tbuckley/cabot-search huggingface dataset:
Atrial fibrillation (AF) in patients with CLL treated with ibrutinib: Assessing prediction models and clinical outcomes.
Authors: William Archibald, Kari G. Rabe, Brian Kabat, Timothy Call, Wei Ding, Neil E. Kay, Saad Kenderian, Eli Muchtar, Jose Francisco Leis, Susan M. Schwager, Amber Koehler, Amie L. Fonder, Susan L. Slager, Tait D. Shanafelt, Sameer Ashok Parikh
Journal: Journal of Clinical Oncology (2019)

7522 Background: Ibrutinib therapy is associated with an increased risk (~15%) of AF. An accurate risk assessment model for the development of AF in pts starting ibrutinib is not established, and outcomes after AF are not well described. Methods: An IRB approved retrospective review of CLL pts treated with ibrutinib at Mayo Clinic between Oct 2012 and Nov 2018 was conducted. Results: 299 pts were identified with a total of 565 years of ibrutinib exposure (Table). After a median follow-up of 24 months (range 0–70 months), 51 pts developed treatment-emergent AF (13 [25%] CTCAE 3 or higher). Our study assessed 3 clinical prediction models, the Framingham (Schanbel:Lancet 2009), Italian (Visentin:Blood 2018;132:3118), and Shanafelt (Shanafelt:Leuk Lymp; 2017) risk scores. Based on a lower Akaike information criteria, the Italian score was best able to predict risk of treatment emergent AF (2-year risk of AF with score 0 6%; 1-2 8%; 3-4 26%; 5+ 47%). Thirty (61%) pts were treated with medical therapy for AF (27 rate control; 2 rhythm control; 1 both). 16 (31%) pts underwent interventional therapy (3 AV node ablation; 11 cardioversion; and 2 pacemaker). Twelve (23%) pts temporarily held ibrutinib and resumed their original dose, 22 (43%) pts continued reduced dose ibrutinib and 11 (22%) continued their initial ibrutinib dose. Six (12%) pts permanently discontinued ibrutinib. Of 51 pts with treatment-emergent AF, 41 (80%) had a CHA 2 DS 2 -VASc score of ≥2 (41% received anticoagulation alone; 12% received antiplatelet therapy alone; 10% received both). No pt developed a thrombotic stroke after treatment-emergent AF. Two major bleeds, (1 GI and 1 intracranial) occurred, one in a pt on concomitant antiplatelet and anticoagulation therapy, and one in a pt receiving neither. The development of AF was associated with shorter event-free survival (HR 2.5, 95%CI 1.5-4.2, p&lt;.001) and shorter overall survival (HR 3.5, 95%CI 2.0-6.3, p&lt;.001). Conclusions: The Italian score was the best predictor of AF development in this cohort of ibrutinib treated pts. Although the vast majority of pts who develop AF after ibrutinib are able to continue therapy, the occurrence of AF appears to be associated with shorter EFS and OS. [Table: see text]
Low Free Sugar Diet in Adolescents With Nonalcoholic Fatty Liver Disease
Authors: George Yizhou Tang, Jiali Gao
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 1389: Single-cell sequencing to identify genetic variant accelerating shedding of CTCs into peripheral blood in gastric cancer patients
Authors: Yilin Li, Xiaotian Zhang, Jifang Gong, Daisy Dandan Wang, Mingxia Qi, Yanyan Li, Dan Liu, Chunxiang Wang, Peter Ping Lin, Lin Shen
Journal: Cancer Research (2019)

Abstract Circulating tumor cells (CTCs) are shed from primary or metastatic tumors into blood circulation, which may carry specific genetic characteristics related to hematogenous metastasis. Drawbacks of conventional EpCAM or cell size-dependent CTC detection and relevant single-cell sequencing technologies have limited discovery of specific genetic variants in CTCs. In the current study, a novel integrated SE-iFISH strategy, despite cell size or epithelial marker status, was applied to detect CTCs in advanced gastric cancer (GC) patients. Obtained CTCs were classified into diverse subtypes upon different chromosome ploidy. Fifty-three aneuploid CTCs identified by iFISH in 6 of naïve GC patients were isolated by a novel non-laser microscopic single cell manipulator (NMSCM), and subjected to modified Multiple Displacement Amplification (MDA) and subsequent single-cell sequencing. Compared with the conventional PCR, MDA generates 2 to 100-kb products with a lower error rate and achieves high fidelity whole genome amplification. Sequencing targeting 50 tumor genes of single CTC as well as paired primary tumor specimens was performed. Moreover, leukocytes genomic DNA as germline controls were included. Obtained results showed that high frequent SNV in genes such as TP53 were detected in both CTCs and the paired primary tumor mass. Furthermore, CTCs had considerable genetic heterogeneity compared to the paired primary tumor lesions. In particular, the CDKN2AA68V variant is frequently detected in CTCs but the paired primary GC tumor. We propose that the specific CDKN2AA68V variant carried by GC CTCs with high frequency, but low in the examined whole population of cancer cells in paired primary tumor lesions, may serve as the driver to promote CTCs shed into peripheral blood and to further facilitate hematogenous metastasis. Systematic in vitro and ex vivo studies are in progress to investigate roles of CDKN2A mutation in hematogenous dissemination in GC. Citation Format: Yilin Li, Xiaotian Zhang, Jifang Gong, Daisy Dandan Wang, Mingxia Qi, Yanyan Li, Dan Liu, Chunxiang Wang, Peter Ping Lin, Lin Shen. Single-cell sequencing to identify genetic variant accelerating shedding of CTCs into peripheral blood in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1389.
Abstract 5293: Celf2 suppresses non-small cell lung carcinoma growth by inhibiting the prex2-pten interaction
Authors: Yiu To Yeung, Suyu Fan, Bingbing Lu, Xiang Li, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2019)

