tbuckley/cabot-search huggingface dataset:
Abstract 14466: Characterisation of Recent Trends in Cardiovascular Risk Factors in Younger Patients With Ischaemic Stroke
Authors: Aditya Bhat, Gary Gan, David Makarious, Elizabeth Tan, Henry Chen, Nigel Wolfe, Lina Lee, Camelia Burdusel, Maria Carmo Nunes, Clara K Chow, Timothy Tan
Journal: Circulation (2020)

Introduction: Strokes in the young are associated with a disproportionately large economic and social impact in addition to their clinical effects. Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes mellitus and smoking) are key drivers of cardiovascular disease including strokes, however recent temporal trends in the young stroke population have not been characterised. Hypothesis: The proportion of patients with non-SMuRFs are on the rise in a cohort of younger patients with ischaemic stroke/transient ischaemic attack. Methods: Consecutive patients aged &lt;65 years with clinical and/or radiological diagnosis of ischaemic stroke or transient ischaemic attack in a tertiary referral centre (2013-2017) were retrospectively appraised. The demographic and clinical comorbidities of these patients were assessed including their SMuRF profile. The prevalence over time and clinical associations of patients with no SMuRFs were studied and compared to patients with SMuRFs. Results: Of 487 patients (53.49±9.13yrs, 60% men) analysed, 23% did not have SMuRFs. The proportion of “non-SMuRF” patients increased over time (see Figure; p&lt;0.01) and this trend was not influenced by age (p=0.48) or gender (p=0.68). The presence of SMuRFs was not associated with in-hospital outcomes, however patients without SMuRFs were significantly less likely to be discharged on blood pressure (p&lt;0.01) and lipid-lowering therapies (p=0.03). Conclusions: The proportion of young stroke patients without SMuRFs is substantial and has increased over time. Our findings highlight the need for further research to better understand the mechanisms underlying stroke development in this population and whether less risk factor treatment of this population could impact longer term outcomes.
Abstract 14467: Left Atrial Functional Index is a Predictor of Persistent/permanent Non-valvular Atrial Fibrillation
Authors: Aditya Bhat, Henry H Chen, Shaun Khanna, Gary C Gan, Fernando Fernandez, C. Raina MacIntyre, Timothy C Tan
Journal: Circulation (2020)

Introduction: Chronicity of atrial fibrillation (AF) has been associated with poor cardiovascular outcomes. Left atrial function index (LAFI) is a rhythm-independent measure of LA reservoir function adjusted for LA size and stroke volume and is an established marker of risk for cardiac disease states. We sought to evaluate the role of LA function by LAFI in predicting persistent/permanent AF. Hypothesis: LAFI is a predictor of chronicity of AF. Methods: Patients attending our institution between Jan 2013 and Dec 2017 were assessed. Patients with history of non-valvular AF who received transthoracic echocardiogram (TTE) evaluation were included. In these patients, we evaluated demographic profiles, AF history, clinical comorbidities and echocardiographic data. We excluded patients with valvular AF, poor quality TTE images and incomplete clinical data. Results: Of the 665 patients (67.78±13.62years, 52% male) included, 27.8% had persistent/permanent AF. Persistent/permanent AF was associated with older age (p&lt;0.01), heart failure (p&lt;0.01), diabetes mellitus (p=0.02), ischaemic heart disease (p=0.02), obstructive sleep apnoea (p=0.04), renal impairment (p&lt;0.01), lower left ventricular ejection fraction (p&lt;0.01), higher E/e’ (p&lt;0.01), larger LA volume index (p&lt;0.01) and lower LAFI (p&lt;0.01). Multi-variable analysis revealed both heart failure (OR 3.024, 95%CI 1.737 to 5.265, p&lt;0.01) and LAFI (OR 4.881, 95%CI 2.503 to 9.519, p&lt;0.01) as independent predictors of persistent/permanent AF. Receiver operating characteristic curve showed LAFI (see Figure; AUC 0.75, 95%CI 0.703 to 0.793, p&lt;0.01) of less than 16.5 to have a 70% sensitivity and 70% specificity in detecting persistent/permanent AF. Conclusions: LAFI, an echocardiographic measure of atrial mechanical function, may be a useful tool in risk stratification for patients with non-valvular AF.
Abstract 16039: Impact of Different Annuloplasty Methods for Tricuspid Regurgitation; a Network Meta-analysis
Authors: Yujiro Yokoyama, Hisato Takagi, Toshiki Kuno
Journal: Circulation (2020)

