tbuckley/cabot-search huggingface dataset:
An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases
Authors: Jerome Robert, Nicholas L. Weilinger, Li-Ping Cao, Stefano Cataldi, Emily B. Button, Sophie Stukas, Emma M. Martin, Philip Seibler, Megan Gilmour, Tara M. Caffrey, Elyn M. Rowe, Jianjia Fan, Brian MacVicar, Matthew J. Farrer, Cheryl L. Wellington
Journal: Molecular Neurodegeneration (2020)

The neurovascular unit (NVU) - the interaction between the neurons and the cerebrovasculature - is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU.We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries.This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer's disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model.This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.
Abstract 290: The Association of Regional Intra-arrest Transport Practices for Out-of-hospital Cardiac Arrest with Survival and Neurological Status at Hospital Discharge
Authors: Brian E Grunau, Takahisa Kawano, Masashi Okubo, Joshua Reynolds, Matthieu Heidet, Frank Scheuermeyer, Sheldon Cheskes, Chris Fordyce, Ian R Drennan, Brian J Twaites, Jim Christenson
Journal: Circulation (2020)

Background: There is substantial regional variation in out-of-hospital cardiac arrest (OHCA) outcomes. We investigated whether regional-level intra-arrest transport practices were associated with patient outcomes. Methods: We performed a secondary analysis of the “CCC Trial” dataset, which included EMS-treated adult non-traumatic OHCA enrolled from 49 regional clusters. The exposure of interest was regional-level intra-arrest transport practices (RIATP), calculated as the proportion of cases within the enrolling cluster transported prior to return of spontaneous circulation (“intra-arrest transport”), divided into quartiles. We fit a multilevel mixed-effects logistic regression model to estimate the association of RIATP quartile and both survival and favorable neurologic status (mRS ≤ 3) at hospital discharge, adjusted for patient-level Utstein variables. Results: We included all 26,148 CCC-enrolled patients, 36% of whom were female, 97% were treated with prehospital ALS, and 23% had shockable initial rhythms. The median RIATP of the 49 clusters was 20% (IQR 6.2 - 30%). The figure shows outcomes stratified by RIATP quartile. Compared to the first quartile (&lt;6.2%), increasing RIATP had the following adjusted associations with: (i) favourable neurological status: OR 0.87 (95% CI 0.60-1.26), 0.74 (95% CI 0.51-1.07), 0.36 (95% CI 0.25-0.53); and (ii) survival: 0.63 (95% CI 0.47-0.85), 0.60 (95% CI 0.45-0.79), 0.44 (95% CI 0.33-0.59). Conclusion: Treatment within a region that utilizes intra-arrest transport less frequently was associated with improved patient survival. These results may, in part, explain differences between regional OHCA survival outcomes.
Abstract 15467: Impact of Thrombocytopenia on Clinical Outcomes in Atrial Fibrillation Patients With Anemia: The Fushimi Af Registry
Authors: Kenjiro Ishigami, Syuhei Ikeda, KOSUKE DOI, Yasuhiro Hamatani, Akiko Fujino, Yoshimori An, MITSURU ISHII, Moritake Iguchi, Nobutoyo Masunaga, Hisashi Ogawa, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2020)

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p&lt;0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.
Abstract 16628: Cognitive Dysfunction, Instrumental Activities of Daily Living, and Health-related Quality of Life in Heart Failure
Authors: Miyeon Jung, Bruno Giordani, Sujuan Gao, Heather Burney, Marita G Titler, Dean G Smith, Susan Dorsey, Christine Haedtke, Kelly L Wierenga, Clark G David, Irmina Gradus-Pizlo, Susan J Pressler
Journal: Circulation (2020)

