assess relevant risk factors including renal disease, antiphospholipid antibody, and anti-Ro/SS-A and anti-La/SS-B antibodies...
September 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686020/cardiac-pacing-and-defibrillation-devices-cost-and-effectiveness
#18
Peter W Groeneveld, Sanjay Dixit
Implantable cardiac pacing and defibrillation devices are effective and commonly used therapies for patients with cardiac rhythm disorders. Because device implantation is not easily reversible, as well as the high healthcare costs inherent in device use, a clear understanding of the clinical benefits relative to costs is essential for both appropriate clinical use and rational policy making. Cardiac implantable electronic devices (CIEDs) have been among the best-investigated therapies in medicine; these devices have been the topic of numerous clinical and economic evaluations during the past 30 years...
September 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27686019/neprilysin-inhibitors-emerging-therapy-for-heart-failure
#19
Anjali Tiku Owens, Susan Brozena, Mariell Jessup
Biologically active natriuretic peptides (NPs) are an integral part of cardiac homeostasis as they help to maintain sodium and fluid balance. When homeostasis is perturbed by neurohormonal activation in heart failure, levels of NPs rise in response. Neprilysin (NEP) is a naturally occuring enzyme that breaks down NPs. Scientists have recently discovered a novel pharmacologic agent that combines a NEP inhibitor and an angiotensin receptor blocker. In a large clinical trial, this new drug was found to reduce hospitalization and mortality in systolic heart failure...
September 21, 2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/27618750/management-of-rectal-cancer-without-radical-resection
#20
Geerard L Beets, Nuno F Figueiredo, Regina G H Beets-Tan
The basis of the current treatment of rectal cancer is a radical total mesorectal excision of the rectum, and although this provides excellent oncological control, it is associated with morbidity and functional problems in cancer survivors. Organ-preservation alternatives are local excision alone for very early tumors, chemoradiation followed by either local excision of a small tumor remnant or, when there is a complete clinical response, a nonoperative watch-and-wait approach. The functional advantage of these alternatives is clear, but there is some concern about the oncological risk...
September 8, 2016: Annual Review of Medicine
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