tbuckley/cabot-search huggingface dataset:
Abstract 369: Noninvasive Cerebral Perfusion Pressure and Neurologic Outcome in Post-cardiac Arrest Patients with Targeted Temperature Management
Authors: Minjung K Chae, Sung Eun Lee, Sumin Cho, Taeyoung Kim, Dukyong Yoon
Journal: Circulation (2020)

Introduction: Hypoxic ischemic brain injury (HIBI) is the leading cause of mortality and long-term neurologic disability in survivors of cardiac arrest. Recently, the role of cerebral monitoring is emphasized for individualizing therapy and mitigating secondary brain injury in HIBI patients after return of spontaneous circulation (ROSC). The first step of cerebral monitoring is checking the driving force by cerebral perfusion pressure (CPP). However, as CPP is calculated by mean arterial pressure (MAP) minus intracranial pressure (ICP), the process of obtaining ICP is invasive. Noninvasive CPP can be estimated by parameters obtained from transcranial doppler (TCD). Therefore, we aimed to investigate non-invasively measured CPP from TCD and its association with neurologic outcome in post cardiac arrest patients that underwent targeted temperature management (TTM). Methods: This retrospective single-center study included patients who had been treated with TTM following cardiac arrest and who underwent TCD evaluation between July 2017 and July 2019. We aimed to perform TCD evaluation within 48h of ROSC, but sometimes this could not be achieved due to limited resources. Patients with TCD that was performed after 72 hours were excluded. The MFV was calculated using the peak systolic flow velocity (PSV) and the end-diastolic flow velocity (EDV) as below. Two methods of estimating CPP non-invasively was calculated as below.MFV = PSV+(EDVх2) / 3 eCPP_A= MAP*diastolic FVmca/MFVmca + 14eCPP_B= MFVmca*(MAP-DBP)/FVmean-FVdia Results: Table 1. Baseline characteristics of study population Data are presented as mean (standard deviation), number (%) or median (interquartile range).OHCA, out of hospital cardiac arrest; CPR, cardiopulmonary resuscitation; AED, automated external defibrillator; TCD, transcranial doppler; CPP, cerebral perfusion pressure. Table 2. Cut off values and diagnostic values in predicting poor neurologic outcome with 100% specificityCPP, cerebral perfusion pressure. Conclusion: eCPP cut off values of &lt;50 mmHg and &lt;60mmHg predicted poor neurological outcome with high specificity. This study suggests that eCPP obtained from TCD may be feasible to predict neurologic outcome.
Abstract 14078: Ros-dependent Sumoylation of Cu Chaperone Atox1 Drives Its Nuclear Translocation to Promote Inflammatory Angiogenesis Induced by Ischemic Injury
Authors: Archita Das, Sudhahar Varadarajan, David Fulton, Yali Hou, Xuexiu Fang, Malgorzata McMenamin, Junichi Abe, Masuko Ushio-fukai, Tohru Fukai
Journal: Circulation (2020)

