tbuckley/cabot-search huggingface dataset:
Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial
Authors: Elvin Kedhi, Enrico Fabris, Martin van der Ent, Pawel Buszman, Clemens von Birgelen, Vincent Roolvink, Alexander Zurakowski, Carl E Schotborgh, Jan C A Hoorntje, Christian Hasbø Eek, Stéphane Cook, Marco Togni, Martijn Meuwissen, Niels van Royen, Ria van Vliet, Hans Wedel, Ronak Delewi, Felix Zijlstra
Journal: BMJ (2018)

Abstract Objective To show that limiting dual antiplatelet therapy (DAPT) to six months in patients with event-free ST-elevation myocardial infarction (STEMI) results in a non-inferior clinical outcome versus DAPT for 12 months. Design Prospective, randomised, multicentre, non-inferiority trial. Setting Patients with STEMI treated with primary percutaneous coronary intervention (PCI) and second generation zotarolimus-eluting stent. Participants Patients with STEMI aged 18 to 85 that underwent a primary PCI with the implantation of second generation drug-eluting stents were enrolled in the trial. Patients that were event-free at six months after primary PCI were randomised at this time point. Interventions Patients that were taking DAPT and were event-free at six months were randomised 1:1 to single antiplatelet therapy (SAPT) (ie, aspirin only) or to DAPT for an additional six months. All patients that were randomised were then followed for another 18 months (ie, 24 months after the primary PCI). Main outcome measures The primary endpoint was a composite of all cause mortality, any myocardial infarction, any revascularisation, stroke, and thrombolysis in myocardial infarction major bleeding at 18 months after randomisation. Results A total of 1100 patients were enrolled in the trial between 19 December 2011 and 30 June 2015. 870 were randomised: 432 to SAPT versus 438 to DAPT. The primary endpoint occurred in 4.8% of patients receiving SAPT versus 6.6% of patients receiving DAPT (hazard ratio 0.73, 95% confidence interval 0.41 to 1.27, P=0.26). Non-inferiority was met (P=0.004 for non-inferiority), as the upper 95% confidence interval of 1.27 was smaller than the prespecified non-inferiority margin of 1.66. Conclusions DAPT to six months was non-inferior to DAPT for 12 months in patients with event-free STEMI at six months after primary PCI with second generation drug-eluting stents. Trial registration Clinicaltrials.gov NCT01459627 .
Aspirin and Chemoprevention—Have We Arrived?
Authors: Victoria L. Seewaldt
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
The role of TERT promoter mutations in differentiating recurrent nevi from recurrent melanomas: A retrospective, case-control study
Authors: Kara E. Walton, Erin M. Garfield, Bin Zhang, Victor L. Quan, Katherine Shi, Lauren S. Mohan, Alexandra M. Haugh, Timothy VandenBoom, Pedram Yazdan, Maria Cristina Isales, Elnaz Panah, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2018)
2-Arachidonoylglycerol mobilizes myeloid cells and worsens heart function after acute myocardial infarction
Authors: Maximilian J Schloss, Michael Horckmans, Raquel Guillamat-Prats, Daniel Hering, Estelle Lauer, Sebastien Lenglet, Christian Weber, Aurelien Thomas, Sabine Steffens
Journal: Cardiovascular Research (2018)

Myocardial infarction (MI) leads to an enhanced release of endocannabinoids and a massive accumulation of neutrophils and monocytes within the ischaemic myocardium. These myeloid cells originate from haematopoietic precursors in the bone marrow and are rapidly mobilized in response to MI. We aimed to determine whether endocannabinoid signalling is involved in myeloid cell mobilization and cardiac recruitment after ischaemia onset.Intravenous administration of endocannabinoid 2-arachidonoylglycerol (2-AG) into wild type (WT) C57BL6 mice induced a rapid increase of blood neutrophil and monocyte counts as measured by flow cytometry. This effect was blunted when using cannabinoid receptor 2 knockout mice. In response to MI induced in WT mice, the lipidomic analysis revealed significantly elevated plasma and cardiac levels of the endocannabinoid 2-AG 24 h after infarction, but no changes in anandamide, palmitoylethanolamide, and oleoylethanolamide. This was a consequence of an increased expression of 2-AG synthesizing enzyme diacylglycerol lipase and a decrease of metabolizing enzyme monoacylglycerol lipase (MAGL) in infarcted hearts, as determined by quantitative RT-PCR analysis. The opposite mRNA expression pattern was observed in bone marrow. Pharmacological blockade of MAGL with JZL184 and thus increased systemic 2-AG levels in WT mice subjected to MI resulted in elevated cardiac CXCL1, CXCL2, and MMP9 protein levels as well as higher cardiac neutrophil and monocyte counts 24 h after infarction compared with vehicle-treated mice. Increased post-MI inflammation in these mice led to an increased infarct size, an impaired ventricular scar formation assessed by histology and a worsened cardiac function in echocardiography evaluations up to 21 days. Likewise, JZL184-administration in a myocardial ischaemia-reperfusion model increased cardiac myeloid cell recruitment and resulted in a larger fibrotic scar size.These findings suggest that changes in endocannabinoid gradients due to altered tissue levels contribute to myeloid cell recruitment from the bone marrow to the infarcted heart, with crucial consequences on cardiac healing and function.
Abstract 15032: Health Impacts of the Southeast Asian Haze Problem - A Time-Stratified Case Crossover Study of the Relationship Between Ambient Air Pollution and Sudden Cardiac Deaths in Singapore
Authors: Marcus E Ong, Andrew F Ho, Win Wah, Arul Earnest, Yih Yng Ng, Zhenjia Xie, Nur Shahidah, Susan Yap, Pin Pin Pek, Nan Liu, Sean S Lam
Journal: Circulation (2017)

