tbuckley/cabot-search huggingface dataset:
Abstract P171: Effect of Intensive and Standard Clinic-Based Hypertension Management on the Concordance Between Clinic and Ambulatory Blood Pressure and Blood Pressure Variability: Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Lama Ghazi, Nicholas M Pajewski, Dena E Rifkin, Jeffrey T Bates, Tara I Chang, Wlliam C Cushman, Stephen P Glasser, William E Haley, Karen C Johnson, William J Kostis, Vasilios Papademetriou, Mary Pinion, Mahboob Rahman, Debra L Simmons, Addison Taylor, Paul K Whelton, Jackson T Wright, Paul E Drawz
Journal: Circulation (2019)

Blood pressure (BP) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on the concordance between BP measurements is unknown. The goal of this analysis was to evaluate concordance in: 1) clinic BP and ambulatory BP, 2) clinic visit-to-visit variability and ambulatory BP variability and 3) initial and repeat ambulatory BP. We also sought to evaluate whether treatment assignment of intensive vs standard BP target affected these relationships. The Systolic Blood Pressure Intervention Trial (SPRINT) ambulatory blood pressure monitoring ancillary study obtained ambulatory BP readings in 897 SPRINT participants at the 27 month follow up visit and 203 consecutive repeat ambulatory BP readings taken an average of 9.8 months later. There was poor agreement between clinic systolic BP and daytime ambulatory systolic BP (limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive treatment group and -26 to 32 mm Hg in the standard treatment group). There was poor agreement between clinic visit-to-visit variability (coefficient of variation) and ambulatory BP variability (coefficient of variation of a 24 hr ambulatory BP) with correlation coefficients for systolic BP &lt;0.16. While there was a high correlation between ambulatory BP at 27 months and repeat ambulatory BP (r ~0.56), there was significant variability between repeat ambulatory BP assessments (limits of agreement of -27 to 21 mm Hg in the intensive group and -23 to 20 mm Hg in the standard group). In conclusion, irrespective of treatment target, we found low concordance in BP and BP variability between clinic BP and ambulatory BP, and additionally between repeat ambulatory BP assessments. These results reinforce the need for multiple guideline adherent BP measurements prior to clinical decision making.
Apixaban for the prevention of thromboembolism in immunomodulatory‐treated myeloma patients: Myelaxat, a phase 2 pilot study
Authors: Brigitte Pegourie, Lionel Karlin, Lotfi Benboubker, Frédérique Orsini‐Piocelle, Mourad Tiab, Sophie Auger‐Quittet, Philippe Rodon, Bruno Royer, Xavier Leleu, Benoit Bareau, Manuel Cliquennois, Jean‐Gabriel Fuzibet, Eric Voog, Karim Belhadj‐Merzoug, Olivier Decaux, Philippe Rey, Bohrane Slama, Cecile Leyronnas, Charles Zarnitsky, Eileen Boyle, Jean Luc Bosson, Gilles Pernod
Journal: American Journal of Hematology (2019)

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.
