tbuckley/cabot-search huggingface dataset:
Abstract MP76: Trends in Adherence to Statin Therapy Among US Adults With Health Insurance Between 2007 and 2014
Authors: Lisandro D Colantonio, Robert S Rosenson, Luqin Deng, Keri L Monda, Yuling Dai, Michael E Farkouh, Monika M Safford, Kiran Philip, Katherine E Mues, Paul Muntner
Journal: Circulation (2018)

Background: Statins are effective for the primary and secondary prevention of coronary heart disease (CHD) events. However, studies from the early 2000s have suggested that many patients have low adherence to statin therapy. Objective: To analyze trends in adherence among US adults initiating treatment with a statin. Methods: We identified US adults 21-64 years of age with commercial health insurance in Marketscan and ≥65 years of age with government health insurance through Medicare who initiated statin therapy in 2007-2014. Three populations were analyzed, those initiating statin therapy 1) following myocardial infarction (n=52,828 in Marketscan, n=148,745 in Medicare), 2) with diabetes without a history of CHD (n=565,573 in Marketscan, n=42,411 in Medicare), and 3) without diabetes or a history of CHD (n=2,134,501 in Marketscan, n=105,948 in Medicare). Adherence to statin therapy was defined by having a statin available to take for ≥80% of the 365 days following treatment initiation. Results: Adherence to statin therapy increased in each population analyzed ( Figure ). In 2014, 68.1% and 62.7% of patients initiating treatment following myocardial infarction in Marketscan and Medicare, respectively were adherent to their statin. Less than half of patients initiating treatment with diabetes without CHD and without diabetes or CHD in Marketscan and Medicare were adherent to their statin. Adherence to statin therapy in the overall Marketscan and Medicare populations was higher among men (relative risk [95% CI] 1.16 [1.15, 1.18] and 1.10 [1.08, 1.12], respectively), and those with cardiologist visits (1.22 [1.21, 1.24] and 1.27 [1.25, 1.30], respectively), and lower among those with kidney disease diagnosed after treatment initiation (0.89 [0.85, 0.94] and 0.92 [0.88, 0.96], respectively). Conclusion: Adherence to statins improved slightly between 2007 and 2014 but remains suboptimal. Management by a cardiologist is associated with better adherence to statins.
First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): Results from KEYNOTE-427 cohort B.
Authors: David F. McDermott, Jae-Lyun Lee, Marek Ziobro, Rustem Airatovich Gafanov, Vsevolod Borisovich Matveev, Cristina Suárez, Frede Donskov, Frederic Pouliot, Boris Y. Alekseev, Pawel Wiechno, Piotr Tomczak, Miguel Angel Climent Duran, Sang Joon Shin, Rachel Kloss Silverman, Rodolfo F. Perini, Charles Schloss, Michael B. Atkins
Journal: Journal of Clinical Oncology (2019)

546 Background: PD-1/L1 pathway inhibitors are effective in clear cell (cc)RCC, but efficacy of PD-1 inhibitors (or any therapy) in nccRCC has not been established. KEYNOTE-427 is a single-arm, open-label, phase 2 study of pembro monotherapy in patients (pts) with advanced ccRCC (cohort A) and nccRCC (cohort B). Cohort B results are presented. Methods: 165 pts with histologically confirmed nccRCC, no prior systemic therapy, measurable disease (RECIST v1.1), and KPS ≥70% enrolled. Pts received pembro 200 mg IV Q3W for 35 cycles (~2 y) or until progressive disease (PD), unacceptable toxicity, or withdrawal. Pts were followed after PD for overall survival. Primary end point: objective response rate (ORR) per RECIST v1.1 by blinded independent central review. Secondary end points included duration of response (DOR) and population description by International Metastatic RCC Database Consortium (IMDC) risk. Exploratory end points: ORR by histology and PD-L1 expression (combined positive score [CPS] ≥1 for PD-L1+). Results: Histology was confirmed by a central pathologist: papillary 72% (n=118), chromophobe 13% (n=21), unclassified 16% (n=26). 68% of patients were at intermediate/poor IMDC risk, and 62% were PD-L1+. At analysis, 49 pts had died and 3 had withdrawn. At a median follow-up duration of 11.1 mo (range, 0.9-21.3), 56% of pts discontinued pembro due to PD or clinical progression. Overall ORR was 24.8% (95% CI, 18.5-32.2; 8 [4.8%] CRs, 33 [20%] PRs); median DOR was not reached. ORR (95% CI) was 25.4% (17.9-34.3) with papillary, 9.5% (1.2-30.4) with chromophobe, and 34.6% (17.2-55.7) with unclassified nccRCC. ORR (95% CI) was 28.3% (16.8-42.3) with favorable and 23.2% (15.8-32.1) with intermediate/poor IMDC risk and 33.3% (24.3-43.4) and 10.3% (3.9-21.2) with CPS≥1 and CPS&lt;1, respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 11% of pts; 6% discontinued due to TRAEs. 6 pts died due to AEs, 2 of which were TRAEs (pneumonia and cardiac arrest). Conclusions: Single-agent pembro showed encouraging antitumor activity in nccRCC, especially with papillary or unclassified histology. Safety profile of pembro was generally as expected. Clinical trial information: NCT02853344.
