tbuckley/cabot-search huggingface dataset:
Abstract 12973: Intra-Procedural Change in Platelet Occlusion Time to Predict Hemodynamic and Clinical Outcomes Following Transcatheter Aortic Valve Replacement
Authors: Sebastien Hecht, Jeremy Bernard, Lionel Tastet, Rami Abu-Alhayja’a, Jonathan Beaudoin, Nancy Cote, Robert DeLarochellière, Jean-Michel Paradis, Marie-annick A Clavel, Josep Rodes-Cabau, Philippe Pibarot
Journal: Circulation (2021)

Background and Objectives: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement for the therapeutic treatment of severe aortic stenosis. However, intraprocedural hemodynamic assessment by echocardiography is not always optimal and new tools are needed. A new approach using the blood biomarker measuring platelet occlusion time (CT-ADP) and more specifically its change between the pre-intervention and post-intervention (ΔCT-ADP) could be useful to overcome the lack of accuracy of echocardiography, but also to prevent adverse clinical events following TAVI. The objective of this study is to examine the association between ΔCT-ADP and i) intraprocedural valve hemodynamic performance; and ii) occurrence of all-cause death and rehospitalization for heart failure (HF) in TAVI patients. Methods: Three hundred and thirty-eight patients who underwent TAVI at our institute were recruited. Clinical and echocardiographic data were collected before and after the procedure. Two blood samples were collected prior to- and at the end of- TAVI to assess the immediate changes (Δ: pre minus post) in CT-ADP following TAVI. A percentage (Δ/pre-intervention value) was determined for CT-ADP and mean gradient (MG) for each patient. Results: Prior to TAVI, 135(40.0%) patients had a prolonged CT-ADP (&gt;180 s). There was a significant but modest correlation between ΔCT-ADP and the change in mean transvalvular gradient immediately after TAVI (r=0.15, p=0.007). A ΔCT-ADP (i.e. decrease) &gt;10% (i.e. median of cohort) was associated with a higher rate of transcatheter valve regurgitation ≥ moderate (0.0% vs 3.0%, p=0.030) following TAVI, and a longer length of hospital stay (7.8±8.3 vs. 9.7±9.0 days, p=0.002). During a median follow-up of 1.2 (1.0-2.4) years, there were 87 clinical events (30 rehospitalizations and 57 deaths). A ΔCT-ADP &gt;10% tended toward higher risk of events in univariable analysis (HR[95%CI]: 1.49[0.94-2.37], p=0.090), but not after adjustment for other risk factors (HR[95%CI]: 1.10[0.53-2.28], p=0.79). Conclusion: A &gt;10% decrease in CT-ADP immediately after TAVI is associated with worse hemodynamic outcomes. This association is not independent and appears to be related to other risk factors.
Abstract 11016: Long-Term Outcomes of Bovine versus Porcine Mitral Valve Replacement - A Multi-Center Analysis
Authors: Michael P Robich, Benjamin M Westbrook, Anthony DiScipio, Niveditta Ramkumar, Fuyuki Hirashima, Robert S Kramer, Reed D Quinn, Cathy S Ross, Alexander Iribarne
Journal: Circulation (2021)

Introduction: Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in increased utilization of mitral bioprostheses. We examined long-term survival and risk of re-operation between patients having bovine vs porcine MVR. Methods: A retrospective analysis of MVR or MVR+CABG from 2001 - 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,308 patients undergoing MVR (811 bovine and 497 porcine). Baseline comorbidities were balanced using 1:1 propensity score matching with 432 patients in each group. . The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. Results: In the analytic cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; P&lt;.001), COPD (21% bovine vs. 27% porcine; P=.01), dialysis or creatinine &gt;2 mg/dL (4% bovine vs. 7% porcine; P=.03) and coronary artery disease (65% bovine vs. 76% porcine; P&lt;.001). In the overall cohort there was no difference in long-term survival (porcine HR 1.17 [95% CI 1.00-1.37; P=0.050]) or reoperation (porcine HR 0.56 [95% CI 0.23-1.32; P=0.19). In the propensity-matched cohort, the bovine valve patients were less likely to return to the OR for bleeding (6% vs. 9.3%; absolute standardized difference 0.12), but were more likely to have a stroke (3.7% vs. 1.9%; absolute standardized difference 0.11). There was no difference in in-hospital and 30-day mortality. After 1:1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 [95% CI 0.81-1.17; P=0.76]) or risk of reoperation (porcine HR 0.54 [95% CI 0.20-1.47; P=0.23). Conclusions: In this multicenter analysis of patients undergoing bioprosthetic MVR there was no difference in long-term survival, and risk of reoperation.
SURG-08. SARCOPENIA IS A PROGNOSTIC FACTOR OF 90-DAY MORTALITY AND OVERALL SURVIVAL IN ELDERLY PATIENTS WITH GLIOBLASTOMA
Authors: Ramin Morshed, Jacob Young, Megan Casey, Elaina Wang, Manish K Aghi, Mitchel Berger, Shawn Hervey-Jumper
Journal: Neuro-Oncology (2021)