Introduction: Cognitive dysfunction is common in heart failure (HF), but relationships are unclear among cognitive dysfunction, performance-based instrumental activities of daily living (IADL), and health-related quality life (HRQL). Objectives: Guided by HRQL and IADL theories, hypotheses were: 1) worse cognitive function in global cognition, memory, executive function is associated with worse performance in IADL; 2) worse performance in IADL is associated with worse HRQL; and 3) IADL mediates the relationship between cognitive dysfunction and HRQL. Methods: In a cross-sectional analysis, baseline data were used from a randomized controlled trial of cognitive training in HF (N=256, mean age 66; 54% women; EF 49%; NYHA Class I=9%, II=36%, III=55%). Measures were: global cognition-Montreal Cognitive Assessment; memory-Hopkins Verbal Learning Test; executive function-Category fluency; IADL-Everyday Problem Test; and HRQL-Living with Heart Failure Questionnaire. Higher scores of cognitive and IADL measures indicate better performance. Higher scores of HRQL indicate worse HRQL. Covariates were age, gender, education, NYHA, and depressive symptoms. Multiple linear regressions were used to test hypotheses. Results: Hypothesis 1 was supported. Worse cognitive function in global cognition, memory, executive function was associated with worse IADL (β=0.38~0.45, p&lt;.001, R 2 =0.19~0.22). Age and education were significant covariates. Hypothesis 2 was supported. Worse IADL was associated with worse HRQL (β =0.79, p &lt;.001, R 2 =0.55). Gender, NYHA Class, and depressive symptoms were significant covariates. Hypothesis 3 was not tested because cognitive function was not significantly related to HRQL. Conclusions: Cognitive dysfunction was associated with worse performance in IADL. Worse performance in IADL was associated with worse HRQL. Interventions to improve HRQL may need to target improving performances in both cognitive function and IADL.
Abstract 157: Multicenter Evaluation of Etiology and Observed Transition Intensities Between Pulseless Electrical Activity and Return of Spontaneous Circulation
Authors: Eirik Unneland, Anders Norvik, Shaun K. McGovern, David G. Buckler, Unai Irusta, Abhishek Bhardwaj, Elisabete Aramendi, Trond Nordseth, Benjamin S. Abella, Dana P Edelson, Jan Terje Kvaløy, Eirik Skogvoll
Journal: Circulation (2020)

Background: Cardiac arrest presents with one of three clinical states; Cardiac standstill (asystole), Pulseless Electrical Activity (PEA), or ventricular fibrillation/tachycardia (VF/VT). PEA results from multiple etiologies and accounts for most in-hospital cardiac arrests. We quantified the dynamic nature of transitions in and out of PEA, in terms of hospital sites and presumed etiology. Methods: We analyzed 538 episodes of cardiac arrest at one Norwegian hospital and three U.S. hospitals. ECG, chest compressions and ventilations were recorded by defibrillators during CPR. Each event was assessed using a graphical application. We quantified the transition intensity, i.e. the immediate probability of a transition given the current state, between PEA and ROSC using Aalen’s additive model for time-to-event data. Results: The overall transition intensity from PEA to ROSC was about 0.10 min -1 , so an average patient in PEA has about 10 % chance to gain ROSC the following 1 minute. The intensity peaked at 7 minutes of CPR (Figure), with some heterogeneity between hospitals (0.07 to 0.11 min -1 ). The reverse transition intensity from ROSC to PEA was rather constant at 0.10 min -1 (range 0.05-0.11). Information regarding assumed cardiac or non-cardiac etiology was available in 208 episodes (123 cardiac). Patients with a cardiac etiology had a marginally smaller (-0.03 min -1 ) chance of making the transition from PEA to ROSC (p=0.049), but etiology did not impact on the ROSC to PEA transition (p=0.39). Discussion: For transitions between PEA and ROSC we observed an overall intensity of 0.1 min -1 , with some hospital heterogeneity. This may be due to heterogeneity in the underlying patient populations. We found the probability of transitioning from PEA to ROSC to increase from the start event recording until an average peak intensity at 7 minutes. This information may increase the clinicians’ understanding of the process from PEA to ROSC.
Covalent grafting of hyperbranched poly-L-lysine on Ti-based implants achieves dual functions of antibacteria and promoted osteointegration in vivo
Authors: Zhijian Yang, Yue Xi, Jun Bai, Zhiwei Jiang, Shuqin Wang, Haolan Zhang, Wei Dai, Chaozhen Chen, Zhongru Gou, Guoli Yang, Changyou Gao
Journal: Biomaterials (2020)
Abstract 15025: Visceral Adiposity and Muscle Composition in Heart Failure With Preserved Ejection Fraction and Association With Exercise Tolerance
Authors: Wendy Ying, Kavita Sharma, Lisa R Yanek, Dhananjay Vaidya, Michael Schar, Michael Markl, Vinita Subramanya, Sahar Soleimanifard, Pamela Ouyang, Erin D Michos, Sanjiv J Shah, Allison G Hays
Journal: Circulation (2020)

