tbuckley/cabot-search huggingface dataset:
Abstract P308: The Association of Height With Incident Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Steven P Menez, Lucia Kwak, Ning Ding, Caitlin Hicks, Morgan Grams, Aaron Folsom, Gerardo Heiss, Elizabeth Selvin, Bernard Jaar, Kunihiro Matsushita
Journal: Circulation (2019)

Background: A number of cross-sectional studies have reported shorter height as a risk factor for peripheral artery disease (PAD) defined by low ABI. People of shorter stature may have a naturally lower ABI stemming from a relatively lower ankle blood pressure, as function of the shorter distance from the heart to the distal leg arteries. If shorter height is related to PAD, height should also be associated with clinical PAD. We aimed to investigate the association of height with clinical PAD and critical limb ischemia (CLI) in a prospective cohort analysis. Methods: Using data from the ARIC Study, we investigated the association of height with development of PAD and CLI, defined based on ICD-9 codes, for the 14,668 participants at Visit 1 without prevalent PAD/CLI over a median follow-up time of 25.9 years. We modeled risk for PAD and CLI over time using Cox proportional hazards regression. Results: 6,652 (45.4%) participants were men, with a mean age of 55 (SD 6) years old, compared to 54 (SD 6) years old in women. 1,460 (22%) men and 2,321 (29%) women were African American. Men tended to be taller and have a higher weight compared to women. Within each sex, there were no significant differences by quartile of height in terms of demographic factors or clinical comorbidities. For men in height quartile 2 compared to quartile 1, there was a decreased risk of PAD in unadjusted analysis (HR=0.69; 95% CI 0.51-0.94). However, this HR was no longer significant after full adjustment (Table 1). In women, the risk of CLI was higher in the fourth quartile of height compared to quartile 1 after adjustment for demographic factors (HR=1.69; 95% CI: 1.00-2.84). However this HR also became non-significant after full adjustment. For both genders, the HR of either PAD or CLI per one SD increase in height was not significant. Conclusions: In contrast to previous cross-sectional studies which showed and association between shorter height and PAD based on ABI, our prospective study showed null associations between height and clinical PAD.
Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death
Authors: Fatima Gasset-Rosa, Shan Lu, Haiyang Yu, Cong Chen, Ze’ev Melamed, Lin Guo, James Shorter, Sandrine Da Cruz, Don W. Cleveland
Journal: Neuron (2019)
Abstract P214: Adherence to Dietary Recommendations of the AHA 2020 Goals and Risk of Preeclampsia Among Danish Women
Authors: Mariel Arvizu, Anne A Bjerregaard, Marie T Madsen, Charlotta Granström, Thorhallur I Hallsorsson, Sjurdur F Olsen, Audrey J Gaskins, Janet W Rich-Edwards, Bernrad A Rosner, Jorge E Chavarro
Journal: Circulation (2019)

Objective: Because the role of diet in preeclampsia is unclear, we examined the association between adherence to the American Heart Association’s (AHA) 2020 dietary recommendations and risk of preeclampsia. Methods: We followed 66,161 singleton pregnancies from 62,310 women participating in the Danish National Birth Cohort. Diet was assessed around gestation week 20 with a semi-quantitative food frequency questionnaire (FFQ). Adherence to the AHA dietary recommendations was calculated by a score, which addressed 5 dietary components: fruits and vegetables, fish, whole grains, sodium and sugar-sweetened beverages. Preeclampsia was ascertained by linkage to the Danish National Patient Registry. We estimated relative risks [RR] and 95% confidence intervals [95% CI] of preeclampsia according to increasing quintiles of adherence to the AHA recommendations using logistic regression models with generalized estimating equations to account for repeated pregnancies per woman while adjusting for energy intake, age, BMI, parity, smoking status, socio-economic status, height, region, education, and vitamin C and E intakes. Results: We identified 1,319 (2%) cases of preeclampsia, including 307 (0.5%) cases of severe preeclampsia. The AHA score ranged from 4 to 49 points with a maximum possible score of 50 points. Stronger adherence to the AHA score was inversely associated with the risk of preeclampsia. The adjusted RR [95%CI] among women categorized with the highest AHA score compared to women in the lowest score category was 0.81 (95%CI 0.68, 0.96). When each component of the score was separately examined, the association with risk of preeclampsia was largely driven by sodium. Specifically, women with the highest sodium intake (median 3,729 mg/day [range: 3611, 3922]) had 20% (95%CI 2, 43%) higher risk of developing preeclampsia compared to women with the lowest sodium intake (median 2,602 mg/day [range 2,435, 2,710]). When sodium intake was excluded from the AHA score, greater adherence to AHA recommendations was no longer related to risk of PE (RR 0.87, 95%CI 0.60, 1.28). Conclusions: Higher adherence to the AHA 2020 dietary recommendations during pregnancy was associated with a lower risk of preeclampsia. Although diet sodium tends to be underestimated when measured by FFQ, we found that sodium intake was related to risk of preeclampsia.
Abstract 15417: Paced QRS Morphology on Synthesized Right-Sided Electrocardiogram is a Simple and Novel Technique for Differentiating the Free Wall Position of Right Ventricular Pacing Leads
Authors: Junji Yamaguchi, Yasutoshi Nagata, Yuichiro Sagawa, Keita Watanabe, Masahiro Sekigawa, Naoyuki Miwa, Tetsuo Yamaguchi, Takamichi Miyamoto, Toshihiro Nozato
Journal: Circulation (2017)

