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This commentary was written as a collaboration between the Board of the Metastasis Research Society and two patients with metastatic breast cancer. It was conceived in response to how preclinical scientific research is sometimes presented to non-scientists in a way that can cause stress and confusion. Translation of preclinical findings to the clinic requires overcoming multiple barriers. This is irrespective of whether the findings relate to exciting responses to new therapies or problematic effects of currently used therapies. It is important that these barriers are understood and acknowledged when research findings are summarized for mainstream reporting. To minimize confusion, patients should continue to rely on their oncology care team to help them interpret whether research findings presented in mainstream media have relevance for their individual care. Researchers, both bench and clinical, should work together where possible to increase options for patients with metastatic disease, which is still in desperate need of effective therapeutic approaches.
Hypertension is a global epidemic affecting over one billion people worldwide. Despite this, the etiology of most cases of human hypertension remains obscure, and treatment remains suboptimal. Excessive dietary salt and inflammation are known contributors to the pathogenesis of this disease. Recently, it has been recognized that salt can accumulate in the skin and skeletal muscle, producing concentrations of sodium greater than the plasma in hypertensive animals and humans. Such elevated levels of sodium have been shown to alter immune cell function. Here, we propose a model in which tissue salt accumulation causes an immune response leading to renal and vascular inflammation and hypertension.
Copyright © 2017 the American Physiological Society.
CONTEXT - - ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.
OBJECTIVES - - To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.
DESIGN - - The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.
RESULTS - - The panel is proposing 11 recommendations with strong agreement from the open-comment participants.
RECOMMENDATIONS - - The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.
CONCLUSIONS - - This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.
Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.
Copyright ©ERS 2015.
BACKGROUND - Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear.
METHODS - We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients.
RESULTS - The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8).
CONCLUSIONS - Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
BACKGROUND - With the use of the framework advocated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, our aims were to perform a systematic review and to develop evidence-based recommendations that may be used to answer the following PICO [Population, Intervention, Comparator, Outcomes] question:In the obtunded adult blunt trauma patient, should cervical collar removal be performed after a negative high-quality cervical spine (C-spine) computed tomography (CT) result alone or after a negative high-quality C-spine CT result combined with adjunct imaging, to reduce peri-clearance events, such as new neurologic change, unstable C-spine injury, stable C-spine injury, need for post-clearance imaging, false-negative CT imaging result on re-review, pressure ulcers, and time to cervical collar clearance?
METHODS - Our protocol was registered with the PROSPERO international prospective register of systematic reviews on August 23, 2013 (REGISTRATION NUMBER: CRD42013005461). Eligibility criteria consisted of adult blunt trauma patients 16 years or older, who underwent C-spine CT with axial thickness of less than 3 mm and who were obtunded using any definition.Quantitative synthesis via meta-analysis was not possible because of pre-post, partial-cohort, quasi-experimental study design limitations and the consequential incomplete diagnostic accuracy data.
RESULTS - Of five articles with a total follow-up of 1,017 included subjects, none reported new neurologic changes (paraplegia or quadriplegia) after cervical collar removal. There is a worst-case 9% (161 of 1,718 subjects in 11 studies) cumulative literature incidence of stable injuries and a 91% negative predictive value of no injury, after coupling a negative high-quality C-spine CT result with 1.5-T magnetic resonance imaging, upright x-rays, flexion-extension CT, and/or clinical follow-up. Similarly, there is a best-case 0% (0 of 1,718 subjects in 11 studies) cumulative literature incidence of unstable injuries after negative initial imaging result with a high-quality C-spine CT.
CONCLUSION - In obtunded adult blunt trauma patients, we conditionally recommend cervical collar removal after a negative high-quality C-spine CT scan result alone.
LEVEL OF EVIDENCE - Systematic review, level III.
UNLABELLED - Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment.
PERSPECTIVE - The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.
Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.