Showing papers by "Vanderbilt University published in 2017"
University of Texas Health Science Center at Houston1, University of South Florida2, Washington University in St. Louis3, University of Miami4, Stanford University5, Harvard University6, Yeshiva University7, Vanderbilt University8, City of Hope National Medical Center9, Mayo Clinic10, University of California, Los Angeles11, Loyola University Chicago12, University of Rochester13, Sarah Cannon Research Institute14, Rutgers University15, Cleveland Clinic16, Wayne State University17, University of Iowa18, University of Texas MD Anderson Cancer Center19, Tel Aviv University20, University of California, San Diego21
TL;DR: Patients with refractory large B‐cell lymphoma who received CAR T‐cell therapy with axi‐cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events.
Abstract: BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%)....
3,363 citations
St George’s University Hospitals NHS Foundation Trust1, New York University2, McMaster University3, Brown University4, Catholic University of the Sacred Heart5, Autonomous University of Barcelona6, University of Manitoba7, Emory University8, Hebrew University of Jerusalem9, University of Toronto10, University of Pittsburgh11, St Thomas' Hospital12, University College London13, Vanderbilt University14, Keio University15, Memorial Hospital of South Bend16, Rowan University17, University of Mississippi18, Rush University Medical Center19, University of Ulsan20, Universidade Federal do Rio Grande do Sul21, Federal University of São Paulo22, Regions Hospital23, Washington University in St. Louis24, University of Ottawa25, University of Sydney26, University of New South Wales27, Fujita Health University28, University of Copenhagen29, Sapienza University of Rome30, Christiana Care Health System31, Stanford University32, King Abdullah University of Science and Technology33, University of Kansas34, Harvard University35, California Pacific Medical Center36, University of Amsterdam37, Université libre de Bruxelles38, Houston Methodist Hospital39
TL;DR: A consensus committee of 55 international experts representing 25 international organizations was assembled at key international meetings (forSurviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012 as discussed by the authors ).
Abstract: Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for
2,414 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, NorthShore University HealthSystem3, University of Michigan4, Boston University5, University of Missouri–Kansas City6, University of Maryland, Baltimore7, University of Washington8, Oslo University Hospital9, University of Zurich10, University of North Carolina at Chapel Hill11, Harvard University12, University of Toronto13, University at Buffalo14, University of Melbourne15, University of California, San Francisco16, Medical College of Wisconsin17, Boston Children's Hospital18, Princeton University19, Vanderbilt University Medical Center20, Vanderbilt University21, Toronto Western Hospital22
TL;DR: This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level, and provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC.
Abstract: The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement.
This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps.
A series of specific clinical questions were developed as part of the consensus process for the Berlin 2016 meeting. Each consensus question was the subject of a specific formal systematic review, which is published concurrently with this summary statement. Readers are directed to these background papers in conjunction with this summary statement as they provide the context for the issues and include the scope of published research, search strategy and citations reviewed for each question. This 2017 consensus statement also summarises each topic and recommendations in the context of all five CISG meetings (that is, 2001, 2004, 2008, 2012 as well as 2016). Approximately 60 000 published articles were screened by the expert panels for the Berlin …
2,388 citations
TL;DR: A meta-analysis of studies that have attempted to longitudinally predict a specific STB-related outcome suggests the need for a shift in focus from risk factors to machine learning-based risk algorithms.