Abstract The phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway is important in the regulation of cell proliferation through its production of phosphatidylinositol 3,4,5-triphosphate (PIP3). Activation of this pathway is frequently observed in human cancers, including non-small cell lung cancer. The PI3- K/Akt pathway is negatively regulated by the dual-specificity phosphatase and tensin homolog (PTEN) protein. PTEN acts as a direct antagonist of PI3-K by dephosphorylating PIP3. Studies showed that PTEN phosphatase activity is inhibited by PREX2, a guanine nucleotide exchanger factor (GEF). Multiple studies revealed that CELF2, an RNA binding protein, cooperates synergistically with PTEN as a tumor suppressor in many cancers. However, the underlying mechanism as to how CELF2 enhances PTEN activity remains unclear. Here, we report that CELF2 interacts with PREX2 and reduces the association of PREX2 with PTEN. Consistent with this observation, PTEN phosphatase activity is upregulated with CELF2 overexpression and overexpression of CELF2 represses both Akt phosphorylation and cell proliferation only in the presence of PTEN. CELF2 gene delivery significantly inhibited PDX tumor growth. We analyzed 87 paired clinical lung adenocarcinoma samples and results showed that CELF2 protein expression is down-regulated in tumor tissues and associated with poor prognosis. Analysis of TCGA datasets showed that CELF2 expression is also associated with shorter patient survival time in many cancers. Overall, our work suggests that CELF2 plays a novel role in PI3-K signaling by antagonizing the oncogenic effect of PREX2. Citation Format: Yiu To Yeung, Suyu Fan, Bingbing Lu, Xiang Li, Ann M. Bode, Zigang Dong. Celf2 suppresses non-small cell lung carcinoma growth by inhibiting the prex2-pten interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5293.
Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer
Authors: Ning Zhao, Stephanie O. Peacock, Chen Hao Lo, Laine M. Heidman, Meghan A. Rice, Cale D. Fahrenholtz, Ann M. Greene, Fiorella Magani, Valeria A. Copello, Maria Julia Martinez, Yushan Zhang, Yehia Daaka, Conor C. Lynch, Kerry L. Burnstein
Journal: Science Translational Medicine (2019)

Antagonism of arginine vasopressin receptor 1a inhibits growth of emergent, established, and bone metastatic castration-resistant prostate cancer.
Abstract 1479: Cardiac Neural Crest Specific Deletion of Notch2 Causes Defective Development of the Outflow Tract.
Authors: Prajakta Varadkar, Ma Ge, Brenton McCright
Journal: Circulation (2007)

Notch signaling is an evolutionarily conserved pathway that influences cell fate decisions required for the development of most organ systems including the heart. To study the functional requiremen...
Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis
Authors: Falak Sher, Mir Hossain, Davide Seruggia, Vivien A. C. Schoonenberg, Qiuming Yao, Paolo Cifani, Laura M. K. Dassama, Mitchel A. Cole, Chunyan Ren, Divya S. Vinjamur, Claudio Macias-Trevino, Kevin Luk, Connor McGuckin, Patrick G. Schupp, Matthew C. Canver, Ryo Kurita, Yukio Nakamura, Yuko Fujiwara, Scot A. Wolfe, Luca Pinello, Takahiro Maeda, Alex Kentsis, Stuart H. Orkin, Daniel E. Bauer
Journal: Nature Genetics (2019)
Abstract 16073: Quality of Life for Patients and Caregivers After Implantation of a Ventricular Assist Device
Authors: Julie T Bidwell, James O Mudd, Jill M Gelow, Karen S Lyons, Shirin O Hiatt, Christopher V Chien, Kathleen L Grady, Christopher S Lee
Journal: Circulation (2015)