Abstract Elderly patients with glioblastoma (GBM) have worse overall prognosis compared to younger patients and are less likely to undergo tumor resection and adjuvant therapy. The goal of this study was to identify patient and treatment factors as well as preoperative imaging features associated with worse overall survival and death within 3 months of surgery in elderly GBM patients. A single-center retrospective study was conducted with patients who met the following inclusion criteria: 1) age ≥ 79 at surgery (past the average age of life expectancy), 2) underwent biopsy or resection of an IDH-wildtype WHO Grade IV GBM at the time of initial diagnosis, and 3) had no prior radiation or chemotherapy. Patient, imaging, and treatment data were collected retrospectively from the electronic medical record. Univariate and multivariate Cox proportional hazard and logistic regression analyses were performed to identify factors associated with overall survival and 90-day mortality. The cohort consisted of 110 patients with a mean age of 82.8 (range 79 to 94.1) at surgery and a median preoperative KPS of 80. Thirty-seven (33.6%) and 73 (66.4%) patients underwent biopsy and resection, respectively. Adjuvant chemo- and/or radiation therapy were used in 72.5% of cases. On multivariate analysis, age (HR 1.13 by year, p=0.01), increased masseter thickness (HR 0.88 by mm, p=0.049), adjuvant therapy (HR 0.05, p&amp;lt; .0001), and surgical resection rather than biopsy (HR 0.38, p=0.0007) were associated with improved survival. Decreased masseter thickness was the only preoperative factor on analysis that predicted 90-day mortality in the cohort (p=0.038). GBM patients past the average age of life expectancy still fare better when undergoing resection followed by adjuvant chemotherapy and radiation therapy. In addition to treatment factors that predict survival, smaller masseter diameter on preoperative imaging, a marker of sarcopenia, is associated with shorter survival and death within 90 days of surgery.
Abstract 14129: S18 Alleviates The Inflammatory Responses In Interstitial Cells Of Aortic Valves Through Up-regulation Interleukin 37
Authors: Li Shunyi, Zeng Jingxin, Su Shuwen, Xie Kaiji, Yang Xi, Xian Gaopeng, Xu Dingli, Zeng Qingchun
Journal: Circulation (2021)

Background: Calcific aortic valve disease (CAVD) is a common cardiovascular disease,which leads to the failure of valvular function in the elderly. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation of aortic valve interstitial cells (AVICs). Anti-CAVD agents with new mechanisms of action are urgently needed. S18 is obtained from a marine-derived Streptomyces strain, and it has a potent anti-inflammatory effect. However, its effect on CAVD is unknown. This study is sought to investigate the role of the natural product S18 in alleviating CAVD progression. Methods and Results: Human AVICs treated with LPS showed up-regulation of inflammatory factors ICAM-1, IL-8, and MCP-1, and significant calcification evaluated by Alizarin Red staining. S18 (2 μM) attenuated LPS-induced human AVICs inflammation. RNA-sequencing was used to identify differentially expressed genes (DEGs) in human AVICs treated with LPS or LPS + S18. Transcriptome data indicated the common DEGs enrichment in NF-κB pathway. Further, S18 inhibited phosphorylation of NF-κB induced by LPS. Previous studies suggested that IL-37 is a potential anti-inflammatory target of S18 in AVICs. Knockdown of IL-37 by siRNA exaggerated LPS-induced inflammation, and attenuated the anti-inflammatory effect of S18 on AVICs. Conclusion: Our results demonstrate that S18 attenuates LPS-mediated inflammation in human AVICs through inhibiting NF-κB activation, and underlying the mechanism of the anti-inflammatory effect involving up-regulation of IL-37. Our finding provides a novel avenue of preventing the progression of valve calcification.
Abstract 10285: The Association of Food Deserts with Sudden Death in Wake County, North Carolina
Authors: Andrew P Cesmat, Elizabeth Senter, Feng-Chang Lin, Susan Keen, Ross J Simpson
Journal: Circulation (2021)

