tbuckley/cabot-search huggingface dataset:
Abstract 12035: Higher Numbers of Circulating CD34+ Cells Are Associated With More Pronounced Effects of Neprilysin Inhibitors in Patients With Chronic Heart Failure
Authors: Gregor Poglajen, Neža orž, Ema Ajda Gomezelj, Ana Milovanovic, Sabina Frljak, Bojan Vrtovec
Journal: Circulation (2021)

Introduction: Preliminary evidence suggests that neprilysin inhibitors (ARNI) may affect angiogenesis in heart failure with reduced ejection fraction (HFrEF). Hypothesis: Since CD34+ cells represent one of the key determinants of vasculogenesis and angiogenesis, we investigated a potential association between clinical effects of ARNI and circulating CD34+ cell count in HFrEF. Methods: We performed a prospective single center pilot cohort study in 27 HFrEF patients. After enrollment, all patients received standard heart failure therapy including ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARB) for 3 months. At this point, ACE-I/ARB were switched to ARNI. At the time of switch, we measured circulating CD34+ cell count using Beckman-Coulter Navios EX flow cytometry with standard antibodies according to ISAGE protocol. All patients were followed for 6 months after the switch. Favorable response to ARNI therapy was defined as an increase in left ventricular ejection fraction (LVEF) ≥5% at 6-month follow-up. Results: At 6 months we found a favorable response to ARNI in 18 patients (64%, Group A), and 10 had less favorable response (36%, Group B). Before ARNI introduction the groups did not differ in gender (male: 94% in Group A vs. 78% in Group B, P=0.21), heart failure etiology (ischemic: 35% vs. 23%, P=0.49), diabetes (11% vs. 22%, P=0.46), renal dysfunction (22% vs. 43%, P=0.25), hypertension (28% vs. 55%, P=0.17), LVEF (36±5% vs. 34±7%, P=0.41), LVEDV (181±57 mL vs. 185±36 mL, P=0.83), TAPSE (1.8±0.8 vs. 1.9±0.4, P=0.91) or NT-proBNP (980±1438 pg/mL vs. 780±603 pg/mL, P=0.70). Compared to Group B, patients in Group A were younger (52±13 years vs. 64±9 years, P=0.03) and had a higher CD34+ cell count (2.9±2.0x106/L vs. 1.2±0.5x106/L, P=0.02). When compared to the remainig cohort, patients with CD34+ cell count above the median displayed a significantly higher increase in LVEF (+8.1±3.2% vs. +4.7±3.7%, P=0.03), and a trend of increase in TAPSE (+0.4±0.4 cm vs. -0.1±0.7 cm, P=0.06). Conclusion: Higher numbers of circulating CD34+ cells appear to be associated with more pronounced beneficial effects of ARNI therapy in HFrEF patients. Thus, the effects or ARNI in heart failure may be partly mediated through modulation of vascular homeostasis.
