- Home
- A-Z Publications
- Annual Review of Medicine
- Previous Issues
- Volume 68, 2017
Annual Review of Medicine - Volume 68, 2017
Volume 68, 2017
-
-
Cardiac Pacing and Defibrillation Devices: Cost and Effectiveness
Vol. 68 (2017), pp. 1–13More LessImplantable 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. However, many important questions remain unclarified. We review the evidence supporting the clinical benefits of CIEDs, including effectiveness in extending survival as well as improving quality of life. We also summarize the economic studies that have investigated costs associated with these devices and their overall cost effectiveness, and we highlight important potential areas for future research.
-
-
-
Transcatheter Aortic Valve Replacement: State of the Art and Future Directions
Vol. 68 (2017), pp. 15–28More LessTranscatheter 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. Finally, there is intense interest in identifying patients in whom the risk-benefit ratio of TAVR is not favorable and should not be performed.
-
-
-
Tissue Engineering: Toward a New Era of Medicine
Vol. 68 (2017), pp. 29–40More LessThe 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. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.
-
-
-
Neprilysin Inhibitors: Emerging Therapy for Heart Failure
Vol. 68 (2017), pp. 41–49More LessBiologically 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. The challenges of implementing this therapy include patient selection, cost, and risk of side effects including angioedema and Alzheimer's disease.
-
-
-
Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models
Vol. 68 (2017), pp. 51–67More LessThoracic aortic diseases, including aneurysms and dissections of the thoracic aorta, are a major cause of morbidity and mortality. Risk factors for thoracic aortic disease include increased hemodynamic forces on the ascending aorta, typically due to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease either disrupt smooth muscle cell (SMC) contraction or adherence to an impaired extracellular matrix, or decrease canonical transforming growth factor beta (TGF-β) signaling. Paradoxically, TGF-β hyperactivity has been postulated to be the primary driver for the disease. More recently, it has been proposed that the response of aortic SMCs to the hemodynamic load on a structurally defective aorta is the primary driver of thoracic aortic disease, and that TGF-β overactivity in diseased aortas is a secondary, unproductive response to restore tissue function. The engineering of mouse models of inherited aortopathies has identified potential therapeutic agents to prevent thoracic aortic disease.
-
-
-
Lymphangioleiomyomatosis: A Monogenic Model of Malignancy
Vol. 68 (2017), pp. 69–83More LessLymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure. Dysregulated cellular signaling results in a shift from oxidative phosphorylation to glycolysis as the preferred mode of energy generation, to allow for the accumulation of biomass required for cell growth and tolerance of nutrient-poor, anaerobic environments. Symptomatic LAM occurs almost exclusively in females after menarche, highlighting the central but as yet poorly understood role for sex-restricted anatomical structures and/or hormones in disease pathogenesis. LAM is an elegant model of malignancy because biallelic mutations at a single genetic locus confer all features that define cancer upon the LAM cell—metabolic reprogramming and proliferative signals that drive uncontrolled growth and inappropriate migration and invasion, the capacity to exploit the lymphatic circulation as a vehicle for metastasis and access to the lungs, and destruction of remote tissues. The direct benefit of the study of this rare disease has been the rapid identification of an effective FDA-approved therapy, and the collateral benefits have included elucidation of the pivotal roles of mTOR signaling in the regulation of cellular metabolism and the pathogenesis of cancer.
-
-
-
Nonalcoholic Steatohepatitis
Vol. 68 (2017), pp. 85–98More LessNonalcoholic 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.
-
-
-
Obstructive Sleep Apnea: Update and Future
Vol. 68 (2017), pp. 99–112More LessObstructive 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. Technological advances allow patients to participate in their own care, and doing so improves CPAP compliance. We are entering a future where we can focus efforts to predict and prevent OSA on an individual level.
