tbuckley/cabot-search huggingface dataset:
Immune-related adverse events correlate with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access programme
Authors: E. Baldini, A. Lunghi, E. Cortesi, D. Turci, M.C. Garassino, V. Stati, A. Ardizzoni, B. Ricciuti, A. Frassoldati, G. Romano, A. Illiano, F. Verderame, G. Fasola, P. Marchetti, C. Pinto, G. Carteni, V. Scotti, C. Tibaldi, L. Fioretto, D. Giannarelli
Journal: Annals of Oncology (2018)

Background: The incidence of any and of severe grade immune-related adverse events (irAEs) with second-line Nivolumab (N) monotherapy is 26% and 6% respectively. While potentially serious and even fatal, in the absence of appropriate therapy, such events might be an indicator of the activation of the immune system and, potentially, of efficacy. Methods: We collected the records of 1.959 NSCLC patients (pts) including those with Squamous (S) and non-Squamous (non-S) histology, treated with N in the Italian expanded access programme and we recorded the appearance of any and of severe grade irAEs. We then retrospectively searched for potential correlations between this type of toxicity and efficacy parameters by using cox regression analysis. Results: A total of 1.585 and 374 pts had non-S and S cell carcinoma respectively and 57% received N as second-third line of therapy. Overall 342 (17.8%) developed an irAE of any grade. We observed that pts developing any grade irAE achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to pts who did not. IrAEs correlate with clinical outcomes in both non-S and S histology. At multivariate analysis the development of an irAE remained an independent indicator of N efficacy (HR 1.44[95% CI: 1.22-1.71] p < 0.0001). Conclusions: This is the first report performed in a large series of Caucasian NSCLC pts showing that the activation of the immune system induced by N and documented by the appearance of irAEs correlates with outcome. A careful management of pts with such an event could lead to a maximum clinical benefit. Legal entity responsible for the study: Editta Baldini. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
A New Era of Cardiac Cell Therapy: Opportunities and Challenges
Authors: Ke Huang, Shiqi Hu, Ke Cheng
Journal: Advanced Healthcare Materials (2018)

Myocardial infarction (MI), caused by coronary heart disease (CHD), remains one of the most common causes of death in the United States. Over the last few decades, scientists have invested considerable resources on the study and development of cell therapies for myocardial regeneration after MI. However, due to a number of limitations, they are not yet readily available for clinical applications. Mounting evidence supports the theory that paracrine products are the main contributors to the regenerative effects attributed to these cell therapies. The next generation of cell-based MI therapies will identify and isolate cell products and derivatives, integrate them with biocompatible materials and technologies, and use them for the regeneration of damaged myocardial tissue. This review discusses the progress made thus far in pursuit of this new generation of cell therapies. Their fundamental regenerative mechanisms, their potential to combine with other therapeutic products, and their role in shaping new clinical approaches for heart tissue engineering, are addressed.
First-Line Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed Accelerated Phase Chronic Myeloid Leukemia Patients.
Authors: Marie Balsat, Vincent Alcazer, Gabriel Etienne, Gaelle Fossard, Francoise Huguet, Marc G. Berger, Emilie Cayssials, Aude Charbonnier, Martine Escoffre-Barbe, Hyacinthe Johnson-Ansah, Viviane Dubruille, Laurence Legros, Lydia Roy, Alain Jacques Delmer, Jean-Christophe Ianotto, Martine Gardembas, Fabrice Larosa, Stephane Courby, Shanti Ame, Stephane Morisset, Francois-Xavier Mahon, Delphine Rea, Franck Emmanuel Nicolini
Journal: Blood (2018)
Optimizing novel anti-4-1BB antibodies on a in vivo drug screening platform
Authors: Y. Yang, Y. Guo, Y. Shen, J. Ni
Journal: Annals of Oncology (2018)

