tbuckley/cabot-search huggingface dataset:
Abstract 11020: Clinical, Psychosocial and Socioeconomic Predictors of Outpatient Cardiac Rehabilitation Participation: The Atherosclerosis Risk in Communities Study
Authors: Lena Mathews, Yejin Mok, Ning Ding, KRISTIN A RIEKERT, Anna Kucharska-Newton, Josef Coresh, Chiadi E Ndumele, Kuni Matsushita
Journal: Circulation (2021)

Introduction: Despite robust evidence of its effectiveness for secondary prevention, cardiac rehabilitation (CR) is underutilized. Understanding individual-level predictors of CR use can guide interventions to boost CR participation. Hypothesis: Clinical, psychosocial and socioeconomic predictors impact CR participation. Methods: We studied 1,255 participants from the ARIC Study with cardiovascular disease (CVD) events eligible for CR (myocardial infarction, coronary revascularization, valve surgery) from data linked to Medicare claims (1991-2015). Predictors including comorbidities, functional status, cognitive function, social support, social network, educational attainment, and household income were ascertained from study visits and annual follow-up at the time point closest to the index CVD event. CR participation was defined as having Current Procedural Terminology codes 93797 and 93798. We examined multiple predictors using logistic regression with the Modified Allen-Cady stepwise backward selection of covariates in addition to age, race, sex, and ARIC center. Results: The mean age was 72.4 (SD 5.2) years (16% Black, 43% women) and 26% participated in CR. In multivariate analyses, variables associated with lower CR participation were income &lt;$12,000 (odds ratio (OR) 0.46 [95% CI 0.24 - 0.89]) vs. &gt;$50,000; &lt; high school education (OR 0.48 [0.27 - 0.86]) vs. graduate/professional education; lowest quartile of cognitive function (OR 0.52 [0.32 - 0.85]) vs. the highest quartile; lowest quartile of social support (OR 0.65 [0.44 - 0.96]) vs. the highest quartile; and current smoking (OR 0.55 [0.31 - 0.96]). Comorbidities and social network were not associated with CR participation. Conclusions: Cognitive function, social support, and SES were robustly associated with CR participation. Efforts to address the gap in CR participation should focus on interventions that support patients with low cognitive function, social supports, and SES.
SURG-05. Α5Β1 INTEGRIN TARGETING LIPOSOME DELIVERY OF MIR-603 SUPPRESSED GLIOBLASTOMA STEM CELL STATE AND ENHANCED RADIATION SENSITIVITY
Authors: Ahmed Shabana, Beibei Xu, Zachary Shneiderman, Jun Ma, efrosini kokkoli, Clark Chen
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Despite the potential for clinical efficacy, therapeutic delivery of microRNAs (miRNA) remains a major translational barrier. Here, we explore a surgery mediated polyethylenimine (PEI)/liposome-based strategy for the delivery of miR-603, a master regulatory miRNA that suppresses glioblastoma stem cell state by simultaneous down-regulation of insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R). METHODS miR-603 was complexed with PEI, a cationic polymer designed to facilitate miRNA from the endolysosomal compartment. The miR-603/PEI complex was encapsulated into liposomes decorated with polyethylene glycol (PEG) and PR_b, a fibronectin-mimetic peptide that specifically targets the α5β1 integrin that is overexpressed in glioblastoma. RESULTS Patient-derived glioblastoma cells internalized PR_b coated liposomes but not the non-coated liposomes. The internalization of PR_b liposomes encapsulating miR-603/PEI was associated with orders of magnitude increase in intra-cellular miR-603 levels and decreased IGF1 and IGF1R mRNA/protein levels. Moreover, treatment of glioblastoma cells with the PR_b liposomes encapsulating miR-603/PEI showed altered morphology and decreased expression of stem cell marker, suggesting the treated cells have exited the cancer stem cell state. Finally, treatment of the PR_b liposomes encapsulating miR-603/PEI sensitized glioblastoma cells to ionizing radiation (IR) in patient-derived glioblastoma cells. These results were not observed in liposomes missing the PR_b peptide, PEI, or miR-603. CONCLUSION These results suggest that intra-tumoral injection of PR_b functionalized PEGylated liposomes encapsulating miR-603/PEI complexes hold promise as a strategy for glioblastomas therapy. A first-in-human trial is currently underway to test this strategy.
