tbuckley/cabot-search huggingface dataset:
Visit-to-Visit Variability of Hemoglobin A1c in People Without Diabetes and Risk of Major Adverse Cardiovascular Events and All-Cause Mortality
Authors: Jonas Ghouse, Morten W. Skov, Jørgen K. Kanters, Bent Lind, Jonas L. Isaksen, Paul Blanche, Stig Haunsø, Lars Køber, Jesper H. Svendsen, Morten S. Olesen, Anders G. Holst, Thomas A. Gerds, Jonas B. Nielsen
Journal: Diabetes Care (2018)

We aimed to study whether visit-to-visit variability of glycated hemoglobin A1c (HbA1c) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes.We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA1c measurements within normal range (<6.5% [48 mmol/mol]). For each individual, we measured the HbA1c variability as the SD of the residuals obtained from a linear regression on the three HbA1c measurements. From the linear regression, we also obtained the estimated index HbA1c (intercept) and the trend over time (slope). Follow-up began at the date of the third measurement. Associations between HbA1c variability and outcome were analyzed using Cox regression, adjusted for traditional risk factors, intercept, and trend and reported as hazard ratio per SD increase in variability (HRSD).In total, 6,756 individuals were included. During a median follow-up time of 6.3 years, 996 developed MACE, 856 died, and 1,267 developed type 2 diabetes. We found a significant association between increasing HbA1c variability and incident MACE (HRSD 1.09 [95% CI 1.03-1.15]) and all-cause mortality (HRSD 1.13 [95% CI 1.07-1.20]), whereas there were no associations with type 2 diabetes (HRSD 1.00 [95% CI 0.95-1.05]). We calculated 5-year absolute risks of MACE and all-cause mortality and found clinically relevant differences across several age, sex, comorbidity, and HbA1c variability-defined subgroups.In a primary care population free of diabetes and cardiovascular disease, high HbA1c variability was associated with increased risks of MACE and all-cause mortality.
Combined ipilimumab and nivolumab first-line and after BRAF-directed targeted therapies in advanced melanoma patients
Authors: H.C. Dearden, R. Mason, B. Nguyen, J.A. Soon, J.L. Smith, M. Randhawa, A. Mant, L. Warburton, S. Lo, T. Meniawy, A. Guminski, P. Parente, S. Ali, A. Haydon, G.V. Long, M.S. Carlino, M. Millward, V.G. Atkinson, A.M. Menzies
Journal: Annals of Oncology (2018)
P3.11-27 Lung Cancer Diagnosed at Age 50-54 Years: Survival as Poor as Older Patients
Authors: P. Yang, L. Luo, Y. Wang, J. Wampfler, D. Liu, Y. Wang, S. Stoddard, Y. Yang, H. Xie, D. Midthun
Journal: Journal of Thoracic Oncology (2018)
Phrenic nerve stimulation to treat patients with central sleep apnoea and heart failure
Authors: Maria Rosa Costanzo, Piotr Ponikowski, Andrew Coats, Shahrokh Javaheri, Ralph Augostini, Lee R. Goldberg, Richard Holcomb, Andrew Kao, Rami N. Khayat, Olaf Oldenburg, Christoph Stellbrink, Scott McKane, William T. Abraham
Journal: European Journal of Heart Failure (2018)

The presence of central sleep apnoea (CSA) is associated with poor prognosis in patients with heart failure (HF). The aim of this analysis was to evaluate if using phrenic nerve stimulation to treat CSA in patients with CSA and HF was associated with changes in HF-specific metrics.All patients randomized in the remedē System Pivotal Trial and identified at baseline with HF were included (n = 96). Effectiveness data from treatment and former control groups were pooled based on months since therapy activation. Changes from baseline to 6 and 12 months in sleep metrics, Epworth Sleepiness Scale, patient global assessment health-related quality of life, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and echocardiographic parameters are reported. HF hospitalization, cardiovascular death, and the composite of HF hospitalization or cardiovascular death within 6 months are reported by the original randomized group assignment for safety assessment. Sleep metrics and quality of life improved from baseline to 6 and 12 months. At 12 months, MLHFQ scores changed by -6.8 ± 20.0 (P = 0.005). The 6-month rate of HF hospitalization was 4.7% in treatment patients (standard error = 3.3) and 17.0% in control patients (standard error = 5.5) (P = 0.065). Reported adverse events were as expected for a transvenous implantable system.Phrenic nerve stimulation reduces CSA severity in patients with HF. In parallel, this CSA treatment was associated with benefits on HF quality of life.
GW29-e0969 TERT and GDF11 Cooperate in Rejuvenating Senescent Endothelial Progenitor Cells and Predict Prognosis of Elderly Patients with Myocardial Infarction
Authors: Shaoheng Zhang, Zhao Lan, Wang Jiahong, Chen Nannan, Su Feng, Cui Jin, Wei Jiarui
Journal: Journal of the American College of Cardiology (2018)
Abstract 19428: TRAF3IP2 Mediates Aldosterone-induced Cardiac Hypertrophy and Fibrosis
Authors: Siddesha Jalahalli Mariswamy, Siva Sankara Vara Prasad Sakamuri, Yariswamy Manjunath, Anthony J Valente, Ulrich Siebenlist, Jason D Gardner, Chandrasekar Bysani
Journal: Circulation (2014)