Abstract 039: Low Levels of Moderate to Vigorous Physical Activity is Associated With Fewer Years Lived Free of Cardiovascular Disease: The Cardiovascular Lifetime Risk Pooling Project
Authors: Amanda Paluch, Hongyan Ning, Mercedes Carnethon, Kelley Pettee Gabriel, Norrina Allen, Donald Lloyd-Jones, John Wilkins
Journal: Circulation (2019)

Background: Quantifying the associations of moderate to vigorous intensity physical activity (MVPA) with years lived free of cardiovascular disease (CVD) allows for contextualization of the population burden and provides a metric for clinician-patient communication. We hypothesized that individuals with lower levels of MVPA during middle age will have fewer years lived free of CVD compared to those with higher levels. Methods: A standardized z-score for MVPA was created based on participant-reported physical activity in 28,466 middle aged adults aged 40-59 years (43.6% women) in 6 U.S. prospective cohort studies. Z-scores were then categorized into quartiles for each cohort. Rates (person-years) of incident CVD and death were summed for participants up to age 95 years, or to the oldest age of observation. Irwin’s restricted mean was used to calculate years lived free from CVD and overall survival stratified by sex. Results: Over 514,324 person-years of follow-up, 3,556 CVD events were observed. Whereas there was no difference in survival time among participants in the upper 3 quartiles, women in the lowest quartile vs. the next lowest quartile lived 3.2 fewer years and men lived 1.2 fewer years free of CVD. Survival after a CVD event was lower for women in the lowest MVPA quartile (mean±S.E: 0.07±0.32 years) compared to all other quartiles (Q2: 0.67±0.16 years to Q4: 0.96±0.16 years). Survival after CVD events was similar across all quartiles of MVPA for men, ranging from 1.1±0.05 to 1.4±0.05 years. Conclusions: The benefits of physical activity extend multiple decades into older ages. Even modest levels of physical activity during middle age is associated with longer CVD-free survival, particularly among women.
The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells
Authors: Michael Ignarski, Constantin Rill, Rainer W.J. Kaiser, Madlen Kaldirim, René Neuhaus, Reza Esmaillie, Xinping Li, Corinna Klein, Katrin Bohl, Maike Petersen, Christian K. Frese, Martin Höhne, Ilian Atanassov, Markus M. Rinschen, Katja Höpker, Bernhard Schermer, Thomas Benzing, Christoph Dieterich, Francesca Fabretti, Roman-Ulrich Müller
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement RNA-binding proteins (RBPs) are crucial regulators of cellular biology, and recent evidence suggests that regulation of RBPs that modulate both RNA stability and translation may have a profound effect on the proteome. However, little is known about regulation of RBPs upon clinically relevant changes of the cellular microenvironment. The authors used high-throughput approaches to study the cellular RNA‐binding proteome in differentiated tubular epithelial cells exposed to hypoxia. They identified a number of novel RBPs (suggesting that these proteins may be specific RBPs in differentiated tubular epithelial cells), and found quantitative differences in RBP-binding to mRNA associated with hypoxia versus normoxia. These findings demonstrate the regulation of RBPs through environmental stimuli and provide insight into the biology of hypoxia-response signaling in the kidney. Background RNA-binding proteins (RBPs) are fundamental regulators of cellular biology that affect all steps in the generation and processing of RNA molecules. Recent evidence suggests that regulation of RBPs that modulate both RNA stability and translation may have a profound effect on the proteome. However, regulation of RBPs in clinically relevant experimental conditions has not been studied systematically. Methods We used RNA interactome capture, a method for the global identification of RBPs to characterize the global RNA‐binding proteome (RBPome) associated with polyA-tailed RNA species in murine ciliated epithelial cells of the inner medullary collecting duct. To study regulation of RBPs in a clinically relevant condition, we analyzed hypoxia-associated changes of the RBPome. Results We identified &gt;1000 RBPs that had been previously found using other systems. In addition, we found a number of novel RBPs not identified by previous screens using mouse or human cells, suggesting that these proteins may be specific RBPs in differentiated kidney epithelial cells. We also found quantitative differences in RBP-binding to mRNA that were associated with hypoxia versus normoxia. Conclusions These findings demonstrate the regulation of RBPs through environmental stimuli and provide insight into the biology of hypoxia-response signaling in epithelial cells in the kidney. A repository of the RBPome and proteome in kidney tubular epithelial cells, derived from our findings, is freely accessible online, and may contribute to a better understanding of the role of RNA-protein interactions in kidney tubular epithelial cells, including the response of these cells to hypoxia.