Introduction: Neovascularization in response to ischemia depends on inflammation, angiogenesis and reactive oxygen species (ROS). Copper (Cu) is implicated in inflammation and angiogenesis. We reported that cytosolic Cu chaperone Atox1 activates secretory Cu enzymes lysyl oxidase (LOX), while nuclear Atox1 functions as a Cu-dependent transcription factor to promote ROS/NFkB-dependent inflammation in endothelial cells (ECs). However, mechanism of Atox1 nuclear translocation as well as role of endothelial Atox1 in inflammatory angiogenesis in vivo remain unknown. SUMOylation and its deSUMOylation by SENPs regulates transcription factor function. Silica analysis identified a conserved putative SUMOylation motif at Lys(K3) of Atox1. Results: Atox1 expression was dramatically increased in angiogenic ECs in mice hindlimb ischemia model. EC-specific Atox1-deficient mice significantly reduced angiogenesis (CD31+, 67%) and Mac+ inflammatory cells in ischemic tissues. In cultured ECs, inflammatory cytokine TNFα or hypoxia promoted Atox1 nuclear translocation and Atox1 SUMOylation (3.6-fold), which were inhibited by antioxidant NAC or overexpression of “SUMO-dead” Atox1K3R. Mechanistically, TNFα induced Cys603 oxidation/inactivation of SENP1 in cytosol, which in turn increased Atox1 SUMOylation and nuclear translocation. Functionally, siAtox1or Atox1K3R inhibited TNFα-induced inflammatory/angiogenic genes VCAM/ICAM, IL-15 and RANTES. In nucleus with reduced state, ChIP assay using SUMO-Atox1 revealed that Atox1 deSUMOylation by nuclear SENP1 increases Atox1 transcriptional activity for inflammatory genes. In parallel, Atox1K3R which maintains Cu chaperone function inhibited TNFα-induced EC permeability by activating LOX. In vivo, Atox1 SUMOylation was increased after hindlimb ischemia while CRISPR/Cas9-generated SUMO-dead Atox1K3R knock-in mice showed impaired angiogenesis in hindlimb ischemia model. Conclusion: Atox1 SUMOylation via oxidative/inactivation of SENP1 in cytosol promotes: 1) its translocation to nucleus where deSUMOylated Atox1 can function as Cu-dependent transcription factor to drive inflammatory angiogenesis and 2) EC barrier dysfunction in inflamed/hypoxic ECs after ischemic injury.
ENSURING EQUITABLE ACCESS TO HEPATOLOGY TELEMEDICINE DURING THE COVID-19 PANDEMIC
Authors: Burbank, Sarah, Price, Jennifer C., Odisho, Anobel, Hameed, Bilal
Journal: Hepatology (2020)

Background: The COVID-19 pandemic has led to an unprecedented expansion in telemedicine but has also exposed the deep underlying healthcare disparities in the US Vulnerable patients, including those with limited English proficiency, underrepresented minority groups, older adults, and those with lower socioeconomic status, are more likely to experience digital barriers to engaging in telemedicine Although our academic hepatology practice adopted telemedicine several years before COVID-19, there was a concerted effort to assist patients and providers with video visits during the pandemic We aimed to evaluate shifting demographics of patients accessing telemedicine pre- and post-COVID-19 Methods: Patient demographics, appointment date, and visit type were obtained from the electronic health record reporting database for all patients seen by the UCSF Hepatology and Liver Transplant clinic 1/2/2019-5/29/2020  Visits were stratified into pre-COVID-19 (1/2/2019-3/15/2020) and post-COVID-19 (3/15/2020- 5/29/2020) periods We compared characteristics of clinic patients seen 1) in the pre- vs post-COVID-19 periods;2) via in-person vs video visits;and 3) via video visits pre- vs post- COVID-19 Chi-square or Kruskal-Wallis tests were used to compare categorical and continuous variables, respectively Telephone visits were not included in the analysis Results: Pre-COVID-19, a total of 12,017 patients were seen, including 1,509 via video (12 5%) Post-COVID-19, 1,894 patients were seen, including 1,504 via video (79%) Over the entire study period, compared to patients seen in-person (n=9,344), patients seen via video (n=3,013) were younger and more likely to be Caucasian, speak English as their primary language, and have commercial insurance (p < 0 001 across all comparisons) Among all patients who completed video visits, those seen post-COVID-19 were older, were more likely to be non-Caucasian, non-English speaking and utilizing an interpreter for the visit, and have public insurance compared to pre-COVID-19 (p < 0 001 across all comparisons) Conclusion: Prior to COVID-19, video visits were relatively common in our clinic, but disparities in video visit utilization existed  Post-COVID-19, with significant efforts to convert clinic visits to video, the characteristics of patients seen via video changed to include more vulnerable patients If telemedicine is the future of hepatology, we must work to ensure that all of our patients have equitable access  (Table Presented)
Sleep Deprivation Increases Air Hunger rather than Breathing Effort
Authors: Christophe Rault, Quentin Heraud, Stéphanie Ragot, René Robert, Xavier Drouot
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Sleep Deprivation Increases Air Hunger rather than Breathing Effort." American Journal of Respiratory and Critical Care Medicine, 203(5), pp. 642–645
Abstract 16279: Impact of Race and Socioeconomic Status on Rates of Congestive Heart Failure Admissions, Readmissions, and Length of Stay
Authors: Muhammad A Shakir, Meghan E Buckley, William D Surkis, John M Clark
Journal: Circulation (2020)