Introduction: Visceral adipose tissue (AT) promotes inflammation and adverse metabolic changes that mediate disease progression in heart failure with preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but little is known about its relation to the extent and distribution of AT. We characterized regional AT distribution in HFpEF patients and controls and analyzed associations with comorbidities and exercise tolerance. Methods: MRI was performed to quantify epicardial, liver, abdominal and thigh skeletal muscle AT. We assessed NYHA class, 6-minute walk distance (6MWD), and global well-being score (GWBS). Multivariable linear and logistic regression models were used, adjusted for age, sex, and body surface area. Results: We studied 55 HFpEF patients (41 women, mean age 67) and 33 controls (21 women, mean age 57). Epicardial AT (4.6 vs 3.2mm, p = 0.03), thigh intermuscular fat (11.0 vs 5.0cm 2 , p &lt; 0.01) and liver fat fraction (FF) (6.4% vs 4.1%, p = 0.04) were higher in HFpEF patients than controls. Women with HFpEF had higher abdominal (443.9 vs 297.3 cm 2 , p = 0.03) and thigh (228.6 vs 112.3 cm 2 , p &lt; 0.001) subcutaneous AT than men. Higher thigh intermuscular fat was associated with higher blood pressure (β [SE] 14.1 [3.3], p &lt; 0.001) and diabetes (β [SE] 2.6 [1.1], p = 0.02), and liver FF was associated with chronic kidney disease (β [SE] 1.6 [0.6], p = 0.01). Higher thigh intramuscular fat was associated with both higher NYHA class and shorter 6MWD, and higher thigh intermuscular AT FF was associated with higher NYHA class ( Table ). Higher epicardial AT and liver FF were associated with lower GWBS. Conclusions: HFpEF patients have increased epicardial, liver, and skeletal muscle fat compared to controls out of proportion to their body size, and adiposity was associated with worse exercise intolerance in HFpEF. These results provide the basis for further investigation into regional AT distribution in relation to HFpEF symptoms and pathophysiology.
Association Between Preoperative Blood Glucose Level and Hospital Length of Stay for Patients Undergoing Appendectomy or Laparoscopic Cholecystectomy
Authors: Hsiu-Yin Chiang, Kuan-Ting Robin Lin, Ya-Luan Hsiao, Han-Chun Huang, Shih-Ni Chang, Chien-Hui Hung, Ying Chang, Yu-Chun Wang, Chin-Chi Kuo
Journal: Diabetes Care (2020)

To evaluate the effect of preoperative blood glucose (POBG) level on hospital length of stay (LOS) in patients undergoing appendectomy or laparoscopic cholecystectomy.We conducted a retrospective cohort study of patients aged ≥18 years who had undergone appendectomy or laparoscopic cholecystectomy procedures between 2005 and 2016 at a tertiary medical center in Taiwan. The association between POBG level and LOS was evaluated using a multivariable quasi-Poisson regression with robust variance. Multiple imputations were performed to replace missing values.We included 8,291 patients; 4,025 patients underwent appendectomy (appendectomy group) and 4,266 underwent laparoscopic cholecystectomy (laparoscopic cholecystectomy group). In the appendectomy group, patients with POBG levels of ≥123 mg/dL (adjusted relative risk [aRR] 1.19; 95% CI 1.06-1.33) had a 19% higher risk of having a LOS of >3 days than did those with POBG levels of <106 mg/dL. In the laparoscopic cholecystectomy group, patients with POBG levels of ≥128 mg/dL also had a significantly higher risk of having a LOS of >3 days (aRR 1.17; 95% CI 1.07-1.29) than did those with POBG levels of <102 mg/dL. A positive dose-response curve between POBG and an adjusted risk of a LOS of >3 days was observed, although the curve starts to flatten at a POBG level of ∼130 mg/dL.We demonstrated that a higher POBG level was significantly associated with a prolonged LOS for patients undergoing appendectomy or laparoscopic cholecystectomy. The optimal POBG level may be lower than that commonly perceived.
Benefits and Risks of Testosterone Treatment in Men with Age-Related Decline in Testosterone
Authors: Marcelo Rodrigues dos Santos, Shalender Bhasin
Journal: Annual Review of Medicine (2020)

The substantial increase in life expectancy of men has focused growing attention on quality-of-life issues associated with reproductive aging. Serum total and free testosterone levels in men, after reaching a peak in the second and third decade of life, decline gradually with advancing age. The trajectory of age-related decline is affected by comorbid conditions, adiposity, medications, and genetic factors. Testosterone treatment of older men with low testosterone levels improves overall sexual activity, sexual desire, and erectile function; improves areal and volumetric bone density, as well as estimated bone strength in the spine and the hip; corrects unexplained anemia of aging; increases skeletal muscle mass, strength and power, self-reported mobility, and some measures of physical function; and modestly improves depressive symptoms. The long-term effects of testosterone on major cardiovascular events and prostate cancer risk remain unclear. The Endocrine Society recommends against testosterone therapy of all older men with low testosterone levels but suggests consideration of treatment on an individualized basis in men who have consistently low testosterone levels and symptoms or conditions suggestive of testosterone deficiency.
Reduced Cardiorespiratory Fitness and Increased Cardiovascular Mortality After Prolonged Androgen Deprivation Therapy for Prostate Cancer
Authors: Jingyi Gong, David Payne, Jesse Caron, Camden P. Bay, Bradley A. McGregor, Jon Hainer, Ann H. Partridge, Tomas G. Neilan, Marcelo Di Carli, Anju Nohria, John D. Groarke
Journal: JACC CardioOncology (2020)

