tbuckley/cabot-search huggingface dataset:
Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
Authors: Wei Yu, Leilei Zhong, Lutian Yao, Yulong Wei, Tao Gui, Ziqing Li, Hyunsoo Kim, Nicholas Holdreith, Xi Jiang, Wei Tong, Nathaniel Dyment, X. Sherry Liu, Shuying Yang, Yongwon Choi, Jaimo Ahn, Ling Qin
Journal: Journal of Clinical Investigation (2020)

Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone—was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.
Abstract 14209: A New <i>in vitro</i> Methodology to Evaluate Blood Mononuclear Cells Regenerative Capacity in Diabetes Patients With Acute Myocardial Infarction
Authors: Amankeldi A Salybekov, Katsuaki Sakai, Makoto Natsumeda, Kosit Vorateera, Yuji Ikari, Takayuki Asahara
Journal: Circulation (2020)

Introduction &amp; Hypothesis: Diabetes mellitus patients’(DMP) peripheral blood mononuclear cells (PBMNC) regenerative capacity level is impaired. An in vitro evaluation of PBMNC pre/post vasculogenic conditioning (VC) facilitates the assessment of immune cells regenerative potential (H1) and possible cell therapy for DMP with acute myocardial infarction (AMI) (H2). Materials &amp; Methods: Eighteen DMP with the diagnosis of AMI enrolled. Blood drawn in heparin-coated syringes from AMI patients (between day 3 to 7) along with sixteen healthy control. Isolated PBMNC regenerative capability evaluated pre and post VC ( Fig 1 ) with EPCs colony formation assay/unit (EPC-CFA/U) and flow cytometry analysis. Results: An in vitro EPC-CFA revealed that DMP fresh PBMNC derived definitive EPC (DEPC) decreased compared to control. The differentiation rate of EPC, definitive vs. primitive in control groups composed equal (50%, PEPC vs. 50%, DEPC) while in DMP, PEPC prevails (70% vs. 30%). After VC, DEPC-CFU markedly increased while PEPC-CFU decreased, indicating EPC qualitatively and quantitatively improvement in DMP (Control, PBMNC vs. VC P&gt;0.001; DMP, PBMNC vs. VC, P&gt;0.01). DMP glycoalbumin and Hb1Ac inversely correlated with CD34+ cells (r= -0.48, P&gt;0.03) while VC recovered CD34+ cells (r= 0.17, P&lt;0.54). ROC curve analysis also confirmed that the CD34+ cell number is an independent risk classifier of cardiac vessel lesion (AUC=0.85, P&gt;0.002). In contrast, VC preserved from the senescence by expansion and differentiation of CD34+ (AUC=0.54, P&lt;0.7). Proinflammatory M1 type significantly increased in DMP compared to Control (P&gt;0.03), while VC shifted the M1 type phenotype toward M2 type (P&gt;0001). Conclusion: Our EPC-CFA enables us to precisely assess impaired EPC function, while VC enhanced differentiation from PEPC toward DEPC. Furthermore, these methodologies facilitate the evaluation of RACs capacities such as EPC, M1/M2, and Treg cells in DMP with AMI for cell therapy.
Abstract 12785: The American College of Cardiology's NCDR Afib Ablation Registry: A Summary of Initial Data Including Patient Characteristics, Procedural Characteristics, and Adverse Events
Authors: Jonathan C Hsu, Joseph Akar, Joseph E Marine, Sheila Nichols, Gregory M Marcus, Andrea Natale, Peter A Noseworthy, kimberly selzman, Paul D Varosy, Frederick A Masoudi, Chengan Du, James V Freeman, Jeptha P Curtis, Peter R Kowey
Journal: Circulation (2020)