Introduction: Ventricular Assist Device (VAD) implantation is a therapeutic option for many patients with advanced heart failure (HF). Although patient quality of life (QOL) generally improves after VAD, little is known about changes in QOL among caregivers of patients undergoing VAD implantation. Hypothesis: We hypothesized that patient QOL would improve and caregiver QOL would worsen after VAD implantation. Methods: This was a prospective longitudinal study of patients receiving VAD therapy for advanced HF and their informal caregivers (n=27 dyads). QOL was measured pre- VAD implant and at 30 and 90 days post-implant. For patients, QOL was measured with the Kansas City Cardiomyopathy Questionnaire. For caregivers, QOL was measured with the SF-36. Both measures range from 0-100; higher scores indicate better QOL. Pre vs. post VAD comparisons in QOL were examined using paired t-tests. Results: Caregivers and patients were 54.9±10.3 and 54.3±14.6 years of age, respectively. Most patients (88.9%) were male, and most (63.0%) were receiving a VAD as a bridge to transplant. A majority of caregivers were female (85.2%) and the patients’ spouses (77.8%). Patient QOL improved significantly from baseline (28.4±20.7) to 30 days (50.0±25.3; t=-4.1, p&lt;0.01) and 90 days post-implant (62.7±20.0; t=-2.3, p=0.03). Caregiver QOL worsened significantly from baseline (55.2±7.1) to 30 days (51.9±10.3; t=2.4, p=0.03) and remained at that level at 90 days post-implant (52.1±1.9; t=0.3, p=0.76). Conclusions: Although VAD therapy is associated with QOL benefit for patients, clinicians and researchers should recognize that caregivers are at risk for significant worsening of QOL post-implant. Caregivers of patients undergoing VAD implantation may benefit from greater anticipatory guidance and ongoing support.
Cost of metastatic colorectal cancer drugs per month of life gained in Spain
Authors: J. Vieitez de Prado, S. Encinas García, E. Grande Pulido, R. Sánchez Nieto, S. González Moreno, C. Garrán del Río, O. Alonso Casado, G. Ortega Pérez, C. Mombiedro Lozano, S. Grasso Cicala
Journal: Annals of Oncology (2019)
Eliminating Postoperative Radiation to the Pathologically Node-Negative Neck: Long-Term Results of a Prospective Phase II Study
Authors: Jessika A. Contreras, Christopher Spencer, Todd DeWees, Bruce Haughey, Lauren E. Henke, Re-I Chin, Randal Paniello, Jason Rich, Ryan Jackson, Peter Oppelt, Patrik Pipkorn, Jose Zevallos, Rebecca Chernock, Brian Nussenbaum, Mackenzie Daly, Hiram Gay, Douglas Adkins, Wade Thorstad
Journal: Journal of Clinical Oncology (2019)

The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma.Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire.Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7th edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT (P > .05).Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.
Safety analysis of bevacizumab plus NovoTTF-100A in patients with recurrent malignant gliomas.
Authors: Grace Elzinga, Amy T Chung, Eric Wong
Journal: Journal of Clinical Oncology (2013)

2082 Background: Both bevacizumab and the NovoTTF-100A device are treatments approved by the FDA for recurrent glioblastoma. We examined our single-institution experience in using this combination for patients with recurrent malignant gliomas. Methods: We identified retrospectively the side effects experienced by patients while on both bevacizumab and NovoTTF-100A. Overall survival was also tabulated from initiation of this combined modality treatment. Results: There were 14 men and 6 women. Their median age was 54 (range 29-76). All had Karnofsky Performance Status of 60 or above. Fourteen patients received NovoTTF-100A after failure of bevacizumab treatment while the other 6 received both treatments concurrently. The median duration of bevacizumab plus NovoTTF-100A treatments was 2.3 (95% CI 1.8-4.7) months. There were 2 patients who experienced electric shock sensation on the scalp from a poorly-applied transducer array that resulted in minor scalp burns, 3 patients developed scalp rashes (2 moderate and 1 severe), 4 patients experienced liquefied hydrogel from the arrays as a result of high ambient temperature during summer months, 2 experienced vivid dreams of applying the arrays and 3 removed the arrays while periods of sleep or confusion. Only one patient required NovoTTF-100A treatment interruption because of severe scalp rash. No hemorrhage into the malignant glioma or thromboembolism was seen in this cohort. From the time of initiation of bevacizumab plus NovoTTF-100A treatments, the Kaplan-Meier median overall survival was 5.6 (95% CI 4.2-N/A) months. Conclusions: No additive or synergistic side effects were observed when patients were treated with both bevacizumab and NovoTTF-100A. Further evaluation in a prospective manner would be needed to evaluate both side effects and efficacy of this treatment combination.
Abstract 14993: Alteration in b2-ARs Dependent cAMP Signalling Linked to Post Infarction Remodelling of T-tubules in Rat Cardiomyocytes
Authors: Sophie Schobesberger, Sergiy Tokar, Anamika Bhargava, Peter Wright, Markus Sikkel, Niloy Mitra, Aron Monszpart, Alexander Lyon, Sian E. Harding, Julia Gorelik
Journal: Circulation (2013)