Abstract 12401: Cardiovascular Risk Profile and Gestational Diabetes Mellitus by Maternal Nativity and Length of US Residence in Racially Diverse, Urban, Low Income Population in the United States
Authors: Lochan M Shah, Ellen Boakye, Michelle Ogunwole, Wendy L Bennett, Xiaobin Wang, Roger S Blumenthal, Allison Hays, Anum Minhas, Michael J Blaha, Khurram Nasir, Sammy Zakaria, Garima Sharma
Journal: Circulation (2021)

Introduction: Gestational diabetes mellitus (GDM) is independently associated with increased cardiovascular disease (CVD) risk. GDM disproportionately affects non-Hispanic Black (NHB) women in the United States (US). The prevalence of GDM by nativity (US born versus foreign born) and duration of US residence is not well known in other race/ethnicities. Methods: We analyzed 6088 women with data on GDM from the Boston Birth Cohort. We performed multivariable logistic regression to investigate the association of nativity and duration of US residence (&lt;10 versus ≥10 years residence) with GDM by race (NHB, Hispanic, and White). Covariates included sociodemographic characteristics and CVD risk factors. Results: In our sample, 44.3% were NHB, 39.3% Hispanic, and 16.4% White. Foreign born NHB and Hispanic women with duration of US residence &lt;10 years had lower prevalence of CVD risk factors (multiparity, severe stress, chronic hypertension, smoking in pregnancy, obesity BMI ≥ 30 kg/m2) than those with ≥10 years US residence and US born women. Foreign born NHB with duration of US residence &lt;10 years had higher odds of GDM (adjusted OR, aOR: 1.6, 95%CI 0.99-2.6, p=0.05) compared to US born NHB women, while in contrast foreign born Hispanic women with duration of US residence &lt;10 years had lower odds for GDM (aOR 0.54, 95%CI 0.32-0.91, p=0.021). The odds of GDM in Hispanic and NHB women with US residence ≥ 10 years was not significantly different from their US born counterparts. Conclusions: GDM prevalence is higher in foreign-born NHB women with shorter duration of US residence, despite better risk factor profiles. GDM is lower in foreign-born Hispanic women with shorter duration of US residence, mirroring their better risk factor profile. Thus, the “healthy immigrant effect” (health advantages for foreign-born women), appears to not apply to GDM in NHB. Further research is needed to examine why GDM burden in NHB women is not well explained by risk factor burden or environmental stress.
Move over NAIP, DDX17 diversifies the NLRC4 inflammasome
Authors: Katherine C. Barnett, Kaixin Liang, Jenny P.-Y. Ting
Journal: Science Immunology (2021)

DDX17 binds short interspersed nuclear element RNAs to nucleate a dual NLRC4/NLRP3 inflammasome, highlighting the emerging role of endogenous ligands in NLRC4 activation (see the related Research Article by Wang et al.).
Abstract 9539: Treatment of Hyperlipidemia: Assessment of Providers’ Competency With Edocate® Virtual Patient Simulation Application
Authors: Igal Iancu, Boris DRAZNIN
Journal: Circulation (2021)

Management of hyperlipidemia (HL) in patients with Type 2 diabetes (T2DM) has been taught extensively but the real-life competency is difficult to evaluate. Edocate’s proprietary virtual patient simulation smartphone and web-based application (APP) allows an innovative way of learning and objective assessment of the provider’s proficiency in approach to and management of a given medical condition. We utilized this novel educational APP to analyze the real-life knowledge of 894 healthcare providers (HCP) in several projects within multiple geographies in the management of HL in patients with T2DM. The HCP managed 1-3 patients with T2DM and HL in their virtual clinic. HCP chose medications, made diagnostic adjustments, and ordered laboratory tests of their choice. Based on their selections, the APP simulated the course of diabetes and hyperlipidemia throughout multiple virtual visits, requiring diverse management decisions and addressing medications’ side effects, while adhering to guidelines and accepted standards of care. Results: Conclusions: 1. Innovative patient simulation-based learning APP revealed adequate but not perfect HL management skills. 2. NP - DM have the best guideline-recommended approach to therapy, followed by practicing MD/DO. 3. Intensive therapy achieving LDL levels below 50 or even 70 mg/dl remains elusive. 4. Edocate’s patient simulation-based learning application helps identify knowledge gaps, prescription patterns and HCP decision-making processes. 5. This APP accurately assesses the “real-life” knowledge and patterns of practice while offering cutting-edge ways of learning to dramatically improve competency levels.