Predictive value of BubR1 and synuclein- gamma expression in breast cancer.
Authors: Yalcin Cirak, Yavuz Furuncuoglu, Ozlem Yapicier, Andac Argon, Suleyman Alici
Journal: Journal of Clinical Oncology (2015)

e13511 Background: At the cellular level,had been revealed that reduced BubR1 expression resulted in taxane resistance. Synuclein gamma (SNCG) is a new unfavorable prognostic marker for breast cancer and a potential target for cancer treatment. It binds to BubR1, interferes with its interaction with other checkpoint proteins, reduces activity of BubR1, and thus attenuates taxan-caused mitotic cell death. We investigated whether BubR1 and SNCG are predictive markers of taxane sensitivity and associated with clinical parameters in breast cancer. Methods: Cases were selected retrospectively from records of our hospital A total 55 patients with breast cancer administred single agent taxane in neoadjuvant or metastatic setting, were included into the study.The patients were stratified according to treatment responses to taxanes into two groups as responders and non- responders. Immunohistochemical (IHC) staining of paraffin embedded tisue spesimen for BubR1 and SNCG was performed. The respons to taxanes and clinical parameters were compared between the BubR1 and SNCG positive and negative groups and evaluated with χ² test. Results: 40% of all patients were resistant to taxanes. 38% and 61% of tumors showed positive expression for BubR1 and SNCG, respectively. 76% of BubR1 positive tumors had taxane responsive disease,compered with 50% of BubR1 negative tumors (p = 0.054). 47% of SNCG pozitive tumors had taxane responsive disease,compered with 81 % of SNCG negative tumors (P = 0.01). There were no significan association between clinical parameters (tumor grade, estrogen receptor, progesterone recoptor and HER2 status) and expression level of these proteins. However, 61% of triple negative tumors were BubR1 positive, compared with 31% of other molecular subtypes (P = 0.043) (see table). Conclusions: BubR1 positive tumors were more sensitive the taxane than those negative. High SNCG expression was significantly associated with poor respons to taxanes. Moreover, triple negative tumors showed statistically significant more BubR1 expression than other molecular subtypes. Variable n BubR1 SNCG High Low p-value High Low p-value Responder 33 16 17 0.05 16 17 0.01 Non-responder 22 5 17 18 4 Triple negative 13 8 5 0.04 8 9 0.9 Other subtypes 42 13 29 26 16
GLUT-1 and GLUT-14 as independent prognostic factors in gastric adenocarcinoma.
