tbuckley/cabot-search huggingface dataset:
Abstract 9421: The Role of B-type Natriuretic Peptide as a Prognostic Factor for Endocarditis at the Emergency Room
Authors: Danielle M Gualandro, Priscila Goldstein, Luis F Seguro, Rinaldo Siciliano, Tania Strabelli, Viviane Arias, Alfredo J Mansur, Tarso A Accorsi, Max Grinberg, Mucio T Oliveira
Journal: Circulation (2012)

Background: Some prognostic factors for infective endocarditis (IE) are well established, but the role of B-type natriuretic peptide (BNP) at admission has not been well studied. Objective: The purpose of this study was to access the admission BNP value as a prognostic factor in patients with IE. Methods: Between July 2009 and January 2011, consecutive patients with IE admitted to the emergency room were prospectively enrolled. Patients were included if they met possible or definite Duke’s criteria for IE. The association between elevated BNP and in-hospital death was determined. Results: From 104 patients analyzed, 67 were male (48%), the mean age was 52.6±19.1 years. During follow-up, 32 (30.8%) patients died. In univariate analysis, staphylococcal infection (P&lt;0.001, HR 3.94; CI, 1.94-8.0), dyspnea at presentation (P=0.015, HR 2.41; CI, 1.20-4.86), sepsis at presentation (P=0.017, HR 2.34; CI, 1.16-4.72), left ventricular ejection fraction ≤ 55% (P&lt;0.001, HR 3.97; CI, 1.86-8.43), C-reactive protein (CRP) &gt; 120 mg/L, (P&lt;0.001, HR 4.04; CI, 1.91-8.55), creatinine &gt; 1 mg/dL (P=0.006, HR 2.92; CI, 1.26-6.76), and BNP &gt; 200 pg/mL (P&lt;0.001, HR 12.51; CI, 2.98-52.48) were associated with in-hospital mortality. In multivariate analysis, BNP values &gt; 200 pg/ml (P&lt;0.001, HR 2.41; CI, 1.20-4.86), staphylococcal infection (P=0.006, HR 2.89; CI, 1.39-6.02), dyspnea at presentation (P=0.003, HR 3.17; CI, 1.49-6.76), and CRP &gt; 120 mg/L, (P&lt;0.001, HR 3.86; CI, 1.76-8.46) were independent predictors of in-hospital mortality. Conclusion: As important as the classic prognostic factors, elevated BNP levels on admission were related to fatal outcomes in IE patients.
Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia
Authors: Sarah Ramiz, Jan Hartmann, Guy Young, Miguel A. Escobar, Meera Chitlur
Journal: American Journal of Hematology (2018)

Abstract Hemophilia A and B are rare inherited bleeding disorders resulting from deficiency of coagulation factors VIII and IX respectively. In the past few decades, the field of hemophilia has witnessed pivotal management challenges and therapeutic advances. Routine coagulation and factor assays, while useful in the classification of severity and treatment monitoring in hemophilia patients, have been shown to be of limited use in managing clinical presentations and outcomes. This prompted the investigation of viscoelastic studies in hemophilia care, which have established their utility in various bleeding and thrombotic states. In this review, we will discuss and critically assess the current literature highlighting the use of viscoelastic studies in various aspects of hemophilia including the determination of clinical phenotype, management of patients with inhibitors, perioperative management, and monitoring of novel agents.
Analytic validation of tumor mutational burden as a companion diagnostic for combination immunotherapy in non-small cell lung cancer
Authors: D.A. Fabrizio, C. Milbury, W.-K. Yip, L. Ramamurthy, X. Bai, V. Pattani, P. Maness, A. Cowen, K. Fedorchak, P. Ma, G.M. Frampton, C. Connelly, Y. Li
Journal: Annals of Oncology (2018)
CD8+ T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity
Authors: Laura M. Snell, Bethany L. MacLeod, Jaclyn C. Law, Ivan Osokine, Heidi J. Elsaesser, Kebria Hezaveh, Russell J. Dickson, Marc A. Gavin, Cynthia J. Guidos, Tracy L. McGaha, David G. Brooks
Journal: Immunity (2018)
Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma
Authors: G. Fraser, P. Cramer, F. Demirkan, R. Santucci Silva, S. Grosicki, A. Pristupa, A. Janssens, J. Mayer, N. L. Bartlett, M.-S. Dilhuydy, H. Pylypenko, J. Loscertales, A. Avigdor, S. Rule, D. Villa, O. Samoilova, P. Panagiotidis, A. Goy, M. A. Pavlovsky, C. Karlsson, M. Hallek, M. Mahler, M. Salman, S. Sun, C. Phelps, S. Balasubramanian, A. Howes, A. Chanan-Khan
Journal: Leukemia (2018)