Translating Marine Animal Tracking Data into Conservation Policy and Management
Authors: Graeme C. Hays, Helen Bailey, Steven J. Bograd, W. Don Bowen, Claudio Campagna, Ruth H. Carmichael, Paolo Casale, Andre Chiaradia, Daniel P. Costa, Eduardo Cuevas, P.J. Nico de Bruyn, Maria P. Dias, Carlos M. Duarte, Daniel C. Dunn, Peter H. Dutton, Nicole Esteban, Ari Friedlaender, Kimberly T. Goetz, Brendan J. Godley, Patrick N. Halpin, Mark Hamann, Neil Hammerschlag, Robert Harcourt, Autumn-Lynn Harrison, Elliott L. Hazen, Michelle R. Heupel, Erich Hoyt, Nicolas E. Humphries, Connie Y. Kot, James S.E. Lea, Helene Marsh, Sara M. Maxwell, Clive R. McMahon, Giuseppe Notarbartolo di Sciara, Daniel M. Palacios, Richard A. Phillips, David Righton, Gail Schofield, Jeffrey A. Seminoff, Colin A. Simpfendorfer, David W. Sims, Akinori Takahashi, Michael J. Tetley, Michele Thums, Philip N. Trathan, Stella Villegas-Amtmann, Randall S. Wells, Scott D. Whiting, Natalie E. Wildermann, Ana M.M. Sequeira
Journal: Trends in Ecology & Evolution (2019)
Fractures and Linear Growth in a Nationwide Cohort of Boys With Duchenne Muscular Dystrophy With and Without Glucocorticoid Treatment
Authors: Shuko Joseph, Cunyi Wang, Kate Bushby, Michaela Guglieri, Iain Horrocks, Volker Straub, S. Faisal Ahmed, Sze Choong Wong
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Based on studies with relatively small sample size, fragility fractures are commonly reported in glucocorticoid (GC)-treated boys with Duchenne muscular dystrophy (DMD). <h3>Objective</h3> To determine the fracture burden and growth impairment in a large contemporary cohort of boys with DMD in the United Kingdom and in relation to GC regimen. <h3>Design, Setting, and Participants</h3> A retrospective review of fracture morbidity and growth from 832 boys with DMD in the UK NorthStar database (2006-2015), which systematically captures information from 23 participating centers. A total of 564 boys had more than 1 visit. No numbers of boys who refused were collected, but informal data from 2 centers in London and from Scotland show that refusal is very low. Data were analyzed between October 2006 and October 2015. <h3>Main Outcomes and Measures</h3> Fracture incidence rate per 10 000 person-years was determined. Cox regression analysis was used to identify factors associated with first fracture. <h3>Results</h3> Median age at baseline was 6.9 years (interquartile range, 4.9-7.2 years). At baseline, new fractures were reported in 7 of 564 participants (1.2%). During a median follow-up of 4 years (interquartile range, 2.0-6.0 years), incident fractures were reported in 156 of 564 participants (27.7%), corresponding to an overall fracture incidence rate of 682 per 10 000 person-years (95% CI, 579-798). The highest fracture incidence rate was observed in those treated with daily deflazacort at 1367 per 10 000 person-years (95% CI, 796-2188). After adjusting for age at last visit, mean hydrocortisone equivalent dose, mobility status, and bisphosphonate use prior to first fracture, boys treated with daily deflazacort had a 16.0-fold increased risk for first fracture (95% CI, 1.4-180.8;<i>P</i> = .03). Using adjusted regression models, change in height standard deviation scores was −1.6 SD lower (95% CI, −3.0 to −0.1;<i>P</i> = .03) in those treated with daily deflazacort compared with GC-naive boys, whereas there were no statistical differences in the other GC regimen. <h3>Conclusions and Relevance</h3> In this large group of boys with DMD with longitudinal data, we document a high fracture burden. Boys treated with daily deflazacort had the highest fracture incidence rate and the greatest degree of linear growth failure. Clinical trials of primary bone protective therapies and strategies to improve growth in boys with DMD are urgently needed, but stratification based on GC regimen may be necessary.
Novel predictive models of early death less than one year in patients with metastatic RCC treated with first-line tyrosine kinase inhibitors.
Authors: Minyong Kang, Jae Young Joung, Tae Jin Kim, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Hyun Hwan Sung
Journal: Journal of Clinical Oncology (2019)

552 Background: Although the IMDC model can provide useful information on overall survival outcomes in patients with metastatic renal cell carcinoma (mRCC), this model maybe invaluable in patients who experience early death less than one year after initial systemic therapy. Here, we aimed to develop a new prognostic model which can predict early death in patients with mRCC receiving first line tyrosine kinase inhibitors (TKI). Methods: We retrospectively evaluated a total of 498 patients treated with first line line TKI among 537 patients with mRCC at our institution. The primary endpoint was the rate of early death within 1 year after first line TKI administration. We selected statistically significant factors predicting early death by performing multiple logistic regression. Modified IMDC model 1 based on existing IMDC model and model 2 composed of new variables were generated. The prediction accuracy was evaluated by calculating the concordance index (C-index). Area under curve (AUC) and net reclassification index (NRI) using ROC curve analysis were used to compare the predictive power between the models. Results: Overall mortality was 59.0% (n = 294) in 498 patients, and early mortality was 19.7% (n = 98) within 1 year after first line TKI administration. The C-index of the IMDC model for early death was 0.655. Five variables were selected: previous nephrectomy, BMI, multiple metastases, previous metastasectomy and serum albumin level. The C-index of the model 1, which includes five new variables plus variables in the IDMC model, is 0.823, showing a significant improvement over the IDMC model. In model 2, hemoglobin and neutrophil levels were added in new five variables, and the C-index was 0.822. For the IMDC model, there was a significant NRI difference in both models 1 and 2, but no significant difference in NRI between models 1 and 2. (-0.0368 [95% CI = -0.1416 - 0.0681]; p = 0.491). Conclusions: In this study, we suggest modified IMDC models for predicting ‘early death less than one year in patients with mRCC treated with first line TKI. These novel models can provide better treatment strategies and counseling in patients with mRCC who were treated by first line TKI.
Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease
Authors: Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J. Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova, R. Collins, C. Baigent, M.J. Landray, C. Bray, Y. Chen, A. Baxter, A. Young, M. Hill, C. Knott, A. Cass, B. Feldt-Rasmussen, B. Fellström, D.E. Grobbee, C. Grönhagen-Riska, M. Haas, H. Holdaas, L.S. Hooi, L. Jiang, B. Kasiske, U. Krairittichai, A. Levin, Z.A. Massy, V. Tesar, R. Walker, C. Wanner, D.C. Wheeler, A. Wiecek, T. Dasgupta, W. Herrington, D. Lewis, M. Mafham, W. Majoni, C. Reith, J. Emberson, S. Parish, D. Simpson, J. Strony, T. Musliner, L. Agodoa, J. Armitage, Z. Chen, J. Craig, D. de Zeeuw, J.M. Gaziano, R. Grimm, V. Krane, B. Neal, V. Ophascharoensuk, T. Pedersen, P. Sleight, J. Tobert, C. Tomson
Journal: Kidney International (2019)
Molecular and clinical analysis of predictive biomarkers to anti-EGFR inhibitors in metastatic colorectal cancer (mCRC): Interaction among early tumor shrinkage, skin toxicities, and RAS status.
Authors: Rosa Berenato, Giuseppe Giuffre', Valeria Smiroldo, Tindara Franchina, Giuseppe Toscano, Antonino Scimone, Mariangela Zanghì, Maria Ausilia Silvestro, Antonio Ieni, Giovanni Tuccari, Vincenzo Adamo
Journal: Journal of Clinical Oncology (2015)

e14680 Background: Since the introduction in clinical practice of anti-EGFR therapies different studies were focused on the identification of clinical and molecular predictive biomarkers. The purpose of our study is to investigate the predictive value of early tumor-shrinkage (ETS) and skin toxicity (ST) in correlation with KRAS and NRAS status in pts affected by mCRC treated with Cetuximab-regimens (C). Methods: In this observational retrospective study we included a total of 29 mCRC consecutive patients (pts) (18M/11F) RAS status wild type (WT) chemonaïve. Mutant alleles of KRAS exon 3 (codons 59 and 61) and exon 4 (codons 117 and 146) and NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61) and exon 4 (codons 117 and 146) were detected. Clinical data were recorded. ETS was defined as a change of ≥ 20% in the sum of the longest diameters of target lesions compared to baseline. We used for ST is the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0). The correlation between RAS status and outcomes was investigated by Yates' chi-square. Survival analysis was performed by Kaplan-Meier method using RAS status and ETS as strata variable. P-values < 0.05 were considered statistically significant. Results: The median follow-up time was 34.2 months (range 6 – 81). ETS was recorded in 10 pts (52.6%) and was significantly associated with RAS status (p = 0.028). Moreover, RAS status (p = 0.003) and ETS (p = 0.006) were significantly associated with longer OS. Grade 2-3 ST was reported in 15 pts and correlate significantly with OS (p = 0.024). Conclusions: Selecting pts who will benefit most from treatment with anti-EGFR agents is an important goal. ETS represents a new valid clinical biomarker to determine which pts are more likely to receive survival benefit from Cetuximab. Further studies are warranted in order to personalize cancer therapy obtaining best results with less toxicities.