Introduction: Haze occurs annually in Singapore arising from forest fires in the region. We aimed to investigate the association between air pollution andout-of-hospital cardiac arrest (OHCA) incid...
Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families
Authors: Marie-Hélène Dizier, Patricia Margaritte-Jeannin, Lucile Pain, Chloé Sarnowski, Myriam Brossard, Hamida Mohamdi, Nolwenn Lavielle, Marie-Claude C Babron, Jocelyne Just, Mark Lathrop, Catherine Laprise, Emmanuelle Bouzigon, Florence Demenais, Rachel Nadif
Journal: Thorax (2018)

Background A positional cloning study of bronchial hyper-responsiveness (BHR) at the 17p11 locus in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families showed significant interaction between early-life environmental tobacco smoke (ETS) exposure and genetic variants located in DNAH9 . This gene encodes the heavy chain subunit of axonemal dynein, which is involved with ATP in the motile cilia function. Our goal was to identify genetic variants at other genes interacting with ETS in BHR by investigating all genes belonging to the ‘ ATP-binding ’ and ‘ ATPase activity ’ pathways which include DNAH9, are targets of cigarette smoke and play a crucial role in the airway inflammation. Methods Family-based interaction tests between ETS-exposed and unexposed BHR siblings were conducted in 388 EGEA families. Twenty single-nucleotide polymorphisms (SNP) showing interaction signals (p ≤ 5.10 −3 ) were tested in the 253 Saguenay-Lac-Saint-Jean (SLSJ) families. Results One of these SNPs was significantly replicated for interaction with ETS in SLSJ families (p=0.003). Another SNP reached the significance threshold after correction for multiple testing in the combined analysis of the two samples (p=10 −5 ). Results were confirmed using both a robust log-linear test and a gene-based interaction test. Conclusion The SNPs showing interaction with ETS belong to the ATP8A1 and ABCA1 genes, which play a role in the maintenance of asymmetry and homeostasis of lung membrane lipids.
Abstract 18922: Is Treatment for Paroxysmal Atrial Fibrillation With Second-generation Cryoballoon Ablation More Reproducible Than That With Contact Force Guided Radiofrequency Ablation?
Authors: Nobuaki Tanaka, Koichi Inoue, Koji Tanaka, Yuichi Ninomiya, Yuko Hirao, Takafumi Oka, Masato Okada, Ryo Nakamaru, Hiroyuki Inoue, Yasushi Koyama, Atsunori Okamura, Katsuomi Iwakura, Kenshi Fujii
Journal: Circulation (2017)

Introduction: Cryoballoon ablation (CBA) is non-inferior to radiofrequency catheter ablation (RFCA) in efficacy and safety of catheter ablation for paroxysmal atrial fibrillation (AF). But, little ...
Abstract IA02: Identity shifts in pediatric cancers
Authors: Olivier Delattre, G.A. Franzetti, K. Laud-Duval, A. Brisac, Valentina Boeva, Caroline Louis-Brennetot, Agathe Peltier, Simon Durand, Cécile Pierre-Eugène, Didier Surdez, Eve Lapouble, Gaelle Pierron, Sandrine Grossetête-Lalami, Isabelle Janoueix-Lerosey
Journal: Cancer Research (2018)