Introduction: Health disparities due to race and socioeconomic status persist among congestive heart failure (CHF) patients. Our hospital in the Philadelphia area is uniquely situated to study disparities as it sits on the border of a diverse inner city and suburban population. The area west of our hospital is known to have a drastically higher median income than the area to the east. We aimed to evaluate differences in rates of CHF admissions, readmissions, and length of stay (LOS) for patients based on race and socioeconomic status. Methods: From 3/1/2018 to 3/31/2020, 6,785 total patients were admitted to our hospital due to acute decompensated CHF. To compare rates of admission, readmission and a LOS &gt; 5 days based on race and socioeconomic status, we used the SlicerDicer function of the EPIC electronic record platform. For race, we compared data for white and black patients. For socioeconomic status, we included a 10-mile radius around our hospital and used public records to collect median household income for 11 zip codes to the east and 11 to the west. The average yearly median household income for the east and west zip codes were USD $27,171 and $134,390, respectively. Outcomes are expressed as percentages and compared using a Chi-square test of independence and 95% confidence interval (CI) for differences. Significance was assessed at the 0.05 level. Results: Admission rates were significantly higher among Black patients at 67% compared to White patients at 58% (95% CI 7-11%, p&lt;0.05). There was no significant difference between rates of readmission (60% for Black vs. 58% for White patients, 95% CI 0-4%, p=0.11) or LOS &gt; 5 days (56% for Black vs. 55% for White patients, 95% CI 0-3%, p=0.42). Admission rates were significantly higher among patients from low income areas at 70% compared to high income areas at 56% (95% CI 11-17%, p&lt;0.05). Readmission rates were not significantly different, 57% for low income and 56% for high income areas (95% CI 0-4%, p=0.82). Patients from low income areas were significantly more likely to have a LOS &gt; 5 days at 57% compared to patients from high income areas at 53% (95% CI 0.8-8%, p&lt;0.05). Conclusions: Race and socioeconomic status continue to impact CHF patients’ health outcomes including rates of admissions, readmissions, and length of stay.
Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating
Authors: Mathieu Favier, Helena Janickova, Damian Justo, Ornela Kljakic, Léonie Runtz, Joman Y. Natsheh, Tharick A. Pascoal, Jurgen Germann, Daniel Gallino, Jun-II Kang, Xiang Qi Meng, Christina Antinora, Sanda Raulic, Jacob P.R. Jacobsen, Luc Moquin, Erika Vigneault, Alain Gratton, Marc G. Caron, Philibert Duriez, Mark P. Brandon, Pedro Rosa Neto, M. Mallar Chakravarty, Mohammad M. Herzallah, Philip Gorwood, Marco A.M. Prado, Vania F. Prado, Salah El Mestikawy
Journal: Journal of Clinical Investigation (2020)

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.
Abstract 14091: Outcomes of Patients With Recalled Defibrillator Leads: Results From the NCDR-ICD Registry
Authors: Emily P Zeitler, Yongfei Wang, Jeptha P Curtis, Jordan M PRUTKIN
Journal: Circulation (2020)