Background: Aldosterone (Aldo) is a key regulator of blood pressure and electrolyte balance. Aldo/salt has been shown to induce oxidative stress, inflammation, cardiac hypertrophy and fibrosis. TRAF3 interacting protein 2 (TRAF3IP2) is a cytoplasmic redox-sensitive adaptor molecule and an upstream regulator of NF-κB and AP-1. It plays a critical role in the regulation of various proinflammatory cytokines that exert prohypertrophic and profibrotic effects. Therefore, we hypothesized that TRAF3IP2 is a critical mediator of Aldo/salt-induced cardiac hypertrophy and fibrosis. Methods: TRAF3IP2-null and wild type (WT) mice (male, 12-13 weeks) were infused continuously with Aldo for 4 weeks via mini-osmotic pumps (0.2 mg/Kg/day; n = 6-8). Mice were fed 1% NaCl in drinking water. Salt alone served as control. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography, myocardial function by echocardiography, cardiac hypertrophy by heart weight to body weight ratios, cardiac fibrosis by trichrome Gomori, and gene and protein expression by RT-qPCR, immunoblotting and ELISA. Results: Aldo/salt elevated SBP to a similar extent in both TRAF3IP2-null and WT mice. Aldo/salt upregulated TRAF3IP2 expression in left ventricular homogenates from WT mice, and TRAF3IP2 gene deletion (vs. WT) blunted cardiac hypertrophy by 54% (p &lt; 0.05), suppressed ANP expression by 3.5 fold (p &lt; 0.05), prevented concentric LV remodeling (decreased LVPWs; 93%; p &lt; 0.01, LVPWd; 95%; p &lt; 0.05, LVAWs; 29.8%; p &lt; 0.05 and LVAWd; 26.2%, and increased LVIDs; 19.2%; p &lt; 0.01 and LVIDd; 8.53%) and markedly reduced both interstitial and perivascular fibrosis. Further, TRAF3IP2 gene deletion inhibited Aldo/salt-induced p65 and c-Jun activation, and expression of inflammatory cytokine (IL-18 and IL-6), matrix metalloproteinase (MMP2) and extracellular matrix proteins (collagen Iα1 and IIIα1). TRAF3IP2 gene deletion also blunted mRNA and protein expression of lysyl oxidase, an enzyme involved in collagen crosslinking. Conclusions: TRAF3IP2 gene deletion blunts Aldo/salt-induced cardiac hypertrophy and fibrosis by inhibiting proinflammatory, prohypertrophic, and profibrotic effects, signifying its potential as a therapeutic target in hypertrophic heart diseases.
Efficacy and safety of bosutinib vs imatinib in Indian and non-Indian patients with newly diagnosed chronic phase chronic myeloid leukemia: Subgroup analysis from the BELA trial
Authors: H. Malhotra, A. Maru, N. Khattry, M.V. Ramanan, E. Leip, R.J. Crescenzo, C. Gambacorti-Passerini, J.E. Cortes
Journal: Annals of Oncology (2018)
Outcomes of 1,327 patients operated on through twelve multispecialty surgical volunteerism missions: A retrospective cohort study
Authors: Rifat Latifi, Renato Rivera, Mahir Gachabayov, Maria Melinda Borja Chiong, R Dirk Noyes, Michael Kleinmann, Fancy S Baluyot, Elizabeth Tilley, David Samson, Ayman El-Menyar
Journal: International Journal of Surgery (2018)
Transcriptomic and Protein Analysis of Small-cell Bladder Cancer (SCBC) Identifies Prognostic Biomarkers and DLL3 as a Relevant Therapeutic Target
Authors: Vadim S. Koshkin, Jorge A. Garcia, Jordan Reynolds, Paul Elson, Cristina Magi-Galluzzi, Jesse K. McKenney, Kumiko Isse, Evan Bishop, Laura R. Saunders, Aysegul Balyimez, Summya Rashid, Ming Hu, Andrew J. Stephenson, Amr F. Fergany, Byron H. Lee, Georges-Pascal Haber, Afshin Dowlati, Timothy Gilligan, Moshe C. Ornstein, Brian I. Rini, Mohamed E. Abazeed, Omar Y. Mian, Petros Grivas
Journal: Clinical Cancer Research (2018)

