tbuckley/cabot-search huggingface dataset:
Abstract 15002: Socioeconomic Disparities Exist in Access to Accredited Pediatric Care Centers for Infants With Critical Congenital Heart Disease: A Total-Population Analysis Over 30 Years in California
Authors: Flora Nuñez Gallegos, Susan M Fernandes, Olga Saynina, Andrew Shin, Paul Wise, Lisa J Chamberlain
Journal: Circulation (2020)

Introduction: Current research endorses regionalizing the care of infants with critical congenital heart disease (CCHD) to facilities with high levels of obstetrical, neonatal, and surgical volumes. California has a regionalization model that designates these facilities as accredited pediatric cardiac centers (PCCs). The impact of this system on the location of birth and cardiac surgeries for CCHD and for different social groups remains unexplored. Hypothesis: We hypothesize, there has been a trend toward increased accredited PCC utilization for birth and surgical intervention for CCHD in California with accompanying widening in social inequality. Methods: A retrospective, population-based analysis of CCHD hospitalizations between 1984-2018 using the California Office of Statewide Health Planning and Development’s discharge database was conducted. Demographic data and trends in location of birth and surgical procedures for CCHD from delivery to age 1 were evaluated in relation to hospital designation as an accredited PCC. Results: There were 15,091 live births with CCHD and 29,466 surgical admissions meeting inclusion criteria. Births at accredited PCCs increased from 17% in 1984 to 41% in 2018 while surgical admissions were largely above 80%. From 2015-2018, infants with CCHD, born outside an accredited PCC were more likely to have private HMO insurance and live 6-20 miles away. Patients with surgical admission to an accredited PCC were more likely to have private HMO insurance and reside in a zip code where the median income is &gt;2x the federal poverty level. Conclusions: Significant gains have been made in the regionalization of care for infants with CCHD in California over 30 years. However, a substantial number of infants with CCHD do not receive care in accredited PCCs and social disparities in utilization remain. Increased efforts to reduce barriers to access, particularly those related to payer type and resident distance from PCCs are needed.
Abstract 345: Resuscitation Quality in the Intensive Care Unit- A Retrospective, Observational Study
Authors: Lara L Roessler, Mathias J Holmberg, Rahul Pawar, Annmarie T Lassen, Ari Moskowitz
Journal: Circulation (2020)