The T-tubule (TT) network of cardiomyocytes (CMs) compartmentalizes beta-2 adrenergic receptor (β2AR) signalling allowing stringent control of spread of cAMP. In heart failure these structures are disrupted, disturbing cAMP compartmentalization, with TT loss and associated changes in cAMP signalling occurring in a stepwise manner. We studied these changes at different stages of disease progression. Ventricular CMs were isolated from post-myocardial infarction (MI) failing rats at 4 weeks (compensated), 8 and 16 weeks (decompensated). TT density, regularity, and axial junctions were determined by confocal imaging of di-8-ANNEPS stained CMs. Scanning Ion Conductance Microscopy (SICM) generated CM scans allowed assessment of topographical features. cAMP levels were determined using a FRET sensor combined with SICM. β2AR were stimulated with isoproterenol with a β1-specific antagonist CGP20712A, by whole cell perfusion, or locally via SICM nanopipette. NKH477 an adenylate cyclase (AC) activator was applied su...
Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors
Authors: Paloma Cejas, Yotam Drier, Koen M. A. Dreijerink, Lodewijk A. A. Brosens, Vikram Deshpande, Charles B. Epstein, Elfi B. Conemans, Folkert H. M. Morsink, Mindy K. Graham, Gerlof D. Valk, Menno R. Vriens, Carlos Fernandez-del Castillo, Cristina R. Ferrone, Tomer Adar, Michaela Bowden, Holly J. Whitton, Annacarolina Da Silva, Alba Font-Tello, Henry W. Long, Elizabeth Gaskell, Noam Shoresh, Christopher M. Heaphy, Ewa Sicinska, Matthew H. Kulke, Daniel C. Chung, Bradley E. Bernstein, Ramesh A. Shivdasani
Journal: Nature Medicine (2019)
Abstract 17862: Protection From Acute Myocardial Infarction in Humans is Associated With a Genetic Variation Near a Novel Gene Encoding a Human Protein Binding to a Mouse Model of Vulnerable Plaque
Authors: Joseph M Devaney, Mary Susan Burnett, Ronald Reiter, Benjamin D Horne, Marcel O Schmidt, Muredach P Reilly, Heather Gordish-Dressman, Mingyao Li, Liming Qu, Christopher W Knouff, Augusto D Pichard, Kenneth M Kent, Lowell Satler, Joseph M Lindsay, Ron Waksman, Stefan Blankenberg, Stanley L Hazen, Robert Roberts, Alexandre F Stewart, Li Chen, W.H. Wilson Tang, George A Wells, Ruth McPherson, Vincent Mooser, Daniel J Rader, Anton Wellstein, Stephen E Epstein
Journal: Circulation (2010)

Introduction: Human vulnerable plaque (VP) has certain unique phenotypic features. We developed a mouse model with atherosclerotic lesions containing many of these features, and then used a unique ...
Melanoma and skin cancers in airline pilots and cabin crew
Authors: K. Miura, C.M. Olsen, S. Rea, J. Marsden, A.C. Green
Journal: British Journal of Dermatology (2019)

Ultraviolet radiation (UVR) from the sun is a major cause of skin cancer, including melanoma which is the most deadly form of the disease. As part of their jobs, airline pilots and cabin crews are exposed to cosmic radiation, and airline pilots may receive UVR on the flight deck, potentially resulting in skin cancer. The authors, based in Australia and the U.K, therefore systematically reviewed all relevant studies to find out risk of, and mortality (death) from, melanoma and other skin cancers in airline pilots and cabin crews. The majority of the 12 studies identified were conducted in the 1970s to 1990s in Europe or North America. They found that melanoma and other skin cancers were around twice as common in pilots and cabin crews as in the general community. Melanoma deaths were also doubled in the pilots but not in the aircrew. Ultraviolet B radiation from the sun is the main cause of melanoma and other skin cancer, but ultraviolet B radiation is not detectable or not increased above ground level values in modern airline cabins and flight decks. Also occupational levels of cosmic radiation among pilots and cabin crew are assessed not to be hazardous. However, high recreational sun exposure (i.e. time in the sun when not working) among airline pilots and cabin crews cannot be ruled out, especially in the existing published studies reflecting sun exposure patterns of previous decades. The authors concluded that airline pilots’ and cabin crews’ high risk of melanoma and other skin cancers could not be clearly attributed to occupational (job related) factors. They called for up‐to‐date studies of the topic.