The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants
Authors: Chang Liu, Daming Zhou, Rungtiwa Nutalai, Helen M.E. Duyvesteyn, Aekkachai Tuekprakhon, Helen M. Ginn, Wanwisa Dejnirattisai, Piyada Supasa, Alexander J. Mentzer, Beibei Wang, James Brett Case, Yuguang Zhao, Donal T. Skelly, Rita E. Chen, Sile Ann Johnson, Thomas G. Ritter, Chris Mason, Tariq Malik, Nigel Temperton, Neil G. Paterson, Mark A. Williams, David R. Hall, Daniel K. Clare, Andrew Howe, Philip J.R. Goulder, Elizabeth E. Fry, Michael S. Diamond, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton
Journal: Cell Host & Microbe (2021)
Abstract 10472: Impact of Polygenic Risk Scoring for Coronary Artery Disease on the Incidence of Chronic Kidney Disease and Acute Kidney Injury in Patients Undergoing Off Pump Coronary Artery Bypass Surgery
Authors: Muralidhar Kanchi, Ramprasad Vedam, Sangamitra Mishra, Ramesh Menon, Ram Murthy Anjanappa
Journal: Circulation (2021)

Background: This study aims to determine the applicability of genome-wide polygenic risk score (GPS CAD ) to patients who underwent off-pump (OP-CABG) in South-Asian population and influence, on kidney dysfunction and incidence of AKI in OP-CABG. Methods: Study participants were categorized into four cohorts: 1) patients with normal renal function undergoing OP-CABG (eGFR&gt;60ml/min/m 2 ) (n=754; AKI - 81, Non-AKI-673); 2)patients with renal dysfunction (eGFR&lt;60ml/min/m 2 ; not needing dialysis) undergoing OP-CABG (n=263; AKI-169, non-AKI-89); 3) patients with renal dysfunction with no symptomatic/known heart disease (n=92);4) control population (with normal kidney function, without symptomatic/known heart disease) (n=826). Genotyping was performed using Infinium Global Screening Array-24 v3.0 BeadChip from Illumina, which included 6,54,027 markers. The genotype data were imputed using the GenomeAsia reference panel and GPS CAD was determined. The GPS CAD was applied to all patients in the cohort. The following were determined (i) relationship between GPS CAD and CAD (ii) association between GPS CAD and incidence of preoperative renal dysfunction (iii) influence of GPS CAD on development of postoperative AKI and (iv) influence of a composite genetic predisposition to AKI in OP-CABG and GPS CAD on the surgical outcome. Results: The GPS CAD was generated for all samples in the four groups and was binned into 10 groups (deciles), in the ascending order of GPS CAD. The first decile (lowest GPS CAD bin) comprised ~60% of healthy controls, and 22% group A, 11% group B, and 7 % group C. . No difference was observed in GPS CAD between AKI and non-AKI samples belonging to group A. Conclusions: In summary, our results suggest no impact of GPS CAD on the presence of kidney dysfunction and incidence of AKI after off-pump CABG.
Abstract 11519: CHA <sub>2</sub> DS <sub>2</sub> VASc Score as a Predictor of Ablation Success Defined by Continuous Long-Term Monitoring
Authors: Albert Y Liu, Graham Lohrmann, Paul D Ziegler, Joao V Monteiro, Nathan V Varberg, Rod S Passman
Journal: Circulation (2021)

Introduction: There are few readily available and effective risk stratification tools for successful catheter ablation (CA) of atrial fibrillation (AF). CHA 2 DS 2 VASc score is a marker for vascular disease and has been shown to be mildly predictive of CA success, although prior studies have used short-term external monitors to define success. Hypothesis: Lower CHA 2 DS 2 VASc score correlates with CA success as measured by continuous monitoring via cardiac implantable electronic devices (CIED). Methods: Using the Optum® de-identified Electronic Health Record dataset (01/2007 to 06/2019) linked with the Medtronic CareLink device database, we identified patients who underwent a 1 st CA procedure for AF following CIED implantation. CA success was defined as absence of ≥1 hour of AF on any day following a 3-month blanking period. A proportional hazard model was used to estimate hazard ratios (HR) between CHA 2 DS 2 VASc subgroups (0-2, 3-4, ≥5). Results: A total of 665 patients (age 66.9±9.1 years, 73.4% male, CHA 2 DS 2 VASc 3.5±1.8, 37.3% paroxysmal AF, 62.7% persistent AF) were analyzed and included 36.2% insertable cardiac monitor, 28.0% PPM, 21.4% ICD, 13.2% CRT-D, and 1.2% CRT-P. CA success at 24 months post blanking period was 39.8% (95% CI 32.4%-48.9%), 36.9% (95% CI 29.7%-45.8%), and 20.9% (95% CI 13.9%-31.4%) for CHA 2 DS 2 VASc subgroups of 0-2, 3-4, and ≥5, respectively. Kaplan-Meier curves demonstrate a difference in survival free from AF between the three CHA 2 DS 2 VASc subgroups (p=0.007, Figure), with CHA 2 DS 2 VASc score being a significant predictor of CA ablation success (c-statistic 0.533). After controlling for AF type, patients with a score ≥5 remained at higher risk for AF recurrence compared to patients with a score of 0-2 (HR 1.28, 95% CI 1.001-1.63). Conclusions: In this real-world dataset of AF patients with continuous monitoring undergoing CA, CHA 2 DS 2 VASc score is a modest predictor of CA success.
