Annual review of medicine
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Annual review of medicine · Jan 2014
ReviewIdentification of genes for childhood heritable diseases.
Genes causing rare heritable childhood diseases are being discovered at an accelerating pace driven by the decreasing cost and increasing accessibility of next-generation DNA sequencing combined with the maturation of strategies for successful gene identification. The findings are shedding light on the biological mechanisms of childhood disease and broadening the phenotypic spectrum of many clinical syndromes. Still, thousands of childhood disease genes remain to be identified, and given their increasing rarity, this will require large-scale collaboration that includes mechanisms for sharing phenotypic and genotypic data sets. Nonetheless, genomic technologies are poised for widespread translation to clinical practice for the benefit of children and families living with these rare diseases.
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Annual review of medicine · Jan 2014
ReviewNew cost-effective treatment strategies for acute emergency situations.
In an era of ever-increasing healthcare costs, new treatments must not only improve outcomes and quality of care but also be cost-effective. This is most challenging for emergency and critical care. ⋯ We outline recent advances in medical practice that have positively affected both the quality of care and its cost-effectiveness. Future medical care must be smarter and more effective if we are to meet the increasing demands of an aging patient population in the context of ever more limited resources.
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For a decade, the technologies behind DNA sequencing have improved rapidly in cost reduction and speed. Sequencing in large populations of cancer patients is leading to dramatic advances in our understanding of the cancer genome. The wide variety of cancer types sequenced and analyzed using these technologies has revealed many novel fundamental genetic mechanisms driving cancer initiation, progression, and maintenance. ⋯ The molecular mechanisms of resistance to targeted therapies are being elucidated for the first time. The translation of genome-scale variation into clinically actionable information is still in its infancy; nevertheless, insights from sequencing studies have led to the discovery of a variety of novel diagnostic biomarkers and therapeutic targets. Here, we review recent advances in cancer genomics and discuss what the new findings have taught us about cancer biology and, more importantly, how these new findings guide more effective diagnostic and treatment strategies.
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Annual review of medicine · Jan 2013
ReviewThe need for lymph node dissection in nonmetastatic breast cancer.
Determining whether cancer has spread to locoregional lymph nodes is a critical step in the initial staging of breast cancer patients. Although axillary dissection reliably identifies nodal metastases and prevents the recurrence of cancer in the axilla, there is a significant incidence of long-term side effects, notably lymphedema, and the procedure is of no therapeutic benefit in women without axillary metastases. ⋯ Recent clinical trials suggest that for women with metastases to 1 or 2 sentinel nodes, the radiation and systemic therapy that are part of modern multimodality breast cancer treatment can replace axillary dissection when breast-conserving therapy is undertaken. For those with greater disease burden or those undergoing mastectomy, axillary dissection remains standard management.
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Annual review of medicine · Jan 2013
ReviewMolecular mechanisms in progressive idiopathic pulmonary fibrosis.
There is clear evidence that environmental exposures and genetic predisposition contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cigarette smoking increases the risk of developing IPF several-fold, as do other exposures such as metal-fume and wood-dust exposure. Occupations that increase the risk of IPF are agricultural work, hairdressing, and stone polishing, supporting the role of environmental exposure in disease pathogenesis. ⋯ Mutations in surfactant proteins lead to pulmonary fibrosis and are associated with endoplasmic reticulum stress in alveolar type II epithelial cells. Mutations in telomerase have been found in several families with IPF, and shortened telomeres are found in sporadic cases of IPF. A common variant in mucin 5B predisposes to both familial and sporadic IPF and is present in the majority of cases, indicating sporadic IPF occurs in those with genetic predisposition.