Authors: Felix Berlth, Peter Philipp Grimminger, Martin Karl Herbert Maus, Berit Pinther, Patrick Plum, Hans Anton Schloesser, Uta Drebber, Elfriede Bollschweiler, Arnulf Heinrich Hölscher, Stefan Paul Moenig, Hakan Alakus
Journal: Journal of Clinical Oncology (2015)

e15064 Background: Possible Targets and prognostic markers are needed for gastric cancer. The role of glucose transporter 14 (GLUT-14/SLCA14) in tumor biology is entirely unknown and the significance of HIF1-alpha for gastric adenocarcinoma controversial. The impact of glucose transporter 1 (GLUT-1/SLCA1) has never been confirmed in a Caucasian cohort. Methods: 124 patients underwent gastrectomy between 1996 and 2007 for gastric adenocarcinoma. Tumor sections were incubated with GLUT-1, GLUT-14 and HIF1-alpha antibodies. Expression was analyzed for correlations with histopathology, marker coexpression and patient survival by uni- and multivariate analysis. Results: GLUT-1, GLUT-14 and HIF1-alpha expressions were detectable in 50%, 77.4% and 27.1% respectively. GLUT-1 expression was associated with pT- (p = 0.009), pN-category (p = 0.023), tubular (WHO, p = 0.008) and intestinal (Laurén, p = 0.002) histological subtypes. GLUT-14 expression was correlated with pT-category (p = 0.043). HIF1-alpha did not show any correlation with histopathology or survival. The median survival of GLUT-1 positive patients was 14 months (95%CI:9.2-18.8) and 55 months for GLUT-1 negative patients (95%CI:25.8-84.2;p = 0.01). A significant inferior prognosis was also seen for GLUT-14 positive cases compared to GLUT-14 negative cases (p = 0.004). Thus, worst survival was seen with both GLUT-1 and GLUT-14 positive expression followed by single-positive and then double negative cases (p = 0.004). In multivariate analysis with pT-, pN-, pM-, R-category, Laurén classification and grading as covariates, GLUT-1 (p = 0.024) and GLUT-14 expressions (p = 0.005) kept their prognostic independence. Conclusions: Detection of GLUT-1 and GLUT-14 expression is, especially in combination, of high prognostic value. It gives additional information to the UICC categories, is helpful to identify patients with inferior prognosis and should therefore be considered in future staging systems for gastric cancer and for as a possible drug target.
Role of race and socioeconomic status in overall and cancer-specific survival of anal cancer patients.
Authors: Jessica Belmonte, Thomas H. Taylor, Joseph Carmichael, Jason A. Zell
Journal: Journal of Clinical Oncology (2015)

3521 Background: Treatment of anal cancer (AC) relies on a multidisciplinary approach and highly-coordinated care. As such, health disparities may arise in vulnerable populations. Our aim was to analyze the overall and cancer-specific survival (OS, CSS) of AC patients stratified by race/ethnicity while accounting for treatment and socioeconomic (SES) differences, as this has not been studied before. Methods: Incident cases of squamous cell AC were identified in the California Cancer Registry during 2004-2009. In-situ through stage IV AC were included. Univariate OS and CSS estimates were generated using Kaplan-Meier methods. Multivariate analysis (MVA) of OS and CSS were performed using Cox proportional-hazard regression models, adjusting for age, gender, SES, stage, grade, surgery, chemotherapy, and radiation therapy. Results: We identified 4303 incident cases of AC, including 3023 Caucasians (C), 342 African-Americans (AA), 555 Hispanics (H), 115 Asians (As) and 268 Others (O, Native American and unidentified race/ethnicity). Five-year OS for AAs was statistically shorter than for C and H counterparts (see table below). Higher SES was independently associated with a longer OS (p-trend < 0.0001) and CSS (p-trend 0.0101), compared to lower SES in MVA. After adjustment for SES and other covariates, and compared to C as a referent group, AAs were observed to have an independent increased risk of mortality (for OS, HR = 1.9, 95%CI 1.5-2.3 and for CSS, HR = 1.8, CI 1.3-2.4). This risk difference (AA vs. C) was observed in each stage and significant for all except stage II. Conclusions: In squamous cell AC, health disparities exist between racial/ethnic groups as exemplified by worse outcomes in the AA cohort vs. other racial/ethnic groups. The differences in survival cannot be accounted for by SES alone or treatment. SES is independently associated with outcome in AC. Additional determinants of health must be identified to facilitate improvement in outcomes. Univariate overall survival estimates (by Kaplan Meier Method). 12 months 36 months 60 months Caucasian 92% 80% 72% Black 85% 71% 65% Hispanic 92% 78% 68% Asian 91% 79% 70% Native American/Other 97% 94% 90% Log-Rank P-value for the above K-M survival curves < 0.0001
Abstract P166: Subendocardial Viability Ratio Associates With Diastolic Function Parameters: Insights From the Bogalusa Heart Study