Abstract In contrast to adult cancers, most pediatric malignancies display limited genetic heterogeneity. In Ewing sarcoma, the major driver of tumor development is the expression of the chimeric EWSR1-FLI1 transcription factor, which results from a chromosome translocation. Additional recurrent genetic alterations include the CDKN2A, STAG2, and TP53 genes. Through its binding to specific elements including GGAA microsatellite sequences, EWSR1-FLI1 has a major impact on epigenetic landscape of the cancer cells and consequently, obscures the epigenetic makeup of the Ewing cell-of-origin. The Ewing cell is somehow a “neomorphic” cell, the biologic properties of which are tightly dependent upon the expression level of EWSR1-FLI1. When a cell harbors a low level of expression of EWSR1-FLI1, it loses this neomorphic identity and retrieve its cell-of-origin, mesenchymal phenotype. This leads us to propose a new model of phenotypic plasticity whereby the dynamic fluctuation of the expression level of a dominant oncogene is an intrinsic characteristic of its oncogenic potential. The causes of EWSR1-FLI1 expression fluctuations are presently unknown. They may be partly stochastic as they are observed in cell lines in vitro but also dependent upon signals from the surrounding microenvironment. The situation is very different in neuroblastoma where the blueprint of the cell-of-origin, most frequently a noradrenergic progenitor, can be clearly detected whatever the genetic abnormalities of the cancer cells. Our recent data nevertheless suggest that neuroblastoma cells may also exhibit some plasticity and transition between different epigenetic states that witness different cell identities. In conclusion, pediatric cancers constitute simplified cancer systems to investigate the relative and interdependent contributions of genetic and nongenetic factors and to document identity shifts. Citation Format: Olivier Delattre, G.A. Franzetti, K. Laud-Duval, A. Brisac, Valentina Boeva, Caroline Louis-Brennetot, Agathe Peltier, Simon Durand, Cécile Pierre-Eugène, Didier Surdez, Eve Lapouble, Gaelle Pierron, Sandrine Grossetête-Lalami, Isabelle Janoueix-Lerosey. Identity shifts in pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA02.
In Vivo PET Tracking of 89Zr-Labeled Vγ9Vδ2 T Cells to Mouse Xenograft Breast Tumors Activated with Liposomal Alendronate
Authors: Francis Man, Lindsay Lim, Alessia Volpe, Alberto Gabizon, Hilary Shmeeda, Benjamin Draper, Ana C. Parente-Pereira, John Maher, Philip J. Blower, Gilbert O. Fruhwirth, Rafael T.M. de Rosales
Journal: Molecular Therapy (2018)

Gammadelta T (γδ-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion, and favorable safety profile. The development of γδ-T cell therapies would benefit from non-invasive cell-tracking methods and increased targeting to tumor sites. Here we report the use of [89Zr]Zr(oxinate)4 to track Vγ9Vδ2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that 89Zr-labeled Vγ9Vδ2 T cells retained their viability, proliferative capacity, and anti-cancer cytotoxicity with minimal DNA damage for amounts of 89Zr ≤20 mBq/cell. Using a mouse xenograft model of human breast cancer, 89Zr-labeled γδ-T cells were tracked by PET imaging over 1 week. To increase tumor antigen expression, the mice were pre-treated with PEGylated liposomal alendronate. Liposomal alendronate, but not placebo liposomes or non-liposomal alendronate, significantly increased the 89Zr signal in the tumors, suggesting increased homing of γδ-T cells to the tumors. γδ-T cell trafficking to tumors occurred within 48 hr of administration. The presence of γδ-T cells in tumors, liver, and spleen was confirmed by histology. Our results demonstrate the suitability of [89Zr]Zr(oxinate)4 as a cell-labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before γδ-T cell administration. Gammadelta T (γδ-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion, and favorable safety profile. The development of γδ-T cell therapies would benefit from non-invasive cell-tracking methods and increased targeting to tumor sites. Here we report the use of [89Zr]Zr(oxinate)4 to track Vγ9Vδ2 T cells in vivo by positron emission tomography (PET). In vitro, we showed that 89Zr-labeled Vγ9Vδ2 T cells retained their viability, proliferative capacity, and anti-cancer cytotoxicity with minimal DNA damage for amounts of 89Zr ≤20 mBq/cell. Using a mouse xenograft model of human breast cancer, 89Zr-labeled γδ-T cells were tracked by PET imaging over 1 week. To increase tumor antigen expression, the mice were pre-treated with PEGylated liposomal alendronate. Liposomal alendronate, but not placebo liposomes or non-liposomal alendronate, significantly increased the 89Zr signal in the tumors, suggesting increased homing of γδ-T cells to the tumors. γδ-T cell trafficking to tumors occurred within 48 hr of administration. The presence of γδ-T cells in tumors, liver, and spleen was confirmed by histology. Our results demonstrate the suitability of [89Zr]Zr(oxinate)4 as a cell-labeling agent for therapeutic T cells and the potential benefits of liposomal bisphosphonate treatment before γδ-T cell administration.
β-Blockers and bone health
Authors: Lorenz C. Hofbauer, Holger Henneicke
Journal: Journal of Clinical Investigation (2018)