-
-
-
Next-Generation Sequencing and Result Interpretation in Clinical Oncology: Challenges of Personalized Cancer Therapy
Vol. 68 (2017), pp. 113–125More LessThe tools of next-generation sequencing (NGS) technology, such as targeted sequencing of candidate cancer genes and whole-exome and -genome sequencing, coupled with encouraging clinical results based on the use of targeted therapeutics and biomarker-guided clinical trials, are fueling further technological advancements of NGS technology. However, NGS data interpretation is associated with challenges that must be overcome to promote the techniques' effective integration into clinical oncology practice. Specifically, sequencing of a patient's tumor often yields 30–65 somatic variants, but most of these variants are “passenger” mutations that are phenotypically neutral and thus not targetable. Therefore, NGS data must be interpreted by multidisciplinary decision-support teams to determine mutation actionability and identify potential “drivers,” so that the treating physician can prioritize what clinical decisions can be pursued in order to provide cancer therapy that is personalized to the patient and his or her unique genome.
-
-
-
Precision Medicine in Myelodysplastic Syndromes and Leukemias: Lessons from Sequential Mutations
Vol. 68 (2017), pp. 127–137More LessPrecision medicine can be simply defined as the identification of personalized treatment that matches patient-specific clinical and genomic characteristics. Since the completion of the Human Genome Project in 2003, significant advances have been made in our understanding of the genetic makeup of diseases, especially cancers. The identification of somatic mutations that can drive cancer has led to the development of therapies that specifically target the abnormal proteins derived from these mutations. This has led to a paradigm shift in our treatment methodology. Although some success has been achieved in targeting some genetic abnormalities, several challenges and limitations exist when applying precision-medicine concepts in leukemia and myelodysplastic syndromes. We review the current understanding of genomics in myelodysplastic syndromes (MDS) and leukemias and the limitations of precision-medicine concepts in MDS.
-
-
-
CAR T Cell Therapy for Solid Tumors
Vol. 68 (2017), pp. 139–152More LessThe 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. We characterize some of the challenges that CAR T cells have to surmount in the solid tumor microenvironment and new approaches that are being considered to overcome these hurdles.
-
-
-
The End of Nihilism: Systemic Therapy of Advanced Non–Small Cell Lung Cancer
Vol. 68 (2017), pp. 153–168More LessLung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non–small cell lung cancer (NSCLC) comprises 85–90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.
-
-
-
Management of Rectal Cancer Without Radical Resection
Vol. 68 (2017), pp. 169–182More LessThe 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. Although the available studies suggest that with adequate selection and follow-up this risk is small, the evidence is still weak. Because of patients' high interest in preserving quality of life, clinicians should cautiously move ahead and offer the option of organ preservation to patients in a controlled setting while awaiting further evidence.
-
-
-
Resection of Liver Metastases in Colorectal Cancer in the Era of Expanding Systemic Therapy
Vol. 68 (2017), pp. 183–196More LessAbout 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. Molecular analysis of tumor tissue is improving patient stratification, allowing more appropriate treatment selection, but is not yet a regular part of clinical practice. Decision making is limited by a lack of clear prospective evidence, and so multidisciplinary team assessment is essential to optimize outcomes.
-
-
-
Controversies in the Treatment of Ductal Carcinoma in Situ
Vol. 68 (2017), pp. 197–211More LessDuctal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with “low-risk” DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.
-
-
-
Esophageal Adenocarcinoma: Screening, Surveillance, and Management
Vol. 68 (2017), pp. 213–227More LessEsophageal adenocarcinoma (EAC) is a growing problem with a rapidly rising incidence. Risk factors include gastroesophageal reflux disease, central obesity, and smoking. The prognosis of EAC remains poor because it is usually diagnosed late, and many efforts have been made to improve prevention, early detection, and treatment. Acid suppression, nonsteroidal antiinflammatory drugs (NSAIDs), and statins may play a role in chemoprevention. Screening for Barrett's esophagus (BE), the only known precursor lesion of EAC, is indicated for individuals with increased risk. Endoscopic surveillance of patients with BE likely improves overall outcomes. Endoscopic ablation and resection is highly effective for treating dysplastic BE and early EAC, whereas esophagectomy is indicated for patients with locally advanced disease. This review covers epidemiology, staging, screening, and prevention of EAC as well as endoscopic and surgical management.
-
-
-
Why Are There So Many Mastectomies in the United States?
