Institution
University of Colorado Denver
Education•Denver, Colorado, United States•
About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.
Topics: Population, Poison control, Health care, Diabetes mellitus, Cancer
Papers published on a yearly basis
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Seoul National University Hospital1, Fox Chase Cancer Center2, University of Barcelona3, University of Washington4, University of Colorado Denver5, Katholieke Universiteit Leuven6, Huntsman Cancer Institute7, Memorial Sloan Kettering Cancer Center8, Peter MacCallum Cancer Centre9, University Hospital Heidelberg10, University of Duisburg-Essen11, Princess Margaret Cancer Centre12, Novartis13, Harvard University14
TL;DR: The secondary outcomes of overall response, duration of response, and progression-free survival were analysed in all patients who received at least one 750 mg dose of ceritinib, and the maximum tolerated dose has been reported previously.
Abstract: Summary Background ALK -rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood–brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK -rearranged NSCLC. Methods ASCEND-1 was an open-label, phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe, North America, and Asia-Pacific. Eligible patients were aged 18 years or older with ALK -rearranged locally advanced or metastatic cancer that had progressed despite standard therapy (or for which no effective standard therapy existed), who had at least one measurable lesion at baseline. The primary objective (to determine the maximum tolerated dose) has been reported previously. This updated analysis includes all patients with ALK -rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/day in the dose-escalation and expansion phases. Here we report the secondary outcomes of overall response, duration of response, and progression-free survival, analysed in all patients who received at least one 750 mg dose of ceritinib. Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists, in patients with untreated or locally treated neurologically stable brain metastases at baseline. Safety was assessed in all patients who received at least one dose of ceritinib. This study is no longer recruiting patients; however, treatment and follow-up are ongoing. This study is registered with ClinicalTrials.gov, number NCT01283516. Findings Between Jan 24, 2011, and July 31, 2013, 255 patients were enrolled and received at least one dose of ceritinib 750 mg/day, of whom 246 had ALK -rearranged NSCLC. At data cutoff (April 14, 2014), median follow-up was 11·1 months (IQR 6·7–15·2) and 147 (60%) patients had discontinued treatment, 98 (40%) as a result of disease progression. An overall response was reported in 60 (72% [95% CI 61–82]) of 83 ALK inhibitor-naive patients and 92 (56% [49–64]) of 163 ALK inhibitor-pretreated patients. Median duration of response was 17·0 months (95% CI 11·3–non-estimable [NE]) in ALK inhibitor-naive patients and 8·3 months (6·8–9·7) in ALK inhibitor-pretreated patients. Median progression-free survival was 18·4 months (95% CI 11·1–NE) in ALK inhibitor-naive patients and 6·9 months (5·6–8·7) in ALK inhibitor-pretreated patients. Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment, intracranial disease control was reported in 15 (79% [95% CI 54–94]) of 19 ALK inhibitor-naive patients and in 49 (65% [54–76]) of 75 ALK inhibitor-pretreated patients. Of these 94 patients, 11 had measurable brain lesions and no previous radiotherapy to the brain, six of whom achieved a partial intracranial response. Serious adverse events were recorded in 117 (48%) of 246 patients. The most common grade 3–4 laboratory abnormalities were increased alanine aminotransferase (73 [30%] patients) and increased aspartate aminotransferase (25 [10%]). The most common grade 3–4 non-laboratory adverse events were diarrhoea and nausea, both of which occurred in 15 (6%) patients. Two on-treatment deaths during the study were deemed to be related to study drug by the investigators, one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis. Interpretation The durable whole-body responses reported, together with the intracranial activity, support a clinical benefit for treatment with ceritinib in patients with ALK -rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib. A confirmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK -rearranged NSCLC and brain or leptomeningeal metastases. Funding Novartis Pharmaceuticals Corporation.
403 citations
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TL;DR: This practice guideline/guidance constitutes an update of the guidelines on AIH published in 2010 by the American Association for the Study of Liver Diseases (AASLD) and updates the epidemiology, diagnosis, management, and outcomes of AIH in adults and children.