Background: Adherence to quality metrics during in-hospital cardiac arrest (IHCA) have been associated with improved outcomes, however, quality metric adherence in the intensive care unit (ICU) has not been well described. In this study, we assessed trends in adherence to time to epinephrine ≤ 5 min, time to defibrillation ≤ 2 min, and confirmation of endotracheal airway device placement during IHCA in the ICU and identified potential predictors of adherence failure. Methods: This was an observational study using the Get With The Guidelines® - Resuscitation registry, a United-States based IHCA registry. Adult patients (&gt;18 years) with an index cardiac arrest in adult ICUs between 2006 and 2018 in the US were included. Generalized estimation equations were used for the analyses. Results: We included 75668 patients. From 2006-2018, adherence to time to epinephrine ≤ 5 min increased from 93% (95%CI, 93%-94%) to 98% (95%CI, 97%-98%), time to defibrillation ≤ 2 min went from 71% (95%CI, 68%-75%) to 74% (95% CI, 71%-77%) and confirmation of airway device placement increased from 93% (95%CI, 91%-94%) to 97% (95% CI, 96%-98%). Significant predictors of defibrillation &gt;2 min included a non-cardiac (RR, 1.35; 95%CI, 1.25-1.46) and traumatic (RR, 1.67; 95%CI, 1.34-2.09) illness category, a prior history of renal insufficiency (RR, 1.13; 95%CI, 1.06-1.22), no myocardial infarction (RR, 1.09; 95%CI, 1.00-1.19), no metabolic abnormality (RR, 1.10; 95%CI, 1.01-1.20), events occurring at nighttime (RR, 1.08; 95%CI, 1.01-1.14), an initial PVT as opposed to VF rhythm (RR, 1.10; 95%CI, 1.03-1.16), no arterial line in place at time of event (RR, 1.20; 95%CI, 1.09-1.32), and events occurring at a small hospital (RR, 1.17; 95%CI, 1.02-1.34). Conclusions: Overall, quality metric adherence was high in the ICU, with the exception of time to defibrillation ≤ 2 min. Predictors associated with defibrillation &gt;2 min, included a non-cardiac and traumatic illness category and nighttime arrests.
Oncolytic Reovirus (pelareorep) Induces Autophagy in KRAS-mutated Colorectal Cancer
Authors: Jeeshan Jiffry, Thongthai Thavornwatanayong, Devika Rao, Elisha J. Fogel, Durvanand Saytoo, Rishika Nahata, Hillary Guzik, Imran Chaudhary, Titto Augustine, Sanjay Goel, Radhashree Maitra
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To explore the effects of pelareorep on autophagy in multiple models of colorectal cancer, including patient-derived peripheral blood mononuclear cells (PBMCs). Experimental Design: HCT116 [KRAS mutant (mut)] and Hke3 [KRAS wild-type (WT)] cells were treated with pelareorep (multiplicity of infection, 5) and harvested at 6 and 9 hours. LC3 A/B expression was determined by immunofluorescence and flow cytometry; five autophagic proteins were analyzed by Western blotting. The expression of 88 autophagy genes was determined by qRT-PCR. Syngeneic mouse models, CT26/Balb-C (KRAS mut) and MC38/C57B6 (KRAS WT), were developed and treated with pelareorep (10 × 106 plaque-forming unit/day) intraperitoneally. Protein and RNA were extracted from harvested tumor tissues. PBMCs from five experimental and three control patients were sampled at 0 (pre) and 48 hours, and on days 8 and 15. The gene expression normalized to “pre” was determined using 2−ΔΔCt method. Results: Pelareorep induced significant upregulation of LC3 A/B in HCT116 as compared with Hke3 cells by immunofluorescence (3.24 × and 8.67 ×), flow cytometry (2.37 × and 2.58 ×), and autophagosome formation (2.02 × and 1.57 ×), at 6 and 9 hours, respectively; all P &amp;lt; 0.05. Western blot analysis showed an increase in LC3 A/B (2.38 × and 6.82 ×) and Beclin1 (1.17 × and 1.24 ×) at 6 and 9 hours, ATG5 (2.4 ×) and P-62 (1.52 ×) at 6 hours, and VPS-34 (1.39 ×) at 9 hours (all P &amp;lt; 0.05). Induction of 13 transcripts in cell lines (&amp;gt;4 ×; 6 and 9 hours; P &amp;lt; 0.05), 12 transcripts in CT26 (qRT-PCR), and 14 transcripts in human PBMCs (P &amp;lt; 0.05) was observed. LC3 A/B, RICTOR, and RASD1 expression was upregulated in all three model systems. Conclusions: Pelareorep hijacks host autophagic machinery in KRAS-mut conditions to augment its propagation and preferential oncolysis of the cancer cells.
Abstract 13658: Factors Associated With the Unnecessary Continuation of Cardiac Telemetry Through Discharge
Authors: Jordan L Gavin, Raja K MUTHARASAN
Journal: Circulation (2020)