Background: Although moderate-severe tricuspid valve regurgitation (TR) is an independent risk factor for progressive heart failure and increased mortality, the best method for tricuspid repair remains controversial. As such, we conducted a network meta-analysis to compare early and late outcomes for suture, flexible band, and rigid ring as tricuspid annuloplasty (TAP) in patients with TR. Methods: MEDLINE and EMBASE were searched through February 15th, 2020 to identify randomized controlled trials (RCTs) and observational trials that investigated early and late outcomes after TAP for TR. The outcomes of interest were perioperative mortality, long-term survival and TR recurrence. TR recurrence was defined as at least moderate (TR grade 2) on serial echocardiogram. Results: Our systematic literature search identified 2 RCTs and 16 observational trials, including 6,788 patients who underwent TAP. Median follow-up period was 1-7.4 year. There were no significant differences of perioperative and long-term all-cause mortality among three TAP methods. Suture TAP was associated with a significant increase in TR recurrence compared to rigid ring TAP (Hazard ratio, 2.31; 95% Confidence Interval, 1.40-3.80; p =0.001) (Figure). There were no significant differences were observed in other comparisons in TR recurrence. Conclusion: Our network meta-analysis demonstrated significant reduction in TR recurrence for rigid ring TAP compared to Suture TAP. However, there was no significant mortality difference among suture, flexible band, and rigid ring TAP.
Abstract 14106: The Efficacy of Sodium Glucose Co-transporter 2 Inhibitors in Atrial Fibrillation: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Zain Ul Abideen Asad, Ali Jafry, Khawaja Akhtar, Allen Wang, Mohammad S Khan, Safi U Khan, Mina K Chung, Jonathan P Piccini, Stavros Stavrakis
Journal: Circulation (2020)

Background: Atrial Fibrillation (AF) is common in patients with Type 2 diabetes mellitus and it is associated with adverse outcomes. The impact of SGLT-2 inhibitors on incident AF and cardiovascular outcomes is unknown. Methods: A systematic review of Medline, EMBASE and other online sources was conducted on 04/22/2020. All randomized controlled trials (RCTs) comparing SGLT-2 to placebo reporting incident AF were included. Mantel Haenszel random effects modeling was used to estimate risk ratios (RR) and I 2 statistics were used to assess heterogeneity. Results: A total of 33 RCTs (n=65,505 patients) were included. SGTL-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) use was not associated with statistically significant benefit in preventing AF [RR 0.91 (0.80-1.04)] (Figure-1). Subgroup analysis showed that only Dapagliflozin had a statistically significant effect in preventing AF [RR 0.79 (0.66-0.93), p=0.006, I 2 =0%] (p&lt;0.05 compared to others). SGLT-2 inhibitors were associated with a 25% relative risk reduction in the composite outcome of CV mortality or CV hospitalization in patients with history of AF [RR 0.75 (0.62-0.90)] and 27% in patients with no history of AF [RR 0.73 (0.66-0.81)]. Conclusion: SGLT-2 inhibitors prevent adverse cardiovascular outcomes regardless of baseline AF status. The protective effects of SGLT-2 inhibitors in preventing AF appear limited to Dapagliflozin.
68Ga–Prostate-Specific Membrane Antigen Solitary Base of Skull Prostate Adenocarcinoma Metastasis
Authors: Joshua Wei Liang Yip, Luke Hilliar, Ken Le, Han Loh, Robert Mansberg
Journal: Clinical Nuclear Medicine (2020)

Abstract A 74-year-old man with prostate adenocarcinoma (Gleason 7) was referred for 68 Ga–prostate-specific membrane antigen (PSMA-HBED-CC) PET/CT scan for staging. Findings confirmed the prostate malignancy and demonstrated a solitary metastasis in the left skull base, with no evidence of regional or distant metastasis elsewhere. Solitary base of the skull metastasis may be subtle and easily overlooked, highlighting the need for thorough evaluation of the region.
Abstract 15315: SGLT2 Inhibitor Ertugliflozin Decreases Elevated Intracellular Sodium, Improves Myocardial Energetics and Enhances Function in Metabolic Heart Disease
Authors: Dominique Croteau, Tomas Baka, Sara Young, Huamei He, David R Pimentel, Marcello Panagia, James Balschi, Wilson S Colucci, Ivan Luptak
Journal: Circulation (2020)