Introduction: The right ventricular (RV) perforation caused by pacing leads is one of the serious complications of pacemaker. Most of them were placed at RV free wall or apex peak, therefore it is ...
Genomic validation of three-tiered sub-classification of high-risk prostate cancer.
Authors: Vinayak Muralidhar, Jingbin Zhang, Daniel Eidelberg Spratt, Felix Y Feng, Elai Davicioni, Kasra Yousefi, Natalie Wang, Voleak Choeurng, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2019)

17 Background: Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥ 8, or prostate-specific antigen [PSA] &gt; 20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether sub-classification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk. Methods: We identified 3,220 patients with NCCN unfavorable intermediate-risk (n=2,000) or high-risk (n=1,220) prostate cancer. We defined the following sub-classification of high-risk prostate cancer based on previously published data: favorable high-risk (cT1c, Gleason 6, and PSA &gt; 20 ng/mL or cT1c, Gleason 4+4=8, PSA &lt; 10 ng/mL); very high-risk (cT3b-T4 or primary Gleason pattern 5); and standard high-risk (all others with cT3a, Gleason score ≥ 8, or PSA &gt; 20 ng/mL). We used a set of 37 previously published genomic classifiers, including the 22-gene Decipher assay, to determine whether high-risk genomic features correlated with the clinical sub-classification of high-risk prostate cancer. Results: Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, 81.6% had a high-risk Decipher score, respectively (p &lt; 0.001). Among 36 other genomic signatures, 33 had a similar increasing trend across the three sub-classes of high-risk (p &lt; 0.05 after correction for multiple hypothesis testing). Patients in the three sub-classes of high-risk disease were positive for a median number of 5, 7, and 14 high-risk signatures. Under a novel clinical-genomic risk group classification (Spratt et al., 2017), 27.5%, 19.7%, and 7.0% of patients with favorable, standard, or very high-risk disease would be re-classified as intermediate-risk, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score and would be re-classified as clinical-genomic high-risk. Conclusions: Genomic markers of risk correlate with the clinical sub-classification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, validating the prognostic utility of this stratification.
Abstract P147: Longer Duration on a Chronic Disease Management Plan is Associated with Fewer CVD-Related Readmissions by 3 Years Among Australian Survivors of Stroke
Authors: David Ung, Richard P Gerraty, Judith Frayne, Muideen T Olaiya, Joosup Kim, Velandai K Srikanth, Thanh Phan, Dominique A Cadilhac, Mark R Nelson, Christopher F Bladin, Amanda G Thrift
Journal: Circulation (2019)

