tbuckley/cabot-search huggingface dataset:
Abstract 15251: Heart Failure With Preserved Ejection Fraction in Hypertrophic Cardiomyopathy With and Without Septal Myectomy
Authors: Katherine McGee, Stanley Chu, Lubna Choudhury
Journal: Circulation (2020)

Introduction: Hypertrophic cardiomyopathy (HCM) can lead to heart failure with preserved ejection fraction (HFpEF) due to left ventricular outflow tract obstruction (LVOTO). Septal myectomy can relieve LVOTO leading to resolution of HFpEF. However, some patients have persistent HFpEF even after myectomy without LVOTO. We aimed to characterize HCM patients with HFpEF post myectomy compared to those without HFpEF post myectomy and those with HFpEF and non-obstructive HCM. Hypothesis: There are distinct features of HCM patients with HFpEF after myectomy, no HFpEF after myectomy, and non-obstructive HCM with HFpEF. Methods: In this retrospective study, patients over age 18 were screened for HCM diagnosis between years 2003 and 2020, HCM was confirmed with echocardiogram and chart review. HFpEF was defined as use of loop diuretic for decongestion, with a left ventricular ejection fraction 50% or greater. Patients with septal myectomy were identified. Analysis of variance and chi-squared tests were performed. Results: Of 2571 patients with HCM diagnosis, there were 194 patients with HCM and HFpEF, 27 patients had HFpEF after myectomy (30%) compared to 61 patients without HFpEF after myectomy. 106 patients had nonobstructive HCM with HFpEF. A significant number of patients identifying as black or African American were in the nonobstructive HFpEF group. Hypertension was more prevalent in those with HFpEF after myectomy and non-obstructive HCM with HFpEF. Stroke was increased in the non-obstructive HCM with HFpEF (Table). Conclusions: 30% of HCM patients develop HFpEF post myectomy, with a higher incidence of hypertension compared to those without HFpEF. Non-obstructive HCM patients, more frequently black and African American, had higher rates of hypertension and diabetes, and higher risk of ischemic stroke and mortality. These phenotypes of HCM represent an important area of investigation to assess risk for stroke and development of HFpEF after myectomy.
Transcriptomics Identify Thrombospondin‐2 as a Biomarker for NASH and Advanced Liver Fibrosis
Authors: Kazuhiro Kozumi, Takahiro Kodama, Hiroki Murai, Sadatsugu Sakane, Olivier Govaere, Simon Cockell, Daisuke Motooka, Naruyasu Kakita, Yukinori Yamada, Yasuteru Kondo, Yuki Tahata, Ryoko Yamada, Hayato Hikita, Ryotaro Sakamori, Yoshihiro Kamada, Ann K. Daly, Quentin M. Anstee, Tomohide Tatsumi, Eiichi Morii, Tetsuo Takehara
Journal: Hepatology (2021)

NAFLD is the most common liver disease worldwide. NASH, the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers.Global RNA sequencing of liver tissue from 98 patients with biopsy-proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and patients with NASH exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins up-regulated in NASH and/or advanced fibrosis (stage F3-F4), including matricellular glycoprotein thrombospondin-2 (TSP-2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase-mediated cleavage of cytoskeletal proteins, and immune cell infiltration. Serum TSP-2 expression was measured in 213 patients with biopsy-proven NAFLD, was significantly higher in NASH than in NAFL, and increased parallel to fibrosis stage. The AUROCs for predicting NASH and advanced fibrosis were 0.776 and 0.856, respectively, which were comparable to Fibrosis-4 index, serum HA level, and NFS in advanced fibrosis diagnosis. Serum TSP-2 level and platelet count were independent predictors of NASH and advanced fibrosis. Serum TSP-2 levels could stratify patients with NAFLD according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.TSP-2 may be a useful biomarker for NASH and advanced fibrosis diagnosis in patients with NAFLD.
Guiding the Patterned Growth of Neuronal Axons and Dendrites Using Anisotropic Micropillar Scaffolds
Authors: Shengying Fan, Lei Qi, Jiawen Li, Deng Pan, Yiyuan Zhang, Rui Li, Cong Zhang, Dong Wu, Pakming Lau, Yanlei Hu, Guoqiang Bi, Weiping Ding, Jiaru Chu
Journal: Advanced Healthcare Materials (2021)