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic drugs of great interest in cardiology due to their improvement of heart failure outcomes independent of diabetes. As SGLT2 is not expressed in cardiomyocytes, the mechanism of such benefit remains unclear. Elevated myocardial intracellular sodium [Na + ] i has been found in heart failure and SGLT2 inhibition lowers [Na + ] i in isolated cardiomyocytes. Elevated [Na + ] i was shown to decrease mitochondrial calcium via mitochondrial Na/Ca exchanger (NCx MITO ), resulting in decreased mitochondrial ATP synthesis. We have previously shown that mice fed a diet high in fat and sugar (HFHS) develop metabolic heart disease (MHD) characterized by decreased mitochondrial ATP synthesis with decreased phosphocreatine (PCr), worsened diastolic function and contractile reserve. We hypothesize that the SGLT2 inhibitor ertugliflozin (ERTU) decreases the elevated [Na + ] i to improve energetics and contractile function in MHD. Methods and Results: Isolated hearts from mice after 6 months of HFHS vs. control diet (CD), +/- ERTU in the last month, were studied using 31 P and 23 Na NMR spectroscopy to measure PCr/ATP ratio and [Na + ] i , respectively. As expected, HFHS hearts showed lower PCr/ATP, diastolic dysfunction (↑LVEDP) and lack of contractile reserve (↓RPP) during high work protocol compared to CD hearts. Myocardial [Na + ] i was elevated more than 2-fold in HFHS compared to CD. One month of ERTU treatment decreased [Na + ] i and improved energetics and contractile function in HFHS to levels similar to or better than CD. Perfusion with CGP 37157, which inhibits NCx MITO , improved PCr/ATP in HFHS hearts. Conclusion: Lowering of myocardial [Na + ] i by ertugliflozin contributes to improved energetics and function in MHD. These results suggest targeting [Na + ] i as an effective strategy to improve cardiac dysfunction in MHD and other forms of heart disease associated with elevated myocardial [Na + ] i.
Pharmacogenomics of intracellular methotrexate polyglutamates in patients’ leukemia cells in vivo
Authors: Elixabet Lopez-Lopez, Robert J. Autry, Colton Smith, Wenjian Yang, Steven W. Paugh, John C. Panetta, Kristine R. Crews, Erik J. Bonten, Brandon Smart, Deqing Pei, J. Robert McCorkle, Barthelemy Diouf, Kathryn G. Roberts, Lei Shi, Stanley Pounds, Cheng Cheng, Charles G. Mullighan, Ching-Hon Pui, Mary V. Relling, William E. Evans
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Interpatient differences in the accumulation of methotrexate's active polyglutamylated metabolites (MTXPGs) in leukemia cells influence its antileukemic effects.
Abstract PO-020: The NRF2-redox-metabolism axis protects pancreatic cancer cells from radiation toxicity
Authors: Justine Bailleul, Taha Yazal, David Sung, Juan Nathaniel, Daisy Palomera, Anahita Sehgal, Rachel Ruan, Erina Vlashi
Journal: Cancer Research (2020)

Abstract More than 90% of pancreatic ductal adenocarcinomas (PDAC) are driven by activating KRAS mutations (mKRAS), which promote a remarkable resistance to all non-surgical therapies, including radiation therapy (RT). Unfortunately, mKRAS remains undruggable for the vast majority of PDAC tumors. This necessitates the discovery of downstream targets, which most likely govern the oxidative stress response and promote the acquisition of radiation resistance. Notably, the master orchestrator of oxidative stress response, the transcription factor NRF2, is upregulated by mKRAS and in some models, NRF2 is activated by irradiation (IR). This suggests that IR may amplify the already heightened, mKRAS-driven activation of NRF2 in PDAC. NRF2 targets include genes involved in restoring redox balance, likely promoting survival during RT. However, the involvement of NRF2 in PDAC radioresistance remains unknown. To fill this knowledge gap, we have systematically investigated the role of the NRF2 pathway in regulating radiation response in PDAC tumors. Our studies show that depletion of NRF2 via CRISPR/Cas9 targeted gene deletion (NRF2-ko) results in the accumulation of significantly higher levels of reactive oxygen species in irradiated PDAC cells. Importantly, this correlates with increased radiosensitivity of NRF2-ko cells in vitro, compared to NRF2-wt controls. Interestingly, irradiation of PDAC cells upregulates the expression of metabolic genes that drive the generation of various antioxidant species, in a NRF2-dependent manner. At the metabolite level, IR induces re-routing of glycolytic metabolites towards the antioxidant pentose phosphate pathway and the depletion of NRF2 abrogates these changes. Together, these findings suggest that part of the mechanism via which NRF2 promotes radiation survival of PDAC cells is by reprogramming cellular metabolism to drive a metabolic antioxidant response. Altogether, these findings support a crucial role for the NRF2-redox-metabolism axis in driving RT resistance in PDAC. This further suggests that inhibition of the NRF2 pathway would be followed by a failure to resist IR-induced oxidative stress, and subsequently sensitize mKRAS pancreatic cancer to RT. Citation Format: Justine Bailleul, Taha Yazal, David Sung, Juan Nathaniel, Daisy Palomera, Anahita Sehgal, Rachel Ruan, Erina Vlashi. The NRF2-redox-metabolism axis protects pancreatic cancer cells from radiation toxicity [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-020.
Abstract 14097: A 3D Print Low Cost Aortic Arch Endovascular Simulator
Authors: Gabriel Neves, Jamee Schoephoerster, ENio Perez
Journal: Circulation (2020)