NCMP-13. ID8 OVARIAN CANCER MOUSE MODEL MIMICS NEUROLOGICAL SEQUELAE OF OVARIAN CANCER IN WOMEN
Authors: Naomi Lomeli, Daniela Bota, Donovan Argueta, Kalpna Gupta
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVES Chemotherapy-related cognitive impairment (CRCI) and chemotherapy-induced peripheral neuropathy (CIPN) are neurological complications of cancer treatment. Cisplatin is used to treat ovarian malignancies, and over 70% of women experience CRCI/CIPN during and after platinum-based chemoTx. However, over 30% of non-CNS cancer patients experience cognitive impairment prior to chemoTx. To examine the contribution of cancer itself and additional neurological impairment with chemoTx, we used an ID8 syngeneic mouse model of ovarian cancer and assessed hyperalgesia and cognition +/- cisplatin treatment. METHODS C57BL/6 female mice were injected intraperitoneally with 107 ID8 ovarian cancer cells or 0.9% saline. After 10d of ID8 injections, mice received cisplatin (2.3 mg/kg/day, i.p.) or 0.9% saline (OvT+CIS, OvT+VEH, respectively) for 5d, followed by 5d of rest for 2 cycles. Mechanical and cold hyperalgesia were assessed longitudinally. Cognition was assessed 28d post-chemoTx by the open field test (OFT), novel object recognition (NOR), and novel place recognition (NPR) tasks. RESULTS OvT+VEH and OvT+CIS mice developed an increased sensitivity to mechanical ( &amp;gt;200%, p&amp;lt; 0.001) and thermal (cold) stimuli ( &amp;gt;78%, p&amp;lt; 0.004) starting 14d post-ID8 implantation, vs non-tumor controls (CON). In the OFT, OvT+CIS mice had increased anxiogenic behavior (55%, p&amp;lt; 0.001) vs CON, and (46%, p&amp;lt; 0.05) vs OvT+VEH. In NPR, OvT+CIS had reduced discrimination (37%, p&amp;lt; 0.05) vs CON. OvT+VEH and OvT+CIS showed impaired discrimination (25%, p&amp;lt; 0.05 &amp; 33%, p&amp;lt; 0.01, respectively) in NOR vs CON, with trending differences between OvT+CIS vs OvT+VEH in hyperalgesia and cognitive tasks. DISCUSSION: This is the first rodent model to demonstrate that ovarian cancer may evoke sensory and neurocognitive changes in the absence of chemotherapy. Future development of the model will address hyperalgesia and cognitive differences between OvT+VEH vs OvT+CIS. This model has potential for translational studies on the treatment of neurological sequelae of cancer and cisplatin-induced CRCI and CIPN.
Abstract 11422: Galactosyltransferase 1-Associating Protein Prevents Murine Vascular Runx2 Expression, Osteogenesis and Calcification
Authors: Song Gao, Shanshan Gao, Zhen Sun, Mikael Akesson, Harnath S Shelat, Yong-jian Geng
Journal: Circulation (2021)

Introduction and Hypothesis: The ubiquitin-conjugating enzyme, galactosyltransferase 1-associating protein (GTAP), is an E2 ubiquitin-conjugating enzyme (UBE2q1), involved in stem cell proliferation and differentiation. Increased vascular smooth muscle cell (SMC) calcification characterizes atherosclerotic heart disease. We tested here the hypothesis that GTAP plays a role in regulation of SMC calcification and expression of the osteogenic protein Runx2. Methods and Results: Echocardiography was conducted in sv129 (WT) (n=10) and GTAP-knockout (GTAP -/- ) (n=11) mice, displayed reduced contractility in GTAP -/- vs. WT mice. In histopathology patch myocardial fibrosis, arterial hyperplasia and calcification occurred in GTAP -/- but not WT mice. Significantly increased calcium contents/dry proteins were found in the aortic rings of GTAP -/- vs. WT mice when ex vivo exposed to inorganic phosphate media for 9 days (Fig. 1a, p&lt;0.05). To less extents, heterozygous GTAP -/+ mice also had increased calcium contents. Total proteins were extracted from aortic SMC transduced with cDNA coding for WT GTAP and loss-functional mutant GTAP C351A for Western blot assays. As shown in Fig. 1b, compared with mock treated SMC, WT GTAP overexpressing SMC had increased band intensity of the contractile proteins, α-SM-actin and SM22α, but much lower band intensity of Runx2 protein. SMC with overexpression of the GTAP C351A mutant modestly reduction in Runx2 band density, and had little impact on band intensity of the contractile protein α-SM-actin and SM22α. Conclusions: GTAP exerts protective effects on vascular SMC by inhibiting expression of Runx2 and calcification, while promoting expression of the contractile proteins, α-SM-actin and SM22α.