Background: Chronic Disease Management (CDM) plans are usually administered by general practitioners (GPs) to assist those with a chronic medical condition, such as stroke, and provide better management of risk factors. Despite the prevalent use of CDM plans, its comprehensiveness and the fact that there is a government commitment to fund it, there is limited evidence of its effectiveness in Australian survivors of stroke. We aimed to assess the effectiveness of CDM plans on preventing the recurrence of CVD-related serious adverse events. Methods: Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Poisson regression models were used to determine the incidence rate ratio (IRRs) of increasing exposure to being on a CDM plan over 3 years, while adjusting for confounding factors. We used the total count of CVD-related events and deaths within 3 years after stroke/TIA, based on either hospital discharge codes or adjudication by two independent stroke specialists. Results: Five hundred and sixty-three patients were included (median age 70; 36% female). There were 305 CVD-related events over the three years (mean 0.54), in which a third (104) were adjudicated and two-thirds (201) were derived from hospital discharge codes alone. Nearly a quarter (27%) did not take up a CDM plan over the three years, a third (33%) were on plans for less than 1.5 years and 40% were on plans from 1.5 years to 3 years. The factors most strongly associated with decreased incidence of CVD-related events were duration on a CDM plan (Adjusted IRR (aIRR) 0.85, 95% confidence interval (95%CI) 0.77-0.93; p&lt;0.001), higher level of education (aIRR 0.55, 95%CI 0.42-0.71; p&lt;0.001), more physically active occupation (aIRR 0.54, 95%CI 0.41-0.70; p&lt;0.001) and greater Assessment of Quality of Life (AQoL) score (aIRR 0.24, 95%CI 0.15-0.41; p&lt;0.001). Conclusion: Being on a CDM plan for a longer duration appeared to reduce the occurrence of CVD-related events within 3 years after stroke, potentially via more closely controlled risk factors. Patients should be encouraged to return for regular reviews of their CDM plans to enhance secondary prevention strategies, and maintain a better quality of life.
Abstract P146: Trends in Recurrent Coronary Heart Disease Following Myocardial Infarction Among US Men and Women Between 2008 and 2016
Authors: Sanne A Peters, Lisandro D Colantonio, Hong Zhao, Vera Bittner, Michael Farkouh, Paul Dluzniewski, Bharat Poudel, Paul Muntner, Mark Woodward
Journal: Circulation (2019)

Background: In the US, morbidity and mortality from coronary heart disease (CHD) has declined considerably from the 1970’s through the 2000’s. We examined whether rates of recurrent MI, recurrent CHD, heart failure hospitalization, and all-cause mortality among US men and women with a MI hospitalization have continued to decline between 2008 and 2016, and whether this differs between the sexes. Methods: Data were used from 1,369,617 (53% women) US adults &lt;65 years of age with commercial health insurance in the MarketScan database and US adults ≥66 years of age with government health insurance through Medicare who had a MI hospitalization between January 1, 2008 and September 30, 2016. For each year, sex-specific rates of recurrent MI, recurrent CHD, heart failure hospitalization, and all-cause mortality (Medicare only) per 1,000 person-years were calculated at 30 days from the MI discharge date. Results: Between 2008 and 2016, rates of recurrent MI declined by 15%, from 190 to 162/1000 person-years, in men and by 27%, from 220 to 160/1000 person-years, in women. CHD recurrence rates decreased by 22%, from 311 to 244/1000 person-years, in men and by 32%, from 318 to 216/1000 person-years, in women (Figure). Heart failure hospitalization decreased by 4%, from 367 to 352/1000 person-years, in men and by 18%, from 517 to 425/1000 person-years, in women. Rates of 30-day mortality reduced by 5%, from 1,208 to 1,142/1000 person-years, in men and by 4%, from 1,416 to 1,358/1000 person-years, in women. Conclusion: Rates of recurrent MI, recurrent CHD, heart failure hospitalization, and all-cause mortality within 30 days after hospitalization for MI continue to decline in US adults, with greater reductions in the recurrence of CHD among women than men. Factors underpinning these trends warrant further investigation.
Genomic Analysis of Myelodysplastic Syndromes Among Nagasaki Atomic Bomb Survivors
Authors: Masataka Taguchi, Hiroyuki Mishima, Yusuke Shiozawa, Chisa Hayashida, Akira Kinoshita, Shinya Sato, Makiko Horai, Masatoshi Matsuo, Hidehiro Itonaga, Takeharu Kato, Hiroaki Taniguchi, Daisuke Imanishi, Yoshitaka Imaizumi, Tomoko Hata, Motoi Takenaka, Hideki Makishima, Yasuhito Nannya, Yukiyoshi Moriuchi, Seishi Ogawa, Koh-ichiro Yoshiura, Yasushi Miyazaki
Journal: Blood (2018)
Is the occurrence of higher adverse effects associated with better oncological outcome in metastatic urothelial carcinoma patients treated with pembrolizumab?
Authors: Nozomi Hayakawa, Eiji Kikuchi, Koichirou Ogihara, Seiya Hattori, Shunsuke Yoshimine, Suguru Shirotake, Takashi Okabe, Ryo Yamashita, Mototsugu Oya
Journal: Journal of Clinical Oncology (2019)