As we head into a tough winter, the NHS is under huge pressure
Authors: Chris Hopson
Journal: BMJ (2021)

As we head into a tough winter, the NHS is under huge pressure Chris Hopson looks at the impact of ambulance handovers on patients and why everyone in the NHS needs to help rebalance the safety risk Chris Hopson chief executive 1Over recent months, the pressures on ambulance services across the country have risen steeply, frequently making headlines.What's been particularly striking is that this pressure is happening right across the country, with all 10 ambulance trusts in England on sustained high alert.
Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021
Authors: Steven G. Deeks, Nancie Archin, Paula Cannon, Simon Collins, R. Brad Jones, Marein A. W. P. de Jong, Olivier Lambotte, Rosanne Lamplough, Thumbi Ndung’u, Jeremy Sugarman, Caroline T. Tiemessen, Linos Vandekerckhove, Sharon R. Lewin, Steven Deeks, Sharon Lewin, Marein de Jong, Zaza Ndhlovu, Nicolas Chomont, Zabrina Brumme, Kai Deng, Luke Jasenosky, Richard Jefferys, Aurelio Orta-Resendiz, Frank Mardarelli, Monique Nijhuis, Katharine Bar, Bonnie Howell, Alex Schneider, Gabriela Turk, Rose Nabatanzi, Joel Blankson, J. Victor Garcia, Mirko Paiardini, Jan van Lunzen, Christina Antoniadi, Fernanda Heloise Côrtes, Susana Valente, Ole S. Søgaard, Ricardo Sobhie Diaz, Melannie Ott, Richard Dunham, Siegfried Schwarze, Santiago Perez Patrigeon, Josephine Nabukenya, Marina Caskey, Beatriz Mothe, Fu Sheng Wang, Sarah Fidler, Devi SenGupta, Stephan Dressler, Mitch Matoga, Hans-Peter Kiem, Pablo Tebas, Cissy Kityo, Boro Dropulic, Michael Louella, Kumitaa Theva Das, Deborah Persaud, Ann Chahroudi, Katherine Luzuriaga, Thanyawee Puthanakit, Jeffrey Safrit, Gaerolwe Masheto, Karine Dubé, Jennifer Power, Jessica Salzwedel, Udom Likhitwonnawut, Jeff Taylor, Oguzhan Latif Nuh, Krista Dong, Edward Nelson Kankaka
Journal: Nature Medicine (2021)
EXTH-74. INCREASING CANCER CELL MEMBRANE PERMEABILITY THROUGH APPLICATION OF TUMOR TREATING FIELDS (TTFIELDS)
Authors: Tali Voloshin, Bella Koltun, Lilach Koren, Yaara Porat, Alexandra Volodin, Noa Kaynan, Anat Klein-Goldberg, Rom Paz, Boris Brant, Efrat Zemer-Tov, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Tumor Treating Fields (TTFields) are intermediate frequency, alternating electric fields with anti-mitotic effects on cancerous cells. TTFields are delivered non-invasively through arrays placed on the skin at the tumor region. TTFields therapy is approved in several territories for treatment of glioblastoma (GBM) and mesothelioma. Recently, TTFields have been shown to increase GBM cell membrane permeability. The current study aimed to explore this effect in multiple cell lines and examine the potential benefits of combining TTFields with other anticancer agents. METHODS TTFields were delivered to GBM (U-87 MG), uterine sarcoma (MES-SA), and breast adenocarcinoma (MCF-7) cell lines for 72hr across a range of frequencies (50-500kHz). Cytotoxicity of TTFields was examined by cell counts, and intracellular accumulation of 7-aminoactinomycin D (7-AAD) was measured by flow cytometry. Exposing the cells to 7-AAD at different time points relative to TTFields application cessation was used to determine the kinetics of cell membrane permeability. The potential of TTFields to