Authors: Alexander C Razavi, Camilo Fernandez, Rupert P Barshop, Yajun Guo, Lydia Bazzano
Journal: Circulation (2019)

Introduction: Recent evidence has linked coronary microvascular dysfunction to impaired diastolic function and severity in heart failure with preserved fraction (HFpEF). While echocardiography remains pivotal in the assessment of this clinical scenario, information is scant on the role of applanation tonometry-derived estimates of coronary microcirculation, such as the subendocardial viability ratio (SEVR), in the evaluation of diastolic function. Hypothesis: We hypothesized that SEVR is associated with diastolic function parameters in relatively young and healthy adults in a community setting. Methods: We examined 611 participants of the Bogalusa Heart Study (31.3% black, 54.6% female, aged 29 to 51 years) who underwent 2D and Doppler echocardiography as well as pulse-wave analysis via applanation tonometry of the radial artery. Echocardiographic parameters of diastolic function included mitral annular velocity (e’), peak early filling velocity (E), peak velocity cause by atrial contraction (A), isovolumic relaxation time (IVRT), and deceleration time (DT). Diastolic function and SEVR relationships were evaluated with multivariable-adjusted linear regression. Covariates adjusted for included age, race, sex, systolic blood pressure, high density lipoprotein cholesterol, low density lipoprotein cholesterol, serum triglycerides, glucose, body mass index, cigarette smoking as well as blood pressure and lipid medications. Results: Compared to men, women had a lower SEVR (p &lt; 0.001). There were no significant sex or race differences in diastolic function parameters, except that black females had lower E/e’ ratios compared to black males (p=0.003). SEVR was significantly associated with the E/A ratio (β=0.20, p&lt;0.001) as well as DT (β=0.32, p&lt;0.001), while no significant associations were found between SEVR and the E/e’ ratio or IVRT. Neither sex nor race modified the relationship of SEVR with E/A ratio, DT, E/e’ ratio, or IVRT. Conclusion: In middle-aged adults, SEVR is significantly associated with traditional echocardiographic parameters of diastolic function, including both the E/A ratio and DT. Pulse wave analysis via applanation tonometry is an inexpensive non-invasive tool that may aid in accelerating the diagnosis of diastolic dysfunction in the individuals without overt disease.
Positive surgical margins after radical nephrectomy for localized kidney cancer: Impact on survival.
Authors: Stephen Ryan, Reith Sarkar, Ahmet Bindayi, Ahmed Eldefrawy, Zachary Hamilton, James Don Murphy, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2019)

676 Background: Impact of positive surgical margins (PSM) in patients undergoing radical nephrectomy (RN) in localized renal cell carcinoma (RCC) is poorly understood. We sought to understand the impact of PSM for on overall survival (OS) after RN in clinically localized RCC. Methods: Retrospective analysis of patients from the US National Cancer Database who RN for clinically localized (cT1a-cT2b cN0M0) RCC between 2003-13, were stratified into their pathological stage group [pT1a, pT1b, pT2a, pT2b, and pT3a ( = Upstaged)] and analyzed by final margin status. Cox Regression Multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on OS. Kaplan-Meier analysis (KMA) of OS was performed for PSM verses NSM for the overall cohort and by stage. Results: 37,656 RN events [14312 (38%) pT1a, 13598 (36.1%) pT1b, 6551 (17.4%) pT2a, 2937 (7.8%) pT2b, and 4286 (11.3%) with pT3a upstaging]. PSM rate was 0.9% overall (0.4% pT1a, 0.4% pT1b, 0.4% pT2a, 0.4% pT2b, and 4.7% pT3a upstaged). On MVA for all-cause mortality, PSM was independently predictive for decreased OS (HR 1.51, p &lt; 0.001), along with increasing age (HR 1.04, p &lt; 0.001), non-Caucasian race (HR 1.199, p &lt; 0.001), increasing charlson score (HR 2.23, p &lt; 0.001), non-private insurance (HR 1.61, p = 0.001), high grade histology (HR 1.21, p = 0.001), and sarcomatoid histology (HR 3.61, p &lt; 0.001). Pathologic T-stage was also predictive of decreased OS (Referent pT1a, HR 1.17, 1.47, 1.74, and 1.93, for pT1b, pT2a, pT2b, pT3a, respectively; all p &lt; 0.001). KMA revealed worsened 5-year OS for PSM vs. NSM for the overall cohort (62.4% vs. 81%, p &lt; 0.001), pT2a (61% vs. 79.4%, p = 0.013), and pT3a (50% vs. 68.3%, p &lt; 0.001) groups. Conclusions: PSM is a rare event after RN, but is associated with worsened OS, particularly in pT2 and pT3a upstaged patients. Mechanism of decreased OS cannot be clarified given limitations of the NCDB, these suggest that PSM may pose increased oncologic risks in higher pathological stage. Consideration of further definitive strategies (ex: preemptive wide field resection) may be warranted in select circumstances. Furthermore, our findings call for re-consideration of exclusion of PSM patients from adjuvant therapy trials.