Transcriptomic profiling can shed light on the biology of small-cell bladder cancer (SCBC), nominating biomarkers, and novel therapeutic targets.Sixty-three patients with SCBC had small-cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess in vivo efficacy of DLL3-targeting antibody-drug conjugate (ADC).Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most "normal-like" pattern of gene expression had longer overall survival (OS) compared with the other 3 clusters while patients with the most "metastasis-like" pattern had the shortest OS (P = 0.047). Expression of DLL3, PDL1, ASCL1, and CD56 was confirmed by IHC in 68%, 30%, 52%, and 81% of tissue samples, respectively. In a multivariate analysis, DLL3 protein expression on >10% and CD56 expression on >30% of tumor cells were both prognostic of shorter OS (P = 0.03 each). A DLL3-targeting ADC showed durable antitumor efficacy in a SCBC PDX model.Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of DLL3 mRNA and protein is common in SCBC and correlates with shorter OS. A DLL3-targeted ADC demonstrated in vivo efficacy superior to chemotherapy in a PDX model of SCBC.
Abstract 17947: Variation in Practice Patterns and Outcomes Across UNOS Allocation Regions
Authors: Benjamin J Vaccaro, Tariq Ahmad, Pooja Rao, Rohit Ghosh, Prashant Warier, Daniel L Jacoby, Michael Chen, Lavanya Bellumkonda, Jeffrey M Testani, Nihar R Desai
Journal: Circulation (2016)

Background: Efforts are underway to modify the United Network for Organ Sharing (UNOS) regions for cardiac transplantation to ensure more efficient allocation of organs. Little is known about conte...
GW29-e1510 Invasive reperfusion after 12 hours of the symptom onset remains beneficial in patients with ST-segment elevation myocardial infarction: evidence from a meta-analysis of published data
Authors: Haitao Yang, Yitong Ma, Yining Yang, Xiaomei Li, Fen Liu, Bangdang Chen, Xiang Xie
Journal: Journal of the American College of Cardiology (2018)
An Experimental Ethics, but an Ethical Experiment? Anthropological Perspectives on Using Unproven Vaccines on Endangered Primates
Authors: Courtney Addison, Nicholas Malone
Journal: The American Journal of Bioethics (2018)

Edwards and colleagues (2018) propose testing Ebola vaccines in wild primate populations. Their argument is threefold: Field trials could bolster the evidence base for Ebola vaccines’ efficacy in h...
Accounting for All Costs in the Total Cost of Chimeric Antigen Receptor T-Cell Immunotherapy
Authors: Melanie D. Whittington, Daniel A. Ollendorf, Jonathan D. Campbell
Journal: JAMA Oncology (2018)

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Final overall survival results of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) vs R-CHOP in transplantation-ineligible patients (pts) with newly diagnosed mantle-cell lymphoma (MCL): A randomized, open-label, phase III (LYM-3002) study
Authors: F. Cavalli, J. Jin, H. Pylypenko, G. Verhoef, N. Siritanaratkul, J. Drach, M. Raderer, J. Mayer, J. Pereira, G. Tumyan, R. Okamoto, S. Nakahara, P. Hu, C. Appiani, S. Nemat, T. Robak
Journal: Annals of Oncology (2018)
Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis
Authors: Abdullah Kutlar, Julie Kanter, Darla K. Liles, Ofelia A. Alvarez, Rodolfo D. Cançado, João R. Friedrisch, Jennifer M. Knight‐Madden, Andreas Bruederle, Michael Shi, Zewen Zhu, Kenneth I. Ataga
Journal: American Journal of Hematology (2018)

