tbuckley/cabot-search huggingface dataset:
Abstract P183: Incident Chronic Kidney Disease and Myocardial Infarction Without Chest Pain: Results From the Atherosclerosis Risk in Communities Study
Authors: Bailey M DeBarmore, Matthew S Loop, Brad C Astor, Kunihiro Matsushita, Gerardo M HEISS, Wayne D Rosamond, Nora Franceschini
Journal: Circulation (2020)

Background: Chronic kidney disease (CKD) and cardiovascular disease share similar risk factors, such as diabetes, hypertension, and dyslipidemia promoting atherosclerosis. Acute myocardial infarction (MI) presenting without chest pain is associated with higher case fatality compared to MI with chest pain. Patients with non-ST-elevation MI (NSTEMI) are more likely to present without chest pain than patients with ST-elevation MI (STEMI). Few if any studies have examined the risk of incident CKD following MI with and without chest pain. Hypothesis: We hypothesized that MI presenting without chest pain is associated with greater risk of incident CKD after adjustment for demographic factors, in-hospital complications, and comorbidities among adults in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: The ARIC Study is a community-based cohort study that began recruitment in 1987. MI without chest pain includes persons presenting with shortness of breath, nausea, or dyspnea that is determined to be of cardiac origin. Follow-up time for this analysis was calculated from date of MI hospitalization (index date) to incident CKD, death, or administrative censoring in 2017. Incident CKD was defined as eGFR &lt;60 mL/min/1.73 m 2 and ≥25% eGFR decline from previous measurements, CKD-related hospitalization or death, or end-stage renal disease. In-hospital complications included acute heart failure, ventricular fibrillation, and cardiogenic shock. Prevalent CHD and chronic heart failure were measured at visit 1 (1987-1989) and history of diabetes and hypertension were captured from the MI hospitalization record. Results: There was a total of 1,332 MI hospitalizations with data on MI type and symptom presentation. Among 1,038 NSTEMI events, 19% presented without chest pain, compared to 7% of the 294 STEMI events presenting without chest pain. Age greater than 65 years, female gender, and hypertension at the time of the MI as well as in-hospital complications of heart failure and ventricular fibrillation were more common among NSTEMI without chest pain compared to NSTEMI with chest pain. Median follow-up time was 4.9 years (Q1, Q3: 0.9, 11.4 years). Persons with NSTEMI events presenting without chest pain had 1.82 times the risk of incident CKD (95% CI: 1.39, 2.38) compared to NSTEMI events presenting with chest pain. This association was attenuated after adjustment for age at MI, female gender, and black race (HR: 1.36, 95% CI: 1.04, 1.80) and further attenuated after additional adjustment for reperfusion within 24 hours (HR: 1.30, 95% CI: 0.99, 1.72). Conclusion: NSTEMI presenting without chest pain was associated with increased risk of incident CKD, though this association was attenuated after adjustment.
Abstract 04: Gender and Racial Inequalities in the Use of Statins for Secondary Prevention of Cardiovascular Disease Remains Despite Persistent Recommendations in Recent Guidelines - A Call to Action
Authors: Joseph A Salami, Anshul Saxena, Victor Okunrintemi, Oluseye Ogunmoroti, Chintan B Bhatt, Muni Rubens, Obinna Daniel, Patrick Benjamin, Erin D Michos, Emir Veledar
Journal: Circulation (2020)

Introduction: Statins use for secondary cardiovascular disease (CVD) prevention is associated with better health outcomes and lower cost among adults with ASCVD. We aimed to examine the prevalence of statin use among adults with ASCVD in the US and to assess for gender and racial differences in statin use. Methods: We identified adults aged 40-75 years with ASCVD (defined using ICD codes and self-reported history) from the 2008-17 Medical Expenditure Panel Survey (MEPS) data. We estimated the trends in statin use among them, and used joint point regression (JPR) to estimate the annual percentage change in statin use. Logistic regression was used to assess the racial variation in statin use. We applied the weights in the MEPS complex survey design to estimate population sizes, so all results are nationally representative. Results: Between 2008 and 2017, 24896 adults aged 40-75 years with ASCVD were identified. In 2017, there were 2445 patients with ASCVD (equivalent to 24.5 million adults). In 2017, the mean age [SE] was 62.2 [0.3] years, and 42.9% were females. The overall proportion of adults with ASCVD using statin increased from 50.0% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 ( p= 0.01). As shown in Figure 1a , among those with ASCVD, statin use was persistently lower in women than in men. In 2017, compared to White adults with ASCVD, Blacks (OR=0.69; 95% CI: 0.51-0.92) and Hispanics (OR=0.62; 95% CI: 0.45-0.85) were less likely to be on statin. Each year, over 3 million women with ASCVD were not on statin, and majority of them were Blacks and Hispanics. (Figure 1b) Conclusion: Millions of adults with ASCVD are not on statins in the US while gender and racial inequalities in statin use remains, despite persistent guideline recommendations. Herein lies an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps, especially with the 2030 sustainable development goals in view.
Surrogate endpoints for overall survival (OS) in advanced pancreatic cancer (APC): Analysis of randomized clinical trials (RCTs) exploring gemcitabine (G)-based combinations
Authors: M. Milella, E. Bria, P. Carlini, F. Cuppone, A. Gelibter, C. Nisticò, E. M. Ruggeri, E. Terzoli, F. Cognetti, D. Giannarelli
Journal: Journal of Clinical Oncology (2007)