Abstract: Suicidal thoughts and behaviors (STBs) are major public health problems that have not declined appreciably in several decades. One of the first steps to improving the prevention and treatment of STBs is to establish risk factors (i.e., longitudinal predictors). To provide a summary of current knowledge about risk factors, we conducted a meta-analysis of studies that have attempted to longitudinally predict a specific STB-related outcome. This included 365 studies (3,428 total risk factor effect sizes) from the past 50 years. The present random-effects meta-analysis produced several unexpected findings: across odds ratio, hazard ratio, and diagnostic accuracy analyses, prediction was only slightly better than chance for all outcomes; no broad category or subcategory accurately predicted far above chance levels; predictive ability has not improved across 50 years of research; studies rarely examined the combined effect of multiple risk factors; risk factors have been homogenous over time, with 5 broad categories accounting for nearly 80% of all risk factor tests; and the average study was nearly 10 years long, but longer studies did not produce better prediction. The homogeneity of existing research means that the present meta-analysis could only speak to STB risk factor associations within very narrow methodological limits-limits that have not allowed for tests that approximate most STB theories. The present meta-analysis accordingly highlights several fundamental changes needed in future studies. In particular, these findings suggest the need for a shift in focus from risk factors to machine learning-based risk algorithms. (PsycINFO Database Record
2,013 citations
University of South Florida1, University of Kentucky2, Cedars-Sinai Medical Center3, University of Texas MD Anderson Cancer Center4, Stanford University5, Harvard University6, University of Iowa7, Royal Free Hospital8, Mayo Clinic9, Katholieke Universiteit Leuven10, Northwestern University11, University of Cambridge12, Charité13, University of Barcelona14, Vanderbilt University15, Uppsala University16, Erasmus University Rotterdam17
TL;DR: Treatment with lutetium‐177 (177Lu)–Dotatate resulted in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors.
Abstract: BackgroundPatients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)–Dotatate in patients with advanced, progressive, somatostatin-receptor–positive midgut neuroendocrine tumors. MethodsWe randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-ef...
1,975 citations
Ohio State University1, Vanderbilt University2, Heidelberg University3, Iuliu Hațieganu University of Medicine and Pharmacy4, Duke University5, University of Lausanne6, Lehigh University7, McMaster University8, Fox Chase Cancer Center9, University of Texas at Austin10, Nemocnice Na Bulovce11, Bristol-Myers Squibb12
TL;DR: Nivolumab was not associated with significantly longer progression‐free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD‐L1 expression level of 5% or more.
Abstract: BackgroundNivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non–small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)–positive NSCLC. MethodsWe randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. ResultsAmong the 423 patients with a PD-L1 expression level of 5% or more, the media...
1,840 citations
University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, International Centre for Diarrhoeal Disease Research, Bangladesh11, Centers for Disease Control and Prevention12, Tribhuvan University13, University of Bergen14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Otago30, University of Auckland31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
1,470 citations
Michael R. Blanton1, Matthew A. Bershady2, Bela Abolfathi3, Franco D. Albareti4 +412 more•Institutions (91)
TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
1,200 citations
Kyriaki Michailidou1, Kyriaki Michailidou2, Sara Lindström3, Sara Lindström4 +393 more•Institutions (127)
TL;DR: A genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry finds that heritability of Breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome- wide average.
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
1,014 citations
Johns Hopkins University1, Seattle Cancer Care Alliance2, University of Colorado Boulder3, University of Utah4, Fox Chase Cancer Center5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of South Florida9, University of Alabama at Birmingham10, Washington University in St. Louis11, University of California, San Francisco12, Roswell Park Cancer Institute13, Vanderbilt University14, University of Texas MD Anderson Cancer Center15, Harvard University16, University of Wisconsin-Madison17, Yale Cancer Center18, University of Michigan19, Stanford University20, Ohio State University21, City of Hope National Medical Center22, Memorial Sloan Kettering Cancer Center23, Mayo Clinic24, Case Western Reserve University25, University Of Tennessee System26
TL;DR: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastasis disease.
Abstract: This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.
1,003 citations
TL;DR: This review focuses on recent findings and knowledge gaps in the area of EV biogenesis, release, and uptake and highlights examples whereby EV cargoes control basic cellular functions, including motility and polarization, immune responses, and development, and contribute to diseases such as cancer and neurodegeneration.