Abstract The cell adhesion molecule P‐selectin plays a key role in the pathogenesis of a vaso‐occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double‐blind, placebo‐controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti‐P‐selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2‐4/5‐10), SCD genotype (HbSS/non‐HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event‐free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5‐10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time‐to‐first VOC vs placebo in these subgroups. The rates of treatment‐emergent adverse events were similar between treatment arms across all subgroups. This post hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event‐free and delays time‐to‐first VOC.
SAT0616 Ten-year retention rate of infliximab in patients with behÇet’s disease-related uveitis
Authors: J. Sota, C. Fabiani, A. Vitale, G. Emmi, G. Lopalco, V. Venerito, I. Orlando, R. Franceschini, B. Frediani, M. Galeazzi, F. Iannone, G.M. Tosi, L. Cantarini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> To date, a few studies have reported the long-term efficacy of Infliximab (IFX) in Behçet's disease (BD)-related uveitis.<sup>1,2</sup> Nevertheless, it is known that TNF-α inhibitor drugs may lose their efficacy over time due to the formation of anti-drug antibodies, causing secondary failure and influencing the retention rate of these agents.<sup>3</sup> In this regard no previous study has specifically investigated IFX retention-rate in BD-related uveitis. <h3>Objectives</h3> To evaluate the 10 year drug retention rate of IFX in BD-related uveitis, the effect of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on drug survival and differences according to the lines of biologic treatment. <h3>Methods</h3> Cumulative survival rates were studied using the Kaplan-Meier plot, while the Log-rank (Mantel-Cox) test was used to compare survival curves. <h3>Results</h3> Forty patients (70 eyes) were eligible for analysis. The drug retention rates at 12-, 24-, 60- and 120 month follow-up were 89.03%, 86.16%, 75.66% and 47.11% respectively. No differences were identified according to the use of concomitant DMARDs (p=0.20), while a statistically significant difference was observed in relation to the different lines of IFX treatment (p<i>=</i>0.014). Visual acuity improved from baseline to the last follow-up visit (p=0.047) and corticosteroids-sparing effect was observed (p&lt;0.0001) <h3>Conclusions</h3> IFX retention rate in BD-uveitis is excellent and is not affected by concomitant DMARDs <h3>References</h3> [1] Keino H, Okada AA, Watanabe T, et al. Long-term efficacy of infliximab on background vascular leakage in patients with Behçet's disease. Eye (Lond)2014;28(9):1100–6. [2] Keino H, Okada AA, Watanabe T, et al. Efficacy of Infliximab for Early Remission Induction in Refractory Uveoretinitis Associated with Behçet Disease: A 2-year Follow-up Study. Ocul Immunol Inflamm2017;25(1):46–51. [3] Fabbroni M, Cantarini L, Caso F, et al. Drug retention rates and treatment discontinuation among anti-TNF-α agents in psoriatic arthritis and ankylosing spondylitis in clinical practice. Mediators Inflamm2014;2014:862969. <h3>Disclosure of Interest</h3> None declared
Is the Oral Disease Severity Score going to be useful for dermatologists when assessing pemphigus? Reply from the authors
Authors: J.F. Setterfield, M. Ormond, A.N.A. Donaldson, S.J. Challacombe
Journal: British Journal of Dermatology (2018)