Background: 4-1BB, also called TNF receptor super family member 9 or CD137, is mainly expressed on the surface of activated T, NK, and mononuclear cells. 4-1BB is activated by its ligand 4-1BBL or an activating 4-1BB monoclonal antibody, and stimulates T cell activation, proliferation and cytokine production. This co-stimulatory signal can also multiply antigen presenting cells and result in enhanced cell factor secretion. Experiments show that 4-1BB co-stimulation regulates T cell and antigen presenting cell function for antitumor immunity, providing new targets for tumor immunological therapies. Methods: Here, we developed a cohort of 4-1BB specific antibodies using the classic hybridoma technology. Then, we utilized humanized 4-1BB mice (B-h-4-1BB) and implanted syngeneic tumors subcutaneously, followed by treating mice with purified testing antibodies. Via this approach, we are able to discern several clones that effectively inhibited tumor growth without prior knowledge of their in vitro activities. These clones were further selected for humanization. The cohort of recombinant humanized 4-1BB antibodies were screened in B-h4-1BB mice. Results: A cohort of 4-1BB specific antibodies were successfully generated and purified. These purified antibodies were screened by their efficacy to stimulate anti-tumor activity in live animals using Biocytogen's humanized mouse platform. Top clones were humanized and screened by using B-h4-1BB mice. Both the Fv and Fc portion of the lead antibody were optimized using the B-h4-1BB mice, leading to the humanized form of the antibodies. Conclusions: We adopted an in vivo screen approach to discover candidates of 4-1BB specific antibodies that have potent anti-tumor activity. We discovered the leads with the most potent anti-tumor activity. Legal entity responsible for the study: Biocytogen Boston Corp. Funding: Biocytogen Boston Corp. Disclosure: All authors have declared no conflicts of interest.
Trans-ethnic association study of blood pressure determinants in over 750,000 individuals
Authors: Ayush Giri, Jacklyn N. Hellwege, Jacob M. Keaton, Jihwan Park, Chengxiang Qiu, Helen R. Warren, Eric S. Torstenson, Csaba P. Kovesdy, Yan V. Sun, Otis D. Wilson, Cassianne Robinson-Cohen, Christianne L. Roumie, Cecilia P. Chung, Kelly A. Birdwell, Scott M. Damrauer, Scott L. DuVall, Derek Klarin, Kelly Cho, Yu Wang, Evangelos Evangelou, Claudia P. Cabrera, Louise V. Wain, Rojesh Shrestha, Brian S. Mautz, Elvis A. Akwo, Muralidharan Sargurupremraj, Stéphanie Debette, Michael Boehnke, Laura J. Scott, Jian’an Luan, Jing-Hua Zhao, Sara M. Willems, Sébastien Thériault, Nabi Shah, Christopher Oldmeadow, Peter Almgren, Ruifang Li-Gao, Niek Verweij, Thibaud S. Boutin, Massimo Mangino, Ioanna Ntalla, Elena Feofanova, Praveen Surendran, James P. Cook, Savita Karthikeyan, Najim Lahrouchi, Chunyu Liu, Nuno Sepúlveda, Tom G. Richardson, Aldi Kraja, Philippe Amouyel, Martin Farrall, Neil R. Poulter, Markku Laakso, Eleftheria Zeggini, Peter Sever, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, David Conen, Colin Neil Alexander Palmer, John Attia, Daniel I. Chasman, Paul M. Ridker, Olle Melander, Dennis Owen Mook-Kanamori, Pim van der Harst, Francesco Cucca, David Schlessinger, Caroline Hayward, Tim D. Spector, Marjo-Riitta Jarvelin, Branwen J. Hennig, Nicholas J. Timpson, Wei-Qi Wei, Joshua C. Smith, Yaomin Xu, Michael E. Matheny, Edward E. Siew, Cecilia Lindgren, Karl-Heinz Herzig, George Dedoussis, Joshua C. Denny, Bruce M. Psaty, Joanna M. M. Howson, Patricia B. Munroe, Christopher Newton-Cheh, Mark J. Caulfield, Paul Elliott, J. Michael Gaziano, John Concato, Peter W. F. Wilson, Philip S. Tsao, Digna R. Velez Edwards, Katalin Susztak, Christopher J. O’Donnell, Adriana M. Hung, Todd L. Edwards
Journal: Nature Genetics (2018)
Abstract 16810: Validation of an iPhone ECG Application Suitable for Community Screening for Silent Atrial Fibrillation: A Novel Way to Prevent Stroke
Authors: Jerrett Lau, Nicole Lowres, Lis Neubeck, B. Brieger David, W. Sy Raymond, Connor Galloway, E. Albert David, B. Freedman Saul
Journal: Circulation (2012)