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1–45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159–0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454–0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3–4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.
Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin Indicating Different Types of DNA Repair Deficiency
Authors: Zafeiris Zafeiriou, Diletta Bianchini, Robert Chandler, Pasquale Rescigno, Wei Yuan, Suzanne Carreira, Maialen Barrero, Antonella Petremolo, Susana Miranda, Ruth Riisnaes, Daniel Nava Rodrigues, Bora Gurel, Semini Sumanasuriya, Alec Paschalis, Adam Sharp, Joaquin Mateo, Nina Tunariu, Arul M. Chinnaiyan, Colin C. Pritchard, Kevin Kelly, Johann S. de Bono
Journal: European Urology (2018)

Platinum-based regimens have not been proved to increase survival from advanced prostate cancer (PCa). Incontrovertible evidence that a proportion of prostate cancers have homologous recombination DNA (HRD) repair defects, and that such genomic aberrations are synthetically lethal with both poly(ADP)-ribose polymerase inhibition and platinum, has increased interest in the utilisation of these drugs against a subset of these diseases. Here in we report three patients with advanced castration-resistant PCa with HRD defects having exceptional responses to carboplatin.
Safety and outcomes of self-expandable metal stents (SEMS) versus emergency surgery for acute colonic obstruction in metastatic colon cancer patients treated with bevacizumab (BV)
Authors: V.E. Pacheco-Barcia, R. Mondéjar Solís, O. Martínez-Sáez, F. Longo, E. Bermejo, J.A. Moreno, C. Marin, A. Correa, R. Maqueda, J. Rogado, A. García de Paredes, E. Rodriguez de Santiago, V. Pachón Olmos, R. Ferreiro Monteagudo, M. Rodriguez Garrote, A. Carrato Mena, O. Donnay, E. Martin Perez, C. Santander, R. Colomer Bosch
Journal: Annals of Oncology (2018)
Fasting Glucose Variability in Young Adulthood and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Michael P. Bancks, Mercedes R. Carnethon, David R. Jacobs, Lenore J. Launer, Jared P. Reis, Pamela J. Schreiner, Ravi V. Shah, Stephen Sidney, Kristine Yaffe, Yuichiro Yano, Norrina B. Allen
Journal: Diabetes Care (2018)

To determine whether intraindividual variability in fasting glucose (FG) below the threshold of diabetes is associated with cognitive function in middle adulthood beyond increasing FG.
Long-Term Effects of In Vivo Genome Editing in the Mouse Retina Using Campylobacter jejuni Cas9 Expressed via Adeno-Associated Virus
Authors: Dong Hyun Jo, Taeyoung Koo, Chang Sik Cho, Jin Hyoung Kim, Jin-Soo Kim, Jeong Hun Kim
Journal: Molecular Therapy (2018)