4575 Background: G-based combinations often result in an improved overall response rate (ORR) in APC; this improvement in ORR, however, seldom translates into a significant OS advantage. We therefore evaluated the appropriateness of ORR and progression-free survival (PFS) as surrogate endpoints for OS in RCTs comparing single-agent G and G-based combinations as first-line treatment for APC. Methods: Phase III trials reporting ORR or PFS and OS data were considered eligible. Potential correlations were explored according to a linear regression model considering both the actual outcome (ORR or PFS and OS) for each single arm and the calculated relative risk (RR) for each outcome in paired comparisons. Correlation was estimated according to Pearson’s (r) and R 2 coefficients (parametric) and Spearman’s (Rho) coefficient (non-parametric). A model to calculate the target sample size to correctly identify 0.4, 0.7, and 1.5 mos benefits in OS was derived as well. Results: Nineteen (6,288 pts) and 17 (4,882 pts) RCTs were identified for the ORR/OS and PFS/OS correlation, respectively. When considering ORR rates and medians, ORR did not significantly correlate with OS (r=0.23, R 2 =0.06, p=0.14; Rho=0.16, p=0.33), while PFS showed a strong linear correlation (r=0.75, R 2 =0.56, p&lt;0.0001; Rho=0.90, p&lt;0.0001). Similarly, when considering RRs, ORR did not significantly correlate with OS (r=-0.17, R 2 =0.03, p=0.46; Rho=-0.18, p=0.44), while PFS showed a strong linear correlation (r=0.91, R 2 =0.82, p&lt;0.0001; Rho=0.59, p=0.01). Based on these data, we derived a sample size model (beta-coefficient=0.75) to calculate how many patients would be necessary to demonstrate a significant OS advantage of 0.4, 0.7 and 1.5 mos, respectively, using PFS as a surrogate endpoint; according to this model, 0.5, 1, and 2 months improvements in PFS would be necessary to translate into the target OS advantages, requiring 2,370, 678 and 222 pts, respectively. Conclusions: In APC, ORR does not seem to correlate with OS. Conversely, PFS could be a reliable surrogate endpoint for survival in this setting, although the detection of relatively small differences in PFS would require a remarkably large sample size. No significant financial relationships to disclose.
Triple Therapy with Exenatide/Pioglitazone/Metformin vs. Conventional Therapy: Changes in Liver Fibrosis Scores after 2 Years of Treatment in Patients with New-Onset Type 2 Diabetes Mellitus
Authors: Olga Lavrynenko, Muhammad Abdul-Ghani, Mariam Alatrach, Curtiss Puckett, John Adams, Naim Alkhouri, Ralph DeFronzo
Journal: Metabolism (2020)
Glycaemic status during pregnancy and longitudinal measures of fetal growth in a multi-racial US population: a prospective cohort study
Authors: Mengying Li, Stefanie N Hinkle, Katherine L Grantz, Sungduk Kim, Jagteshwar Grewal, William A Grobman, Daniel W Skupski, Roger B Newman, Edward K Chien, Anthony Sciscione, Noelia Zork, Deborah A Wing, Michael Nageotte, Fasil Tekola-Ayele, Germaine M Buck Louis, Paul S Albert, Cuilin Zhang
Journal: The Lancet Diabetes & Endocrinology (2020)
Abstract 14635: Lipoprotein(a), Oxidized Phospholipids and Cardiovascular Risk: Relation to Ethnicity, Age and Family Structure
Authors: Enkhmaa Byambaa, Anuurad Erdembileg, Wei Zhang, Lars Berglund
Journal: Circulation (2019)