Background Atrial fibrillation (AF) is the most common sustained arrhythmia and carries a 5-fold increased risk of stroke. AF is common in the elderly, and previously unrecognised AF is estimated t...
Jessie Campbell Yorston
Authors: Malcolm Yorston, David Yorston
Journal: BMJ (2018)

Jessie Campbell Yorston was one of a small number of women to graduate from Aberdeen in 1953. After house jobs, at the children’s hospital and Woodend Hospital, she became a research fellow in Sir Dugald Baird’s department of obstetrics and obtained her MD for a study of breast feeding. She then was a resident medical officer in the …
Abstract 15096: The Association of Frailty With In-Hospital Bleeding Among Older Adults With Acute Myocardial Infarction: Insights From the Action Registry-GWTG
Authors: John A Dodson, Judith Hochman, Matthew T Roe, Anita Chen, Sarwat I Chaudhry, Stuart Katz, Hua Zhong, Martha Radford, Jacob Udell, Ashkay Bagai, Gregg Fonarow, Martha Gulati, Jonathan Enriquez, Kirk N Garratt, Karen P Alexander
Journal: Circulation (2017)

Introduction: Our aim was to determine whether frailty, a common syndrome in older adults, was associated with increased bleeding risk in the setting of acute myocardial infarction (AMI). Methods: ...
Role of Biologics in Asthma
Authors: Mary Clare McGregor, James G. Krings, Parameswaran Nair, Mario Castro
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Patients with severe uncontrolled asthma have disproportionally high morbidity and healthcare utilization as compared with their peers with well-controlled disease. Although treatment options for these patients were previously limited, with unacceptable side effects, the emergence of biologic therapies for the treatment of asthma has provided promising targeted therapy for these patients. Biologic therapies target specific inflammatory pathways involved in the pathogenesis of asthma, particularly in patients with an endotype driven by type 2 (T2) inflammation. In addition to anti-IgE therapy that has improved outcomes in allergic asthma for more than a decade, three anti-IL-5 biologics and one anti-IL-4R biologic have recently emerged as promising treatments for T2 asthma. These targeted therapies have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life in appropriately selected patients. In addition to the currently approved biologic agents, several biologics targeting upstream inflammatory mediators are in clinical trials, with possible approval on the horizon. This article reviews the mechanism of action, indications, expected benefits, and side effects of each of the currently approved biologics for severe uncontrolled asthma and discusses promising therapeutic targets for the future.
NICE recommends MRI for suspected prostate cancer to reduce biopsies
Authors: Jacqui Wise
Journal: BMJ (2018)

Men with suspected prostate cancer should be offered multi-parametric magnetic resonance imaging (mpMRI) to reduce the number of invasive and unnecessary biopsies, says draft guidance from the UK National Institute for Health and Care Excellence.1 The technology produces a detailed image of the prostate that will help clinicians decide whether a biopsy or subsequent treatment is needed.

Many hospitals already offer mpMRI, but a freedom of information request carried out for the charity Prostate Cancer UK earlier this year found that only half of men with suspected prostate cancer were being offered the scan before biopsy.