Abstract The patterning of axonal and dendritic growth is an important topic in neural tissue engineering and critical for generating directed neuronal networks in vitro. Evidence shows that artificial micro/nanotopography can better mimic the environment for neuronal growth in vivo. However, the potential mechanisms by which neurons interact with true three dimensional (3D) topographical cues and form directional networks are unclear. Herein, 3D micropillar scaffolds are designed to guide the growth of neural stem cells and hippocampal neurons in vitro. Discontinuous and anisotropic micropillars are fabricated by femtosecond direct laser writing to form patterned scaffolds with various spacings and heights, which are found to affect the branching and orientation of axons and dendrites. Interestingly, axons and dendrites tend to grow on an array of 3D micropillar scaffolds of the same height and form functionally connected neuronal networks, as reflected by synchronous neuronal activity visualized by calcium imaging. This method may represent a promising tool for studying neuron behavior and directed neuronal networks in a 3D environment.
Obesity Paradox and the Definition of Obesity in the Patients Admitted with Acute Heart Failure in Japan
Authors: Yamane Takafumi, Yokoyama Hiroyuki, Kanzaki Hideaki, Hashimura Kazuhiko, Sekiguchi Kenichi, Kitakaze Masafumi, Gotoh Yoichi, Nonogi Hiroshi, Tomoike Hitonobu
Journal: Circulation (2011)
Abstract 15361: Comparison of Cardiovascular Outcomes of Supravalvar Aortic Stenosis Patients With Williams Syndrome and Non-williams Supravalvular Aortic Stenosis
Authors: Doaa Shahbah, Justin Weigand, Benjamin Jacob, Icadal Essandro, Taylor Beecroft, Sara Stephen, Ashley Keyes, Gabrielle Spurzem, Melissa Webb, Shaine A Morris
Journal: Circulation (2020)

Introduction: Cardiovascular outcomes in Williams syndrome (WS) with supravalvar aortic stenosis (SVAS) compared to those with non-Williams SVAS (NW-SVAS) have not been well-described in literature. Hypothesis: Cardiovascular outcomes are similar in SVAS patients in WS and those with NW-SVAS as both are typically mediated by elastin ( ELN ) deficiency. Methods: We included all patients (pts) at our institution with 1) WS and SVAS or 2) SVAS with negative testing for WS (2003-2020), excluding pts with Alagille or Turner syndrome, isolated bicuspid aortic valve, postoperative acquired SVAS, or insufficient records. We compared cardiovascular lesions and freedom from intervention using Kaplan-Meier analysis with comparison by log rank. Results: Of 163 included SVAS pts (67 WS, 96 NW-SVAS), 75 (46%) were females. Median age at last follow up was 11.9 years (IQR 5.7, 17). Of ELN testing performed in 13 NW-SVAS patients, 8 had pathogenic variants. The rest of the NW-SVAS cohort included 22 familial and 61 non-familial cases. Branch pulmonary artery stenosis (BPAS), renal artery stenosis (RAS), and hypertension were more prevalent in WS than in NW-SVAS (p=0.001, Table). There was no difference in freedom from BPAS intervention between the groups, but the WS group was significantly more likely to undergo intervention for RAS or be treated for hypertension (Figure). No difference was noted for SVAS, coarctation or coronary outcomes. Conclusion: For most cardiovascular lesions, there was no difference in interventions between WS and NW-SVAS. The increased intervention rate for RAS and hypertension in WS may reflect lower screening rates in NW-SVAS
Abstract 15170: In-hospital Utilization and Outcomes of Palliative Care Consultation in Patients With Advanced Heart Failure Complicated by Cardiogenic Shock Requiring Mechanical Circulatory Support
Authors: Jelani Grant, Louis Vincent, Bertrand Ebner, Jennifer Maning, Igor Vaz, neal olarte, Odunayo P Olorunfemi, Elisse Kavensky, Khin Zaw, Rosario A Colombo
Journal: Circulation (2020)