University of California, Los Angeles1, University of Utah2, University of South Florida3, University of Helsinki4, Primary Children's Hospital5, University of Groningen6, Norfolk and Norwich University Hospital7, Lund University8, Netherlands Cancer Institute9, University of Michigan10, Wake Forest University11, Ohio State University12, Peter MacCallum Cancer Centre13, University of Zurich14, University of Padua15, Pennsylvania State University16, Saint Louis University17, Tom Baker Cancer Centre18, University of Washington19, University of Lausanne20, Guy's and St Thomas' NHS Foundation Trust21, University of Kiel22, Thomas Jefferson University23, Sunnybrook Research Institute24, Vanderbilt University25, University of Queensland26, Fox Chase Cancer Center27, Greenville Health System28, Stony Brook University29, University Health Network30, Memorial Sloan Kettering Cancer Center31, Roswell Park Cancer Institute32, Northwestern University33, University of Wisconsin-Madison34, Rush University Medical Center35, Tel Aviv Sourasky Medical Center36, Dartmouth College37, Johns Hopkins University38, University of Louisville39, University of Barcelona40, University of Sydney41
TL;DR: Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases.
Abstract: BackgroundSentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. MethodsIn an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. ResultsImmediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in t...
TL;DR: An engineering strategy for stabilization of soluble S proteins in the prefusion conformation is described, which results in greatly increased expression, conformational homogeneity, and elicitation of potent antibody responses, and an engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV.
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.
TL;DR: In this mini review, the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM are outlined.
Abstract: Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.
Veterans Health Administration1, Monash University2, University of Florida3, Cincinnati Children's Hospital Medical Center4, Vanderbilt University5, University of Alberta6, University of California, San Diego7, University of New South Wales8, University of Pittsburgh9, Ghent University Hospital10, University of Chicago11, University of California, Berkeley12, University College Dublin13, University of Southern California14, University of Virginia15, University of Toronto16
TL;DR: The Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients, and makes recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
Abstract: Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
Massachusetts Institute of Technology1, University of Erlangen-Nuremberg2, Max Delbrück Center for Molecular Medicine3, Charité4, ETH Zurich5, University of Regensburg6, Dresden University of Technology7, University of Hasselt8, Robert Koch Institute9, Hannover Medical School10, National Institutes of Health11, Vanderbilt University12
TL;DR: This paper showed that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus, and treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T helper 17 (TH17) cells.
Abstract: A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH17) cells, which can also contribute to hypertension. Induction of TH17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased TH17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.
TL;DR: The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo, and directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates.
City of Hope National Medical Center1, American Society of Clinical Oncology2, MedStar Washington Hospital Center3, University of Pennsylvania4, University of Rochester5, University of Ottawa6, Duke University7, Ottawa Hospital8, University of Kansas9, Memorial Sloan Kettering Cancer Center10, Harvard University11, Vanderbilt University12, Mayo Clinic13
TL;DR: Recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers were developed by an expert panel with multidisciplinary representation using a systematic review of meta-analyses, randomized clinical trials, observational studies, and clinical experience.
Abstract: Purpose Cardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers. Methods Recommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology. Results A total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms. Recommendations It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.
TL;DR: Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity.
University of California, San Francisco1, Moffitt Cancer Center2, University of Michigan3, Mayo Clinic4, Roswell Park Cancer Institute5, University of Tennessee Health Science Center6, Northwestern University7, Washington University in St. Louis8, Vanderbilt University9, Yale Cancer Center10, Seattle Cancer Care Alliance11, City of Hope National Medical Center12, Duke University13, Ohio State University14, Fox Chase Cancer Center15, Harvard University16, Case Western Reserve University17, University of Texas MD Anderson Cancer Center18, Stanford University19, University of Wisconsin-Madison20, University of California, San Diego21, Pancreatic Cancer Action Network22, Memorial Sloan Kettering Cancer Center23, University of Alabama at Birmingham24, University of Utah25, University of Colorado Boulder26, Dana Corporation27
TL;DR: The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection, as well as on management of locally advanced unresectable and metastatic disease.
Abstract: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
Duke University1, University of Helsinki2, University of Copenhagen3, University of Nebraska Medical Center4, University of North Carolina at Chapel Hill5, Emory University6, Queen Mary University of London7, Indiana University – Purdue University Indianapolis8, Cleveland Clinic9, University of Hong Kong10, Tufts University11, Tata Memorial Hospital12, Vanderbilt University13, University of Texas MD Anderson Cancer Center14, Columbia University15, Northwestern University16, National Institutes of Health17
TL;DR: An integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of DLBCL patients is performed to comprehensively define the landscape of 150 genetic drivers of the disease and their functional roles to identify new therapeutic opportunities in the disease.