Currently, men with suspected prostate cancer are offered a blood test to look for raised concentrations of prostate specific …
Computed tomographic colonography with the step-clipping method detects a previously bleeding diverticulum
Authors: Hirosato Tamari, Taiki Aoyama, Kenjiro Shigita, Naoki Asayama, Akira Fukumoto, Shinichi Mukai, Shinji Nagata
Journal: Endoscopy (2018)

Low completion rate of endoscopic treatment for colon diverticular bleeding remains troublesome because of the difficulty in determining the responsible diverticulum after spontaneous cessation of bleeding. Extravasation, observed on contrast-enhanced computed tomography (CECT), is an important factor in identifying a bleeding diverticulum. However, the detection rate using colonoscopy is not satisfactory, with a ≤ 60 % chance of lesion detection [1] [2] because colonoscopy does not provide as much precise positional information as CT. The "step-clipping" method uses endoclips to create artificial indicators in the colon [3], formulating a positional relationship between the responsible diverticulum and each clip. Combination of this technique with computed tomographic colonography (CTC), which is recommended for neoplastic lesions [4], may identify a silent lesion ([Video 1]).
Lessons From California’s Discipline of a Popular Physician for Vaccination Exemptions Without Medical Cause
Authors: Ross D. Silverman, Y. Tony Yang
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Incidence of programmed cell death 1 inhibitor-related diarrhea in patients with advanced cancer: A systematic review and meta-analysis
Authors: J.-D. Sui, Y. Wang, Y. Wan, Y.-Z. Wu
Journal: Annals of Oncology (2018)

Background: Programmed cell death 1 (PD-1) inhibitor-related diarrhea is increased due to the rising administration of PD-1 inhibitor across different tumor types. This adverse event is potentially life-threatening, thus requiring appropriate management. However, its incidence among various tumor types is barely known yet. Methods: Thirty-three original articles of PD-1 inhibitor monotherapy trials were identified based on a PubMed search completed on October 6, 2017. The incidences of all-grade and grade ≥3 diarrhea were collected. Results: Thirty-three studies containing 7322 patients were included in the meta-analysis. The overall incidence of diarrhea during PD-1 inhibitor monotherapy was 11.3% (95% CI, 9.7%-12.9%) for all-grade and 0.8% (95% CI, 0.6%-1.1%) for grade ≥3 diarrhea. The incidence was higher in renal cell carcinoma (RCC) for both all-grade (14.4% vs 9.4%) and grade ≥3 diarrhea (1.3% vs 0.7%) compared with non-small-cell lung cancer (NSCLC) but only for all-grade diarrhea (14.4% vs 8.5%) compared with urothelial carcinoma. The incidence in melanoma was higher than in NSCLC (15.7% vs 9.4%) and urothelial carcinoma (15.7% vs 8.5%) for all-grade diarrhea but not for grade ≥3 diarrhea. No significant differences were noted between Nivolumab and Pembrolizumab for allgrade diarrhea (11.7% vs 10.7%) or grade ≥3 diarrhea (0.9% vs 0.8%). Conclusions: The incidence of PD-1 inhibitor-related diarrhea was higher in RCC and melanoma. There was no significant difference in PD-1 inhibitor-related diarrhea between two types of PD-1 inhibitors. These results contribute to heighten clinicians' awareness of potential adverse events in diverse tumor types. Legal entity responsible for the study: Radiation Oncology, Chongqing Cancer Institute & Chongqing Cancer Hospital & Chongqing Cancer Center & Chongqing University Cancer Hospital, Chongqing, CN. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 12891: Predictors of Net Adverse Cardiovascular Events in Patients on Triple Antithrombotic Therapy
Authors: Kuljit Singh, Angel Fu, Joe Abunassar, Nikita Malhotra, Benjamin Hibbert, Aun Y Chong, Derek So
Journal: Circulation (2015)

