tbuckley/cabot-search huggingface dataset:
Abstract 12679: Impact of Mental Health Disorders on Ventricular Assist Device Supported Patients Emergency Resource Use and Outcomes
Authors: Jonathan J Edwards, Jonathan Edelson, Hannah Katcoff, Antara Mondal, Debra Lefkowitz, Nosheen Reza, Thomas Hanff, Heather M Griffis, Jeremy Mazurek, Anjali T Owens, Carol Wittlieb-Weber, Danielle Burstein, Pavan Atluri, Matthew O’Connor, Lee R Goldberg, Payman Zamani, Peter W Groeneveld, Joseph Rossano, Kimberly Y Lin, Edo Birati
Journal: Circulation (2020)

Introduction: There are minimal data describing the prevalence of mental health disorders (MHDO) in VAD-supported patients, or the association between MHDO and resource use or outcomes. Methods: This retrospective analysis utilizes all emergency department (ED) encounter-level data from the 2010-2017 Nationwide Emergency Department Sample (NEDS). Patients with VADs were identified using ICD-9/10 codes, as were associated MHDO diagnoses, which were categorized as depression/anxiety, suicide/self harm, bipolar/psychoses, and substance abuse. Outcomes and characteristics were compared for patients with and without a MHDO via descriptive statistics. Hospital admission and mortality occurring in ED or inpatient was investigated with logistic multivariable regression models adjusted for demographic and clinical characteristics. Results: Of the 47,543 encounters with VADs during the study period, 23% (n=11,103) had at least one MHDO. Depression/anxiety (82%) and substance abuse (22%) were the most prevalent MHDOs. Suicide attempt or self harm was the primary diagnosis for 20 (0.2%) encounters. Patients with MHDOs were more likely to be female (31% vs. 26%), younger (median age 59 vs. 61 years), and to have a non-MHDO chronic condition (77% vs 70%, P&lt;0.0001 for all). Inpatient admission rates (79% vs. 59%) and charges ($33,421 (95% CI 15,074-73,517) vs. $21,346 (95% CI 5,290-56,910) were higher for those with MHDOs (both p&lt;0.0001, Figure). However, mortality (2.0% vs. 3.3%, p=0.003) was lower. After adjusting for age, gender, and non-MHDO diagnoses, patients with MHDOs had higher admission rates (OR 2.3 (95% CI 1.8-2.9), p&lt;0.001) and lower mortality (OR 0.63 (95% CI 0.42-0.94), p=0.03). Discussion: 1 in 5 VAD-supported ED patient encounters also have a MHDO diagnosis. VAD-supported patients with a MHDO had higher resource use but lower mortality. These data underscore the need for greater attention to how MHDO may impact outcomes in VAD-supported patients.
Cell-Autonomous Feedback Loop of RUNX1-p53-CBFB in Acute Myeloid Leukemia Cells
Authors: Mina Noura, Ken Morita, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Toshikazu Bando, Kenichi Yoshida, Hidemasa Matsuo, Seishi Ogawa, Paul P. Liu, Hiroshi Sugiyama, Yasuhiko Kamikubo, Souichi Adachi
Journal: Blood (2017)
Abstract 17314: Flow-Mediated Susceptibility of Cerebral Endothelia to Sars-CoV-2 Infection Using Endothelialized 3D Human Vascular Models
Authors: Naoki Kaneko, Lea Guo, Jennifer An, Visesha Kakarla, Jason D Hinman
Journal: Circulation (2020)