Introduction: Hospitalizations associated with advanced heart failure (HF) requiring mechanical circulatory support (MCS) are usually associated with a high morbidity, mortality and a protracted hospital course. Prior studies have shown that the early inclusion of palliative care specialist is associated with better end-of-life experiences. Methods: The National Inpatient Sample Database was queried from 2012 to 2017 for relevant International Classification of Diseases (ICD)-9 and ICD-10 procedural and diagnostic codes to identify patients above 18 years with advanced HF admitted with cardiogenic shock requiring MCS. Baseline characteristics and in-hospital outcomes were compared among patients evaluated by palliative care and those who were not. A p-value of &lt;0.001 was considered statistically significant. Results: There were 748,360 patients hospitalized for advanced HF complicated by cardiogenic shock requiring MCS, of these a palliative care consult was placed in 118,015 (15.8%) patients. Patients evaluated by palliative care were older (70.6±14.9 vs. 64.9±16.3 years old, p&lt;0.001) and had a higher prevalence of atrial fibrillation (39.3 vs. 35.1%,p&lt;0.001) and chronic kidney disease (40.4 vs. 33.3, p&lt;0.001), however had lower hypertension (57.4 vs. 59.7%, p&lt;0.001), diabetes (35.4 vs. 36.5%, p&lt;0.001), coronary artery disease (51.2 vs. 58.4%, p&lt;0.001) and acute coronary syndromes (39.2 vs. 45.0%, p&lt;0.001). Consulting palliative care was associated with a shorter length of stay (8.8±12.0 vs. 11.9±15.5 days, p&lt;0.001), lower total hospital cost ($161,972±265,156 vs. $219,114±318,387, p&lt;0.001) and higher Do Not Resuscitate (DNR) orders (30.8 vs. 5.8%, p&lt;0.001). Mortality rates were higher in the palliative care cohort (73.4 vs. 29.4%, p&lt;0.001). Conclusions: Despite the high morbidity and mortality associated with advanced HF patients with cardiogenic shock requiring MCS, the overall prevalence of palliative care consultation is exceedingly low. DNR orders were more prevalent in patients seen by the palliative care service. This study highlights the underutilization of palliative care services in this patient population, precluding any perceived benefit in end of life experiences.
Abstract P027: Individualized Protein Based Cardiovascular Risk Stratification: Impact On Patient And Physician Decision Making In Patients With Real World Cardiovascular Disease
Authors: Austin Erben, Sandra Housholder, Rosalynn Gill, Stephen A Williams, Nelson P Trujillo
Journal: Circulation (2021)

There is a growing population of patients with established cardiovascular disease and residual cardiovascular risk. Identification of patients who would benefit most from more advanced risk reduction strategies would be ideal. Hypothesis: Identification of secondary risk of MACE may change both physician recommendations and patient choices regarding goal directed therapy (GDT). Methods: Retrospective review of 244 patients with established CAD with traditional assessment of secondary cardiovascular risk and SomaScan proteomic risk assessment followed over 3 years. Patients were evaluated for GDT and standard measurements were made at baseline. SomaScan protein risk score was obtained. Patients received advice regarding risk and offered GDT with established secondary prevention goals. Willingness to change, physician recommendations to change therapy and therapy changes were recorded. Patients were followed over three years. Results: 244 patients were included in the cohort; 186 males (76%), 58 females (24%). Mean age of 66, range 32-84. Diagnosis of coronary artery disease was made based on imaging in 121 patients (49%) and clinical events including CABG, MI, PCI in 123 patients (51%). Secondary cardiovascular risk of MACE by SomaScan was assessed in 5 predefined risk classes. There were 70 patients in class I (0-9.9%), 116 patients in Class II (10-19.9%), 41 patients in Class III (20-29.9%), 12 patients in Class IV (30-59%) and I patient in Class V (60-100%). GDT was already present in 143 patients including statin therapy, ACE inhibition and daily aspirin. In the cohort, 101 patients were sub-optimally treated. After reviewing results of SomaScan results, 20 patients initiated GDT, 52 patients intensified GDT. This included addition of second lipid lowering agent, initiation of PCSK-9 inhibitors, ACE-inhibition and intense lifestyle management. Overall, 30% of the overall cohort had a change in therapy: 39 patients were advised to alter therapy and did not, 17 patients would not begin goal directed therapy, 22 patients would not intensify management to meet accepted goals. Two deaths occurred during the study period. There were 14 episodes of MACE. Conclusions: In this population of patients with established cardiovascular disease only 58% were on guideline-based therapy. Use of SomaScan results in conjunction with standard assessment allowed an additional 30% of patients to change therapy with initiation of GDT and intensification of GDT to meet current guidelines.
Abstract 052: Hypertensive Diseases In Pregnancy And Hemodynamic Stress Later In Life
Authors: Adebamike A Oshunbade, Seth Lirette, Daisuke Kamimura, Arsalan Hamid, Lena Mathews, Ervin R Fox, Edmund K Kerut, Joey P Granger, Javed Butler, Kenneth R Butler, Thomas Mosley, Michael E Hall
Journal: Circulation (2021)

