tbuckley/cabot-search huggingface dataset:
GPs should lead process of defining diseases to cut overdiagnosis, panel recommends
Authors: Susan Mayor
Journal: BMJ (2019)

GPs should be at the forefront of defining diseases to limit overdiagnosis that can cause unnecessary treatment and potentially harm patients, an international panel has proposed.1

The independent group has recommended that GPs should lead initiatives to review and set diagnostic thresholds for diseases, using evidence based criteria and involving consumers to assess what matters to patients.

Johann Sigurdsson, coauthor from the General Practice Research Unit at the Norwegian University of Science and Technology in Trondheim, Norway, said, “In the current process for defining disease it’s usually experts in a field, for example hypertension, who decide the cut-off points. They consider only that disease and perhaps the mortality associated with that particular disease, …
SAT-379-Myeloid cells require gp130 signalling for protective antiinflammatory functions during sepsis
Authors: Sara Dutton Sackett, Tobias Otto, Antje Mohs, Leif Erik Sander, Sonja Strauch, Roland Sonntag, Konrad L. Streetz, Daniela Kroy, Christian Trautwein
Journal: Journal of Hepatology (2019)
Abstract 17130: Diagnostic and Prognostic Utility of Cardiac Troponin in Post-Cardiac Arrest Care
Authors: Rohan Khera, Vijay Agusala, Daniel Cheeran, Pranitha P Reddy, Mark S Link
Journal: Circulation (2017)

Background: Cardiac troponin is routinely tested in the post-cardiac arrest setting, but its utility in identifying ischemic etiology and predicting left ventricular systolic dysfunction (LVSD) and...
Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells
Authors: Haiying Qin, Justin P. Edwards, Liubov Zaritskaya, Ankit Gupta, C. Jenny Mu, Terry J. Fry, David M. Hilbert, David W. LaFleur
Journal: Molecular Therapy (2019)

Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics. Herein, we describe the identification and characterization of D domains specific for CD123, a therapeutic target for hematologic malignancies, including acute myelogenous leukemia (AML). CARs comprised of these D domains mediate potent T cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We describe a strategy of engineering less immunogenic D domains through the identification and removal of putative T cell epitopes and investigate the binding kinetics and affinity requirements of the resultant D domain CARs. Finally, we extended the utility of D domains by generating functional, bi-specific CARs comprised of a CD123-specific D domain and a CD19-specific scFv. The properties of D domains suggest that this class of targeting domain may facilitate the development of multi-functional CARs where conventional, scFv-based designs may be suboptimal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics. Herein, we describe the identification and characterization of D domains specific for CD123, a therapeutic target for hematologic malignancies, including acute myelogenous leukemia (AML). CARs comprised of these D domains mediate potent T cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We describe a strategy of engineering less immunogenic D domains through the identification and removal of putative T cell epitopes and investigate the binding kinetics and affinity requirements of the resultant D domain CARs. Finally, we extended the utility of D domains by generating functional, bi-specific CARs comprised of a CD123-specific D domain and a CD19-specific scFv. The properties of D domains suggest that this class of targeting domain may facilitate the development of multi-functional CARs where conventional, scFv-based designs may be suboptimal.
FRI-340-In vivo effects of a novel inhibitor of apoptosis signal-regulating kinase 1 in mouse models of liver injury and metabolic disease
Authors: Manuel Roqueta-Rivera, Mary Chau, Guoqiang Wang, Kelsey Garlick, Bindu Ramachandran, Susanne Fyfe, Khanh Hoang, Yat Sun Or, Bryan Goodwin
Journal: Journal of Hepatology (2019)
Pretherapeutic 68Ga-PSMA-617 PET May Indicate the Dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 in Main Organs and Tumor Lesions
Authors: Jingnan Wang, Jie Zang, Hao Wang, Qingxing Liu, Fang Li, Yansong Lin, Li Huo, Orit Jacobson, Gang Niu, Xinrong Fan, Zhaohui Zhu, Xiaoyuan Chen
Journal: Clinical Nuclear Medicine (2019)