Background: Inpatient cardiac telemetry remains over-utilized. Even when ordered judiciously, telemetry may be unnecessarily continued through discharge, adding cost, complexity, and inconvenience to care. Objective: To determine the rate of continuation of cardiac telemetry through time of hospital discharge, and the factors associated with its prolonged use. Methods: We analyzed 37,779 telemetry admissions between January 1 and December 31, 2019 at a 6-hospital healthcare system in the Chicago metropolitan area. We sought to evaluate whether hospital setting, location at time of telemetry order, ICU admission, major diagnostic category, cardiology consultation, or discharge disposition affected telemetry continuation through discharge. Results: In total, 47.1% of all telemetry admissions retained an active telemetry order through hospital discharge. The median and mean durations on telemetry were 71 hours and 101 hours, respectively. Patients admitted to a community hospital, hospitalized with a cardiac-related Medicare Severity-Diagnosis Related Group (MS-DRG), consulted on by cardiology, started on telemetry in the cardiac catheterization lab, or discharged home were more likely to be continued on telemetry through discharge. Odds ratios are shown in the figure, with an odds ratio &gt; 1 indicating increased likelihood of being continued on telemetry through time of discharge. Conclusions: Once started on cardiac telemetry, nearly half of all patients remained on telemetry until discharge. Those with substantial cardiovascular-related care - as evidenced by procedure in the catheterization lab, cardiology consultation, or a cardiac MS-DRG - were more likely to be continued on telemetry through discharge. Quality improvement interventions aiming to reduce telemetry duration should focus on strengthening daily reviews of telemetry need, perhaps leveraging the electronic health record to link telemetry indications and duration.
IN-HOSPITAL MORTALITY IS ASSOCIATED WITH INFLAMMATORY RESPONSE IN NAFLD PATIENTS ADMITTED FOR COVID-19
Authors: Roberta Forlano
Journal: Hepatology (2020)

Background: Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease(NAFLD) We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19 Methods: This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD Clinical data and early weaning score(EWS) were recorded NAFLD diagnosis was based on imaging or past medical history andpatients were stratified for Fibrosis-4(FIB-4)index  Clinical endpoints were admission to intensive care unit(ICU)and in-hospital mortality Results: 561 patients were admitted Overall, 193 patients were included in the study Fifty nine patients(30%) died, 9(5%) were still in hospital, and 125(65%) were discharged  The NAFLD cohort(n=61) was significantly younger(60 vs 70 5 years, p=0 046) at presentation compared to the non-NAFLD(n=132) NAFLD diagnosis was not associated with adverse outcomes However,the NAFLD group had higher C reactive protein(CRP) (107 vs 91 2 mg/L,p=0 05) compared to non-NAFLD(n=132) Among NAFLD patients, male gender(p=0 01), ferritin(p=0 003) and EWS(p=0 047) were associated with in-hospital mortality,while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not Conclusion: The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19 Though NAFLD patients were younger on admission,disease stage was not associated with clinical outcomes Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group
Nasal DNA methylation differentiates severe from non‐severe asthma in African‐American children
Authors: Tao Zhu, Xue Zhang, Xiaoting Chen, Anthony P. Brown, Matthew T. Weirauch, Theresa W. Guilbert, Gurjit K. Khurana Hershey, Jocelyn M. Biagini, Hong Ji
Journal: Allergy (2020)

Abstract Background Asthma is highly heterogeneous, and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and nonsevere asthmatic children and evaluate the impact of environmental exposures. Methods Thirty‐three nonsevere and 22 severe asthmatic African American children were included in an epigenome‐wide association study. Genome‐wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. Twenty‐seven DMPs were associated with traffic‐related air pollution or secondhand smoke. DNAm at 22 DMPs was altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched. Conclusions Significant differences in nasal epithelial DNAm were observed between nonsevere and severe asthma in African American children, a subset of which may be useful to predict disease severity. These CpG sites are subjected to the influences of environmental exposures and may regulate gene expression.
Abstract 14967: Pregnancy Outcomes in Sickle Cell Disease With Elevated Right Ventricular Systolic Pressure - High Thromboembolic Risk
Authors: William H Marshall, Stephen Gee, Payal Desai, Elisa A Bradley, Curt Daniels, Raymond L Benza, Saurabh Rajpal
Journal: Circulation (2020)