Abstract 14280: Trends and Association of Payer Status With Outcomes in Injection Drug Use Related Infective Endocarditis, From National Inpatient Sample (2002-2017)
Authors: Muhammmad Zia Khan, Muhammad U Khan, Salman Zahid, Waqas Ullah, Sudarshan balla
Journal: Circulation (2021)

Introduction: Infective endocarditis (IE) associated with intravenous drug abuse (IDU) is rising in incidence in the United States. Few studies exist on the association of IDU in IE with primary payer and socio-economic status. Hypothesis: Type of primary insurance payer and socio-economic status in patients with IDU related IE may strongly correlate with inpatient morbidity and mortality. Methods: We used the United States National Inpatient Sample (NIS) data from the year 2002 to 2017. International Classification of Diseases (ICD)-9 and ICD-10 codes were used to identify all hospitalizations with IDU-IE above the age of 17 years. Pearson chi-square test and Mann Whitney U test were used for statistical testing. Multivariate logistic regression analysis was done for adjusted cohort. Results: Primary payers of 78,211 weighted admissions of patients with IDU-IE were identified. Most of the patients were Medicare/Medicaid (67.6%), followed by private insurance(13%) and self-pay(19.3%). Patients under Medicaid/Medicare were older (37yrs. [interquartile range (IQR), 29-47) as compared to private pay (34yrs. [IQR, 25-47]) and self-pay(34 yrs. [IQR,28-43]). Comorbid conditions like liver disease, viral hepatitis, peripheral vascular disease (PVD), renal disease, psychosis, depression, and AIDs were more common in Medicare/Medicaid population (Figure). Patients under private insurance had a higher median income. Patients under Medicare/Medicaid had higher adjusted mortality (1.162, [confidence interval (CI), 1.082-1.248]) as compared to private insurance (0.852, [CI, 0.764-0.95]) but no difference in adjusted mortality as compared to self-pay (OR, 0.927, [CI, 0.855-1.006]). Conclusions: The medical coverage of patients with IDU-IE over the years has increased, however, mortality is still higher in patients with Medicare/Medicaid as compared to private insurance, the reason behind this needs further exploration.
Abstract 13872: Atrial Fibrillation and Acute Ischemic Stroke: Evaluation of the Contemporary 2018 National Inpatient Sample Database
Authors: Gursukhman D Sidhu, Saihariharan Nedunchezhian, Abdel Hadi El Hajjar, Aneesh Dhorepatil, Lilas Dagher, Tarek Ayoub, Keith Ferdinand, Nassir Marrouche
Journal: Circulation (2021)

Aims: Atrial Fibrillation (AF) treatment in Acute Ischemic Stroke (AIS) is based on thromboembolism prophylaxis regardless AF type, and degree of atrial myopathy. We aim to investigate morbidity and mortality of persistent AF related stroke. Methods: Patients admitted with AIS and associated paroxysmal and persistent AF were identified in the 2018 National Inpatient Sample. The study compared in-hospital mortality, stroke-related morbidity, hospital cost, length of stay, and discharge disposition between patients with paroxysmal and persistent AF Results: A total of 26,470 patients were admitted for AIS with associated AF. AIS with persistent AF had a longer hospital length of stay (paroxysmal AF Mean(M): 5.7 days, Standard Deviation (SD) 6.8, persistent AF M: 7.4 days, SD 11.9, p&lt;0.001) and in-hospital costs (paroxysmal AF M: $15,449, SD $18,320, persistent AF M: $19,834, SD $23,312, p&lt;0.001). Indirect markers of stroke-related disability, like intracranial hemorrhage (Odds Ratio (OR): 1.9, 95% Confidence Interval (CI): 1.6-2.2), need for gastrostomy (OR: 2.1, 95% CI: 1.8-2.4), and tracheostomy (OR: 3.1, 95% CI: 2.1-4.4) were more associated with AIS and persistent AF (FIGURE 1) Conclusion: Persistent AF is associated with poor in-hospital stroke-related outcomes, possibly due to a higher embolic burden. The current recommendation of using only the CHA2DS2-VASc score without AF pattern needs be reevaluated. Further investigation is required to determine the impact of prevention of AF progression on stroke related morbidity.