Introduction: Simulation-based medical teaching and learning enables trainees to gain competencies in a realistic setting without imposing risks to patients. Within endovascular training, simulations improve patient safety and decrease health care costs. Access of the aortic arch from a femoral puncture site is a key competency in the endovascular field. Here, we show how a low-cost artificial vascular simulator enables accurate replicated catheterization of the aortic arch. Hypothesis: Methods: Digital Imaging and Communications in Medicine (DICOM) data extracted from a computed-angio tomograph (CTA) using an image processing software was selected to include the arterial region of interest. A mold was made with plastisol from the printed 3D toolpath (Fig. 1). After maturation of the mold, the separate sections were assembled into the simulator (Fig. 2). Results: Data extracted from a CTA was processed to create a vascular model that was accessed using an arterial access kit, and guided under fluoroscopy, a radiopaque catheter was navigated to the aortic arch. The total consumable cost of the simulator was U$194.64. Conclusions: In this proof-of-concept study, we demonstrate the process of producing a low-cost 3D printed artificial vascular simulator made from 3-D printing and image examination. This simulator faithfully replicated the endovascular access of the aortic arch from a femoral puncture site. We recognize the scalability of our technique and its possibility of assisting in endovascular navigation of various interventional radiology procedures in a patient specific manner.
Abstract 263: The Relationship Between Time to Extracorporeal Cardiopulmonary Resuscitation and Coronary Reperfusion and Short-term Outcome in Out-of-hospital Cardiac Arrest Patients Due to Acute Coronary Syndrome
Authors: Shoji Kawakami, Yoshio Tahara, Teruo Noguchi, Shujiro Inoue, Satoshi Yasuda
Journal: Circulation (2020)

Background: In out-of-hospital cardiac arrest (OHCA) patients due to acute coronary syndrome (ACS), the association between time to extracorporeal cardiopulmonary resuscitation (ECPR) or coronary reperfusion and clinical outcome has yet to be well-known. Methods: Between June 2014 and 2017, we enrolled a total of 34,754 OHCA patients in multicenter, prospective fashion (JAAM-OHCA registry). Following exclusion criteria, 254 OHCA patients with underwent ECPR and emergent PCI were eligible for this study (59±12 years-old; 92% male). We investigated the association between call-to-ECPR or call-to-reperfusion and the survival at 30 days. Results: The survival patients were 85 (33%). Figure shows the numbers of patients according to call-to-ECPR interval. The call-to-ECPR interval and call-to-reperfusion interval in survival patients were significantly shorter than those in non-survival patients (51±16 vs 61±16 min, p&lt;0.01; 123±50 vs 157±133 min, p=0.03, respectively). Receiver operating curve analysis indicated call-to-ECPR interval cutoff point of 46 min (area under the curve 0.70, sensitivity 48%, specificity 84%) and call-to-reperfusion interval cutoff point of 92 min (0.61, 37% and 81%, respectively) for predicting survival at 30 days. Multivariate logistic regression analysis revealed call-to-ECPR interval and call-to-reperfusion as the independent predictors of survival (OR 0.96, 95%CI 0.94-0.98, p&lt;0.01; OR 1.00, 95%CI 0.99-1.00, p=0.03, respectively). Conclusion: The call-to-ECPR interval and call-to-reperfusion interval are independent predictors of survival at 30 days in OHCA patients due to ACS.
Assessment of Central Nervous System Lymphoma Based on CXCR4 Expression In Vivo Using 68Ga-Pentixafor PET/MRI
Authors: Angelika M. Starzer, Anna S. Berghoff, Tatjana Traub-Weidinger, Alexander R. Haug, Georg Widhalm, Marcus Hacker, Ivo Rausch, Matthias Preusser, Marius E. Mayerhoefer
Journal: Clinical Nuclear Medicine (2020)

