tbuckley/cabot-search huggingface dataset:
Nivolumab versus ipilimumab in the treatment of advanced melanoma: a critical appraisal
Authors: M.T. Wan, M.E. Ming
Journal: British Journal of Dermatology (2018)

To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression‐free survival (PFS) in adults with previously untreated, advanced melanoma. The trial was conducted at 137 sites in 21 countries. Randomization (n =945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status. Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo. Treatment was continued until progression, unacceptable toxicity or withdrawal. OS, PFS and objective response rate were determined. Patients were also assessed for adverse events. The primary end points of interest were OS and PFS, comparing either the nivolumab plus ipilimumab group or the nivolumab‐only group with the patients treated with ipilimumab only. At 3 years, the OS rates were 58%, 52% and 34% for the nivolumab plus ipilimumab, the nivolumab monotherapy and the ipilimumab monotherapy groups, respectively. For the nivolumab plus ipilimumab group, the median OS was not reached at the time of analysis. For the nivolumab‐only group, the median OS was 37·6 months, and the ipilimumab‐only group had a median OS of 19·9 months. The hazard ratio for death was 0·55 [95% confidence interval (CI) 0·45–0·69; P <0·001] comparing nivolumab plus ipilimumab with ipilimumab, and 0·65 (95% CI 0·53–0·80; P <0·001) comparing nivolumab with ipilimumab. The PFS rates at 3 years were 39% for the nivolumab plus ipilimumab group, 32% for the nivolumab monotherapy group and 10% for the ipilimumab monotherapy group, with 95% CIs for the two nivolumab groups that did not overlap with that for ipilimumab alone. Among patients with advanced melanoma, significantly longer OS and PFS occurred with the combination of nivolumab plus ipilimumab or with nivolumab alone compared with ipilimumab alone. Furthermore, survival outcomes favoured the nivolumab‐containing groups over the ipilimumab group in subgroup analyses.
Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA
Authors: S. Claiborne Johnston, J. Donald Easton, Mary Farrant, William Barsan, Robin A. Conwit, Jordan J. Elm, Anthony S. Kim, Anne S. Lindblad, Yuko Y. Palesch
Journal: New England Journal of Medicine (2018)

Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population.In a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days.A total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02).In patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone. (Funded by the National Institute of Neurological Disorders and Stroke; POINT ClinicalTrials.gov number, NCT00991029 .).
Clinicopathologic characteristics and impact of oophorectomy for ovarian metastases (ovmets) in colorectal cancer (CRC).
Authors: Carling Jade Ursem, Margaret Zhou, Alan T Paciorek, Chloe Evelyn Atreya, Andrew H. Ko, Li Zhang, Katherine Van Loon
Journal: Journal of Clinical Oncology (2018)

779 Background: As overall survival (OS) with metastatic colorectal cancer (mCRC) and imaging modalities improve, detection of ovmets may be increasing. The ovary is often a sanctuary site for mCRC; however, there is a paucity of data to guide decision-making regarding the role for oophorectomy. Methods: This is a single-institution retrospective review of patients (pts) who received care for mCRC (incl. appendiceal primaries) with ovmets from 2009-2017. Pts were identified through a hospital-based cancer registry, provider recall, and pathology and radiology databases. Clinicopathologic and treatment data were abstracted. Cox proportional hazards models were used to evaluate for associations with OS. Results: Of 108 pts, median age was 50 (range 19-106), 62 (57%) were Caucasian, and 69 (64%) had ovmets at initial CRC diagnosis. Primary tumor location was left-sided in 54 (50%), right-sided in 27 (25%), appendiceal in 18 (17%), and unknown in 9 (8%). Median OS from diagnosis of mCRC was 29.6 months (mo) with median follow-up of 21.9 mo (range 0.77-172.47). Younger age, absence of signet-ring or mucinous features, well/moderately differentiated grade, and resection of primary tumor were associated with improved OS (p &lt; 0.05). Of 83 (76%) pts who underwent oophorectomy median OS was 36.7 mo vs. 25 mo in those who underwent non-operative management (HR 0.54, 95% CI 0.31-0.94, p = 0.03). Among 94 pts with extra-ovarian disease, 70 (74%) underwent oophorectomy; however, no significant difference in median OS was detected vs. those who did not (30.9 vs 25.0 mo, p = 0.07). In a multivariate model, oophorectomy was not associated with OS (HR 0.63, 95% CI 0.29-1.36, p = 0.24). Conclusions: While ovmets have been previously reported as associated with a poor prognosis, the median OS for this cohort was comparable to existing OS data for mCRC pts. Although oophorectomy for ovmets from mCRC was associated with improved OS in univariate analysis, this effect was not significant in the presence of extra-ovarian metastases. Ovmets from mCRC remain a difficult challenge in clinical care. Oophorectomy may improve OS in select cases; however, further evaluation of predictors of benefit is needed.
Abstract A50: Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells in vivo and in vitro
Authors: Hong Fan, Zheng Sun
Journal: Cancer Research (2018)