Background: Hypertensive diseases in pregnancy have been associated with cardiovascular diseases later in life. However, less is known about the relationship between hypertensive diseases in pregnancy and hemodynamic stress later in life. We evaluated the relationship between hypertensive diseases in pregnancy and plasma levels of biomarkers of hemodynamic stress later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Methods and Results: We investigated 1605 women from the GENOA study (mean age 61±10 years, 57.1% African American).Women were classified as self-reported as nulliparous women (n=140), a history of normotensive pregnancies (n=1,195), a history of a hypertensive pregnancy (n= 229), or a history of preeclampsia (n= 41). We compared adjusted associations among this groups with 4 biomarkers of hemodynamic stress using generalized estimating equations to account for familial clustering. After adjusting for age, race, level of education, smoking history, hypertension, body mass index (BMI), history of coronary artery disease, and diabetes, women with a history of preeclampsia had higher levels of C-terminal proendothelin (CT-proET) compared to women with a history of normotensive pregnancies (Table, p=0.01). There were no significant differences in the levels of midregional proatrial natriuretic peptide (MR-proANP), midregional proadrenomedullin (MR-proADM), and C-Terminal proarginine vasopressin (CT-proAVP) in this groups. Conclusions: Elevated levels of CT-proET (a precursor to the potent vasoconstrictor Endothelin 1) demonstrates a strong relationship among those with a history of preeclampsia. Future studies are warranted to further explore the relationship between CT-proET in the pathogenesis of preeclampsia as well as subsequent changes in cardiovascular structure and function associated with a history of preeclampsia later in life.
Abstract 15986: Plasma Microrna Profiling Reveals Potential Biomarkers of Thiazide Response
Authors: Lakshmi Manasa S Chekka, Taimour Y Langaee, Danxin Wang, Renne Rolf, Arlene B Chapman, John Gums, Stephen T Turner, Rhonda M Cooper-dehoff, Julie A Johnson
Journal: Circulation (2020)

Introduction: Thiazide diuretics (TZDs) are the second most frequently prescribed class of antihypertensives. But &lt;50% patients achieve goal blood pressure (BP) on TZD monotherapy, mostly because therapy is chosen overlooking the heterogeneity in patient responses. Circulating microRNAs (miRNAs) remain attractive as non-invasive biomarkers to predict drug response and tailor therapy for optimal outcomes. Hypothesis: Plasma miRNAs may play a role in TZD response; we aim to identify those associated with hydrochlorothiazide (HCTZ) response. Methods: We profiled 754 miRNAs in baseline (untreated) plasma samples of 36 uncomplicated hypertensive adults (18 Responders (R) and 18 Non-responders (NR) based on their diastolic BP (DBP) response to HCTZ therapy) from the Pharmacogenomic Evaluation of Antihypertensive Responses clinical trial, using the real-time qPCR based TaqMan OpenArray Human microRNA panel. We filtered out miRNAs with low amplification scores and Cq&gt;38 and samples with low miRNA expression. Combination of miR-223 and miR-19b (identified as most stably expressed miRNAs by NormFinder Software) was used to normalize expression across samples. We used MannWhitney U test to identify microRNAs differentially expressed between R and NR; linear and logistic regressions for associations of miRNA expression with BP response. FDA corrected p&lt;0.05 was used as significance threshold, unadjusted p&lt;0.05 as suggestive threshold. Results: Mean systolic BP (SBP)/DBP change in R was 14/10 mmHg and in NR 0/1 mmHg. We found 77 miRNAs to be consistently expressed across samples, of which 11 were upregulated and 14 downregulated with &gt;2-fold difference between R and NR. Though no miRNAs reached FDR p&lt;0.05, miR-376a (fold change(fc)= 10.1, p= 0.035) and miR-17 (fc= -0.45, p= 0.017) were differentially expressed between R and NR and their expression associated with DBP and SBP change, along with miR-10b, miR-24, miR-134 associated with SBP change at p&lt;0.05. Conclusions: In this first ever genome-wide miRNA study of antihypertensive drug response, we discovered circulating miRNAs associated with BP response to HCTZ. Future studies are planned to validate these findings in a larger cohort, across different race group and across different TZD.
Cell and Tissue Therapy for the Treatment of Chronic Liver Disease
Authors: Yaron Bram, Duc-Huy T. Nguyen, Vikas Gupta, Jiwoon Park, Chanel Richardson, Vasuretha Chandar, Robert E. Schwartz
Journal: Annual Review of Biomedical Engineering (2021)