Introduction: Lipoprotein(a) [Lp(a)] is a preferential carrier of proatherogenic and proinflammatory oxidized phospholipids (OxPLs), suggested to promote cardiovascular risk. The associations betwe...
Dietary cellulose prevents gut inflammation by modulating lipid metabolism and gut microbiota
Authors: Yeji Kim, Sung Wook Hwang, Seungil Kim, Yong-Soo Lee, Tae-Young Kim, Su-Hyun Lee, Su Jung Kim, Hyun Ju Yoo, Eun Na Kim, Mi-Na Kweon
Journal: Gut Microbes (2020)

A Western diet comprising high fat, high carbohydrate, and low fiber content has been suggested to contribute to an increased prevalence of colitis. To clarify the effect of dietary cellulose (an insoluble fiber) on gut homeostasis, for 3 months mice were fed a high-cellulose diet (HCD) or a low-cellulose diet (LCD) based on the AIN-93G formulation. Histologic evaluation showed crypt atrophy and goblet cell depletion in the colons of LCD-fed mice. RNA-sequencing analysis showed a higher expression of genes associated with immune system processes, especially those of chemokines and their receptors, in the colon tissues of LCD-fed mice than in those of HCD-fed mice. The HCD was protective against dextran sodium sulfate-induced colitis in mice, while LCD exacerbated gut inflammation; however, the depletion of gut microbiota by antibiotic treatment diminished both beneficial and non-beneficial effects of the HCD and LCD on colitis, respectively. A comparative analysis of the cecal contents of mice fed the HCD or the LCD showed that the LCD did not influence the diversity of gut microbiota, but it resulted in a higher and lower abundance of Oscillibacter and Akkermansia organisms, respectively. Additionally, linoleic acid, nicotinate, and nicotinamide pathways were most affected by cellulose intake, while the levels of short-chain fatty acids were comparable in HCD- and LCD-fed mice. Finally, oral administration of Akkermansia muciniphila to LCD-fed mice elevated crypt length, increased goblet cells, and ameliorated colitis. These results suggest that dietary cellulose plays a beneficial role in maintaining gut homeostasis through the alteration of gut microbiota and metabolites.
Novel Silicon Titanium Diboride Micropatterned Substrates for Cellular Patterning
Authors: Jefferson Friguglietti, Susmi Das, Phi Le, Daniel Fraga, Marcos Quintela, Salvatore A. Gazze, Darius McPhail, Jianhua Gu, Omaima Sabek, A. Osama Gaber, Lewis W. Francis, Wanda Zagozdzon-Wosik, Fatima A. Merchant
Journal: Biomaterials (2020)
Retrospective analysis of phosphorylation status of the estrogen receptor in patients with early stage disease
Authors: R. F. Swaby, M. Huang, K. J. Ruth, E. A. Ross, Y. Gong, R. E. Page, G. M. Freedman, L. J. Goldstein, A. Di Cristofano
Journal: Journal of Clinical Oncology (2007)