GATA2 exosomal mRNA: A novel urine biomarker for the diagnosis of clinically significant prostate cancer.
Authors: Jungreem Woo, Sandra Santasusagna, Benjamin Leiby, Kamlesh K Yadav, Ana Dominguez-Andres, Raffaella Pippa, Kerith Ruoyao Wang, Marc Carceles-Cordon, Shannon Fields, Rachel Weil, Gustavo A. Stolovitzky, Ashutosh Tewari, Grace L. Lu-Yao, William Kevin Kelly, Veronica Rodriguez-Bravo, Josep Maria Prats, Leonard G. Gomella, Josep Domingo-Domenech
Journal: Journal of Clinical Oncology (2019)

18 Background: Prostate specific antigen (PSA) detection in blood is widely used to screen for prostate cancer (PCa). However, PSA has limited utility in discriminating tumors at high risk of progression from indolent-low risk tumors, which leads to PCa overtreatment and highlights the need to identify better biomarkers for the detection of clinically significant PCa (Gleason Score; GS ≥ 7). Here, we introduce a novel mRNA GATA2 exosomal biomarker detected in urine useful to diagnose clinically significant PCa. Exosomes are 50-120 nm sized vesicles shed in body fluids that contain RNA, DNA, and protein that can be used as biomarkers to interrogate the health of the originating cells. GATA2 is a pioneer transcription factor specific to PCa, increased in aggressive tumors. Methods: To evaluate the predictive value of exosomal GATA2 mRNA levels for aggressive PCa, we isolated exosomes using ultracentrifugation in non-DRE urines from 128 males with elevated PSA serum levels (&gt; 4ng/ml) and analyzed them according to their tissue biopsy result. Results: Importantly, prostate origin of GATA2 mRNA detected in urine exosomes was confirmed by observing that exosomal GATA2 mRNA levels significantly dropped after prostatectomy (p &lt; 0.05). Most remarkably, GATA2 exosomal mRNA expression was significantly increased in PCa biopsy positive patients (n=88) when compared to biopsy negative males (n=28, p &lt; 0.001). Furthermore, GATA2 levels in PCa patients were significantly associated with GS, but not with disease stage and PSA levels. Multivariable regression analysis showed that GATA2 exosomal mRNA levels are an independent factor for the diagnosis of aggressive PCa. Urine GATA2 exosome mRNA expression plus SOC (age and PSA) was associated with improved discrimination of GS ≥ 7 versus GS 6 and benign disease: AUC of SOC alone 0.59 (0.49-0.70, p value=0.083) vs SOC plus GATA2 AUC of 0.68 (95% CI, 0.58-0.78, p value=0.0004). Conclusions: The analysis of urine exosomal GATA2 mRNA in individuals with high PSA may help distinguish clinically significant PCa and reduce the number of patients that need biopsy. Future studies are focused on combining this biomarker to others, such as urine exosomal PCA3, already used in the clinic.
Prognostic roles of serum NEDD9 levels in patients with gastric cancer.
Authors: Senem Karabulut, Mehmet Karabulut, Halil Alis, Hamza Ugur Bozbey, Burak Sakar, Sezai Vatansever, Nuri Faruk Aykan
Journal: Journal of Clinical Oncology (2015)

e15103 Background: Neural precursor cell-expressed, developmentally downregulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration, invasion. The prognostic value of NEDD9 has been evaluated before; its expression predictor for poor prognosis of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients. Methods: A total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included in the analysis. Results: The median age at diagnosis was 60 years, range 21 to 84 years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n = 37, 77%). The most frequent histologic subtype was adenocarcinoma (n = 45, 66%).Liver was the most common metastatic site in 32 patients with metastasis (n = 14, 21%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy were chemotheraphy-responsive. The median serumNEDD9 levels of GC patients was significantly higher than controls (1339.51 vs. 1187.91 pg/mL, p = 0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (p > 0.05). Serum NEDD9 levels had a significant impact on progression-free survival (p = 0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on overall survival (p = 0.50). Conclusions: Serum NEDD9 levels are elevated in GC patients and have an unfavorable prognostic value. However, it has no predictive role on chemotherapy response.