Genome editing with CRISPR systems provides an unprecedented opportunity to modulate cellular responses in pathological conditions by inactivating undruggable targets, such as transcription factors. Previously, we demonstrated that the smallest Cas9 ortholog characterized to date, from Campylobacter jejuni (CjCas9) targeted to Hif1a and delivered in an adeno-associated virus (AAV) vector, effectively suppressed pathological choroidal neovascularization in the mouse retina. Before implementation of CjCas9 as an in vivo therapeutic modality, it is essential to investigate the long-term effects of target gene disruption via AAV-mediated delivery of CjCas9 in vivo. In this study, histologic and electroretinographic analyses demonstrated that CjCas9 targeted to Hif1a did not induce any definite toxicity in the retina, although the target gene was mutated with a frequency ranging from 45% to 79% in retinal or retinal pigment epithelial cells. Importantly, at 14 months after injection, no indels were detected at potential off-target sites identified using Digenome-seq and Cas-OFFinder, suggesting that long-term expression of CjCas9 does not aggravate off-target effects. Taken together, our results show that intravitreal injection of AAV encoding CjCas9 targeted to Hif1a effectively induced and maintained mutations in retinal tissues for more than 1 year and did not affect retinal histologic integrity or functions. Genome editing with CRISPR systems provides an unprecedented opportunity to modulate cellular responses in pathological conditions by inactivating undruggable targets, such as transcription factors. Previously, we demonstrated that the smallest Cas9 ortholog characterized to date, from Campylobacter jejuni (CjCas9) targeted to Hif1a and delivered in an adeno-associated virus (AAV) vector, effectively suppressed pathological choroidal neovascularization in the mouse retina. Before implementation of CjCas9 as an in vivo therapeutic modality, it is essential to investigate the long-term effects of target gene disruption via AAV-mediated delivery of CjCas9 in vivo. In this study, histologic and electroretinographic analyses demonstrated that CjCas9 targeted to Hif1a did not induce any definite toxicity in the retina, although the target gene was mutated with a frequency ranging from 45% to 79% in retinal or retinal pigment epithelial cells. Importantly, at 14 months after injection, no indels were detected at potential off-target sites identified using Digenome-seq and Cas-OFFinder, suggesting that long-term expression of CjCas9 does not aggravate off-target effects. Taken together, our results show that intravitreal injection of AAV encoding CjCas9 targeted to Hif1a effectively induced and maintained mutations in retinal tissues for more than 1 year and did not affect retinal histologic integrity or functions.
Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)
Authors: A. Marabelle, R. Andtbacka, K. Harrington, I. Melero, R. Leidner, T. de Baere, C. Robert, P.A. Ascierto, J -F Baurain, M. Imperiale, S. Rahimian, D. Tersago, E. Klumper, M. Hendriks, R. Kumar, M. Stern, K. Öhrling, C. Massacesi, I. Tchakov, A. Tse, J -Y Douillard, J. Tabernero, J. Haanen, J. Brody
Journal: Annals of Oncology (2018)

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.
Abstract 11682: Meta-Analysis of Studies on Coffee Consumption and Atrial Fibrillation Risk
Authors: Chayakrit Krittanawong, Anusith Tunhasiriwet, Hafeez Ul Hassan Virk, Ann M Farrell, Bing Yue, James Tak, Mehta Davendra
Journal: Circulation (2017)