facilitate intracellular accumulation of anthracycline chemotherapeutics was tested in chemotherapy-sensitive and chemotherapy-resistant cells. RESULTS Elevated intracellular accumulation of 7-AAD was observed in all examined cell lines treated with TTFields, at an optimal frequency that differed from that for maximal TTFields-induced cytotoxicity. No intracellular accumulation of 7-AAD was seen for measurements performed after termination of TTFields application, indicating that increased cell membrane permeability by TTFields was temporary and reversible. Lastly, the accumulation of chemotherapeutic agents in chemotherapy-resistant cancer cells was elevated to the same extent as in matched chemotherapy-sensitive cells when TTFields were delivered concomitant with chemotherapy. CONCLUSIONS TTFields increased cancer cell permeability in a transient and reversible manner across multiple cancer cell types. The increased permeability enhanced intracellular accumulation of chemotherapeutics, even within chemotherapy-resistant cells.
Abstract 11620: Long-Term Outcomes and Cost for Impella Compared to Intra-Aortic Balloon Pump in Patients Presenting with Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Elliott Miller, Samantha G Bromfield, Qinli Ma, Geoffrey Crawford, John Whitney, Andrea Devries, Nihar R Desai
Journal: Circulation (2021)

Introduction: Recent reports have demonstrated an association between Impella compared to IABP use with increased risk for short-term clinical outcomes, including stroke, bleeding, and mortality among patients with AMI and cardiogenic shock (CS) undergoing PCI. Data on long-term outcomes and cost are limited. Methods: This retrospective study analyzed administrative claims data from a large commercially insured population from 14 states. Patients undergoing PCI for AMI complicated by CS from 7/1/14 to 4/30/20 were included. Those who had both devices or other mechanical circulatory support were excluded. We performed a 1:1 propensity score-matched analysis in patients receiving an Impella versus IABP. The primary outcome was mortality, and secondary outcomes were stroke, bleeding, repeat revascularization, incident dialysis, and cost at 30-days and 1-year follow-up. Results: Of the 3,347 patients undergoing PCI for AMI complicated by CS, the mean (SD) age was 65.4 (12.5) years, 71% were men, and 32% had a cardiac arrest. Among 820 propensity-matched pairs, at 30-days use of the Impella was associated with a significantly higher mortality (Odds ratio [OR] 1.91; 95% Confidence interval [CI]: 1.54-2.37, P &lt;0.001), incident dialysis (OR 1.55; 95% CI:1.10-2.18, P =0.01), and mean difference in cost ($40,869, Interquartile range: $20,829-$64,200, P &lt;0.001) compared to IABP ( Figure ). Incident stroke, bleeding, and repeat revascularization were not different between groups ( P &gt;0.05). At 1-year, mortality (Hazard ratio [HR] 1.58, 95% CI: 1.33-1.87, P &lt;0.001) and incident dialysis (HR 1.70, 95% CI: 1.25-2.30, P =0.001) remained higher in Impella. Conclusions: In patients undergoing PCI for AMI complicated by CS, use of Impella was associated with an increased 30-day and 1-year mortality, dialysis, and cost compared to IABP. There is need for additional evidence surrounding the optimal management of patients with AMI and CS undergoing PCI.