Introduction: The American College of Cardiology developed the National Cardiovascular Data Registry (NCDR) AFib Ablation Registry to assess prevalence, demographics, procedural management and outcomes of patients undergoing atrial fibrillation (AFib) ablation procedures. The objective of this registry’s first presentation is to summarize initial AFib Ablation Registry data regarding patient characteristics, procedural characteristics, and in-hospital adverse events and outcomes in those undergoing AFib ablation enrolled in the registry. Methods: Data were tabulated and summarized with simple proportions for categorical data, and mean ± standard deviation for continuous data. Results: A total of 31,345 patients who underwent AFib ablation were included in the registry (mean age 65.0 ± 10.4, 65.2% male, 57.6% paroxysmal AFib), with ablations performed at 120 hospitals, by 501 physicians. The mean CHA2DS2-VASc score of was 2.6 ± 1.6, and mean HAS-BLED score was 1.1 ± 0.9. Successful pulmonary vein isolation was able to be achieved in all veins in 94.5% of patients. The prevalence of any complication during procedural admission was 3.1%; the most common were hematoma (0.5%) and pericardial effusion requiring intervention (0.42%). The mean length of stay during the index admission (days) was 1.4 ± 7.6, and in-hospital death prevalence was 0.04% [FIGURE] . Conclusions: In conclusion, the NCDR AFib Ablation Registry is a large, national, multi-center, prospective cohort study to describe events outside the clinical trial or research setting, demonstrating successful pulmonary vein isolation in the majority of patients and a low prevalence of adverse events. Future studies from the registry will be able to help support and develop evidence-based guidelines for AFib ablation treatment and optimize patient outcomes.
Abstract 16322: Safety and Efficacy of Transapical Transcatheter Aortic Valve Replacement in the Treatment of Pure Non-calcified Native Aortic Regurgitation
Authors: Can Shen, Ying Peng, Lulu Liu, Jun Shi, Yingqiang Guo, Li Rao
Journal: Circulation (2020)

Background: Transcatheter aortic valve replacement (TAVR) in patients with pure aortic regurgitation (AR) is still “off-label” use due to the lack of suitable transcatheter heart valve. This study aimed to evaluate the safety and efficacy of TAVR with J-Valve TM (JieCheng Medical Technology Co., Ltd., Suzhou, China) transcatheter heart valve for the treatment of patients with pure non-calcified native AR. Methods: The clinical and follow-up data of patients with pure non-calcified native AR treated by TAVR with J-Valve TM between April 2014 and November 2019 in the West China Hospital were summarized. Procedural results and clinical outcomes were analyzed using Valve Academic Research Consortium-2 criteria. Results: A total of 123 patients were enrolled with a mean age of 72.1±6.4 years. There were 28 cases with bicuspid aortic valve and 95 cases with trilobal aortic valve. The median follow-up period was 18 months. Transapical implantation with J-Valve TM was successful in all patients (100%). By the end of the follow up, the rate of all-cause mortality was 5.7%, among which 5 cases died during the perioperative period. Other results include stroke (1.6%), new permanent pacemaker implantation (8.9%), major bleeding (6.5%), acute kidney injury (2.4%) and aortic valve-related re-intervention (3.3%, they were given surgical aortic valve replacement for thrombosis of artificial valve (2 cases) or severe post-procedural paravalvular leakage (2 cases)). Among the 112 survival cases without re-intervention, Echocardiography revealed that none of them had moderate or severe paravalvular leakage; mild and mild-moderate paravalvular leakage occurred in 9.8% and 8.0% cases, respectively. Mean transvalvular gradient after valve implantation was 9.2±3.5 mmHg. At 6 months of follow up, left ventricular end diastolic diameter was remarkably smaller compared to that before procedure (53.5±8.2 mm vs 64.3±8.9 mm, P&lt;0.001) and left ventricular ejection fraction was significantly increased (56.3±11.8 % vs 54.2±12.4 %, P=0.031). Conclusions: TAVR with J-Valve TM transcatheter heart valve system for treatment of patients with pure non-calcified native AR is safe and effective which may be a reasonable option in the future treatment.
Abstract 16097: Impact of Device Miniaturization on Implantable Loop Recorder Utilization in the Pediatric Population: An Analysis of the Marketscan Database
Authors: Dustin Nash, Hannah Katcoff, Jennifer Faerber, Ramesh Iyer, Michael L O’Byrne, Maully Shah, Christopher Janson
Journal: Circulation (2020)