F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL.Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests.Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI).Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.
Giant Liver Hemangioma Mimicking a Hydronephrotic Kidney on 99mTc-DTPA Scintigraphy
Authors: Ching Yeen Boey, Farahnaz Mohamed Aslum Khan, Siti Zarina Amir Hassan
Journal: Clinical Nuclear Medicine (2020)

Abstract We report a case of a 56-year-old woman who underwent 99m Tc-DTPA renal scintigraphy for the evaluation of a right pelviureteric junction calculi, which incidentally showed radiotracer uptake in a giant liver hemangioma. The initial scintigraphic images showed a large lobulated lesion with peripheral uptake of radiotracer at the right abdominal region, resembling a large hydronephrotic kidney. However, the pattern of progression of the radiotracer, coupled with the clinical history and available corresponding radiologic images, confirmed the uptake to be that of a giant liver hemangioma.
Early-Onset Osteopenia and Osteoporosis in Patients with Pyruvate Kinase Deficiency
Authors: Hanny Al-Samkari, Rachael F. Grace, Andreas Glenthoej, Oliver Andres, Wilma Barcellini, Frédéric Galactéros, Kevin H.M. Kuo, D. Mark Layton, Marta Morado, Vip Viprakasit, Yan Dong, Feng Tai, Peter Hawkins, Sarah Gheuens, Chris Bowden, John B. Porter, Eduard van Beers
Journal: Blood (2020)
Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality
Authors: Diana Averbuch, Gloria Tridello, Jennifer Hoek, Malgorzata Mikulska, Thomas Pabst, Lucrecia Yaňez San Segundo, Hamdi Akan, Tülay Özçelik, Irene Donnini, Galina Klyasova, Aida Botelho de Sousa, Tsila Zuckerman, Cristina Tecchio, Rafael de la Camara, Sahika Zeynep Aki, Per Ljungman, Zafer Gülbas, Emmanuelle Nicolas-Virelizier, Elisabetta Calore, Katia Perruccio, Ron Ram, Claudio Annaloro, Rodrigo Martino, Batia Avni, Peter J. Shaw, Alexandra Jungova, Katia Codeluppi, Tracey O'Brien, Anna Waszczuk-Gajda, Montserrat Batlle, Anastasia Pouli, Catherina Lueck, Lidia Gil, Simona Iacobelli, Jan Styczynski, Dan Engelhard, Simone Cesaro
Journal: Journal of Infection (2020)
Community, Complicity, and Critique: Christian Concepts in Secular Bioethics
Authors: Aline H. Kalbian, Courtney S. Campbell, James F. Childress
Journal: The American Journal of Bioethics (2020)

This article is referred to by:The Social Context of Religion in the Jurisdictions of BioethicsResponse to Open Peer Commentaries for “There’s No Harm in Talking: Reestablishing the Relationship Between Theological and Secular Bioethics”
Abstract 215: Adam17 Regulates Renal Function
Authors: Bo Zhang, Kai Chen, Zhongjie Sun
Journal: Circulation (2020)

A disintegrin and metalloproteinase 17 (ADAM17) is a ubiquitously expressed membrane-bound sheddase that cleaves a diverse variety of membrane-bound molecules, including cytokines, growth factors, and their receptors to activate or inactivate various cellular signaling pathways. Although it was reported that ADAM17 may mediate renal diseases, the role of ADAM17 in the regulation of normal kidney function has never been identified. The objective of this study is to investigate whether renal ADAM17 plays a role in maintaining normal kidney function and structure. Tamoxifen-inducible kidney-specific cre (Ksp) and ADAM17-floxed mice were cross-bred for generating Ksp/ADAM17-floxed mice. Injection of tamoxifen initiated deletion of the ADAM17 gene in renal tubule cells. We found that conditional kidney-specific knockout of ADAM1 7 gene (Ksp-ADAM17 -/-) decreased urinary creatinine and sodium excretion were decreased in Ksp-ADAM17 -/- mice, indicating that ADAM17 gene deficiency impairs kidney function. H&amp;E staining showed glomerulus collapse and tubule dilation in Ksp-ADAM17 -/- mice. The epithelial cells fall off into the lumen in the renal tubule. Mesangial expansion and fibrosis were found in glomeruli in Ksp-ADAM17 -/- mice. Moreover, apoptosis was increased in tubule cells in both cortex and medulla areas in Ksp-ADAM17 -/- mice. In conclusion, ADAM17 is critical to the maintenance of normal renal function and structure.