Introduction: The clinical syndrome associated with Sars-CoV-2 infection is associated with an increased rate of cerebrovascular events, predominantly ischemic stroke. Direct viral invasion of the cerebral endothelium could be a significant driver of Sars-CoV-2-mediated stroke through expression of ACE2 and viral entry co-factors including TMPRSS2. Prior work indicates that ACE2 mRNA and protein are expressed in the endothelial cells of the brain, yet the effect of flow-mediated phenomena on ACE2 expression and the susceptibility of human cerebral endothelia to Sars-CoV-2 infection is unknown. Methods: 3D printed models of the human middle cerebral artery were endothelialized with either human umbilical vein endothelial cells (HUVECs) or human brain microvascular endothelial cells (HBMECs). Endothelialized models were subjected to 3D rotational perfusional culture at variable pulsatile flow rates (0-22.5 dynes/cm 2 ). ACE2 and TMPRSS2 expression were measured by Taqman qPCR. Biotinylated recombinant Sars-CoV-2 S protein was used to judge regional vessel binding of virus using confocal microscopy. Results: In 3D models endothelialized with either HUVECs or HBMECs, ACE2 mRNA expression is significantly modulated by vessel diameter and the presence of of flow (15 dynes/cm 2 ) (p&lt;0.0001 by two-way ANOVA). Pulsatile flow drives ACE2 expression more robustly in HUVECs than in HBMECs (11.5-fold vs. 4.9-fold; p&lt;0.001). Higher flow rates (22.5 dynes/cm 2 ) produced further increases in ACE2 expression in both cell types. Gene expression analysis demonstrated no detection of the Sars-CoV-2 viral entry co-factor TMPRSS2 in HBMECs. Flow-mediated ACE2 expression was associated with binding of recombinant Sars-CoV-2 S protein to the vessel wall suggesting direct cerebrovascular susceptibility to Sars-CoV-2. Conclusion: The Sars-CoV-2 cellular receptor ACE2 is expressed by human cerebral endothelia in a flow-dependent manner. Cerebral vessels are susceptible to Sars-CoV-2 infection and bind viral S protein under flow conditions but likely requires unique co-factors for viral entry. Identification of the molecular mechanisms triggered by Sars-CoV-2 infection in brain vasculature can alleviate the burden of stroke associated with COVID-19.
Abstract 17023: Adipose Tissue Specific Temporal Deletion of <i>Ager</i> Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis
Authors: Robin Wilson, Lakshmi Arivazhagan, Henry Ruiz, Jay Pendse, Laura Frye, Kaamashri Mangar, Ravichandran Ramasamy, Ann Marie SCHMIDT
Journal: Circulation (2020)

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.
Abstract 13302: The Depression and Anxiety Paradox Following Percutaneous Coronary Intervention: A National Inpatient Sample Analysis
Authors: Hawa O Abu, Efehi Igbinomwanhia, Olakanmi Olagoke, Abdulkareem O Lukan, Chiamaka S Diala, Habeeb Sanni, Keziah E Aibangbee, Oluwafisayo Fasanmi, Oseiwe B Eromosele, Vivian Chukwuma, Adedotun A Ogunsua
Journal: Circulation (2020)

Introduction: Depression and Anxiety are prevalent among patients with cardiovascular diseases. However, their impact on important clinical outcomes, such as length of hospital stay (LOS) and mortality, is incompletely understood. Objective: Examine the magnitude and impact of major depressive disorder (MDD) and anxiety on LOS and in-hospital mortality in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI). Hypothesis: Patients with MDD or anxiety will have poorer clinical outcomes after PCI. Methods: Data were obtained from the National Inpatient Survey (NIS). Admissions in 2017 with a primary diagnosis of ACS and undergoing PCI were identified based on ICD10 codes. Patients with MDD or anxiety were further delineated with ICD10 codes. The association between MDD or anxiety and LOS and in-hospital mortality was analyzed using linear and logistic regression models, respectively. Various sociodemographic (age, race, sex, income), clinical (history of hypertension, hyperlipidemia, stroke, peripheral artery disease, valvular heart disease, chronic kidney disease, anemia, obesity, smoking) and hospital-level (region, location, payer type) factors were adjusted for in the analysis. Results: Among 130,712 patients admitted for ACS who underwent PCI, the prevalence of MDD and anxiety were 8.7% (n=11,303) and 10.8% (n=14,066), respectively. Patients were on average aged 67 years (SD=13.5), 38% were females, and 73% non-Hispanic White. Overall, the mean LOS was 4.4 days (SD=5.4) and 4.7% of patients died while hospitalized. Patients with MDD (4.6 vs 4.4, p=0.001) or anxiety (4.7 vs 4.4, p=0.001) had longer LOS than those without these conditions. Contrary to our hypothesis, patients with MDD (OR: 0.82; 95% CI: 0.73-0.91) or anxiety (OR: 0.72; 95% CI: 0.64-0.79) had significantly lower odds of mortality than those without MDD or anxiety after adjusting for several factors of prognostic importance. Conclusions: Among ACS patients who underwent PCI, MDD and anxiety were associated with increased LOS but paradoxically lower in-hospital mortality. These findings reinforce the need for future investigations to evaluate the impact of psychological factors on clinical outcomes in ACS patients who undergo PCI.
Abstract P150: Association Of Leisure Time Physical Activity (LTPA) With Left Atrial Function In Older Adults: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Romil Parikh, Riccardo M Inciardi, Wendy Wang, Sheila M Hegde, Faye L Norby, Michael J Zhang, Jorge L Reyes, Alvaro Alonso, Amil M Shah, Scott Solomon, Lin Y Chen
Journal: Circulation (2021)