Abstract 10916: Management of Chronic Hypertension Prior to Pregnancy Among Women Veterans
Authors: Ceshae C Harding, Karen M Goldstein, Sarah A Goldstein, Sarahn M Wheeler, Nia S Mitchell, Laurel A Copeland
Journal: Circulation (2021)

Introduction: Maternal chronic hypertension (MCH), defined as chronic hypertension affecting pregnancy, has increased rapidly in prevalence among civilians. Although women Veterans have more risk factors for chronic hypertension than civilian women, little is known about MCH in this group. Methods: This descriptive, observational study used data from the Surgical Treatment Outcomes for Patients with Psychiatric Disorders (STOPP) project, which includes 11 million Veterans with and without mental illness using the Veterans Health Administration. Women Veterans aged 18-60 years at time of pregnancy identification were included if they had chronic hypertension before pregnancy in fiscal years 2010-2019. We identified chronic hypertension and first pregnancy based on diagnosis codes and defined uncontrolled blood pressure as ≥140/90 mm Hg on at least one measurement in the year prior to pregnancy. For antihypertensive medications (AHMs) that are recommended or not recommended for use in pregnancy, multivariable logistic regression was used to assess the association of comorbidities with (a) non-recommended AHM received 0-6 months before pregnancy, (b) non-recommended AHM received during pregnancy (c) recommended AHM received 0-6 months before pregnancy, and (d) recommended AHM received during pregnancy. Results: In total, 9.9% (4,302/43,251) of women Veterans who became pregnant had MCH, with mean age 37.0 years (SD=8.2). Among those with MCH who met inclusion criteria, 62% (N=1,839) had uncontrolled blood pressure in the year prior to pregnancy. Furthermore, 20% (N=611) received a non-recommended AHM 0-6 months before pregnancy, 19% (N=564) received a non-recommended AHM during pregnancy, 26% (N=784) received a recommended AHM 0-6 months before pregnancy, and 33% (N=995) received a recommended AHM during pregnancy. Chronic kidney disease (OR 3.0, 95% CI: 1.6-5.6) and diabetes (OR 2.5, 95% CI:1.9-3.2) were most strongly associated with use of a non-recommended AHM during pregnancy. Conclusion: Interventions are needed among women Veterans to decrease the prevalence of MCH, increase blood pressure control prior to pregnancy, and ensure antihypertensives not recommended for use in pregnancy are transitioned to safe alternatives.
EXTH-59. GENERATION OF A THIRD GENERATION CAR T CELL THAT SIMULTANEOUSLY TARGETS WILDTYPE EGFR AND ITS MUTANT ISOFORM EGFRVIII FOR TREATMENT OF GLIOBLASTOMA
Authors: Daniel Wilkinson, Katherine Ryan, Vidyalakshmi Chandramohan, Daniel Landi, Darell Bigner, Peter Fecci
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most aggressive primary brain cancer with a median survival of less than 16 months. This dire prognosis signifies the urgent need for improved treatment options, such as immunotherapy. Chimeric antigen receptor (CAR) T cells have helped revolutionize immunotherapy, achieving considerable success in eliminating hematological cancers but generally failing to control solid tumors. One major hindrance to CAR T cell success in solid tumors is tumor heterogeneity. Tumor-associated or tumor-specific antigens (TAA or TSA, respectively) are rarely expressed by all malignant cells within a tumor. As a specific example in GBM, the most prevalent TSA, EGFRvIII, is present in just 30% of tumors, and then on only 30-50% of cells. Our pre-clinical and clinical experiences with CAR T cells reveal that tumors possessing as few as 5-10% EGFRvIII-negative cells will easily escape EGFRvIII-targeted CARs. Tumor cells that lack EGFRvIII expression often overexpress the wildtype isoform of EGFR (EGFRwt). Notably, EGFR is absent on normal brain. Therefore, a superior approach would be to simultaneously target EGFRvIII and EGFRwt, an approach that would bypass EGFR heterogeneity in EGFRwt/EGFRvIII-expressing tumors. Here, we generated a third generation CAR using the D2C7 single-chain variable fragment (scFv) targeting moiety that recognizes an epitope present in EGFRwt and EGFRvIII. Initial in vitro characterization of D2C7 CAR validated the specificity and function of D2C7 CAR, as it potently killed murine cell lines engineered to express either EGFRwt or EGFRvIII, but not a cell line expressing neither. Concomitant IFN-γ release supported these conclusions. Additionally, D2C7 CAR killed the human-derived GBM cell line U87 and vIII-transfected U87, U87vIII. Importantly, intracranially-administered D2C7 CAR significantly prolonged survival of mice bearing orthotopic U87vIII or U87/U87vIII heterogeneous tumors compared to mock-treated controls. Altogether, these data provide evidence that D2C7 CAR T cells represent a viable therapeutic option for EGFRwt/EGFRvIII heterogeneous tumors.