Introduction: Implantable loop recorders (ILRs) are an effective technology in the detection of paroxysmal arrhythmias, but utility in the pediatric population has been limited by device size. In 2014, a miniaturized ILR was introduced with a less invasive implant technique. The impact of this technology on ILR utilization in pediatric patients has not been evaluated. Hypothesis: We hypothesize an increase in annual pediatric ILR implants since 2014 due to device miniaturization. Methods: A retrospective observational study was conducted using administrative claims from Marketscan Medicaid and Commercial insurance claims databases. Utilization of ILR between 1/2013 and 12/2018 was measured (normalized to the total enrolled population ≤18 years) and compared to two balancing measures (Holter ambulatory monitors and encounters with syncope as a diagnosis). Secondary analyses included evaluations of subsequent interventions and complications. Results: The study cohort included 33,532,185 individual subjects, of which 769 underwent ILR implantation. ILR subjects were 52% male, with a median age of 16 years (IQR 10-17 yrs). 71% had a history of syncope, 43% had a history of palpitations, and 28% had a history of congenital heart disease. Utilization of ILR increased in 2014, from 5 procedures per million enrollees in 2013 to 11 per million between 2015-2018, while balancing measures remained static (see Figure).Of 393 subjects with ≥1 year of follow-up post-implant, interventions included catheter ablation in 24 (6%), pacemaker implant in 15 (4%) and ICD implant in 7 (1.8%). Among this group, 14 (3.6%) had a device infection and 5 (1.3%) had an erosion. Conclusions: Following introduction of the miniaturized ILR, pediatric utilization has rapidly increased. The effect of this change on outcomes and value deserves further attention.
Production of the Cytokine VEGF-A by CD4+ T and Myeloid Cells Disrupts the Corneal Nerve Landscape and Promotes Herpes Stromal Keratitis
Authors: Hongmin Yun, Michael B. Yee, Kira L. Lathrop, Paul R. Kinchington, Robert L. Hendricks, Anthony J. St. Leger
Journal: Immunity (2020)
Abstract 14534: In vitro Assessment of Transvalvular Peak Velocity Measurement for Various Orifice Shapes: Comparison Between 4D Flow MRI vs. Doppler Echocardiography
Authors: Jeesoo Lee, Nadia El hangouche, Liliana Ma, Michael Scott, Michael Markl, James D Thomas
Journal: Circulation (2020)

Introduction: 4D flow MRI can assess transvalvular velocity, but validation against continuous wave (CW) Doppler echo is limited in high-velocity regurgitation and stenosis situations. We sought to compare 4D flow MRI and echo peak velocity using a pulsatile echo-MRI flow phantom. Materials and Methods: An MRI-compatible flow phantom with restrictive orifice situated was driven by a left ventricular assist device at 50 bpm (figure 1A). Three orifice shapes were tested: circular, elliptical and 3D-printed patient-specific mitral regurgitant orifice model of prolapse with areas of 0.5, 0.41 and 0.35 cm 2 , respectively. CW Doppler was acquired with peak velocity extracted from the profile. Retrospectively-gated 4D flow MRI was performed (spatial resolution = 2 mm isotropic, temporal resolution = 36 ms, encoding velocity = 400 cm/s). Maximal velocity magnitude was extracted volumetrically (figure 1B). An echo-mimicking profile was also obtained with a “virtual” ultrasound beam in the 4D flow data to simulate CW Doppler (figure 1C). Bland-Altman analysis was used to assess the agreement of temporal peak velocities. Results: 4D flow MRI demonstrated a centrally directed jet for the circular and elliptical orifices and an oblique jet for the prolapse orifice (figure 1B). Peak velocities were in excellent agreement between 4D flow MRI vs. echo for the circular (peak: 5.13 vs. 5.08 m/s, bias = 0.06 ± 0.66 m/s, figure 1D) and the elliptical orifice (peak: 4.95 vs. 4.79 m/s, bias = 0.07 ± 0.87 m/s, figure 1E). The prolapse orifice velocity was underestimated somewhat by MRI by ~10% (peak: 4.41 vs. 4.90 m/s, bias=0.26±1.18, figure 1F). Conclusion: 4D flow MRI can quantify high velocities like echo for simple geometries while underestimating for more complex geometry, likely due to partial volume effects. Further investigation is warranted to systematically investigate the effects of 4D flow MRI spatial and temporal resolution as well as the jet angle on velocity quantification accuracy.
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Authors: Sean X. Gu, Tarun Tyagi, Kanika Jain, Vivian W. Gu, Seung Hee Lee, Jonathan M. Hwa, Jennifer M. Kwan, Diane S. Krause, Alfred I. Lee, Stephanie Halene, Kathleen A. Martin, Hyung J. Chun, John Hwa
Journal: Nature Reviews Cardiology (2020)
Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction
Authors: Carlos G. Santos-Gallego, Ariana P. Vargas-Delgado, Juan Antonio Requena-Ibanez, Alvaro Garcia-Ropero, Donna Mancini, Sean Pinney, Frank Macaluso, Samantha Sartori, Merce Roque, Fernando Sabatel-Perez, Anderly Rodriguez-Cordero, M. Urooj Zafar, Icilma Fergus, Farah Atallah-Lajam, Johanna P. Contreras, Cathleen Varley, Pedro R. Moreno, Vivian M. Abascal, Anuradha Lala, Ronald Tamler, Javier Sanz, Valentin Fuster, Juan J. Badimon
Journal: Journal of the American College of Cardiology (2020)
Abstract 15010: Myocardial Injury in Sepsis With Acute Respiratory Distress Syndrome
Authors: Eunice S Dugan, Robert S Stephens, Steven P Schulman, Thomas S Metkus
Journal: Circulation (2020)