Prolonged androgen deprivation therapy (ADT) is favored over short-term use in patients with localized high-risk prostate cancer (PC).This study sought to compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure and to explore how duration of ADT exposure influences CRF and CV mortality.Retrospective cohort study of patients referred for exercise treadmill testing (ETT) after a PC diagnosis. PC risk classification was based on Gleason score (GS): high risk if GS ≥8; intermediate risk if GS = 7; and low risk if GS <7. CRF was categorized by metabolic equivalents (METs): METs >8 defined as good CRF and METs ≤8 as reduced CRF. ADT exposure was categorized as short term (≤6 months) versus prolonged (>6 months).A total of 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0, 7.9 years) after PC diagnosis. Of those, 150 patients (24.3%) received ADT prior to the ETT; 99 with short-term and 51 with prolonged exposure. 504 patients (81.8%) had ≥2 CV risk factors. Prolonged ADT was associated with reduced CRF (odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.31 to 5.61; p = 0.007) and increased CV mortality (hazard ratio [HR]: 3.87; 95% CI: 1.16 to 12.96; p = 0.028) in adjusted analyses. Although the association between short-term ADT exposure and reduced CRF was of borderline significance (OR: 1.71; 95% CI: 1.00 to 2.94; p = 0.052), there was no association with CV mortality (HR: 1.60; 95% CI: 0.51 to 5.01; p = 0.420) in adjusted Cox regression models.Among patients with PC and high baseline CV risk, prolonged ADT exposure was associated with reduced CRF and increased CV mortality.
Re-Print- The effect of cost and reimbursement on treatment choice
Authors: Victor Gurewich
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Treatment of acute myocardial infarction (AMI) has been with tissue plasminogen activator (tPA) alone since 1987, at an original cost of $2,000 which has risen to $5,000. Over the past decade tPA has been replaced by percutaneous coronary intervention (PCI), an invasive, more time-consuming hospital procedure. The mortality results of the two treatments were similar, but the PCI cost and reimbursement are at least 5-fold higher. At the time, another fibrinolytic regimen was developed which is more effective, but it was ignored, and PCI continued to be the treatment choice and major source of revenue.
Abstract 14296: Differential Left and Right Ventricle Response to Cold Storage Followed by Reperfusion in Heart Transplantation
Authors: Ienglam Lei, Wei Huang, Francis D Pagani, Eugene Chen, Zhong Wang, Jordan S Pober, George Tellides, Robin Perelli, Vandana Shashi, Andrew P Landstrom, Paul C TANG
Journal: Circulation (2020)

Introduction: In heart transplantation, the supply of donor hearts is contributed by the short tolerable preservation period with risk for primary graft dysfunction. Understanding the differential biological responses to preservation between the left ventricle (LV) and right ventricle (RV) may provide critical insights. Methods: Murine donor hearts were infused with cold HTK solution and stored on ice for 0h, 4h and 8h followed by 90minutes perfusion with Krebs Buffer. The LV and RV were collected at the end of reperfusion for gene expression and protein analysis by RNA-sequencing and western blot. Results: Differential gene expression analysis showed that RV has 1092 upregulated genes and 291 downregulated genes compared to LV after cold storage followed by perfusion. GO analysis show that gene sets related to immune response (padj=7e-27), cell responses to interferon-beta (padj=8.90e-19) were enriched in RV upregulated genes (figure). We also confirmed the upregulation of immune response genes such IL1-β, Myd88 by qPCR and western blot. Moreover, we found that active β-catenin, a potential upstream regulator of IL1- β, also upregulated in RV. Wnt/β-catenin downstream target genes were also enriched in human donor RVs during prolonged preservation. Importantly, donor hearts from murine Myd88-/- showed reduced differences in the transcriptome of the LV vs RV (figure) and demonstrated improved heart function after prolonged cold storage with reperfusion. Conclusions: The RV demonstrates more extensive inflammatory response to storage compared to the LV. Selective upregulation of Wnt/β-catenin signaling in the RV may be important for enhancing this inflammatory response to preservation. Deficiency of MyD88 mediated innate immune signaling improved cardiac contractility after prolonged preservation and likely have important clinical implications for transplantation.