Introduction: Pulmonary hypertension (PH) diagnosed by elevated right ventricular systolic pressure (RVSP) is present in 6-11% of patients with sickle cell disease (SCD) and is associated with increased mortality. PH, independent of SCD, is associated with increased maternal mortality. While there are reports of adverse outcomes during pregnancy in patients with SCD, pregnancy outcomes of patients with SCD and PH have not been well studied. Methods: Using our institutional electronic data warehouse we searched for pregnant women who had an echocardiogram between November 1, 2011 and April 30, 2018, and met criteria for pulmonary hypertension with report of either RVSP &gt; 35 mmHg or tricuspid regurgitant (TR) velocity of more than 2.8 m/s. We assessed maternal and fetal outcomes in this group of patients. Results: We identified 136 women with elevated RVSP, of which 7 (5%) had SCD (mean maternal age 29 ± 3 years, mean RVSP 47 ± 11 mmHg, mean TR velocity 3.1 ± 0.4 m/s). RVSP was known to be elevated before pregnancy in 5 (71%). There were no maternal deaths during pregnancy or up to 1-year post-partum. Thromboembolic complications occurred in 3 (43%); including 1 deep vein thrombosis with presumed pulmonary embolism (PE) at 20 weeks gestational age (GA), 1 catheter associated right atrial thrombus at 22 weeks GA, and 1 PE at 16 weeks GA. There were no heart failure complications. Cesarean section occurred in 5 (71%), all for obstetric indications. There were no fetal or neonatal deaths. Pre-eclampsia occurred in 2 (28%). The average gestational age was 35 ± 4 weeks. Preterm birth and low birth weight occurred in 3 (43%) patients. Conclusion: In conclusion, there was no maternal mortality or heart failure in pregnant women with SCD and elevated RVSP at our high-volume center, however 3 of 7 patients (43%) had thromboembolic complications. Further studies of women with PH and SCD are needed to assess the thromboembolic risk during pregnancy.
THU0041 IFNΑ AND IL21 PROMOTE DISTINCT POPULATIONS OF EFFECTOR B CELLS
Authors: M. Boudigou, A. Grasseau, N. Chriti, J. O. Pers, L. Le Pottier, S. Hillion
Journal: Annals of the Rheumatic Diseases (2020)

Background: B cells play a crucial role in the pathogenesis of systemic autoimmunity through various effector functions, including auto-antibody production, secretion of pro-inflammatory cytokines and antigen presentation to T cells. Interferon alpha (IFNα), mainly produced by innate cells (Menon et al., 2016), and interleukin (IL)-21 which is secreted by follicular helper T cells (Berglund et al., 2013), promote the generation of auto-reactive IgG-secreting plasma cells. However, it is suggested that IFNα participate also to the generation of regulatory B cells. Objectives: To further understand the disturbing microenvironmental signals leading to autoimmune diseases, we aim to define a coherent framework integrating the B-cell subsets having different ability to respond to microenvironmental signals, and the signalling pathways driving the differentiation and the functional fate of B cells. Methods: Naïve and several populations of memory B cells were isolated from peripheral blood of healthy donors and differentiated in vitro in the presence of IL21 or IFNα. The phenotype and the expression of transcription factors were analysed by flow cytometry and molecular identity of these cells was further determined by transcriptomic approaches. Functional analyses were performed to assess the effector functions of B cells and their potential regulatory effects on T cells. Results: IFNα, in synergy with CpG, promote the generation of CD27 high CD38 high plasmablasts (PB), mainly arising from memory subsets, but not IL21. However, IFNα and IL21 induce the transcriptional program of B-cell differentiation by up-regulating IRF4 and Blimp1 expression. Unlike IFNα, IL21 drive the expansion of CD11c + T-bet + cells only from switched memory subsets, suggesting T-bet may be a footprint of long-lived memory B cells. Even though subtle differences were observed in the antibody production between IFNα and IL21-stimulated memory B cells, naïve cells secreted less amount of IgM and IL10 when stimulated with IL21. Transcriptomic studies are still in progress to further define the molecular profile of those distinct effector B cells. Conclusion: Taken together, these findings suggest that IFNα promote a rapid differentiation of B cells into IL10 and Ig-secreting PB whereas IL21 contributes to the generation of T-bet + atypical pre-PB that may have a role in chronic autoimmune disorders. References: [1]Berglund, L.J., Avery, D.T., Ma, C.S., Moens, L., Deenick, E.K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P.D., et al. (2013). IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood 122 , 3940–3950. [2]Menon, M., Blair, P.A., Isenberg, D.A., and Mauri, C. (2016). A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity 44 , 683–697. Disclosure of Interests: None declared
Abstract 13303: Cardio-ankle Vascular Index Predicts New Onset Stroke in Patients With Heart Failure
Authors: Yu Hotsuki, Akiomi YOSHIHISA, Yu Sato, Yasuhiro Ichijo, Koichiro Watanabe, Yusuke Kimishima, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Yasuchika Takeishi
Journal: Circulation (2020)