405 Background: Pembrolizumab is an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody and a recently approved and long-awaited drug for the treatment of metastatic urothelial carcinoma (UC). It is an immune checkpoint inhibitor, which has been shown to trigger new autoimmune disorders. We investigated the association of occurrence of adverse effects (AE) with clinical outcome in Japanese UC treated with pembrolizumab. Methods: We identified 50 cases treated with pembrolizumab for chemo-resistant UC between December 2017 and August 2018 at our 5 institutions. Pembrolizumab-induced AE were reported by using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. We evaluated the association between pembrolizumab-induced AE and response rate as well as patient survival. Results: The median age of the patients was 73 years (range, 46-89 years). The male/female ratio was 36/14. The primary tumor location was the pelvis in 10, ureter in 10, and bladder in 30. The median course of pembrolizumab was 4 (1-11). In the 50 patients, 36 AEs were observed, 11 of which were classified as CTCAE grade 2/3 . These patients were defined as the high AE groups. No grade 4 AE was encountered. In the high AE groups the most common AE was adrenal dysfunction (n = 4). Patients with no or CTCAE grade 1 were defined as the no/low AE groups. In the 45 cases who had measurable lesions, at the point of maximum effect the sum of the target lesion longest diameter (SLD) was decreased in 17 cases (37.8%) compared to baseline. SLD decreased in 7 (70%) patients in the high AE groups, which was significantly lower than those in the no/low AE groups (10, 28.6%, p = 0.027). The disease control rate defined by RECST ver. 4.0 at best response in the high AE groups was 81.8%, which was significantly higher than that in the no/low AE groups (46.2%, p = 0.046). The 6-month progression-free survival rate and the 6-month cancer-specific survival rate for the high AE groups was not different from that for the no/low AE groups. Conclusions: In patients with metastatic UC, the occurrence of CTCAE grade 2/3 might be associated with a better clinical response to pembrolizumab treatment.
Abstract P151: Plasma Cyclic Guanosine Monophosphate (cGMP) and Heart Failure With Preserved Ejection Fraction: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Di Zhao, Eliseo Guallar, Chiadi E Ndumele, Dhanajay Vaidya, Pamela Ouyang, Wendy S Post, Joao A Lima, Wendy Ying, Vinita Subramanya, David A Kass, Ron C Hoogeveen, Sanjiv J Shah, Erin D Michos
Journal: Circulation (2019)

Introduction: Cyclic guanosine monophosphate (cGMP) is an intracellular second messenger, synthesized through nitric oxide (NO) and natriuretic peptide (NP) pathways, with two different downstream effects on the cardiovascular system. Stimulators of cGMP are potential candidates in treating heart failure with preserved ejection fraction (HFpEF). However, the associations between plasma cGMP, HFpEF, and atherosclerotic cardiovascular disease (ASCVD) in the general population are unknown. We hypothesized that cGMP mediates HFpEF and ASCVD events, and that associations differ by sex. Methods: We included 1,034 ARIC participants selected by case-cohort design with over-sampling of participants with incident HFpEF. cGMP was measured using visit 4 plasma samples. Cox proportional hazard regression models were used to assess the relationship of cGMP with incident HFpEF, coronary heart disease (CHD), and ASCVD (CHD + stroke). Models were adjusted for sampling weights to provide estimates applicable to the overall ARIC population. Covariates included demographics and CVD risk factors. Models also adjusted for NT-proBNP, which is upstream of cGMP production in the NP regulated pathway. Results: Mean (SD) age was 63.2 (5.6) years and median (IQR) cGMP was 3.4 pmol/mL (2.4, 4.6). During 16.7 years of follow-up, there were 272 HFpEF, 179 ASCVD, and 129 CHD incident events. In models adjusted for CVD risk factors, the HRs (95% CI) comparing 3 rd tertile with 1 st tertile of cGMP for ASCVD, CHD and HF were 1.8 (1.1, 2.9), 1.9 (1.2, 3.0) and 2.0 (1.2, 3.3), respectively. In models further adjusted for NT-proBNP, associations were attenuated and not significant [HRs 1.2 (0.7, 2.0), 1.5 (0.96, 2.5) and 1.7 (0.98, 2.9), respectively]. There were no significant interactions by sex. Conclusions: cGMP levels are associated incident HFpEF, ASCVD, and CHD; however, after NT-proBNP adjustment, associations were attenuated, suggesting that plasma cGMP levels reflect a greater effect as a downstream messenger in NP than NO signaling pathways.
Targeting mediator subunits CDK8/CDK19 for treatment of advanced prostate cancer.
Authors: Marie C. Hupe, Anne Offermann, Finn Becker, Vincent Joerg, Wenzel Vogel, Johannes Braegelmann, Sven Perner, Axel Stuart Merseburger
Journal: Journal of Clinical Oncology (2019)