Introduction: The etiology of atrial fibrillation (AF) is multifactorial, including comorbidities such as hypertension, diabetes, or advanced age. Coffee is increasingly consumed worldwide, particu...
Phase Ib/II, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)
Authors: E.E.W. Cohen, A. Algazi, D. Laux, D.J. Wong, A. Amin, L. Nabell, M. Chisamore, E. Gamelin, R. Janssen, S. Bishnoi
Journal: Annals of Oncology (2018)
Role of immunotherapy (I) for advanced, pre-treated, non-squamous NSCLC (APNS-NSCLC): Preliminary data of a pooled analysis with network meta-analysis
Authors: C. Cherubini, M. Papi, L. Gianni, C. Gianni, S.V.L. Nicoletti, M. Fantini, L.A. Lazzari Agli, D. Tassinari
Journal: Annals of Oncology (2018)
GW29-e1222 Effects of levosimendan on right ventricular function in patients with acute decompensated heart failure
Authors: Yanbo Wang, Guozhen Hao, Yunfa Jiang, Xianghua Fu, Weize Fan, Qing Miao, Qing Wang, Hongxiao Li, Xinshun Gu
Journal: Journal of the American College of Cardiology (2018)
Large-scale nationwide genomic screening system for small cell lung cancer in Japan (LC-SCRUM-Japan)
Authors: Norio Okamoto, Shigeki Umemura, Taku Nakagawa, Shingo Miyamoto, Kenichiro Kudo, Mika Nakao, Yuki Kataoka, Naoki Furuya, Hiroshi Yokouchi, Shingo Matsumoto, Hibiki Udagawa, Kiyotaka Yoh, Koichi Goto
Journal: Annals of Oncology (2018)
The Aravind Pseudoexfoliation Study
Authors: Aravind Haripriya, Pradeep Y. Ramulu, Shivkumar Chandrashekharan, Rengaraj Venkatesh, Kalpana Narendran, Madhu Shekhar, Rengappa Ramakrishnan, Ravilla D. Ravindran, Alan L. Robin
Journal: Ophthalmology (2018)
Targeted demethylation at the CDKN1C/p57 locus induces human β cell replication
Authors: Kristy Ou, Ming Yu, Nicholas G. Moss, Yue J. Wang, Amber W. Wang, Son C. Nguyen, Connie Jiang, Eseye Feleke, Vasumathi Kameswaran, Eric F. Joyce, Ali Naji, Benjamin Glaser, Dana Avrahami, Klaus H. Kaestner
Journal: Journal of Clinical Investigation (2018)

The loss of insulin-secreting β cells is characteristic among type I and type II diabetes. Stimulating proliferation to expand sources of β cells for transplantation remains a challenge because adult β cells do not proliferate readily. The cell cycle inhibitor p57 has been shown to control cell division in human β cells. Expression of p57 is regulated by the DNA methylation status of the imprinting control region 2 (ICR2), which is commonly hypomethylated in Beckwith-Wiedemann syndrome patients who exhibit massive β cell proliferation. We hypothesized that targeted demethylation of the ICR2 using a transcription activator–like effector protein fused to the catalytic domain of TET1 (ICR2-TET1) would repress p57 expression and promote cell proliferation. We report here that overexpression of ICR2-TET1 in human fibroblasts reduces p57 expression levels and increases proliferation. Furthermore, human islets overexpressing ICR2-TET1 exhibit repression of p57 with concomitant upregulation of Ki-67 while maintaining glucose-sensing functionality. When transplanted into diabetic, immunodeficient mice, the epigenetically edited islets show increased β cell replication compared with control islets. These findings demonstrate that epigenetic editing is a promising tool for inducing β cell proliferation, which may one day alleviate the scarcity of transplantable β cells for the treatment of diabetes.
Autoimmunity and benefit from trastuzumab treatment in breast cancer: Results from the HERA phase III trial
Authors: A. Sonnenblick, A. Bailey, B. Uziely, M. Untch, I. Smith, L. Gianni, J. Baselga, C. Jackisch, D. Cameron, R. Bell, D. Zardavas, N. Al-Sakaff, R. Gelber, M. Dowsett, B. Leyland-jones, M. Piccart, E. de Azambuja
Journal: Annals of Oncology (2018)
Abstract 17228: Prevalence and Correlates of Depression, Anxiety and Stress Among Filipinos in the Philippines
Authors: Jo Leah Flores, Josefina A Tuazon, Mary Abigail Hernandez, Lorraine S Evangelista
Journal: Circulation (2017)

Introduction: Psychological determinants of health such as depression, anxiety and stress are important considerations in cardiovascular health promotion and illness prevention efforts. However, ps...
Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors
Authors: Zhiqing Li, Shuxun Liu, Junfang Xu, Xiang Zhang, Dan Han, Juan Liu, Meng Xia, Lin Yi, Qicong Shen, Sheng Xu, Linrong Lu, Xuetao Cao
Journal: Immunity (2018)
Diagnosis of “mystery” conditions improves with advanced US network approach
Authors: Susan Mayor
Journal: BMJ (2018)

Just over one in three patients with undiagnosed conditions despite thorough medical evaluation had a diagnosis identified when referred to a US network coordinating genetic testing with multidisciplinary specialist assessment, a study has found.1

The study, reported in the New England Journal of Medicine ,1 showed that this approach established a diagnosis in 35% of nearly 400 patients who were fully evaluated.