Aim Combined 68 Ga-PSMA-617 PET imaging and 177 Lu-PSMA-617 therapy is a precise targeted theranostic approach for patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of this study was to determine whether pretherapeutic standard uptake value (SUV) in 68 Ga-PSMA-617 PET could indicate the effective dose in the main organs and absorbed dose in tumor lesions. Methods After institutional review board approval and informed consent, 9 patients with mCRPC were recruited and underwent 68 Ga-PSMA-617 PET/CT scans. Five patients received 177 Lu-PSMA-617 (1.30–1.42 GBq, 35–38.4 mCi) and then underwent serial whole-body planar imaging and SPECT/CT imaging of both thoracic and abdominal regions at 0.5-, 2-, 24-, 48-, and 72-hour time points. The other 4 patients received 177 Lu-EB-PSMA-617 (0.80–1.1 GBq, 21.5–30 mCi) and then underwent the same imaging procedures at 2-, 24-, 72-, 120-, and 168-hour time points. The effective dose in the main organs and the absorbed dose in tumor lesions were calculated. Detailed correlations between the pretherapeutic SUV in 68 Ga-PSMA-617 PET and effective dose in the main organs as well as absorbed dose in the tumor lesions were analyzed. Results SUV of 68 Ga-PSMA-617 PET was moderately correlated with effective dose in main organs ( r = 0.610 for 177 Lu-PSMA-617, r = 0.743 for 177 Lu-EB-PSMA-617, both P &lt; 0.001). SUV of tumor lesions in 68 Ga-PSMA-617 PET had high correlation with those in 177 Lu-PSMA-617 ( r = 0.915, P &lt; 0.001) and moderate correlation with those in 177 Lu-EB-PSMA-617 ( r = 0.611, P = 0.002). Conclusions Pretherapeutic 68 Ga-PSMA-617 PET may indicate the dosimetry of 177 Lu-PSMA-617 and 177 Lu-EB-PSMA-617. Both the effective dose in main organs and absorbed dose in tumor lesions correlate with SUV of 68 Ga-PSMA-617 PET. This relationship may help select appropriate candidates for peptide receptor radionuclide therapy. Further investigations of larger cohorts are needed to confirm these initial findings.
Abstract P198: Racial Disparities in Cardiovascular Outcomes in REGARDS Persist After Using Inverse Probability Weighting to Account for Missing Data
Authors: D. Leann Long, George Howard, Suzanne Judd, Jennifer Manly, Leslie McClure, Monika Safford, M. Maria Glymour, Ronit Katz
Journal: Circulation (2017)

Introduction: When data are missing, analysts often choose to perform ‘complete case’ analysis, restricting statistical analysis to those participants with all necessary fields completed. However, this analysis is subject to selection bias if those participants excluded are somehow inherently different from those included. One approach to address the potential selection bias is inverse probability weighting, where participants with complete data are weighted to reflect the original population. We compare estimated racial disparities in hypertension and left ventricular hypertrophy using complete cases to those estimates from inverse probability weighted analysis. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,183 participants aged 45+ between 2003 and 2007 to study racial and geographic differences in stroke and cardiovascular health. When the second in-home visits were conducted, 18% (5542) of participants had died and 23% (7071) of participants had withdrawn. For the baseline population, the probabilities of being a complete case are estimated through logistic regression models using baseline characteristics. These predicted probabilities are inverted to create the weights used in statistical analysis, such that the complete participants are weighted to represent the enrolled population. Through logistic regression, we estimate the association between race and hypertension and left ventricular hypertrophy at the second in-home visit for complete data and compare these results to the results from inverse probability weighted analysis. All models are adjusted for sex, age and region. Results: The logistic models for dropout and death have low and moderate predictive abilities (c-statistics 0.602 and 0.811, respectively). For incident hypertension, the estimated odds ratio comparing blacks to whites differs little between the complete case (1.87 (1.66, 2.10)) and the weighted (1.83 (1.61, 2.09)) analysis. For left ventricular hypertrophy, the estimated odds ratio comparing blacks to whites changes little from the complete case analysis (1.54 (1.32, 1.79)) to the weighted analysis (1.45 (1.21, 1.74)). Discussion: Estimated racial inequalities in the odds of incident hypertension and left ventricular hypertrophy were similar in the complete case and inverse probability weighting analyses, indicating little evidence of selection bias in the estimation of racial inequalities for these outcomes.
The Evidence on Estrogen, Progesterone, and Spontaneous Coronary Artery Dissection
Authors: Marysia S. Tweet, Virginia M. Miller, Sharonne N. Hayes
Journal: JAMA Cardiology (2019)