Introduction: Food deserts (FD) are low-income areas with limited access to healthy foods associated with an individual’s risk of diabetes, hypertension, and atherosclerosis. These factors likely contribute to the risk of sudden death, but their association with sudden death is unknown. In this study, we aim to determine the impact of living in a food desert on sudden death. Hypothesis: Sudden death will occur more often in FD census tracts than in non-FD low-income tracts and high-income tracts. Methods: Census tract designations of income and FD status were determined from the United States Department of Agriculture's Food Access Research Atlas. The incidence of sudden death in each census tract was determined using a registry of 399 adjudicated out-of-hospital sudden deaths ages 18-64 in Wake County, North Carolina reported by emergency medical services from 2013-2015. A Poisson regression model was fit with FD status as a covariate and adjusted for the population size, percentage of males, and percentage of African Americans in the census tract. A Wald statistic was used to calculate sudden death incidence ratios (IR) with 95% confidence intervals (95% CI) for the populations living in FD tracts and in non-FD low-income tracts, compared with the population residing in high-income tracts (non-low-income and non-FD) as the reference group. Results: After adjusting for population size, sex, and race, the incidence of sudden death in FDs was higher than high-income census tracts (IR=1.466, 95% CI: 1.021-2.105). The incidence in non-FD low-income census tracts was also higher than high-income tracts (IR=1.398, 95% CI: 0.993-1.968). However, the FD census tracts had similar incidence to the non-FD low-income tracts (IR=0.954, 95% CI: 0.665-1.367). Conclusion: Living a food desert in Wake County, NC is associated with sudden death. Public health initiatives addressing healthy food access and income inequality may reduce the incidence of sudden death. However, a larger study, with a greater geographic distribution, is in development to explore the independent association of poverty and availability of healthy foods.
Thyroid Complications Negatively Affect Therapeutic Response and Survival in Waldenstrom Macroglobulinaemia/ Lymphoplasmacytoid Lymphoma
Authors: Xinting Hu, Hua Wang, Hongzhi Xu, Xin Liu, Ying Li, Xianghua Wang, Na Wang, Dai Yuan, Huiting Qu, Ya Zhang, Xin Wang
Journal: Blood (2021)
Abstract 13346: Sociobehavioral and Clinical Risk Factors Associated With Severe Asymptomatic Hypertension: A 1999-2018 National Health and Nutrition Examination Survey Analysis
Authors: Aayush Visaria, Ehimare Akhabue, Soko Setoguchi
Journal: Circulation (2021)

Introduction: Individuals with severe asymptomatic hypertension (SAH) are at high risk of CVD. It is unclear which risk factors are associated with SAH and whether they are different in patients with &amp; without awareness of hypertension (HTN). We hypothesized self-reported HTN status would significantly modify the effect of factors associated with SAH. Methods: We included adults ≥20 years from the 1999-2018 National Health and Nutrition Examination Surveys. Mean BP was calculated as the average of 3 consecutive BP readings 30 seconds apart. SAH was defined as mean SBP≥180 or DBP≥120. We used survey design-adjusted multivariable logistic regression to identify demographic, behavioral, comorbid, and medication-related factors for SAH. We then determined the modifying effect of self-reported HTN on the independent associations between covariates and SAH. Results: Among the 44,622 participants (mean age 47, 51% female, 69% White, and 30% HTN), 0.9% had SAH. Nearly 26% with SAH did not report HTN diagnosis and 62% were taking ≤1 BP medication. SAH individuals were more likely to be older, female, non-Hispanic Black, of lower socioeconomic status, have CVD, and report lower alcohol and salt intake than those without SAH (Table). The significant associations between Black race, female sex, lower income, &amp; BMI and SAH were not different by self-reported HTN (Table). Self-reported HTN significantly modified the effect of older age (OR [95% CI]; HTN: 1.07 [1.06, 1.08], No HTN: 1.10 [1.08, 1.13]), lower education (HTN: 1.04 [0.77, 1.42], No HTN: 2.26 [1.15, 4.44]), lack of insurance (HTN: 2.82 [1.86, 4.28], No HTN: 1.01 [0.52, 1.96]), and CKD (HTN: 1.49 [1.12, 1.98], No HTN: 2.24 [1.25, 4.03]) on SAH. Conclusions: Regardless of self-reported HTN status, non-Hispanic Blacks, females, and lower socioeconomic individuals were independently associated with SAH in the U.S. Older age, low education level, and CKD may confer greater risk of SAH in patients lacking HTN awareness.
Abstract 11598: Post-Developmental Deletion of Cardiomyocytes PR Domain Containing 16 (prdm16) Causes Pathological Hypertrophy
Authors: Rajeshwary Ghosh, Amir N Fatahian, Vishaka Vinod, Patrice Mimche, Junco S Warren, Kenneth S Campbell, Stavros G Drakos, Sihem Boudina
Journal: Circulation (2021)