Introduction: Whether to reuse, abandon, or extract functioning, recalled ICD leads at the time of generator replacement is an area of uncertainty as lead failure is more common following generator replacement, and long term failure rates of recalled ICD leads are unknown. We sought to evaluate outcomes following various lead management strategies at the time of generator replacement. Hypothesis: Functional St. Jude Riata and Medtronic Sprint Fidelis leads at the time of elective generator replacement are more frequently reused than replaced, and extracting them poses significant procedural risk. Methods: We queried the NCDR ICD Registry for Medicare patients undergoing elective generator replacement with a normal Fidelis or Riata lead from 2010-2016 and categorized patients based on the fate of the recalled lead: reused, abandoned, or extracted. We report pre-discharge complications by group. Results: There were 9937 generator replacement patients between 2010-2016 with a functioning Riata or Fidelis lead in which lead management was reported. The lead was reused in 9806 (98%) patients, extracted in 55 (0.6%), and abandoned in 76 (0.8%). Compared with the reused group, extracted patients were &gt;10 years younger, had less heart failure and fewer comorbidities. In-hospital death occurred in 4 (7.3%) patients in the extracted group and 7 (0.07%) in the reused group (P&lt;0.0001). The combination of death or any pre-discharge event occurred in 11% of extracted patients compared with 0.3% and 0% in the reused and abandoned groups, respectively.(Table) Conclusions: At the time of generator replacement, a small percentage of functional Riata and Fidelis leads were extracted. Even in this highly selected extraction population, extraction posed significant risk of in-hospital mortality and severe complications. Future work will help clarify whether these peri-procedural risks may be justified by improved medium and long term outcomes.
Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation
Authors: Zhi Zeng, Luoxing Xia, Shunyang Fan, Junmeng Zheng, Jinhong Qin, Xuejiao Fan, Yunfeng Liu, Jun Tao, Yingying Liu, Kang Li, Zhenwei Ling, Yun Bu, Kathleen A. Martin, John Hwa, Renjing Liu, Wai Ho Tang
Journal: Circulation (2020)

Background: Aberrant expression of circular RNA contributes to human diseases. Circular RNAs regulate gene expression by sequestering specific microRNAs. In this study, we investigated whether circMAP3K5 (circular mitogen-activated protein kinase 5) could act as a competing endogenous microRNA-22-3p (miR-22-3p) sponge and regulate neointimal hyperplasia. Methods: Circular RNA profiling from genome-wide RNA sequencing data was compared between human coronary artery smooth muscle cells (SMCs) treated with or without platelet-derived growth factor. Expression levels of circMAP3K5 were assessed in human coronary arteries from autopsies on patients with dilated cardiomyopathy or coronary heart disease. The role of circMAP3K5 in intimal hyperplasia was further investigated in mice with adeno-associated virus 9–mediated circMAP3K5 transfection. SMC-specific Tet2 (ten-eleven translocation-2) knockout mice and global miR-22-3p knockout mice were used to delineate the mechanism by which circMAP3K5 attenuated neointimal hyperplasia using the femoral arterial wire injury model. Results: RNA sequencing demonstrated that treatment with platelet-derived growth factor–BB significantly reduced expression of circMAP3K5 in human coronary artery SMCs. Wire-injured mouse femoral arteries and diseased arteries from patients with coronary heart disease (where platelet-derived growth factor–BB is increased) confirmed in vivo downregulation of circMAP3K5 associated with injury and disease. Lentivirus-mediated overexpression of circMAP3K5 inhibited the proliferation of human coronary artery SMCs. In vivo adeno-associated virus 9–mediated transfection of circMap3k5 (mouse circular Map3k5) specifically inhibited SMC proliferation in the wire-injured mouse arteries, resulting in reduced neointima formation. Using a luciferase reporter assay and RNA pull-down, circMAP3K5 (human circular MAP3K5) was found to sequester miR-22-3p, which, in turn, inhibited the expression of TET2. Both in vitro and in vivo results demonstrate that the loss of miR-22-3p recapitulated the antiproliferative effect of circMap3k5 on vascular SMCs. In SMC-specific Tet2 knockout mice, loss of Tet2 abolished the circMap3k5-mediated antiproliferative effect on vascular SMCs. Conclusions: We identify circMAP3K5 as a master regulator of TET2-mediated vascular SMC differentiation. Targeting the circMAP3K5/miR-22-3p/TET2 axis may provide a potential therapeutic strategy for diseases associated with intimal hyperplasia, including restenosis and atherosclerosis.
Abstract 16359: Incidence of Fontan Associated Liver Disease and Its Impact on Mortality in Patients With Single Ventricle Physiology
Authors: Carlos Guerrero, judith Therrien, Aihua Liu, Liming Guo, Masaki Kodaira, Pierre-luc Bernier, Christo tchervenkov, Ariane J Marelli
Journal: Circulation (2020)