Introduction: Prior research indicates that higher LTPA is associated with better left ventricular (LV) diastolic function, but not with left atrial volume index (LAVI). Left atrial (LA) strain is a more sensitive marker of LA pathology. Hence, we evaluated association of LTPA with LA strain in the ARIC study, a community-based cohort study. Hypothesis: Higher LTPA is associated with better LA reservoir, conduit and contractile function. Methods: We included 4005 participants (mean age 75 years, 63% female, 21% black) with 2D echocardiographic (2DE) LA % strain data, LTPA data, and without prevalent coronary heart disease, valvular heart disease, heart failure, atrial fibrillation, and stroke at Visit 5 (V5, 2011-13). We estimated LTPA as metabolic equivalent-minutes per week from validated Baecke questionnaire and categorized it as poor, intermediate, or ideal as per AHA recommendation. We categorized change in LTPA from V3 (1993-95) to V5 as persistently poor (referent), decreasing, increasing, or persistently active. LA reservoir, conduit, and contractile % strain were measured from speckle-tracking 2DE. Linear regression was used to evaluate association of LTPA with LA function. We modeled LTPA (1) cross-sectionally at V5 as a continuous variable and (2) change from V3 to V5, as continuous and categorical variables (referent- persistently poor). Results: Higher LTPA at V5 (Table) and persistently high (vs poor) LTPA from V3 to 5 (β estimate -0.89, 95% CI -1.40, -0.38) were significantly associated with better LA conduit function after adjusting for CV risk factors, LV function, and LAVI. The same associations with LA reservoir function were no longer significant after adjusting for CV risk factors. LTPA was not associated with LA contractile function (Table). Conclusions: Consistent with LTPA’s salutary effect on LV diastolic function, higher LTPA is associated with better LA conduit function. Maintaining high LTPA from midlife to late-life may be beneficial in mitigating age-related changes in cardiac function.
Abstract 15689: Resistant Rapid Atrial Flutter With Left Atrial Thrombus: A Therapeutic Dilemma
Authors: Kinjal Patel, Joaquim J Correia, Krunal Trivedi
Journal: Circulation (2020)

Introduction: Electrical cardioversion (ECV) is highly successful in the treatment of typical atrial flutter (AFL). Patients with AFL with a rapid ventricular rate (RVR) of ≥150 beats per minute (BPM) and significant hemodynamic compromise benefit from urgent CV. This is a unique case of managing chemically resistance AFL with a left atrial (LA) thrombus. Case Presentation: A 48-year-old male with medical history of bioprosthetic mitral and aortic valve was admitted for new onset AFL with RVR. Patient complain of (c/o) progressively worsening dyspnea and chest palpitation from 3 days. The patient denied chest pain, dizziness, diaphoresis. On admission blood pressure (BP) was 122/80 mmHg with heart rate (HR) of 158 BPM. ECG showed 2:1 block AFL with RVR. Patient was started on IV heparin and diltiazem drip. However, as the HR remained &gt;150 and patient continued to c/o palpitations, IV amiodarone was added. The BP started to fall with the HR still &gt;150 BPM. An emergent TEE done showed LA thrombus. Hence, the ECV was not performed. Instead a synchronized (sync) 3-joule (J) shock on R wave was attempted to induce atrial fibrillation (AF), to achieve better rate control. Immediately after delivering the shock the cardiac rhythm was successfully converted to AF with HR of &lt;80 BPM. Discussion: LA thrombus and clinical thromboembolic events are highly prevalent in AFL. TEE is usually done to exclude thrombus in a patient with AFL for &gt;48 hrs and if presence of thrombus cannot be confidently excluded on TEE, CV should not be performed. As a shock provided during the relative refractory period (RRP) of the ventricle corresponding to the latter part of the T wave, can possibly induce ventricular fibrillation (the so-called “R-on-T Phenomenon”), with similar concept a low voltage sync shock on R wave, the RRP of the atria can possibly induce AF. AF can be more easily rate controlled on antiarrhythmics compared to AFL and a patient with LA thrombus on anticoagulants is at lower risk from embolic events in AF than SR. Conclusions: This clinical noninvasive maneuver may be useful and desired in the management of a deteriorating patient with AFL not responsive to chemical rate control and LA thrombus such as ours or for an instance when AF in a patient with LA thrombus was inadvertently converted to SR.
Abstract 13383: The Vascular Endothelial Barrier: A Novel Therapeutic Target for Preventing Atrial Fibrillation
Authors: Louisa Mezache, Heather Struckman, Anna Phillips, Stephen Baine, Amara Greer-short, Sandor Gyorke, Przemyslaw Radwanski, Thomas J Hund, Rengasayee Veeraraghavan
Journal: Circulation (2020)