Diagnosing patients’ conditions led to changes in treatment in 21% of the cases diagnosed, further diagnostic testing in 37%, and variant specific genetic counselling in 36%. A total of 31 new syndromes were identified.

The patients were all referred to the Undiagnosed Diseases Network, a …
Assessment of Cardiovascular Risk in Older Patients With Gout Initiating Febuxostat Versus Allopurinol
Authors: MaryAnn Zhang, Daniel H. Solomon, Rishi J. Desai, Eun Ha Kang, Jun Liu, Tuhina Neogi, Seoyoung C. Kim
Journal: Circulation (2018)

Background: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. Methods: Using US Medicare claims data (2008–2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score–matched cohorts of febuxostat and allopurinol initiators. Results: We included 24 936 febuxostat initiators propensity score–matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94–1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91–0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (&gt;3 years) was 1.25 (95% CI, 0.56–2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups. Conclusions: Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for &gt;3 years versus allopurinol for &gt;3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.
Health-related quality of life (HR-QoL) in elderly soft tissue sarcoma (STS) patients from the randomized phase II EPAZ study comparing pazopanib (PAZ) and doxorubicin (DOX) in first line
Authors: V. Grünwald, M. Schuler, P. Schöffski, H.-G. Kopp, S. Bauer, B. Kasper, L.H. Lindner, J.M. Chemnitz, M. Crysandt, A. Stein, B. Steffen, S. Richter, M. Kneba, G. Egerer, S. Zimmermann, A. Karch, A. Kunitz
Journal: Annals of Oncology (2018)
Abstract 18361: Lipidomic Profiles are Associated With Incident Coronary Heart Disease in Women
Authors: Kathryn M Rexrode, Raji Balasubramanian, Nina Paynter, Shuba Gopal, Franco Guilianini, Matthew Allison, Charles B Eaton, Lisa W Martin, Barbara V Howard, Lesley Tinker, JoAnn E Manson, Nancy Cook, Christine A Albert, Clary Clish
Journal: Circulation (2015)

Background: Advances in lipidomics allow profiling of hundreds of lipid compounds, but prior studies have been limited by relatively small case numbers and scant data in women. Methods: Four hundred confirmed, incident cases of MI and fatal CHD in the Women’s Health Initiative (WHI-OS) were frequency matched to 400 controls by age, race, hysterectomy, and time-period (mean age 62.7 years; no hormone use). Lipidomic analysis of 196 lipid species from 13 different lipid classes including cholesterol esters (CE), diacylglycerols (DAG),and triacylglycerols [TAG) was performed by liquid chromatography mass spectroscopy. Two independent modeling approaches were used: 1) Individual lipids were studied in logistic regression models and a false-discovery rate (FDR) correction was used to adjust for multiple comparisons (FDR corrected p-value of &lt; 0.05); 2) Lipids were simultaneously considered using a least absolute shrinkage and selection operator (LASSO) algorithm. Metabolites selected by both approaches were included in combined multivariable logistic regression models. Results: In multivariable-adjusted logistic models, 17 lipid metabolites were individually and significantly associated with CHD controlling for multiple comparisons, while in mutually adjusted LASSO regression, 8 lipids were significantly associated with CHD. Five lipids were associated with CHD by both methods (Table). When modeled together, only C18.1 CE and C34.3 DAG were associated with risk in fully adjusted models. Results will be validated in separate replication dataset of women from the WHI (396 cases/ 396 controls; to be presented). Conclusions: Three long chain highly unsaturated triacylglycerols and one diacylglycerol were associated with decreased risk, while a short chain monounsaturated lipid CE (18.1) was associated with increased risk of CHD in women. Lipidomics may offer insights into biological mechanisms of CHD as well as identify potential markers of risk.