Abstract 11307: Meta-Analysis Evaluating Dapagliflozin in Heart Failure Reduced Ejection Fraction: A Focus on Left Ventricular Remodeling
Authors: Rohan M Prasad, Mark T Mujer, Mohammad Fahad Salam, Abdullah Al-abcha, Zulfiqar Q Qutrio Baloch, george Abela
Journal: Circulation (2021)

Introduction: Through an unknown mechanism, anti-diabetic sodium-glucose cotransporter-2 inhibitors have been shown to be effective in patients with heart failure reduced ejection fraction (HFrEF). Specifically, dapagliflozin significantly decreased the risk of cardiovascular death and hospitalization for heart failure. However, the effects on left ventricular remodeling have not been well reported or analyzed. Methods/Results: We conducted a meta-analysis of all randomized controlled trials that reported left ventricular remodeling outcomes in patients with HFrEF comparing dapagliflozin versus placebo. The outcomes in this study were analyzed as changes in values compared to baseline levels. Statistical analysis was conducted using Review Manager 5.4. Two-sided p values of &lt;0.05 were considered as statistical significance. A total of 254 patients with a median-weighted follow-up duration of 13.13 months were included amongst four RCTs. Heterogeneity was low-high across the trials (0-85%). Stroke volume significantly favored the dapagliflozin arm (mean difference 1.85, 95% confidence interval 0.10 to 3.60, p=0.04, I 2 =0%). However, left ventricular mass index, left atrial volume index, left ventricular end systolic volume, left ventricular end diastolic volume, and E/e’ were determined to be insignificant between the dapagliflozin and placebo arms. The first outcome was assessed by cardiac magnetic resonance imaging, while the former were seen on echocardiograms. Conclusion: This meta-analysis illustrates that dapagliflozin significantly increased SV in HFrEF patients, but had an insignificant effect in the other left ventricular remodeling outcomes. One limitation of this meta-analysis is low power due to only a few trials in the literature. Therefore, further trials with larger sample size and longer follow-up periods should be conducted to determine the dapagliflozin’s outcome on left ventricular remodeling in patients with HFrEF.
Is early activity resumption after paediatric concussion safe and does it reduce symptom burden at 2 weeks post injury? The Pediatric Concussion Assessment of Rest and Exertion (PedCARE) multicentre randomised clinical trial
Authors: Andrée-Anne Ledoux, Nick Barrowman, Vid Bijelić, Michael M Borghese, Adrienne Davis, Sarah Reid, Gurinder Sangha, Keith Owen Yeates, Mark S Tremblay, Candice McGahern, Kevin Belanger, Joel D Barnes, Ken J Farion, Carol A DeMatteo, Nick Reed, Roger Zemek
Journal: British Journal of Sports Medicine (2021)

Objective Investigate whether resuming physical activity (PA) at 72 hours post concussion is safe and reduces symptoms at 2 weeks, compared with resting until asymptomatic. Methods Real-life conditions, multicentre, single-blinded randomised clinical trial, conducted in three Canadian paediatric emergency departments (ED). Children/youth aged 10–&lt;18 years with acute concussion were recruited between March 2017 and December 2019, and randomly assigned to a 4-week stepwise return-to-PA protocol at 72 hours post concussion even if symptomatic (experimental group (EG)) or to a return-to-PA once asymptomatic protocol (control group (CG)). The primary outcome was self-reported symptoms at 2 weeks using the Health and Behaviour Inventory. Adherence was measured using accelerometers worn 24 hours/day for 14 days post injury. Adverse events (AE) (worsening of symptoms requiring unscheduled ED or primary care visit) were monitored. Multivariable intention-to-treat (ITT) and per-protocol analyses adjusting for prognostically important covariates were examined. Missing data were imputed for the ITT analysis. Results 456 randomised participants (EG: N=227; mean (SD) age=13.3 (2.1) years; 44.5% women; CG: N=229; mean (SD) age=13.3 (2.2) years; 43.7% women) were analysed. No AE were identified. ITT analysis showed no strong evidence of a group difference at 2 weeks (adjusted mean difference=−1.3 (95% CI:−3.6 to 1.1)). In adherent participants, initiating PA 72 hours post injury significantly reduced symptoms 2 weeks post injury, compared with rest (adjusted mean difference=−4.3 (95% CI:−8.4 to –0.2)). Conclusion Symptoms at 2 weeks did not differ significantly between children/youth randomised to initiate PA 72 hours post injury versus resting until asymptomatic; however, many were non-adherent to the intervention. Among adherent participants, early PA was associated with reduced symptoms at 2 weeks. Resumption of PA is safe and may be associated with milder symptoms at 2 weeks. Level of evidence 1b. Trial registration number NCT02893969 . Registry name Pediatric Concussion Assessment of Rest and Exertion (PedCARE).