University of Toronto1, University of Düsseldorf2, German Cancer Research Center3, University of Pittsburgh4, Ontario Institute for Cancer Research5, Seoul National University6, University of Warsaw7, University of Lyon8, Mayo Clinic9, The Chinese University of Hong Kong10, Johns Hopkins University11, University of Alabama at Birmingham12, Fred Hutchinson Cancer Research Center13, University of Washington14, University of California, San Francisco15, Hamilton Health Sciences16, McMaster University17, Vanderbilt University18, University of Colorado Denver19, Semmelweis University20, Erasmus University Rotterdam21, University of Ulsan22, Kitasato University23, Mexican Social Security Institute24, Masaryk University25, Emory University26, University of Debrecen27, University of Naples Federico II28, Washington University in St. Louis29, McGill University30, Montreal Children's Hospital31, Virginia Commonwealth University32, Chonnam National University33, University of Queensland34, University of Calgary35, University of São Paulo36, University of Cincinnati37, University of Arkansas for Medical Sciences38, The Catholic University of America39, University of California, Los Angeles40, University of Sydney41, Kumamoto University42, Saint Louis University43, Case Western Reserve University44
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.
TL;DR: A fully-fledged particle-flow reconstruction algorithm tuned to the CMS detector was developed and has been consistently used in physics analyses for the first time at a hadron collider as mentioned in this paper.
Abstract: The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer. A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider. For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification. This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods. The data collected by CMS at a centre-of-mass energy of 8\TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.
The Centre for Applied Genomics1, Google2, University of Toronto3, McGill University4, University of Alberta5, McMaster University6, Dalhousie University7, Queen's University8, University of Western Ontario9, Autism Speaks10, University of Illinois at Chicago11, University of Washington12, Trinity College, Dublin13, Vanderbilt University14, Newcastle University15, Boston Children's Hospital16, Utrecht University17, University of California, San Diego18, Memorial University of Newfoundland19, Children's Hospital of Eastern Ontario20, Stanford University21, Centre for Addiction and Mental Health22, Drexel University23
TL;DR: Se sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal that identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability.
Abstract: We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.
Vanderbilt University1, Sarah Cannon Research Institute2, University of Chicago3, Duke University4, Heidelberg University5, Russian Academy6, Fox Chase Cancer Center7, Autonomous University of Barcelona8, Curie Institute9, City of Hope National Medical Center10, Bosch11, Aix-Marseille University12, University of South Florida13, Memorial Sloan Kettering Cancer Center14, Bristol-Myers Squibb15, Johns Hopkins University16, University of Duisburg-Essen17
TL;DR: Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC and is reported on in a pooled analysis of the two studies.
Abstract: PurposeNivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non–small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies.MethodsPatients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks). Minimum follow-up for survival was 24.2 months.ResultsTwo-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death w...
Oregon Health & Science University1, Emory University2, Centers for Disease Control and Prevention3, University of Colorado Denver4, California Department of Public Health5, Foundation for Innovative New Diagnostics6, McGill University7, University of Southampton8, Vanderbilt University9, University of Arkansas for Medical Sciences10
TL;DR: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided and six of the recommendations are strong, whereas the remaining 17 are conditional.
Abstract: Background Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. Methods A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. Conclusions These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
TL;DR: Findings indicate that the broad domain of emotion regulation and adaptive coping and the factors of primary control coping and secondary control coping are related to lower levels of symptoms of psychopathology.