Aim: We aimed to evaluate the implication of cardio-ankle vascular index (CAVI) to predict new onset stroke in patients with heart failure (HF). Methods and Results: This was a prospective observational study, which recruited clinical data of a total of 898 patients hospitalized for HF. According to the survival classification and regression tree analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.6. We divided patients into two groups: the high CAVI group (CAVI &gt; 9.6, n = 230, 25.6%) and the low CAVI group (CAVI ≤ 9.6, n = 668, 74.4%). We compared the patients’ characteristics and occurrence of new onset stroke. The high CAVI group was older (73.5 vs. 66.0 years old, P &lt; 0.001) and had a higher prevalence of male sex (74.3% vs. 62.0%, P = 0.001) and prior stroke (23.5% vs. 17.5%, P = 0.047). The high CAVI group showed higher levels of B-type natriuretic peptide (246.0 vs. 165.1 pg/mL, P &lt; 0.001) and lower levels of estimated glomerular filtration rate (51.6 vs. 61.8 mL/kg/1.73 m2, P &lt; 0.001). In contrast, left ventricular ejection fraction, and prevalence of other co-morbidities such as hypertension, diabetes mellitus, dyslipidemia, chronic obstructive pulmonary disease was comparable between the two groups. The Kaplan-Meier analysis demonstrated that rate of new onset stroke was higher in the high CAVI group than in the low CAVI group ( Figure , log-rank P = 0.001). After adjusting for potential confounding factors, high CAVI was an independent predictor of new onset stroke (hazard ratio 2.359, 95% confidence interval 1.223-4.513, P=0.010). Conclusions: CAVI independently predicts new onset stroke in patients with HF.
LHRH‐Targeted Redox‐Responsive Crosslinked Micelles Impart Selective Drug Delivery and Effective Chemotherapy in Triple‐Negative Breast Cancer
Authors: Kai Xiao, Qiangqiang Liu, Nell Suby, Wenwu Xiao, Rinki Agrawal, Michael Vu, Hongyong Zhang, Yan Luo, Yuanpei Li, Kit S. Lam
Journal: Advanced Healthcare Materials (2020)

Abstract Systemic chemotherapy is efficacious against triple‐negative breast cancer (TNBC), but it is often associated with serious side effects. Here, a luteinizing hormone‐releasing hormone (LHRH) receptor‐targeted and tumor microenvironment‐responsive nanoparticle system to selectively deliver chemotherapeutic drugs to TNBC cells, is reported. This delivery system (termed “LHRH‐DCMs”) contains poly(ethylene glycol) and dendritic cholic acid as a micellar carrier, reversible intra‐micellar disulfide bond as a redox‐responsive crosslink, and synthetic high‐affinity (D‐Lys)‐LHRH peptide as a targeting moiety. LHRH‐DCMs exhibit high drug loading efficiency, optimal particle size, good colloidal stability, and glutathione‐responsive drug release. As expected, LHRH‐DCMs are more efficiently internalized into human TNBC cells through receptor‐mediated endocytosis, resulting in stronger cytotoxicity against these cancer cells than the non‐targeted counterpart when encapsulated with paclitaxel (PTX). Furthermore, near‐infrared fluorescence and magnetic resonance imaging demonstrate that LHRH‐DCMs facilitate the tumor distribution and penetration of payloads in three different animal models of breast cancer, including cell line‐derived xenograft (CDX), patient‐derived xenograft (PDX), and transgenic mammary carcinoma. Finally, in vivo therapeutic studies show that PTX‐LHRH‐DCMs outperform both the corresponding nontargeted PTX‐DCMs and the current clinical formulation (Taxol) in an orthotopic TNBC model. These results provide new insights into approaches for precise drug delivery of TNBC.