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
Anti-atherogenic effects of CD36-targeted epigallocatechin gallate-loaded nanoparticles
Authors: Jia Zhang, Shufang Nie, Yujiao Zu, Mehrnaz Abbasi, Jun Cao, Chuan Li, Dayong Wu, Safaa Labib, Gordon Brackee, Chwan-Li Shen, Shu Wang
Journal: Journal of Controlled Release (2019)
Abstract 16316: Angiographic Outcomes After Percutaneous Coronary Intervention for Definite Stent Thrombosis
Authors: Shunsuke Kubo, Kazushige Kadota, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Circulation (2013)

Background: Angiographic outcomes after percutaneous coronary intervention (PCI) for stent thrombosis (ST) have not been reported. In this study, we compared angiographic outcomes after PCI for ST ...
Advanced non-small cell lung cancer patients with low tumor mutation burden might derive benefit from anti-programmed cell death (PD)-1 and anti-programmed deathligand 1 (PD-L1) blockade
Authors: W. Nie, M.-D. Xu, L. Gan, Y. Zhang, B.-H. Han
Journal: Annals of Oncology (2019)

Background: We aimed to investigate the association between tumor mutation burden (TMB) and survival in non-small cell lung cancer (NSCLC) patients with anti–programmed cell death (PD)-1 and anti--programmed cell deathligand 1 (PD-L1) blockade. Methods: Five retrospective cohorts using PD1/PDL1 blockades and The Cancer Genome Atlas (TCGA) lung cancer data set were included in this study. The restricted cubic spline (RCS) analysis was used to explore the association between TMB and survival. The cut-off values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS) and progression-free survival (PFS). The associations between TMB and intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, and T cell populations were also investigated. Results: TMB showed an inverted J-shaped curve with survival risk in RCS plot. Two cut-off values were determined by X-tile software in each cohort. In addition to high TMB, low TMB was an independent prognostic indicator for OS and PFS in NSCLC patients treated with PD1/PDL1 blockades. Objective response rate (ORR), disease control rate (DCR), and 1-year OS rate in the low TMB group were higher than that in the medium TMB group. In TCGA lung cancer data set, low TMB was also associated with longer OS in comparison with medium TMB. Furthermore, NSCLC patients with low TMB had significantly lower intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, T helper type 2 (Th2) cells, and CD8+ T cells, but higher levels of Th1 and Th17 cells. Conclusions: NSCLC patients with low TMB might benefit from anti-PD1/PDL1 immunotherapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Assisted dying: case of man who helped his wife to die reignites Spain’s euthanasia debate
Authors: Aser García Rada
Journal: BMJ (2019)

Spain’s acting president, Pedro Sanchez, has promised to try to push through legislation to legalise euthanasia if he wins the general election later this month.

His commitment was prompted by the death of Maria Jose Carrasco, a 61 year old woman with multiple sclerosis, who was helped to die by her husband, Angel Hernandez, on 3 April.

Hernandez videotaped a conversation with Carrasco, who had multiple sclerosis for three decades, in which she confirmed several times that she wanted to end her life. He also recorded the moment he offered her a glass containing the sodium pentobarbital that she had acquired online, as well as her death.