Despite recent medical advances, heart failure (HF) remains to be the leading cause of mortality worldwide. Delineating the underlying molecular mechanisms involved in the pathogenesis of HF is critical for the development of new therapies. The transcription factor PRDM16 is involved in cell fate determination and differentiation. We previously showed that PRDM16 variants/deletion resulted in left ventricular non-compaction cardiomyopathy in humans and mice indicating its involvement in cardiac development. Here, we investigated the role of PRDM16 in adult cardiac physiology. We showed that patients with HF exhibited a significant reduction in cardiac PRDM16 mRNA expression compared to control individuals. These results were substantiated by the significant attenuation of Prdm16 mRNA 2 weeks post- transverse aortic constriction (TAC) in mice when compared to age matched sham controls. Additionally, cultured neonatal rat ventricular cardiomyocytes treated with the hypertrophy inducing agent, phenylephrine, demonstrated a suppression of Prdm16 gene expression while fibrotic gene expression was elevated. To directly assess the contribution of PRDM16 to cardiac hypertrophy and HF, we generated mice with tamoxifen-inducible cardiomyocyte-specific Prdm16 deletion (CiPrdm16). CiPrdm16 KO mice developed concentric hypertrophy as evidenced by enhanced heart weight/tibia length, elevated left ventricular mass and increased cardiomyocyte hypertrophy. Initially, ciPrdm16 KO mice exhibited enhanced contractility but progressively developed contractile dysfunction and impaired diastolic function. Consistent with these findings, transcriptomic analysis revealed an increase in protein synthesis pathways in ciPrdm16 KO hearts compared to wild-type controls. Collectively, these data show for the first time that PRDM16 transcriptionally regulates pro-hypertrophic signaling in the adult mouse heart and may contribute to the progression of HF in humans.
Abstract 14303: Structural Remodeling in the Left Ventricular Myocardium Underlies Systolic Dysfunction in Myocardial Infarction
Authors: Sunder Neelakantan, Qian Xiang, Saurabh Chavan, Ke Li, Xiao Ling, Richard A Dixon, Michael Sacks, Peter Vanderslice, Reza Avazmohammadi
Journal: Circulation (2021)

Introduction: Myocardial infarction (MI) leads to myofiber death and the formation of a fibrotic scar in the left ventricular free wall (LVFW) myocardium. Acute MI induces remodeling events in the LV consisting of alterations in the architecture and biomechanical properties of the LVFW, collectively leading to LV systolic dysfunction. We implemented a multi-modality pipeline bridging architectural remodeling, LVFW passive behavior adaptation, and ventricular dysfunction in MI. We hypothesize that biomechanical remodeling of the LV serves as an important predictor of clinical outcomes in MI. Methods: MI was induced in rats via the ligation of the LAD artery, and hearts were harvested at five time points: pre-MI, and 1-wk to 4-wk post-MI (n=6 for each time point). Echocardiography and terminal LV catheterization were performed. LVFW specimens were harvested and subjected to biaxial testing, followed by picrosirius red staining. Histological slides were analyzed to quantify fiber architecture. Results: Comparisons for 3-wk MI versus control groups are reported (animal-specific results for representative rats are shown in Fig. 1). Echocardiography imaging showed a decrease in EF (84±5 vs 73±10%; p=0.053) and a decrease in ESV (0.122±0.045 vs 0.31±0.195ml; p=0.013). LV catheterization revealed a decrease in SV (50±0.86 vs 10±0.38μL; p&lt;0.001) and an increase in peak systolic pressure (36.62±0.87 vs 44.91±0.99 mmHg; p&lt;0.001), indicating systolic dysfunction. Biaxial testing revealed longitudinal stiffening of the LVFW at 3-wk post-MI. Scarring and a shift in myofiber orientation towards the longitudinal direction corroborated changes in the LVFW mechanical behavior in the MI group. Conclusions: LV systolic dysfunction in MI is significantly influenced by disruption in myofiber architecture and fiber orientation remodeling in the LVFW. Assessment of LVFW remodeling events provides important incremental information over traditional organ-level indices.
Mechanistic differences in DNA nanoparticle formation by oligo- and poly-lysine and temperature effects on nanoparticle stability
Authors: Irina Nayvelt, Thresia Thomas, T J Thomas
Journal: Cancer Research (2006)