21034 Background: The AKT kinase, when phosphorylated to its activated form (pAKT), mediates many proliferative and survival effects of growth factor receptors such as members of the epidermal growth factor receptor (EGFR) family. Overexpression of AKT in breast neoplasms suggests that AKT activation is involved in breast cancer development and/or progression, and contributes to poor outcome. pAKT is frequently upregulated in Her-2/neu positive breast cancers. Activated AKT is able to phosphorylate in vitro serine 167 (pS167) of estrogen receptor alpha (ERa), resulting in ER-mediated transcriptional activity in the absence of estrogen and possibly contributing to tamoxifen resistance in ERa positive breast cancers. In addition, ERa is phosphorylated at S118 (pS118) by MAPK. Thus, it is possible that pAKT- mediated ERa phosphorylation is implicated in tumorigenesis and resistance to treatment with hormonal therapy in patients with breast cancer. Methods: Utilizing commercially available antibodies, IHC analysis of 125 paraffin-embedded, ERa positive, early breast cancer cases, stratified for stage, were tested for pAKT, PTEN, pS167, and pS118. Staining intensity and number of positive cells were assessed by 4 independent graders. Fisher's exact test was used to determine the significance of associations with a two-sided type I error of 5%. Results: Phosphorylation of AKT occurred in approximately one-half of cases. pS167 was phosphorylated in 66% of pAKT positive cases compared to 35% of pAKT negative cases (p&lt;0.0001). When we analyzed nuclear pAKT staining, this association was more pronounced: 76% of pAKT(+) vs. 37% of pAKT(-) (p&lt;0.0001). 69% of pS118(+) cases were pS167(+) compared to only 15% pS167(+) when pS118 was negative (p&lt;0.0001). In approx. 32% of cases pAKT was present in both the cytoplasm and nucleus. 20% of samples had only cytoplasmic pAKT, while in 4% of cases pAKT was nuclear only, supporting the hypothesis that cytoplasmic phosphorylation of AKT may precede nuclear accumulation. Conclusions: Phosphorylation of pS167ERa is significantly associated with AKT activation (especially in the nucleus) in early breast cancer, supporting the hypothesis that these two events may be causally linked and contribute to breast cancer pathogenesis. No significant financial relationships to disclose.
Long-distance modulation of bystander tumor cells by CD8+ T-cell-secreted IFN-γ
Authors: Mirjam E. Hoekstra, Laura Bornes, Feline E. Dijkgraaf, Daisy Philips, Iris N. Pardieck, Mireille Toebes, Daniela S. Thommen, Jacco van Rheenen, Ton N. M. Schumacher
Journal: Nature Cancer (2020)
Abstract P320: Temporal Trends In Prevalence &amp; Prognostic Implications Of Cardiac And Non-cardiac Comorbidities Among Patients With Acute Decompensated Heart Failure: Aric Study Community Surveillance
Authors: Ambarish Pandey, Muthiah Vaduganathan, Sameer Arora, Arman Qamar, Robert J Mentz, Sanjiv J Shah, Patricia Chang, Stuart D Russell, Wayne D Rosamond, Melissa Caughey
Journal: Circulation (2020)

Introduction: Patients with HF have multiple co-existing CV and non-CV comorbidities. The temporal trends in the burden of co-morbidities and associated risk of mortality among patients with acute decompensated HF (ADHF) is not well-established. Methods: HF related hospitalizations were captured in the ARIC surveillance cohort study across 4 US communities 2005 to 2014 using ICD-9 codes. HF hospitalizations were adjudicated using validated algorithm to identify ADHF with reduced ejection fraction (HFrEF, ejection fraction &lt;50%) and preserved ejection fraction (HFpEF). Data on prevalence of CV and non-CV co-morbidities were obtained from medical record review. Mortality outcomes were ascertained for up to 1-year post-admission, by linking hospital records with death files. Results: Of the 22,805 hospitalizations sampled between 2005-2004, 8914 were classified as ADHF corresponding to 41,146 weighted hospitalizations for ADHF (53% HFrEF, 47% HFpEF). The burden of CV co-morbidities remained stable while that of and that of non-CV comorbidities increased significantly over time among patients with HFpEF and HFrEF. The overall burden of CV co-morbidities was not significantly associated with risk of mortality among patients with HFrEF and HFpEF. In contrast, greater burden of non-CV comorbidities was significantly associated with higher risk of in-hospital, 28-day, and 1-year mortality for both HFpEF and HFrEF. Among patients with HFrEF, the risk of mortality associated with higher burden of non-CV comorbidities did not change over time. In contrast, for HFpEF, there was a significant temporal decline in the non-CV burden associated risk of in-hospital mortality and an increase in the risk of 1-year mortality over time. Conclusion: The burden of non-CV co-morbidities among patients with ADHF has increased over time. Higher burden of non-CV comorbidities was associated with higher risk of mortality, with stable temporal associations in HFrEF and an increasing risk over time for 1-year mortality for HFpEF.
Abstract P243: Psychosocial Strengths in Childhood Reduce Cardiometabolic Risk in Midlife: Longitudinal Findings From the 1958 British Birth Cohort
Authors: Julia K Boehm, Laura Kubzansky
Journal: Circulation (2020)