Abstract Oral squamous cell carcinoma (OSCC) is the most common epithelial cancer worldwide. Despite improvements and innovations in diagnostic techniques and treatments, the survival rate of patients with oral cancer has not increased. We previously demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a vital role in OSCC. However, the underlying mechanism of Nrf2 is unclear in OSCC. This study aimed to clarify the mechanism of Nrf2 regulating the tumorigenesis and progression of OSCC in vivo and in vitro. We confirmed that overexpression of Nrf2 promotes cell growth, migration, invasion, and colony formation in established stable Nrf2 overexpression OSCC cell lines. Quantitative real-time reverse transcription-PCR and Western blotting assays revealed that silencing the endogenous Nrf2 markedly reduced the expression levels of Notch1, the Notch1 intracellular domain (NICD1), and Hairy and enhancer of split-1 (Hes1) in OSCC cells. As expected, the transcriptional levels of Notch1 and Hes1 and the protein expression level of NICD1 and Hes1 were increased in Nrf2-overexpressing OSCC cell lines. In addition, we demonstrated that the expression of Notch1, NICD1 and Hes1were increased in the tongue tissues of 4NQO induced dysplasia and OSCC mouse model by immunohistochemistry, but their expression was lower in Nrf2-/- mice than in wild-type mice. In conclusion, Nrf2 may play a role in promoting cancer through regulating the Notch signaling pathways in oral cancer in vivo and in vitro. Citation Format: Hong Fan, Zheng Sun. Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells in vivo and in vitro [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A50.
Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error
Authors: Milly S. Tedja, Robert Wojciechowski, Pirro G. Hysi, Nicholas Eriksson, Nicholas A. Furlotte, Virginie J. M. Verhoeven, Adriana I. Iglesias, Magda A. Meester-Smoor, Stuart W. Tompson, Qiao Fan, Anthony P. Khawaja, Ching-Yu Cheng, René Höhn, Kenji Yamashiro, Adam Wenocur, Clare Grazal, Toomas Haller, Andres Metspalu, Juho Wedenoja, Jost B. Jonas, Ya Xing Wang, Jing Xie, Paul Mitchell, Paul J. Foster, Barbara E. K. Klein, Ronald Klein, Andrew D. Paterson, S. Mohsen Hosseini, Rupal L. Shah, Cathy Williams, Yik Ying Teo, Yih Chung Tham, Preeti Gupta, Wanting Zhao, Yuan Shi, Woei-Yuh Saw, E-Shyong Tai, Xue Ling Sim, Jennifer E. Huffman, Ozren Polašek, Caroline Hayward, Goran Bencic, Igor Rudan, James F. Wilson, Peter K. Joshi, Akitaka Tsujikawa, Fumihiko Matsuda, Kristina N. Whisenhunt, Tanja Zeller, Peter J. van der Spek, Roxanna Haak, Hanne Meijers-Heijboer, Elisabeth M. van Leeuwen, Sudha K. Iyengar, Jonathan H. Lass, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Johannes R. Vingerling, Terho Lehtimäki, Olli T. Raitakari, Ginevra Biino, Maria Pina Concas, Tae-Hwi Schwantes-An, Robert P. Igo, Gabriel Cuellar-Partida, Nicholas G. Martin, Jamie E. Craig, Puya Gharahkhani, Katie M. Williams, Abhishek Nag, Jugnoo S. Rahi, Phillippa M. Cumberland, Cécile Delcourt, Céline Bellenguez, Janina S. Ried, Arthur A. Bergen, Thomas Meitinger, Christian Gieger, Tien Yin Wong, Alex W. Hewitt, David A. Mackey, Claire L. Simpson, Norbert Pfeiffer, Olavi Pärssinen, Paul N. Baird, Veronique Vitart, Najaf Amin, Cornelia M. van Duijn, Joan E. Bailey-Wilson, Terri L. Young, Seang-Mei Saw, Dwight Stambolian, Stuart MacGregor, Jeremy A. Guggenheim, Joyce Y. Tung, Christopher J. Hammond, Caroline C. W. Klaver
Journal: Nature Genetics (2018)
Sugar in food: critics urge tougher regulation as industry fails to meet reduction target
Authors: Jacqui Wise
Journal: BMJ (2018)

Retailers and manufacturers have managed to cut sugar in foodstuffs by only 2% in the first year of the government’s voluntary reduction programme, failing to meet the 5% target.