Introduction: Sepsis is common and associated with high morbidity and mortality; novel prognostic biomarkers are needed. The association of myocardial injury with mortality in sepsis has not been fully characterized. Hypothesis: We hypothesized that elevated plasma high-sensitivity troponin I (hs-TnI) would be associated with 60-day mortality in patients with sepsis and acute respiratory distress syndrome (ARDS). Methods: We conducted a retrospective multicenter cohort study of subjects from the MI-ARDS study with ARDS and sepsis. The exposure variable was plasma hs-TnI on intubation (Day 0) and Day 3. Hs-TnI was measured using Abbott Laboratories’ ARCHITECT STAT assay. Patients were divided into four hs-TnI (ng/L) groups (Grp): GrpA: &lt;2 (undetectable), GrpB: ≥2-&lt;26 (&lt;99 th percentile of population), GrpC: ≥26-&lt;130 (&lt;5 times upper limit of normal [ULN]), GrpD: ≥130 (&gt;5 times ULN). The primary outcome was 60-day mortality. We determined the association between hs-TnI and mortality using Cox proportional hazards models. Results: Of 320 subjects, there were 15 (4%) in GrpA, 97 (30%) in GrpB, 88 (28%) in GrpC, and 120 (38%) in GrpD. Mean age was 50 years and 172 subjects (54%) required vasopressors. Higher plasma levels of hs-TnI were associated with higher SOFA score and creatinine, and more vasopressor use. Overall mortality was 33%. There was no significant difference in 60-day survival between clinical categories of Day 0 hs-TnI (Fig 1-A). Rising troponin between Day 0 and Day 3 was associated with a higher risk of mortality after adjusting for age, sex, trial assignment, and SOFA score (HR: 1.75, CI: 1.11-2.77, p=0.02) (Fig 1-B), and additionally adjusting for Day 0 hs-TnI (HR: 1.72, CI: 1.03-2.85, p=0.04). Conclusions: Initial hs-TnI in patients with sepsis and ARDS was not associated with mortality. Increase in hs-TnI of at least 20% by Day 3 was associated with 60-day mortality. Future studies should assess mechanism and treatment of myocardial injury in sepsis.
Abstract 16184: Lamin A Deficiency Leads to Electrophysiological and Nuclear Abnormalities Reminiscent of Atrial Cardiomyopathy in Zebrafish
Authors: Ryota Teramoto, Kenshi Hayashi, Manu Beerens, David Chiang, Tuomas O Kiviniemi, Masahiro Satoh, Ashmita KC, Micah Burch, Wandi Zhu, Wei Dai, Jing Liu, Aparna Mahadevan, Eva Buys, Calum MacRae
Journal: Circulation (2020)