152 Background: The mediator complex plays a pivotal role in the regulation of gene transcription. The subunits CDK8 and CDK19 are overexpressed in advanced prostate cancer (PCa) and promote migration and invasion, as shown previously by our group. The aim of this study was to analyze if CDK8/CDK19 inhibition can impede PCa progression. Methods: Immunohistochemistry for CDK8 and CDK19 was performed on a large PCa cohort (376 radical prostatectomy (RP) specimens, 39 locally advanced tumors, 32 lymph node metastases, 24 distant metastases, 73 benign prostatic specimens). PCa cell lines (DU145, PC3) were treated with CDK8/CDK19 small molecule inhibitors followed by MTT assay, wound healing assay, and Western Blot for epithelial/mesenchymal markers. Results: CDK19 is higher expressed in primary PCa vs. benign specimens and locally advanced PCa/distant metastases vs. primary PCa. CDK8 and CDK19 are higher expressed in castration-resistant specimens vs. hormone-naive specimens. CDK19 significantly correlates with grade group in RP specimens. Biochemical recurrence free survival rates are lower for patients with high vs. medium vs. no/low CDK19 expression in the tumor. CDK19 predicts recurrence free survival independently from grade group and PSA. CDK8/CDK19 inhibition results in decreased migration, while there is no effect on proliferation. Mesenchymal markers are reduced while epithelial markers are induced following CDK8/CDK19 inhibition. Conclusions: CDK19 qualifies as a prognostic marker predicting biochemical recurrence following RP. CDK8/CDK19 inhibition leads to decreased migratory potential and mesenchymal phenotype. CDK8/19 expression increases during progression to castration-resistance. Collectively, CDK8/CDK19 represents a new target for treatment of advanced and/or castration-resistant PCa.
Longer-term effectiveness of protease-inhibitor-based second line antiretroviral therapy in four large sub-Saharan African clinics
Authors: Fred S. Sarfo, Barbara Castelnuovo, Iuri Fanti, Torsten Feldt, Francesca Incardona, Rolf Kaiser, Isaac Lwanga, Gaetano Marrone, Anders Sonnerborg, Tafese B. Tufa, Maurizio Zazzi, Andrea De Luca
Journal: Journal of Infection (2019)
Characterization of PSA at death in patients with metastatic castration-resistant prostate cancer.
Authors: Krishna Bikkasani, Qian Qin, Justin Lin, Matt D. Galsky, Bobby Chi-Hung Liaw, William K. Oh, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2019)

184 Background: Prostate Specific Antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer (PC). Currently, the significance of PSA at death is undefined. In this single institution retrospective study, we aim to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we stratified patients into the following cohorts based on their PSA at death: &lt; 10, 10-100, 100-1000, and &gt; 1000 ng/ml. We excluded data of patients who had less than 3 visits to the Mount Sinai Hospital. A descriptive analysis was performed to assess clinical characteristics of disease, treatment response, and outcomes. Results: We identified 1097 PC patients, and 101 were found to be deceased following a diagnosis of mCRPC. Cohorts of higher PSA level at death were associated with: a lower Gleason score at diagnosis, a longer time to castration resistance, higher burden of metastatic disease at death (non-visceral and visceral), and longer OS in patients with mCRPC (see table). Conclusions: In this study, PSA at death is associated with several important clinical characteristics and outcome, including overall survival. These differences may be attributed to their underlying biologic behavior. These results are hypothesis generating, and larger studies will be needed to further assess the significance of these findings. [Table: see text]