The slow progress has been criticised by academics and campaigners, who say that change will come about only by regulation. Public Health England, however, branded it an encouraging start,1 adding that more sugar reduction plans that had not been included in its analysis were in the pipeline.

In 2016 the government published its childhood obesity plan for England, which challenged the food industry to cut 20% of sugar from a range of products by 2020, including 5% in the first year.2 The plan was roundly condemned by doctors’ leaders, …
Abstract 12708: Adherence to Healthy Lifestyle and Cardiovascular Diseases in Chinese
Authors: Lu Qi, Jun Lv, Canqing Yu, Yu Guo, Zheng Bian, Ling Yang, Yiping Chen, Xuefeng Tang, Weiyuan Zhang, Yijian Qian, Yuelong Huang, Xiaoping Wang, Junshi Chen, Zhengming Chen, Liming Li
Journal: Circulation (2016)

Introduction: Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in non-white populations. Methods: We examined the associations of six lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants aged 30-79 years without cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as non-smoking or having stopped for reasons other than illness, alcohol consumption of &lt;30 g/day, median or higher level of physical activity, diet rich in vegetables and fruits and low in red meat, body mass index of 18.5-23.9 kg/m 2 , and waist-to-hip ratio &lt;0.90 for men and &lt;0.85 for women. Results: During a median of 7.2 years of follow-up, we documented 3,331 incident major coronary events (MCE) and 19,348 incident IS. In multivariable-adjusted analyses, current non-smoking, light-to-moderate alcohol, high physical activity, diet rich in vegetables and fruits and low in red meat, and low adiposity were independently associated with reduced risks of MCE and IS. Compared with participants without any low-risk factors, the hazard ratio (95% confidence interval) for those with ≥5 low-risk factors was 0.37 (0.16, 0.84) for MCE and 0.50 (0.40, 0.64) for IS. Approximately 60.8% (33.4%, 78.8%) of the MCE and 29.3% (17.6%, 40.1%) of the IS were attributable to poor adherence to healthy lifestyle. Conclusions: Our data indicate that adherence to healthy lifestyle may substantially lower the burden of cardiovascular diseases in Chinese.
Rheumatology 4.0: big data, wearables and diagnosis by computer
Authors: Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2018)

> We must dare to think ‘unthinkable’ thoughts. We must learn to explore all the options and possibilities that confront us in a complex and rapidly changing world. J. William Fulbright, US Politician. 9 April 1905–9 February 1995

> Nothing is unthinkable, nothing impossible to the balanced person, provided it comes out of the needs of life and is dedicated to life’s further development. Lewis Mumford, US historian, sociologist, philosopher and literary critic. 19 October 1895–26 January 1990

Let’s jump into the future, about 10 years from now. Sandy Myers (fictional name) is a 44-year-old female IT specialist. She is suffering from joint pain, morning stiffness, swollen finger joints and toes, as well as fatigue since 4 months. What should she do now? You would say, she should see rheumatologist as soon as possible and attend an early arthritis clinic. But will we have enough rheumatologists in 10 years, will this be common practice? Instead, she walks into the living room in the morning and addresses Alessia (fictional name), her cloud-based voice service machine. She tells Alessia about her health problems, and the machine takes a detailed history asking her several questions, which have been elaborated by a EULAR initiative (EULAR recommendations on core rheumatology questions in cloud-based voice service. Annals of the Rheumatic Diseases 2025): how can I help you?, where do you have your pain?, is it more pronounced in the morning?, do non-steroidals help?, do you feel like having an influenza? and some others. The answers are entered online into a structured patient history databank.