Abstract P376: Clinical Use of a Proteomic Cardiovascular Risk Score for Assessing How Personal Risk Assessment Positively Drives Patient Attitudes and Behavior Change
Authors: Nelson P Trujillo jr, Kirsten Wall, Leigh Alexander, Sandy Housholder, Jordan Zach, Rosalyn Gill, Stephen williams
Journal: Circulation (2019)

Background: The ACC has outlined a strategic goal where innovation and knowledge optimize cardiovascular care and outcomes. We tested whether sharing with patients a personal 7-protein cardiovascular risk score might motivate them to better adhere to cardiovascular risk reduction measures. Methods: The 7-protein risk score (SOMAscan® CVD Secondary Risk Panel, SomaLogic) provides % risk by year for experiencing a cardiovascular event up to 5 years. Patients with stable coronary heart disease received a baseline lifestyle and behavior survey, chart abstraction, and blood draw for the 7-protein risk score. Results were shared with the patient by their physician. One month after receiving the panel results, patients were surveyed on the overall impact of the panel on health, lifestyle, and medication changes. Results: Among the 138 patients, 23.9% had ≥ 20% predicted risk of a cardiovascular event in 5 years. Higher risk patients reported higher rates of desirable lifestyle changes, including healthier diet (Figure 1). Lower risk patients stated they would maintain their lifestyle to remain healthy. Conclusions: Patients presented with their personal 7-protein cardiovascular risk score were motivated to improve their lifestyle and adherence to medications. The additional motivation from the test results, if sustained long-term, may translate into improved outcomes in patients with coronary heart disease.
Assessment of the androgen receptor (AR) activity score versus AR expression in muscle invasive bladder cancer (MIBC).
Authors: Paulo Gustavo Bergerot, Leonidas Arvinitis, Nazli Dizman, Meghan Salgia, Sumanta K. Pal, Jeremy Jones
Journal: Journal of Clinical Oncology (2019)

463 Background: Previous studies have demonstrated that a considerable proportion of BCs express androgen receptor (AR), and that AR might drive tumor growth. The RNA-based AR activity score is a novel analytic tool that may better quantify the functional role of AR. Methods: Samples were obtained from patients (pts) with MIBC who had cystectomy or transurethral resection of bladder tumor (TURBT). AR expression was quantified by pathologist scoring of immunohistochemistry (IHC). The AR activity score was quantified using RNA isolates from benign and cancerous sections of slides adjacent to those used for IHC. RT-qPCR of a panel of AR-regulated genes was performed with comparison of transcript levels to those in LNCaP prostate cancer cells. Clinical results were validated in the RT-112 cell line. Results: A total of 37 pts (81.8% male) were analyzed with a median of age of 67. The majority were diagnosed as cT3 (54.5%) and 62.2% underwent neoadjuvant chemotherapy (86.9% with cisplatin/gemcitabine). IHC demonstrated a range of AR positivity from 0.0% to 90.0%, with most samples (46.0%) having no staining. In contrast, the AR activity score was between 2.1% and 178.9% (relative to LNCaP cells) with a median activity of 32.2% in cancerous tissues and 44.0% in benign regions. AR expression and score showed no direct correlation. A strong association was seen between AR activity score in cancerous tissue and DFS (P = 0.005). Interestingly, AR score in benign tissue was inversely correlated with DFS (P = 0.04). Pts who received neoadjuvant chemotherapy were noted to less likely develop metastases (P = 0.05). A more marginal correlation was noted between AR activity score and pathologic downstaging. Treatment of cells transfected with an AR expression plasmid along with an AR-responsive luciferase reporter demonstrated a dose-dependent effect of cisplatin in this assay. Conclusions: IHC and AR activity scores represent independent measures in this MIBC cohort. Our study suggests that pts with higher AR activity may be more susceptible to chemotherapy, and may have prolonged DFS. Additional studies in larger cohorts are warranted.