In the video Hernandez says that his wife wanted to end her life “the sooner, the better” and explains that he …
Follow-up of a French national cohort of melanoma stage IV and unresectable stage III patients, MelBase.
Authors: Clara Allayous, Stephane Dalle, Philippe Saiag, Caroline Dutriaux, Laurent Mortier, Alain Dupuy, Thierry Lesimple, Philippe Bahadoran, Sophie Dalac, Marie- Beylot-Barry, Eve Maubec, Pierre-Emmanuel Stoebner, Francois Aubin, Jean-Philippe Arnault, Laurence Verneuil, Brigitte Dreno, Anita Kowal, Raphael Porcher, Marie Thérèse Leccia, Celeste Lebbe
Journal: Journal of Clinical Oncology (2015)

e20113 Background: Recent advances in treatment of metastatic melanoma highlight how important collecting and building databases are, for a better health care management (overall survival, safety, costs…). Methods: MelBase is a French multidisciplinary cohort initiated by the French National Skin Cancer Group (GCC-GMFmel) and administered by AP-HP Clinical Research and Development Department. Approved by the French National Cancer Institute (INCa) and national ethic committees, MelBase is a prospective, multicentric cohort enrolling adults with unresectable stage III or stage IV melanoma. The project is consistent with the ethical chart of the hospital tumor banks published by INCa and managed by a chart ensuring centers autonomy. A multidisciplinary scientific advisory board identifies research priorities based on clinical practice and scientific knowledge. Results: Since March 2013, 426 patients were enrolled with a 3 years median follow-up, in 25 centers, all associated with Biological Resource Centers. Different types of data are collected in an electronic CRF, including both clinical (primary melanoma, tumor kinetics, AJCC stage, therapeutic interventions and strategies, evaluation of response, tolerance, impact on quality of life…) and biological data via a virtual Tumorbank (primary melanoma, metastatic samples DNA from peripheral blood mononuclear cells, plasma, RNA). Based on real-life Vemurafenib treated patients, enrolled in MelBase (n = 60), preliminary analysis show similar results in term of overall survival (11.9 months), progression free survival (4.9 months) and safety, compared to previous clinical trials and data from expanded access programs. MelBase also points out that Vemurafenib is used according to approved indication. Conclusions: This first analysis highlights MelBase potential. Associated with a biological virtual bank, economical and epidemiological data, and combined to other national/European cohorts, MelBase exploitation will lead to validate and identify new clinical, epidemiological, and biological prognostic, risk-benefit, management cost of patients in real-life, treated with validated and future treatments of metastatic melanoma.
Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma
Authors: Maroulio Pertesi, Maxime Vallée, Xiaomu Wei, Maria V. Revuelta, Perrine Galia, Delphine Demangel, Javier Oliver, Matthieu Foll, Siwei Chen, Emeline Perrial, Laurent Garderet, Jill Corre, Xavier Leleu, Eileen M. Boyle, Olivier Decaux, Philippe Rodon, Brigitte Kolb, Borhane Slama, Philippe Mineur, Eric Voog, Catherine Le Bris, Jean Fontan, Michel Maigre, Marie Beaumont, Isabelle Azais, Hagay Sobol, Marguerite Vignon, Bruno Royer, Aurore Perrot, Jean-Gabriel Fuzibet, Véronique Dorvaux, Bruno Anglaret, Pascale Cony-Makhoul, Christian Berthou, Florence Desquesnes, Brigitte Pegourie, Serge Leyvraz, Laurent Mosser, Nicole Frenkiel, Karine Augeul-Meunier, Isabelle Leduc, Cécile Leyronnas, Laurent Voillat, Philippe Casassus, Claire Mathiot, Nathalie Cheron, Etienne Paubelle, Philippe Moreau, Yves–Jean Bignon, Bertrand Joly, Pascal Bourquard, Denis Caillot, Hervé Naman, Sophie Rigaudeau, Gérald Marit, Margaret Macro, Isabelle Lambrecht, Manuel Cliquennois, Laure Vincent, Philippe Helias, Hervé Avet-Loiseau, Victor Moreno, Rui Manuel Reis, Judit Varkonyi, Marcin Kruszewski, Annette Juul Vangsted, Artur Jurczyszyn, Jan Maciej Zaucha, Juan Sainz, Malgorzata Krawczyk-Kulis, Marzena Wątek, Matteo Pelosini, Elzbieta Iskierka-Jażdżewska, Norbert Grząśko, Joaquin Martinez-Lopez, Andrés Jerez, Daniele Campa, Gabriele Buda, Fabienne Lesueur, Marek Dudziński, Ramón García-Sanz, Arnon Nagler, Marcin Rymko, Krzysztof Jamroziak, Aleksandra Butrym, Federico Canzian, Ofure Obazee, Björn Nilsson, Robert J. Klein, Steven M. Lipkin, James D. McKay, Charles Dumontet
Journal: Leukemia (2019)