Sandy is now asked by Alessia to perform a self-examination that is helped by a large screen on her living room wall. Showing examples of diseased joints and with the help of animated pictures, Sandy examines her painful joints and records if they are swollen. This is …
Prognostic value of cardiovascular parameters in computed tomography pulmonary angiography in patients with acute pulmonary embolism
Authors: Ludo F.M. Beenen, Patrick M.M. Bossuyt, Jaap Stoker, Saskia Middeldorp
Journal: European Respiratory Journal (2018)

The value of various computed tomography parameters for prognosis and risk stratification in acute pulmonary embolism is controversial. Our objective was to evaluate the impact of specific cardiovascular computed tomography pulmonary angiography parameters on short- and long-term clinical outcomes. We analysed radiological and clinical data of 1950 patients with acute pulmonary embolism who participated in an international randomised clinical trial on anticoagulants. Parameters included right/left ventricular ratio, septal bowing, cardiothoracic ratio, diameters of pulmonary trunk and aorta, and intrahepatic/azygos vein contrast medium backflow. Associations with mortality, recurrent venous thromboembolism (VTE), hospitalisation, bleeding and adverse events were assessed over the short term (1 week and 1 month) and long term (12 months). Pulmonary trunk enlargement was the only parameter significantly associated with mortality over both the short and long term (OR 4.18 (95% CI 1.04–16.76) at 1 week to OR 2.33 (95% CI 1.36–3.97) after 1 year), as well as with recurrent VTE and hospitalisation. Most of the evaluated radiological parameters do not have strong effects on the short- or long-term outcome in patients with acute pulmonary embolism. Only an enlarged pulmonary trunk diameter carries an increased risk of mortality and recurrent VTE up to 12 months, and can be used for risk stratification.
Hunt’s ACOs could undermine NHS principles, judge hears
Authors: Clare Dyer
Journal: BMJ (2018)

A “radical and significant” change to how the NHS in England operates could allow private companies to make decisions about healthcare provision, a High Court judge has been told.

The campaign group JR4NHS is seeking a judicial review of plans by Jeremy Hunt, England’s secretary for health and social care, to introduce accountable care organisations (ACOs).1 The campaigners say that ACOs could be wholly or partly private organisations and that the plans could lead to for-profit bodies making decisions on long term NHS provision.

JR4NS (@jr4nhs) was founded by former medical director of NHS England Graham Winyard, former consultant eye …
Has Reconstruction of the Central Airways Been Transformed?
Authors: Valerie W. Rusch
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk <i>MYCN</i>-Not-Amplified Human Neuroblastoma
Authors: Jun S. Wei, Igor B. Kuznetsov, Shile Zhang, Young K. Song, Shahab Asgharzadeh, Sivasish Sindiri, Xinyu Wen, Rajesh Patidar, Sushma Najaraj, Ashley Walton, Jaime M. Guidry Auvil, Daniela S. Gerhard, Aysen Yuksel, Daniel Catchpoole, Stephen M. Hewitt, Paul M. Sondel, Robert Seeger, John M. Maris, Javed Khan
Journal: Clinical Cancer Research (2018)

Purpose: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease, including a focus on tumor-infiltrating lymphocytes (TIL).Experimental Design: We performed deep RNA-seq on pretreatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas. We used single-sample gene set enrichment analysis to detect gene expression signatures of TILs in tumors and examined their association with clinical and molecular parameters, including patient outcome. The expression profiles of 190 additional pretreatment diagnostic neuroblastomas, a neuroblastoma tissue microarray, and T-cell receptor (TCR) sequencing were used to validate our findings.Results: We found that MYCN-not-amplified (MYCN-NA) tumors had significantly higher cytotoxic TIL signatures compared with MYCN-amplified (MYCN-A) tumors. A reported MYCN activation signature was significantly associated with poor outcome for high-risk patients with MYCN-NA tumors; however, a subgroup of these patients who had elevated activated natural killer (NK) cells, CD8+ T cells, and cytolytic signatures showed improved outcome and expansion of infiltrating TCR clones. Furthermore, we observed upregulation of immune exhaustion marker genes, indicating an immune-suppressive microenvironment in these neuroblastomas.Conclusions: This study provides evidence that RNA signatures of cytotoxic TIL are associated with the presence of activated NK/T cells and improved outcomes in high-risk neuroblastoma patients harboring MYCN-NA tumors. Our findings suggest that these high-risk patients with MYCN-NA neuroblastoma may benefit from additional immunotherapies incorporated into the current therapeutic strategies. Clin Cancer Res; 24(22); 5673-84. ©2018 AACR.
Additional Factors in Considering Patent Foramen Ovale Closure to Prevent Recurrent Ischemic Stroke
Authors: William J. Powers
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Assessment of in vivo degradation profiles of hyaluronic acid hydrogels using temporal evolution of chemical exchange saturation transfer (CEST) MRI
Authors: Mohammed Salman Shazeeb, Rubina Corazzini, Paul A. Konowicz, Robert Fogle, Dinesh S. Bangari, Jennifer Johnson, Xiaoyou Ying, Pradeep K. Dhal
Journal: Biomaterials (2018)