Bone metabolism is controlled by endocrine, paracrine, and inflammatory signals that continuously operate in health and disease. While these signals are critical for skeletal adaptation during development, longitudinal growth, and repair, disturbances such as sex hormone deficiency or chronic inflammation have unambiguously been linked to bone loss and skeletal fragility across species. In the current issue of the JCI, Khosla et al. evaluated the role of sympathetic outflow and present evidence to support the idea that the sympathetic nervous system regulates bone metabolism in humans, primarily via the β1-adrenergic receptor.
A PILOT STUDY OF THE ACCEPTANCE AND TOLERABILITY OF TUMOUR TREATING FIELDS IN ADULT GLIOBLASTOMA PATIENTS
Authors: Andrew Brodbelt, Matthew Williams, Antonia Thorpe, Samantha Mills, Stephen Price, Elvira Lekka, Colin Watts, Charles Davis, Michael Jenkinson
Journal: Neuro-Oncology (2018)

Tumour treating fields are a novel anticancer treatment that uses alternate electrical fields to disrupt cell division. It has been shown in a randomized controlled trial to significantly improve survival in patients with Glioblastoma. Use of the device is intensive for patients, with almost constant electrode application and battery use. The acceptability and tolerability for this new treatment is not known in a UK setting. The treatment currently costs €21,000 per month. Three UK centres were offered support for trialling the treatment. Patients with proven MGMT unmethylated glioblastoma, had completed Stupp, had a performance score >70, and had social support (for placing the electrodes), where approached. Monthly assessments of compliance and quality of life (QOL) (ECOG BT 30), and quarterly MRIs and tolerability questionnaires were completed. Oncologists in one centre refused to support any use of the device, so no patients were approached in that centre. 8 patients were approached in the other two centres, 5 accepted, and 1 further patient had treatment started elsewhere. All patients tolerated the treatment, with no reduction in QOL outcomes. Patients approached were grateful to have been offered the treatment. The main reason for refusal was monthly travelling for compliance checks. The main adverse comments related to the weight of the mobile battery. One patient had skin irritation, and two patients found that the only aspect of life affected was showering. Two patients have progressed on treatment, with one having second line surgery, and both second line chemotherapy. Tumour treating fields is a well tolerated but intensive treatment, and acceptable to a UK population. A significant reduction in cost is required to allow routine UK use on the NHS.
Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration
Authors: Xu Zhang, Hui Shi, Xiao Yuan, Pengcheng Jiang, Hui Qian, Wenrong Xu
Journal: Molecular Cancer (2018)

Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.
THE DEVELOPMENT OF AN INTERDISCIPLINARY ASSESSMENT CLINIC TO ADDRESS THE HEALTH RELATED QUALITY OF LIFE (HRQOL) ISSUES OF PATIENTS WITH A MENINGIOMA
Authors: Serena Hartley, Philip Kane, Anil Varma
Journal: Neuro-Oncology (2018)

Evidence demonstrating the impact a meningioma brain tumour may have on the HRQOL of a patient undergoing neurosurgery has supported the development of an interdisciplinary assessment clinic and highlighted their therapeutic and supportive care needs. Meningiomas are often benign, yet they can have a complex presentation. NICE (2006) recommend that supportive care should be available for all brain tumour patients, however this can be limited for patients with a meningioma, as surgery is deemed to be curative and support has focussed on patients with malignant tumours. Self-reported HRQOL outcomes are now recognised as providing further understanding of the effects of the condition and treatments. The interdisciplinary clinic provides comprehensive Neuropsychology and Allied Health Professional assessment before and after surgery. The clinic, alongside addressing their needs, provides understanding of the physical and psychosocial effects of the tumour, to support rationalised clinical decision-making for proceeding with surgery. The HRQOL of 30 consecutive patients attending the interdisciplinary clinic were compared before and six months following surgery using the FACT-BR, a disease-specific PROM and both were compared to normal controls. The HRQOL of patients before and following surgery was significantly lower than normal controls. The HRQOL of 60% of patients improved and 40% deteriorated following surgery, although this was not statistically significant. The main issues before and following surgery were identified. These results support that patients with a meningioma experience HRQOL issues, indicating the need for an interdisciplinary clinic to address their therapeutic and supportive care needs. The increase in incidental findings due to more frequent neuroimaging has also raised the importance of the need for careful consideration of the risk/benefits for proceeding with surgery, due to the potential negative impact on HRQOL, as conservative management may be preferable in some instances due to the slow-growing nature of the tumour.