Vol. 68 (2017), pp. 229–241More LessBreast-conserving therapy (BCT) and mastectomy result in equivalent long-term survival. Locoregional recurrence rates after BCT have decreased over time and are now similar to those after mastectomy. Contralateral breast cancer rates are declining as well owing to the widespread use of adjuvant systemic therapy. Despite these improved outcomes, increasing rates of bilateral mastectomy for unilateral cancer have been observed in the United States. Medical indications for mastectomy are well defined and present in a minority of patients, and women at increased risk for contralateral cancer are a small proportion of the breast cancer population. Evidence indicates that increasing use of mastectomy is a patient-driven trend that is most pronounced among younger, educated, and well-insured women, and reflects fear of recurrence and in some cases misunderstanding of future cancer risks. Although satisfaction levels are generally high among patients choosing contralateral prophylactic mastectomy, complications and procedure extent may be underestimated. Improved communication strategies are essential to facilitate this complex decision-making process.
-
-
-
Biosimilars: The US Regulatory Framework*
Vol. 68 (2017), pp. 243–254More LessWith 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. Although questions and concerns about the biosimilars pathway remain and may slow uptake, a robust scientific program has been put in place. With three biosimilars already licensed and numerous development programs under way, clinicians can expect to see many new biosimilars come onto the US market in the coming decade. [Note added in proof: Since the writing of this article, a fourth biosimilar has been approved.]
-
-
-
Highly Effective New Treatments for Psoriasis Target the IL-23/Type 17 T Cell Autoimmune Axis
Vol. 68 (2017), pp. 255–269More LessPsoriasis vulgaris, affecting the skin, is one of the most common organ-specific 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. Thus, psoriasis is a model for the success of a translational-medicine approach based on cellular and molecular dissection of disease pathogenesis in humans.
-
-
-
Management of Systemic Lupus Erythematosus During Pregnancy
Vol. 68 (2017), pp. 271–285More LessReproductive 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. With careful planning, monitoring, and care, most women with SLE can anticipate a successful pregnancy.
-
Previous Volumes
-
Volume 75 (2024)
-
Volume 74 (2023)
-
Volume 73 (2022)
-
Volume 72 (2021)
-
Volume 71 (2020)
-
Volume 70 (2019)
-
Volume 69 (2018)
-
Volume 68 (2017)
-
Volume 67 (2016)
-
Volume 66 (2015)
-
Volume 65 (2014)
-
Volume 64 (2013)
-
Volume 63 (2012)
-
Volume 62 (2011)
-
Volume 61 (2010)
-
Volume 60 (2009)
-
Volume 59 (2008)
-
Volume 58 (2007)
-
Volume 57 (2006)
-
Volume 56 (2005)
-
Volume 55 (2004)
-
Volume 54 (2003)
-
Volume 53 (2002)
-
Volume 52 (2001)
-
Volume 51 (2000)
-
Volume 50 (1999)
-
Volume 49 (1998)
-
Volume 48 (1997)
-
Volume 47 (1996)
-
Volume 46 (1995)
-
Volume 45 (1994)
-
Volume 44 (1993)
-
Volume 43 (1992)
-
Volume 42 (1991)
-
Volume 41 (1990)
-
Volume 40 (1989)
-
Volume 39 (1988)
-
Volume 38 (1987)
-
Volume 37 (1986)
-
Volume 36 (1985)
-
Volume 35 (1984)
-
Volume 34 (1983)
-
Volume 33 (1982)
-
Volume 32 (1981)
-
Volume 31 (1980)
-
Volume 30 (1979)
-
Volume 29 (1978)
-
Volume 28 (1977)
-
Volume 27 (1976)
-
Volume 26 (1975)
-
Volume 25 (1974)
-
Volume 24 (1973)
-
Volume 23 (1972)
-
Volume 22 (1971)
-
Volume 21 (1970)
-
Volume 20 (1969)
-
Volume 19 (1968)
-
Volume 18 (1967)
-
Volume 17 (1966)
-
Volume 16 (1965)
-
Volume 15 (1964)
-
Volume 14 (1963)
-
Volume 13 (1962)
-
Volume 12 (1961)
-
Volume 11 (1960)
-
Volume 10 (1959)
-
Volume 9 (1958)
-
Volume 8 (1957)
-
Volume 7 (1956)
-
Volume 6 (1955)
-
Volume 5 (1954)
-
Volume 4 (1953)
-
Volume 3 (1952)
-
Volume 2 (1951)
-
Volume 1 (1950)
-
Volume 0 (1932)