Introduction: Data on the burden of clinically significant Fontan associated liver disease (FALD) and its relationship to mortality is scant. We performed a retrospective cohort study to assess the incidence of FALD and its association with mortality. Methods: Data source was the Quebec Congenital Heart Disease (CHD) Database, a population-based cohort of over 100,000 CHD patients followed from 1983-2017. Fontan patients surviving longer than 30 days post-Fontan were identified, each were matched to 20 VSD patients on age and sex. The Fontan-VSD cohort were used to assess the association between Fontan and the risk of developing FALD. The VSD cohort served as “Non-exposed to Fontan” group. FALD was defined as at least one hospitalization due to liver disease. Kaplan-Meier curves were used to estimate and compare the cumulative probability of 1) developing FALD between Fontan and VSD patients; and 2) mortality between Fontan patients w/o FALD. Results: A total of 512 Fontan patients and 10,232 VSD patients were included. The cumulative probability of developing FALD at 10 and 25 years of follow-up was higher in Fontan patients (13.0% and 37.1%, respectively), compared to 0.7% and 2.0% for VSD patients respectively (p-value &lt;0.0001-Logrank test). In Fontan patients with FALD, the cumulative probability of mortality by 5 years after the diagnosis of FALD was 12.6%, 11 times higher than the risk in Fontan Patients without FALD (Figure) . Calendar year of Fontan operation was found to be an important predictor of developing FALD. Conclusions: This is the first study documenting the impact of FALD on mortality, using a large cohort with long-term follow up. The findings support the use of well-defined surveillance protocols to identify potential precipitants of FALD before liver disease becomes irreversible.
Abstract 13361: How Does Depression Influence Symptom Perception in Patients With Heart Failure?
Authors: Solim Lee, Amy Ketcham, Julie Guerin, Brittany Koons, Lea Ann Matura, Corrine Y Jurgens, Victoria V Dickson, Barbara J Riegel
Journal: Circulation (2020)

Despite the high prevalence of depression in HF, little is known about how depression affects symptom perception processes of monitoring, detection, and evaluation. If depression impairs symptom perception, it may delay care-seeking. Aim: To explore how depression influences HF symptom perception. Methods: We enrolled a purposive sample of patients with an unplanned HF hospitalization in this convergent mixed-methods study. Semi-structured in-person interviews were used to explore how patients monitored, detected, and evaluated symptoms prior to hospitalization. HF symptom monitoring, physical symptom presence/severity, and symptom evaluation were measured using the Self-care HF Index, the HF Somatic Perception Scale, and the Illness Perception Scale, respectively. Depression was measured using the Patient Health Questionnaire (PHQ8); score≥10 indicates moderate/severe depression. Qualitative data were analyzed using content analysis to yield categories of symptom type, detection time, and barriers/facilitators for symptom monitoring, detection, and evaluation. To integrate the data, qualitative data were quantified by assigning binary values (e.g. immediacy of symptom detection). Pearson’s correlation and Chi 2 were used to analyze associations. Results: A sample of 40 patients (age 62±13 years, 50% female, 55% White, median HF duration 6 years, 75% NYHA III-IV, 58% PHQ8≥10) was enrolled. There was no significant association between depression and HF symptom monitoring, but moderate/severe depression was described as a barrier to symptom monitoring ("When I get into my depression days, I won't get on the scale, or I just won't do anything."). Depressed patients appeared to detect symptoms more rapidly (p=0.051). More depressed patients reported greater physical symptom severity (r=0.44, p=0.005), but the number of symptoms was not associated with depression. More depressed patients had stronger belief in negative consequences of HF (r=0.46, p=0.003), more negative emotional responses to HF (r=0.60, p&lt;0.001), and less perceived control over HF (r= -0.35, p=0.028). Conclusion: Depressed patients may have difficulties in symptom monitoring, but not in symptom detection. Depression negatively influences symptom evaluation.