French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Central Processing of Itch in the Midbrain Reward Center
Authors: Xin-Yu Su, Ming Chen, Yuan Yuan, Ying Li, Su-Shan Guo, Huo-Qing Luo, Chen Huang, Wenzhi Sun, Yong Li, Michael X. Zhu, Ming-Gang Liu, Ji Hu, Tian-Le Xu
Journal: Neuron (2019)
FRI-388-Hepatitis C ilnfected liver grafts transplanted into non-infected recipients are safe in the era of highly effective direct-acting antiviral therapy
Authors: Heather O’dell, Alison Rafferty, Natasha Schneider, Andrew Scanga, J. Kelly Wright, Sunil Geevarghese, Lea Matsuoka, Sophoclis Alexopoulos, Seth Karp, Roman Perri, Joseph Awad, Lee Gorden
Journal: Journal of Hepatology (2019)
Preliminary Results of a Trial of Atabecestat in Preclinical Alzheimer’s Disease
Authors: David Henley, Nandini Raghavan, Reisa Sperling, Paul Aisen, Rema Raman, Gary Romano
Journal: New England Journal of Medicine (2019)

Atabecestat in Preclinical Alzheimer’s Disease A preliminary analysis of a trial involving participants with brain amyloid deposition who are at risk for dementia due to Alzheimer’s disease showed ...
FRI-497-Shifting to sorafenib is beneficial for hepatocellular carcinoma patients with transarterial chemoembolization refractoriness: A real world experience
Authors: Lin Po-Ting, RachelWen-Juei Jeng, Yi-Chung Hsieh, Wei Teng, Chen-Fu Hung, Chien-Hao Huang, Kar-Wai Lui, Yi-Cheng Chen, Chen-Chun Lin, Chun-Yen Lin, Shi-Ming Lin, I-Shyan Sheen
Journal: Journal of Hepatology (2019)
THU-045-Natural history of sepsis, organ failure and organ dysfunction in critically ill patients with acute on chronic liver failure
Authors: Manjul Mishra, Shiv Kumar Sarin, Vijayraghavan Rajan, Ashok Choudhury, Guresh Kumar, Priyanka Jain, Irene Paulson, Mamun Al-Mahtab, Salimur Rahman, Shahinul Alam, Harshad Devarbhavi, Yogesh Chawla, Radha Krishan Dhiman, Ajay Duseja, Sunil Taneja, Qin Ning, Ke Ma, Tao Chen, Zhongping Duan, Yu Chen, Ce Eapen, Ashish Goel, Soek-Siam Tan, Saeed Sadiq Hamid, Amna Subhan, Wasim Jafri, DongJoon Kim, Jinhua Hu, Deepak Amarapurkar, Ajit Sood, Vandana Midha, Omesh Goyal, Akash Shukla, Hasmik Ghazinian, Manoj Sahoo, Sombat Treeprasertsuk, Guan Huei Lee, Seng Gee Lim, Laurentius A. Lesmana, Rinaldi Lesmana, Samir Shah, Chetan Kalal, Zaigham Abbas, Joyes s, Gian Carpio, V GM, Diana Payawal, A. Kadir Dokmeci, Ananta Shrestha, George Lau, Man-Fung Yuen
Journal: Journal of Hepatology (2019)