Introduction: Mutations in the lamin A/C ( LMNA ) gene have been causally linked to atrial arrhythmias and cardiac conduction disease (CCD) in young adults. However, the mechanism by which the laminopathy leads to perturbed cardiac electrophysiology has not been fully elucidated. Hypothesis: We hypothesize that protein-truncating variants in LMNA will impair the mechano-protection force in the nuclear envelope and will lead to early-onset cardiomyocyte degeneration and CCD. Methods: In a multi-regional registry of early-onset CCD and atrial fibrillation in Japan, we performed whole-exome DNA sequencing of 23 probands. Using CRISPR/Cas9, we generated indels of candidate gene homologues in zebrafish and characterized cardiac physiology using optical mapping technology and immunohistochemistry. Results: Among all probands, our study revealed four rare nonsense variants in the nuclear protein-coding genes. We focused on a LMNA protein-truncating variant, c.339dupT (p.K114X fsX1), and created a variant in the zebrafish lmna that produced a similar truncation. Lmna -/- zebrafish larvae showed shortened atrial action potential duration (APD) (msec.) compared to wild-type controls (162 ± 19 vs 227 ± 79, p&lt;0.05), while conduction velocities (CV) did not vary between the genotypes. In contrast, the atrioventricular canal of lmna -/- embryos exhibited prolonged APD (399 ± 51 vs 322 ± 47, p&lt;0.05) and slower CV (mm/sec.) (0.37 ± 0.12 vs 0.57 ± 0.12, p&lt;0.05) than controls. Immunohistochemistry demonstrated that atrial cardiomyocytes of embryonic lmna -/- zebrafish displayed significantly decreased cell numbers and smaller cell size compared to those of controls, which in turn developed into abnormal nuclear structures in adult. Conclusions: These findings suggest that lamin A is a prerequisite for proper atrial cardiomyocyte morphology in embryonic zebrafish, and is indispensable for correct cardiac electrophysiology and -conduction.
Abstract 14579: Impact of Hospital MitraClip Volume on Short-term Outcomes of Transcatheter Mitral Valve Replacement
Authors: Toshiaki Isogai, Anas M Saad, Shashank Shekhar, Omar M Abdelfattah, Keerat Rai Ahuja, Mohamed M Gad, Samir R Kapadia
Journal: Circulation (2020)

Introduction: Transcatheter mitral valve replacement (TMVR) is an alternative to surgical mitral valve replacement for patients at prohibitive or high surgical risk. Both transseptal TMVR and MitraClip procedures require transseptal puncture and subsequent manipulation of a catheter within the left atrium and ventricle. Hypothesis: Higher MitraClip experience leads to better procedural outcomes of transseptal TMVR. Methods: We retrospectively identified patients who underwent transseptal-TMVR using the Nationwide Readmissions Database 2016-2017. We defined hospital volume as the annual number of MitraClip cases in each hospital and categorized hospitals into high- (≥26 cases/year) and low- (&lt;26 cases/year) volume groups by the median value. We compared the in-hospital and 30-day outcomes between the two groups. Results: A total of 1,023 TMVR patients (median 74 years; female 56.1%) were divided into the high- (n=487) and low- (n=536) volume groups. The high-volume group had a higher prevalence of prior valve implantation (30.8% vs. 24.8%; p=0.036), prior coronary artery bypass grafting (28.7% vs. 22.7%; p=0.031), and heart failure (86.7% vs. 79.5%; p=0.003) than the low-volume group. There was no significant difference in the rates of in-hospital death (9.0% vs. 9.5%; p=0.830), stroke (2.1% vs. 3.2%; p=0.330), and pacemaker implantation (2.5% vs. 4.5%; p=0.091), while surgical bailout was less frequent in the high-volume group (2.5% vs. 6.5%; p=0.002). Multivariable logistic regression analyses showed that high volume was significantly associated with a lower risk of surgical bailout, prolonged hospital stay, cardiovascular-cause readmission, but not with other outcomes including in-hospital death (Figure). Conclusions: Centers with greater MitraClip experience had a lower risk of surgical bailout, prolonged hospital stay, and early readmission after transseptal-TMVR, although mortality was high irrespective of MitraClip experience.