Linked Articles: Murrell et al. Br J Dermatol 2018; 179:816‐817. Ormond et al. Br J Dermatol 2018; 179:872–881.
Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma
Authors: Nizar J. Bahlis, Heather Sutherland, Darrell White, Michael Sebag, Suzanne Lentzsch, Rami Kotb, Christopher P. Venner, Cristina Gasparetto, Aldo Del Col, Paola Neri, Donna Reece, Michael Kauffman, Sharon Shacham, T. J. Unger, Jacqueline Jeha, Jean-Richard Saint-Martin, Jatin Shah, Christine Chen
Journal: Blood (2018)
The prognostic value of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status in left- and right-sided metastatic colorectal cancer (mCRC): A Belgian population-based study
Authors: K. Janssens, G. van Camp, K. Op de Beeck, E. Fransen, F. Calay, N. van Damme, M. Peeters
Journal: Annals of Oncology (2018)
GW29-e0446 The Biomarker of Atrial Fibrillation in Patients with Essential Hypertension-Aldosterone
Authors: Juan Xu, BaoZhen Qi, SiYu Wen, XuGuang Li, XueBin Fu, Phillip Yang, Zhi-Min Wang, Li-Qun Zhao, ShaoWen Liu
Journal: Journal of the American College of Cardiology (2018)
An effect of comprehensive geriatric assessment in elderly patients with non-Hodgkin lymphoma treated with chemotherapy
Authors: Nobuhiko Nakamura, Yuto Kaneda, Takuro Matsumoto, Hiroshi Nakamura, Soranobu Ninomiya, Junichi Kitagawa, Takeshi Hara, Masahito Shimizu, Hisashi Tsurumi
Journal: Annals of Oncology (2018)
The phase II study of nab-paclitaxel for relapsed NSCLC (NLCTG1302)
Authors: Tomohiro Tanaka, Satoshi Shoji, Koichiro Nozaki, Satoru Miura, Satoshi Watanabe, Takashi Ishida, Hiroki Tsukada, Kazuhiro Sato, Toru Hiura, Masaaki Okajima, Kosuke Ichikawa, Tetsuya Abe, Hiroshi Tanaka, Hirohisa Yoshizawa, Toshiaki Kikuchi
Journal: Annals of Oncology (2018)
Targeting MEK in vemurafenib-resistant hairy cell leukemia
Authors: Rebecca Caeser, Grace Collord, Wen-Qing Yao, Zi Chen, George S. Vassiliou, Philip A. Beer, Ming-Qing Du, Mike A. Scott, George A. Follows, Daniel J. Hodson
Journal: Leukemia (2018)

Hairy cell leukemia (HCL) is a chronic, incurable B cell malignancy that presents with splenomegaly, bone marrow infiltration, and cytopenias [1].Long remissions are typically achieved with purine analogs such as cladribine, but most cases will relapse and require further therapy.The discovery of the
GW29-e0478 Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation
Authors: Di Sun, Bingyang Zhou, Sha Li, Yuanlin Guo, Naqiong Wu, Chenggang Zhu, Ying Gao, Chuanjue Cui, Geng Liu, Jianjun Li
Journal: Journal of the American College of Cardiology (2018)
Abstract A02: Targeting EWS-FLI1 dose-dependent epithelial-to-mesenchymal transition
Authors: Anna M. Katschnig, Maximilian O. Kauer, Raphaela Schwentner, Eleni M. Tomazou, Dave N.T. Aryee, Heinrich Kovar
Journal: Cancer Research (2018)

Abstract Reversible transitions from a proliferative to a nonproliferative but highly migratory and invasive phenotype, widely known as epithelial-to-mesenchymal transition (EMT), is a prerequisite for wound healing and organ development but also a hallmark of cancer. Recently, phenotypic changes resembling EMT were described to occur in Ewing sarcoma upon modulation of expression of the driver oncogene EWS-FLI1. Evidence was provided for the presence of highly migratory EWS-FLI1-low cells in Ewing sarcoma cell lines as well as in about 20% of primary tumors at low frequency (Franzetti et al., 2017). Importantly, when injected into the tail vein of immunosuppressed mice, EWS-FLI1-low cells were more likely to result in lung metastases than EWS-FLI1-high cells upon re-expression of the oncogene. In our study, we identified a mechanism for the cytoskeletal reprograming underlying EWS-FLI1 dose-dependent phenotypic transitions in Ewing sarcoma. We provide evidence for EWS-FLI1 blocking access of the transcriptional coactivators MRTFB and TAZ to the YAP/TEAD transcription factor complex on enhancers of EWS-FLI1 anti-correlated genes. Upon modulation of EWS-FLI1 expression, TEADs get activated downstream of Rho signaling through recruitment of MRTFB/YAP/TAZ, leading to the expression of key cytoskeletal components and regulators involved in the reorganization of the actin cytoskeleton. Based on these findings, we hypothesized that small-molecule inhibitors of the YAP/TAZ/TEAD pathway should interfere with the migratory phenotype of EWS-FLI1-low cells. In fact, the YAP/TAZ inhibitor verteporfin (Visudyne®), which is clinically used as a photosensitive drug in the treatment of age-related macular degeneration, was able to block Ewing sarcoma cell migration at low nanomolar concentrations without affecting tumor cell proliferation. These results suggest that YAP/TAZ inhibitors may be considered as a promising add-on to conventional combination treatments to prohibit tumor cell dissemination and metastasis. Citation Format: Anna M. Katschnig, Maximilian O. Kauer, Raphaela Schwentner, Eleni M. Tomazou, Dave N.T. Aryee, Heinrich Kovar. Targeting EWS-FLI1 dose-dependent epithelial-to-mesenchymal transition [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 A02.