Atrial fibrillation (AF), the most common arrhythmia, is associated with inflammation and vascular dysfunction. AF patients have elevated levels of vascular endothelial growth factor (VEGF; 90-580 pg/ml), which promotes vascular leak and edema. We have previously identified edema-induced disruption of sodium channel (Na V 1.5) -rich intercalated disk (ID) nanodomains as a novel arrhythmia mechanism. We hypothesized that (i) elevated VEGF levels promote AF by disrupting ID nanodomains, and slowing atrial conduction, and (ii) protection of the vascular barrier can prevent these arrhythmias. Clinically-relevant VEGF levels (500 pg/ml, 60 minutes) increased FITC-dextran extravasation (99.3% vs. 24.3% in vehicle controls) in WT mouse hearts, consistent with increased vascular leak. Electron microscopy revealed ID nanodomain swelling, near both gap junctions (perinexi; 64±9nm vs 17±1nm) and mechanical junctions (63±4nm vs 27±2nm) in VEGF-treated hearts relative to controls. Super-resolution STORM microscopy revealed Na V 1.5 enrichment at perinexi (9±2 fold) and N-cadherin-rich sites (7±1 fold) relative to non-junctional ID sites in control hearts. VEGF reduced Na V 1.5 enrichment at both sites (6±1 and 4±1 fold, respectively), consistent with Na V 1.5 translocation from ID nanodomains. Atrial conduction, assessed by optical mapping, was slowed by VEGF (10±0.4 cm/s vs 21.3±1.3 cm/s at baseline). VEGF increased atrial arrhythmia burden both ex vivo (80% vs 0% in vehicle controls) and in vivo (70% vs 20% in vehicle controls). Next, we tested two strategies shown to prevent vascular barrier breakdown. Blocking connexin43 hemichannels (αCT11 peptide) decreased both incidence (40%) and duration (1.45±3.42s) of VEGF-induced arrhythmias. Likewise, blocking pannexin1 channels (Panx1-IL2 peptide) shortened VEGF-induced arrhythmias (2.48±0.83s). Mefloquine and spironolactone, which are small molecules that respectively inhibit Cx43 hemichannels and pannexin channels, were also found to effectively prevent VEGF-induced atrial arrhythmias. These results highlight VEGF-induced vascular leak as a novel mechanism for AF, and suggest vascular barrier protection as an anti-arrhythmic strategy.
Covid-19: Senior hospital doctors have been left with moral injury, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2021)

The covid-19 pandemic has left some hospital consultants suffering from moral injuries after they were forced to act against their moral compass, the chair of the BMA's Consultants Committee has warned.Speaking at the BMA's annual consultants conference held online on 19 May, Rob Harwood said that consultants had faced the pandemic head on, working long hours, sometimes without correct or adequate personal protective equipment, and had seen their patients and colleagues die in unprecedented numbers.He said that the psychological impact of being unable to do what they believed was right had been too much for some doctors, who had been left with moral injury as a result.He also renewed calls for a pay uplift for consultants of at least 5%, as part of the BMA's Fairness for the Frontline campaign. 1"We have been called heroes and received applause, but lofty rhetoric and claps can't capture the reality of our situation," said Harwood."After all the clapping from the Cabinet, the government's proposal of a 1% pay rise was disappointing, mean spirited, and insulting-although not surprising."Earlier this month Sarah Hallett, chair of the BMA's Junior Doctors Committee, called on the government, the NHS, and education bodies to provide better support for trainee doctors to deal with the psychological effects of the pandemic. 1
Abstract 16833: Trends in Primary Payer Status and Association With Outcomes in Pediatric Heart Transplantation
Authors: Kathryn Restaino, Xuemei Zhang, Kimberly Y Lin, Joseph Rossano, Danielle Burstein, Carol Wittlieb-Weber, Christopher Mascio, Matthew J O'Connor
Journal: Circulation (2020)