Abstract 12912: Cardiovascular Magnetic Resonance Characterization of Rheumatic Mitral Stenosis: Findings From India, China, and Mexico
Authors: Mahesh K Vidula, Ziqian Xu, Yuanwei Xu, Abdullah Alturki, Bhavana Nagabhushana Reddy, Sanjaya Viswamitra, Prayaag Kini, Angel Alberto-Delgado, Ron Jacob, Lilia M Sierra Galan, yucheng chen, Yuchi Han
Journal: Circulation (2021)

Introduction: Cardiac remodeling in rheumatic mitral stenosis (MS) is incompletely understood. Cardiac magnetic resonance (CMR) imaging has the potential to provide more precise characterization of morphologic and functional changes that occur in response to MS. The objective of this study was to describe CMR findings in rheumatic MS to characterize cardiac structural and functional changes in this population. Methods: This retrospective study included 40 patients with rheumatic MS, including 15 patients from China, 19 patients from India, and 6 patients from Mexico. Patients were included in the rheumatic MS cohort if they did not have a prior mitral valve procedure, other concomitant moderate-severe or severe valve disease, or other known cardiovascular conditions. Twenty patients were included in the control group from India. CMR variables pertaining to morphology and function were collected. Late gadolinium enhancement (LGE) sequences were acquired for tissue characterization. Results: Forty patients with rheumatic MS (median (interquartile range (IQR)) age: 45 (34-55) years; 75% women) were studied. Compared to the control group, patients with MS had lower left ventricular (LV) ejection fraction (EF) (51% (42%-55%) vs 60% (57%-65%), p = 0.0001), lower right ventricular (RV) EF (44% (40%-52%) vs 64% (59%-67%), p &lt; 0.0001), larger RV end-diastolic volumes (72 (58-87) mL/m 2 vs 59 (49-69) mL/m 2 , p = 0.003), and larger LA and RA sizes. LGE was prevalent in patients with MS, located at the RV insertion sites. Representative CMR images are shown in the Figure, with the arrows pointing to areas of LGE at the RV insertion sites. Conclusions: These findings further our understanding of the structural and functional changes that occur in response to rheumatic MS, and demonstrate that biventricular dysfunction is underappreciated in contemporary rheumatic MS. Further studies are required to understand the prognostic implications of these findings.
Evaluation of a DNA demethylating agent in combination with <i>all-trans</i> retinoic acid for <i>IDH1-</i>mutant gliomas
Authors: Marina da Costa Rosa, Alex Shimura Yamashita, Gregory J Riggins
Journal: Neuro-Oncology (2021)

Isocitrate Dehydrogenase 1/2 (IDH1/2) mutations are diagnostic for Astrocytoma or Oligodendroglioma, IDH-mutant. In these IDH-mutant gliomas, retinoic acid-related gene expression is commonly silenced by DNA hypermethylation. DNA demethylating agents can epigenetically reprogram IDH-mutant cells and reduce proliferation, likely by re-expression of silenced tumor suppressor pathways. We hypothesized that DNA demethylation might restore the retinoic acid pathway and slow tumor growth. This was the rationale for a preclinical evaluation combining the DNA demethylating agent, 5-Azacytidine (5-Aza), and retinoic acid pathway activation with all-trans retinoic acid (atRA) in IDH-mutant glioma.In this study, we evaluated the effect of 5-Aza and atRA combination on cell proliferation, apoptosis, and gene expression in human glioma cells. In addition, the efficacy of this combination was tested in patient-derived xenograft (PDX) bearing the IDH1R132H mutation, utilizing subcutaneous and orthotopic models.5-Aza reduced the DNA methylation profile and increased the gene expression of retinoic acid-related genes. Combination of 5-Aza and atRA reduced cell growth, increased differentiation marker expression, and apoptosis in IDH1R132H glioma cells. Mechanistically, 5-Aza sensitized IDHIR132H glioma cells to atRA via upregulation of the retinoic acid pathway. Importantly, the drug combination reduced significantly the growth rate of subcutaneous tumors, but in an orthotopic mouse model, the combination did not improve survival and 5-Aza alone provided the best survival benefit.Use of DNA demethylating agent in combination with retinoids shows promise, but further optimization and preclinical studies are required for treatment of intracranial IDH-mutant gliomas.