Abstract: In this meta-analytic and narrative review, we examine several overarching issues related to the study of coping, emotion regulation, and internalizing and externalizing symptoms of psychopathology in childhood and adolescence, including the conceptualization and measurement of these constructs. We report a quantitative meta-analysis of 212 studies (N = 80,850 participants) that measured the associations between coping and emotion regulation with symptoms of internalizing and externalizing psychopathology. Within the meta-analysis we address the association of broad domains of coping and emotion regulation (e.g., total coping, emotion regulation), intermediate factors of coping and emotion regulation (e.g., primary control coping, secondary control coping), and specific coping and emotion regulation strategies (e.g., emotional expression, cognitive reappraisal) with internalizing and externalizing symptoms. For cross-sectional studies, which made up the majority of studies included, we examine 3 potential moderators: age, measure quality, and single versus multiple informants. Finally, we separately consider findings from longitudinal studies as these provide stronger tests of the effects. After accounting for publication bias, findings indicate that the broad domain of emotion regulation and adaptive coping and the factors of primary control coping and secondary control coping are related to lower levels of symptoms of psychopathology. Further, the domain of maladaptive coping, the factor of disengagement coping, and the strategies of emotional suppression, avoidance, and denial are related to higher levels of symptoms of psychopathology. Finally, we offer a critique of the current state of the field and outline an agenda for future research. (PsycINFO Database Record
TL;DR: There is some evidence that the teenage years, particularly high school, might be the most vulnerable time period for having persistent symptoms—with greater risk for girls than boys.
Abstract: Objective A systematic review of factors that might be associated with, or influence, clinical recovery from sport-related concussion. Clinical recovery was defined functionally as a return to normal activities, including school and sports, following injury. Design Systematic review. Data sources PubMed, PsycINFO, MEDLINE, CINAHL, Cochrane Library, EMBASE, SPORTDiscus, Scopus and Web of Science. Eligibility criteria for selecting studies Studies published by June of 2016 that addressed clinical recovery from concussion. Results A total of 7617 articles were identified using the search strategy, and 101 articles were included. There are major methodological differences across the studies. Many different clinical outcomes were measured, such as symptoms, cognition, balance, return to school and return to sports, although symptom outcomes were the most frequently measured. The most consistent predictor of slower recovery from concussion is the severity of a person’s acute and subacute symptoms. The development of subacute problems with headaches or depression is likely a risk factor for persistent symptoms lasting greater than a month. Those with a preinjury history of mental health problems appear to be at greater risk for having persistent symptoms. Those with attention deficit hyperactivity disorder (ADHD) or learning disabilities do not appear to be at substantially greater risk. There is some evidence that the teenage years, particularly high school, might be the most vulnerable time period for having persistent symptoms—with greater risk for girls than boys. Conclusion The literature on clinical recovery from sport-related concussion has grown dramatically, is mostly mixed, but some factors have emerged as being related to outcome.
Fox Chase Cancer Center1, Ohio State University2, University of Tennessee Health Science Center3, University of Utah4, University of Alabama5, Brigham and Women's Hospital6, Duke University7, Northwestern University8, University of Colorado Boulder9, Stanford University10, University of Texas MD Anderson Cancer Center11, University of California, San Diego12, University of Michigan13, Memorial Sloan Kettering Cancer Center14, Moffitt Cancer Center15, Harvard University16, University of Washington17, Case Western Reserve University18, Roswell Park Cancer Institute19, City of Hope National Medical Center20, Mayo Clinic21, Vanderbilt University22, National Comprehensive Cancer Network23
TL;DR: The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
Abstract: The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
University of Calgary1, Florey Institute of Neuroscience and Mental Health2, Princeton University3, Rutgers University4, University at Buffalo5, La Trobe University6, University of Otago7, University of Michigan8, University of Ottawa9, Medical College of Wisconsin10, Vanderbilt University11, University College Hospital12, University of Sheffield13, University of Washington14, University of North Carolina at Chapel Hill15
TL;DR: This paper presents the Sport Concussion Assessment Tool 5th Edition (SCAT5), which is the most recent revision of a sport concussion evaluation tool for use by healthcare professionals in the acute evaluation of suspected concussion.
Abstract: This paper presents the Sport Concussion Assessment Tool 5th Edition (SCAT5), which is the most recent revision of a sport concussion evaluation tool for use by healthcare professionals in the acute evaluation of suspected concussion. The revision of the SCAT3 (first published in 2013) culminated in the SCAT5. The revision was based on a systematic review and synthesis of current research, public input and expert panel review as part of the 5th International Consensus Conference on Concussion in Sport held in Berlin in 2016. The SCAT5 is intended for use in those who are 13 years of age or older. The Child SCAT5 is a tool for those aged 5–12 years, which is discussed elsewhere.