Introduction: Reaching middle age with even one cardiovascular risk factor increases risk for morbidity and mortality. Yet once cardiovascular risk factors are in place, repairing or improving them can be difficult. One alternative is to promote healthy cardiovascular functioning during childhood. Although evidence indicates that adversity and psychological distress in childhood increase cardiovascular risk in adulthood, less research has examined protective childhood factors that enhance cardiovascular functioning and reduce risk over time. This research investigated if psychosocial strengths in childhood - such as positive emotions, optimism, purpose, satisfaction, and social connections - were associated with midlife cardiometabolic risk. Hypothesis: We hypothesized children with more versus fewer psychosocial strengths would have lower cardiometabolic risk in middle age. Methods: Data came from individuals in the 1958 British Birth Cohort, who have been repeatedly assessed from birth through adulthood. A subset of 11 year olds wrote an essay imagining their lives at age 25. Two trained judges rated 5,463 essays for the extent to which 9 psychosocial strengths were present (1=not at all; 7=very). The average rating across judges was calculated for each strength. All strengths were then averaged together for an overall score (α=.82). A cardiometabolic risk score was derived at age 45 from clinically-assessed systolic and diastolic blood pressure, resting heart rate, high-density lipoprotein cholesterol (reversed), total cholesterol, triglycerides, glycosylated hemoglobin, fibrinogen, and C-reactive protein. Each biomarker was standardized and then summed (higher numbers indicated more cardiometabolic risk). Missing values were multiply imputed, then linear regression analyses determined associations between psychosocial strengths and cardiometabolic risk. Results: In unadjusted models, having more psychosocial strengths was significantly associated with lower cardiometabolic risk (b=-.42, se=.08, p&lt;.0001). After adjusting for sex and financial hardship in childhood, the association was maintained (b=-.20, se=.08, p=.009). However, adding childhood cognitive ability and essay word count (b=-.09, se=.08, p=.24), as well as childhood health-related variables (heart complaints, height, weight) and adulthood cardiovascular medication use (b=-.10, se=.07, p=.18), attenuated the association. Conclusions: Children with more psychosocial strengths tended to have reduced cardiometabolic risk in midlife. These associations were accounted for by other child attributes that may cluster with psychosocial strengths. With a primordial prevention framework and innovative methods to assess childhood psychosocial strengths, this study contributes to growing evidence about factors in early life that may reduce cardiometabolic risk across the lifespan.
Trastuzumab and paclitaxel or vinorelbine for HER2+ metastatic breast cancer: A retrospective study and analysis of economic cost
Authors: A. Scola, H. Koussis, A. Jirillo, C. Ghiotto, S. Lonardi, A. Bortolami, S. Monfardini
Journal: Journal of Clinical Oncology (2007)

11517 Background: We analyses a mono institutional series of patients treated with metastatic breast cancer (MBC). Methods: From 2000 to 2006 forty consecutive patients affected by MBC were evaluated. The average age was 50 years (range: 30–79). All patients had HER2+ tumors (IHC 3+ or FISH+) and LVEF &gt; 50%. Metastatic sites were: liver 18, lymph nodes 10, bone 9, skin 7, lung 5 pts. In 11 cases the sites of metastases were multiple (1–3). All patients were treated with Trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly thereafter with weekly Paclitaxel 80 mg/m 2 or weekly Vinorelbine 25 mg/m 2 ; specifically, Paclitaxel was used in 26 patients and Vinorelbine in 14 patients. The endpoints were time to progression (TTP), duration of response, toxicity (including cardiologic) and overall survival. Results: A total of 1271 courses of weekly Trastuzumab were administered (average 28 courses per patient: range 8–72). There were 22 complete and partial responses (CR+PR=55%). In the association of Trastuzumab and Paclitaxel were seen :11 CR, 6 PR, 3 SD and 6 PD, (RR 65.3%). In the combination of Trastuzumab and Vinorelbine: 2 CR, 3 PR, 4 SD and 5 PD (RR 35.7%) . The most responsive sites were: liver 15 CR+PR (37.5%), lung 11 CR+PR (27.5%), lymph nodes 8 CR+PR (20%), and skin 6 CR+PR (15%). TTP was 7 months (2–27 months) and response duration 6.7 months (2–26 months). Overall survival at 5 years was estimated at 26.4 months. Toxicity rates were: hematological grade 4 in 2 pts, grade 3 in 3 pts, neurological grade 3 in 19 pts. No important cardiologic toxicity was observed: LVEF was reduced to 40% in 4 pts. Seven patients developed brain metastasis during therapy. The patients in PD continued Trastuzumab with other chemotherapy, no responses were observed. The median cost of treatment with Trastuzumab for patient was 16.147 € (range 3.987–39.959 €. Conclusions: Treatment with Trastuzumab plus chemotherapy has been shown to be effective and well-tolerated providing a good quality of life. The economic impact is important and is to define. The cost/benefit in this cohort of the patients is ongoing. No significant financial relationships to disclose.