402 citations
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Emory University1, Johns Hopkins University2, Temple University3, University of Utah4, Swiss Institute of Allergy and Asthma Research5, University of Chicago6, Ghent University7, Humanitas University8, Eskişehir Osmangazi University9, Imperial College London10, University of California, San Diego11, University of North Carolina at Chapel Hill12, Rutgers University13, University of Amsterdam14, University of Missouri15, University of Texas Southwestern Medical Center16, Aarhus University17, Hannover Medical School18, Case Western Reserve University19, Stanford University20, Harvard University21, University of Turku22, University of Colorado Boulder23, University of Texas at Austin24, San Antonio Military Medical Center25, University of Pittsburgh26, University of Texas Health Science Center at Houston27, Ochsner Health System28, Uniformed Services University of the Health Sciences29, Karolinska Institutet30, Wake Forest University31, University of Pavia32, University of Barcelona33, University of Colorado Denver34, Loyola University Chicago35, Nippon Medical School36, Heidelberg University37, Boston University38, Cornell University39, University of Calgary40, Medical University of South Carolina41, Brown University42, George Washington University43, University of Edinburgh44, Oregon Health & Science University45, Mahidol University46, National University of Singapore47, University of Michigan48
TL;DR: To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).
Abstract: BACKGROUND:
Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).
METHODS:
Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.
RESULTS:
The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.
CONCLUSION:
This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
401 citations
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TL;DR: ROS1 inhibition may be an effective treatment strategy for the subset of patients with NSCLC whose tumors express ROS1 fusion genes, and this patient showed tumor shrinkage upon treatment with crizotinib.
Abstract: Purpose: Oncogenic gene fusions involving the 3′ region of ROS1 kinase have been identified in various human cancers. In this study, we sought to characterize ROS1 fusion genes in non–small cell lung cancer (NSCLC) and establish the fusion proteins as drug targets. Experimental Design: An NSCLC tissue microarray (TMA) panel containing 447 samples was screened for ROS1 rearrangement by FISH. This assay was also used to screen patients with NSCLC. In positive samples, the identity of the fusion partner was determined through inverse PCR and reverse transcriptase PCR. In addition, the clinical efficacy of ROS1 inhibition was assessed by treating a ROS1-positive patient with crizotinib. The HCC78 cell line, which expresses the SLC34A2–ROS1 fusion, was treated with kinase inhibitors that have activity against ROS1. The effects of ROS1 inhibition on proliferation, cell-cycle progression, and cell signaling pathways were analyzed by MTS assay, flow cytometry, and Western blotting. Results: In the TMA panel, 5 of 428 (1.2%) evaluable samples were found to be positive for ROS1 rearrangement. In addition, 1 of 48 patients tested positive for rearrangement, and this patient showed tumor shrinkage upon treatment with crizotinib. The patient and one TMA sample displayed expression of the recently identified SDC4–ROS1 fusion, whereas two TMA samples expressed the CD74–ROS1 fusion and two others expressed the SLC34A2–ROS1 fusion. In HCC78 cells, treatment with ROS1 inhibitors was antiproliferative and downregulated signaling pathways that are critical for growth and survival. Conclusions: ROS1 inhibition may be an effective treatment strategy for the subset of patients with NSCLC whose tumors express ROS1 fusion genes. Clin Cancer Res; 18(17); 4570–9. ©2012 AACR .
401 citations
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TL;DR: The GWTG-HF risk score provides clinicians with a validated tool for risk stratification that is applicable to a broad spectrum of patients with heart failure, including those with preserved left ventricular systolic function.
Abstract: Background— Effective risk stratification can inform clinical decision-making. Our objective was to derive and validate a risk score for in-hospital mortality in patients hospitalized with heart fa...
401 citations
Authors
Showing all 27683 results
Name | H-index | Papers | Citations |
---|---|---|---|
Matthew Meyerson | 194 | 553 | 243726 |
Charles A. Dinarello | 190 | 1058 | 139668 |
Gad Getz | 189 | 520 | 247560 |
Gordon B. Mills | 187 | 1273 | 186451 |
Jasvinder A. Singh | 176 | 2382 | 223370 |
David Haussler | 172 | 488 | 224960 |
Donald G. Truhlar | 165 | 1518 | 157965 |
Charles M. Perou | 156 | 573 | 202951 |
David Cella | 156 | 1258 | 106402 |
Bruce D. Walker | 155 | 779 | 86020 |
Marco A. Marra | 153 | 620 | 184684 |
Thomas E. Starzl | 150 | 1625 | 91704 |
Marc Humbert | 149 | 1184 | 100577 |
Rajesh Kumar | 149 | 4439 | 140830 |
Martin J. Blaser | 147 | 820 | 104104 |