Background: Pediatric heart transplantation (HT) is resource-intensive. Adult studies have shown an increase in the proportion of adult HT funded by public insurance with outcomes inferior to those with private coverage. Trends in the funding of pediatric HT and associations with outcomes in children have not been described. Methods: We queried the United Network for Organ Sharing (UNOS) database for patients less than 18 years of age, listed for and undergoing HT from 1994 to 2018. We identified primary payer at listing (TCR), transplant (TRR), 1 year follow up, and between 1-5 years following HT. Trends in primary payer were analyzed using generalized logit regression. Cox regression was used to evaluate the impact of insurance on survival. Results: An increase in the proportion of patients with public insurance at the time of HT was observed. Forty eight percent of HT patients in 1994 and 59% in 2018 were publicly insured (P&lt;0.0001). Eight percent of patients changed from private to public insurance between TCR and TRR, and 15% transitioned from private to public from TRR to 1 year post-HT. Of those who changed insurance at one year follow up, 57% transitioned from private to public insurance. For patients undergoing HT, unadjusted long-term survival was worse for patients with public insurance (P &lt;0.0001). When adjusted for age and region, black race (HR 1.57, P &lt;0.001) and age 13-17y (HR 1.44, P&lt;0.0001) were independently associated with mortality. When evaluating outcomes based on change of insurance and adjusting for age and region, age 13-17y (ref &lt;1y, HR 2.3 P &lt;0.0001), white race (ref. black race, HR 0.54, P &lt;0.0001), continuous public insurance (ref continuous private insurance, HR 1.49, P &lt;0.0001), and transition to public insurance (ref continuous private insurance, HR 1.37, P&lt;0.007) were associated with increased mortality. Conclusion: There has been a statistically significant trend towards increasing public insurance for patients awaiting, at the time of, and after HT. Patients that maintain or transition to public insurance following transplant have worse long term outcomes. As the number of patients undergoing HT with public insurance funding continues to increase, understanding of how insurance status impacts long-term outcomes is important.
Air pollution‐induced tanning of human skin*
Authors: S. Grether‐Beck, I. Felsner, H. Brenden, A. Marini, T. Jaenicke, N. Aue, T. Welss, I. Uthe, J. Krutmann
Journal: British Journal of Dermatology (2021)

Melanism is more frequent in animals living in polluted areas on urban-industrial sites. Given that an increasing number of people are exposed to elevated air pollution levels, it is possible that environmental pollutants affect melanogenesis in human skin. Epidemiological studies have shown that exposure to traffic-related air pollutants such as diesel exhaust particles (DEP) is associated with more clinical signs of hyperpigmentation. However, mechanistic evidence linking DEP exposure to pigmentation has been elusive.To develop an ex␣vivo skin model to allow for repetitive topical application of relevant ambient DEP, and to provide proof of concept in humans.We measured skin pigmentation, melanin and pigmentation-associated gene expression, and evaluated oxidative stress.Repetitive exposure of ex␣vivo skin to DEP at nontoxic concentrations increased skin pigmentation. This increase was visible to the naked eye, time dependent, and associated with an increase in melanin content and the transcription of genes involved in de novo melanin synthesis. Similarly, in healthy participants (n = 76), repetitive topical application of DEP at nontoxic concentrations increased skin pigmentation. DEP-induced pigmentation was mediated by an oxidative stress response. After the application of DEP, epidermal antioxidants were depleted, lipid peroxidation and oxidative DNA damage were enhanced, and in a vehicle-controlled, double-blind clinical study DEP-induced pigmentation was prevented by the topical application of an antioxidant mixture.Similar to solar radiation, air pollutants cause skin tanning. As eumelanin is an antioxidant, it is proposed that this response serves to protect human skin against air pollution-induced oxidative stress.