1092  DNA nanoparticle formation is a pre-requisite for non-viral cellular transport of DNA for gene therapy applications. Several agents, including biological macromolecules, have been used to provoke DNA condensation to nanoparticles. Poly-L-lysine and its substituted derivatives have attracted much attention as potential gene delivery vehicles. We studied the effectiveness of trilysine (Lys3)-, tetralysine (Lys4)-, pentalysine (Lys5)- and poly-L-lysine (PLL) on λ-DNA nanoparticle formation under various ionic conditions, and characterized the size, shape and stability of the resulting nanoparticles. Light scattering experiments showed the following EC50 (concentration of lysine at 50% DNA compaction) values for the lysines: PLL, 0.0036 μM; Lys5, 2 μM; and Lys4, 20 μM. However, Lys3 could not provoke DNA condensation to nanoparticles. The plot of log[EC50] versus log[Na+] showed positive slopes for both tetralysine (1.09) and pentalysine (1.72). In contrast, such a plot gave a negative slope (-0.1) for PLL. Hydrodynamic radii (Rh) of oligolysine condensed particles increased (48-173 nm) with increasing salt concentration, whereas no significant change occurred on the size of DNA nanoparticles formed in the presence of PLL. When the temperature was increased >40 °C, there was a dramatic increase in the size of the nanoparticles formed with oligolysines. However, the size of the particles formed with PLL did not undergo major changes when the temperature was increased from 20 °C to 80 °C. The helix-coil transition temperature (Tm) of DNA increased in a concentration- and positive charge- dependent manner for the oligolysines; however, there was no change in the Tm of DNA in the presence of PLL. These results indicate distinct differences in the mechanism(s) by which oligolysines and PLL provoke DNA condensation to nanoparticles. Our data on temperature dependent changes in nanoparticle stability are important to assess the long-term stability of nanoparticles as pharmaceutical agents for cancer therapy.
Transformation of Follicular Lymphoma into Primary Mediastinal B-Cell Lymphoma-like Large B-Cell Lymphoma
Authors: Tristan Loveday, Gerben Duns, Lisa M. Rimsza, Karen Rech, James R. Cook, Ryan S. Robetorye, Allison C. Rosenthal, Colleen Ramsower, Tameson Yip, Catherine McKinney, Steven H. Swerdlow, Shweta Bhavsar, Christian Steidl, Sarah E. Gibson
Journal: Blood (2021)
Abstract 13199: Generalizability and Prognostic Implications of Dapagliflozin and Finerenone in a Community-Based Cohort of Individuals With Diabetes and Chronic Kidney Disease
Authors: Matthew W Segar, Mohammad S Khan, Wai Hong W Tang, Javed Butler, Gregg C Fonarow, Darren K McGuire, Ambarish Pandey
Journal: Circulation (2021)

Introduction: Dapagliflozin (DAPA-CKD) and finerenone (FIDELIO-DKD) have shown to improve renal and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Hypothesis: We hypothesize individuals in a community-cohort who meet trial criteria will have higher rates of adverse outcomes. Methods: Adults with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study were included. The inclusion criteria from each trial were applied to participants with T2D. Differences in characteristics and composite kidney and CV outcomes were assessed between trial eligibility groups. The estimated number of events prevented (NEP) over 3 years were calculated based on relative risk reduction estimates. Results: Among 2816 participants (mean [SD] age 62 [10], 41% female, 48% Black), 1545 (54.9%), 1458 (51.8%), and 1314 (46.7%) met DAPA-CKD, FIDELIO-DKD, and both inclusion criteria, respectively. Participants who met DAPA-CKD but not FIDELIO-DKD enrollment criteria were more likely to be Black and have higher CV, T2D, and kidney disease severity. Participants who met DAPA-CKD criteria (vs. ineligible) had higher rates of composite kidney (17.6% vs. 14.6%; p=0.006) and CV (15.5% vs. 12.6%; p=0.03) outcomes. Conversely, FIDELIO-DKD eligible participants had lower incidence of composite kidney outcomes (12.6% vs. 19.4%; p&lt;0.001) and no differences in CV outcomes (14.2 vs. 14.2%; p=0.99). The estimated NEP per 1000 patients with dapagliflozin was 60 and 43 for kidney and CV outcomes, respectively, compared with 21 and 19 for finerenone ( Fig ). Notable differences in NEP were observed between races for dapagliflozin but not finerenone treatment, with Black patients having significantly higher kidney and CV NEP ( Fig ). Conclusions: In a community-based registry of CKD patients, approximately half of patients would be eligible for dapagliflozin or finerenone. The estimated NEP was higher with dapagliflozin compared to finerenone.