Introduction: Patients on dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). While TT may decrease ischemic complications, it may confer increased bleeding risk. Hypothesis: We set to determine predictors of complications in patients on TT. In particular, we sought to determine if use of ticagrelor in TT is associated with higher complications. Methods: Patients discharged on TT after PCI were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and bleeding (Bleeding Academic Research Consortium (BARC)) complications or net adverse clinical event (NACE). A major secondary endpoint was BARC Types 2, 3 or 5 bleeding. Outcomes were compared between ticagrelor and clopidogrel treated patients. Multivariable analyses were performed to elucidate predictors of complications. Results: Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% and BARC 2, 3 or 5 bleeding occurred in 18% of patients. There was no difference in the primary or secondary outcome between ticagrelor versus clopidogrel sub-group. On multiple logistic regressions (Figure 1 and 2), use of TT in patients with acute coronary syndrome (ACS) (p = 0.002) and bridging in with ticagrelor (p=0.02) was associated with increased NACE. Low eGFR was an independent predictor of bleeding (p = 0.03). Conclusions: From our analysis ticagrelor was not found to be an independent predictor of higher bleeding in TT. Instead, low eGFR is associated with higher risk of bleeding. Use of bridging anticolagulation with ticagrelor is associated with higher NACE.
CHIPping Away at the Pathogenesis of Heart Failure
Authors: Peter Libby, Siddhartha Jaiswal, Amy E. Lin, Benjamin L. Ebert
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Assessing the Prognostic Value of the Automated Bone Scan Index for Prostate Cancer
Authors: Ryan Sun, Huili Zhu, Lee-Jen Wei
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Administration of Rimiducid Following Haploidentical BPX-501 Cells in Children with Malignant or Non-Malignant Disorders Who Develop Graft-Versus-Host-Disease (GvHD)
Authors: Reem Elkeky, David A. Jacobsohn, Rajni Agarwal, Swati Naik, Neena Kapoor, Lakshmanan Krishnamurti, Mary Slatter, Federica Galaverna, Pietro Merli, Melissa Aldinger, Franco Locatelli
Journal: Blood (2018)
Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation
Authors: Dennis Jung, Rafael Heiss, Viktoria Kramer, Oana-Maria Thoma, Adrian P. Regensburger, Wolfgang Rascher, Michael Uder, Markus F Neurath, Ferdinand Knieling, Maximilian J. Waldner
Journal: Theranostics (2018)

Rationale: To develop a simple and fast protocol for the assessment of acute and chronic experimental intestinal inflammation using contrast-enhanced µCT.Methods: For the imaging studies, an acute 2% and 3% dextran sodium sulfate (n = 15, female, 8-12 weeks) and a chronic adoptive transfer colitis model (n = 10, female, 8-9 weeks) were established over 9 days or 6 weeks, respectively.Throughout the experiments, longitudinal measurement of murine intestinal wall thickness and time dependent perfusion was performed on a small animal µCT system (90 kV, 160 μA, FOV: 60 mm, scan time: 17 s, image size: 512x512, layer thickness: 118 µm) between 0.5 and 30 min after intravenous bolus injection of an iodine contrast agent.Weight development, small animal endoscopy, and histological ex vivo analysis were compared to contrast-enhanced µCT imaging findings.Results: Murine intestinal wall thickness was significantly increased in inflamed colons of acute colitis at day 9 in comparison to pre-inflamed state.Perfusion analysis revealed a late contrast enhancement in acute inflamed colons and the renal medulla at day 9 compared to control mice.An increasing intestinal wall thickness was monitored 3, 5 and 6 weeks after on-set of chronic colitis in comparison to controls.A good correlation with endoscopic (r = 0.75, p < 0.0001) and histologic degree of inflammation (r = 0.83, p = 0.04) was found.Conclusion: Contrast-enhanced µCT is a simple and fast method to assess acute intestinal inflammation and to monitor disease progression in experimental models of chronic colitis.According to our findings, one single contrast-enhanced µCT-scan is a valid non-invasive modality to quantify the degree of inflammation in the entire digestive tract in murine inflammatory models.