Liver disease is an important clinical problem, impacting 600 million people worldwide. It is the 11th-leading cause of death in the world. Despite constant improvement in treatment and diagnostics, the aging population and accumulated risk factors led to increased morbidity due to nonalcoholic fatty liver disease and steatohepatitis. Liver transplantation, first established in the 1960s, is the second-most-common solid organ transplantation and is the gold standard for the treatment of liver failure. However, less than 10% of the global need for liver transplantation is met at the current rates of transplantation due to the paucity of available organs. Cell- and tissue-based therapies present an alternative to organ transplantation. This review surveys the approaches and tools that have been developed, discusses the distinctive challenges that exist for cell- and tissue-based therapies, and examines the future directions of regenerative therapies for the treatment of liver disease.
The Value of Magnetic Resonance Imaging for Assessing Disease Extent and Prediction of Relapse in Early Peripheral Spondyloarthritis
Authors: Thomas Renson, Philippe Carron, Ann‐Sophie De Craemer, Liselotte Deroo, Manouk de Hooge, Simon Krabbe, Lennart Jans, Mikkel Østergaard, Dirk Elewaut, Filip Van den Bosch
Journal: Arthritis & Rheumatology (2021)

This study was undertaken to assess the inflammatory burden in peripheral spondyloarthritis (SpA) by magnetic resonance imaging (MRI) of the legs in an early remission-induction strategy study of tumor necrosis factor (TNF) blockade. Furthermore, we sought to determine the value of MRI to predict disease relapse versus sustained remission after treatment discontinuation.Thirty-two patients with early peripheral SpA with involvement of the legs determined on clinical examination and confirmed by ultrasonography (US) participated in a remission-induction trial of a TNF inhibitor (TNFi). Patients underwent MRI of the joints and entheses of the legs at baseline and at clinical remission, after which TNFi treatment was withdrawn. Images were evaluated for joint effusion, joint osteitis, entheseal soft tissue inflammation, and entheseal osteitis.Joint effusion and enthesitis on clinical examination and US correlated well with MRI abnormalities. In addition, a substantial amount of subclinical involvement was seen on MRI, mainly in the ankle joints and heel entheses. Inflammation scores were markedly lower in the subclinically involved joints and entheses versus those that were clinically involved (P values ranged from 0.01 to <0.001). Inflammatory load on MRI decreased significantly upon TNFi treatment (P < 0.001). Whereas 80% of the joints that were clinically involved at baseline showed no effusion on remission MRI, 2 of 3 entheses involved at baseline showed residual inflammation. In addition, patients who experienced a relapse after treatment discontinuation displayed more entheseal soft tissue inflammation on remission MRI compared to those who maintained drug-free remission (P = 0.028).Our findings delineate a differential response of synovitis and enthesitis, with enthesitis on MRI being less responsive to TNFi treatment. Furthermore, residual entheseal inflammation might be indicative of the need for continuous therapy.
Outcomes of EAU-endorsed Live Surgical Events over a 5-year Period (2015–2020) and Updated Guidelines from the EAU Live Surgery Committee
Authors: Bhaskar Somani, Evangelos Liatsikos, Alexandre Mottrie, Ali S. Gözen, Alberto Breda, Thomas Knoll, Giampaolo Bianchi, Kemal Sarica, Jens Bedke, Jens Rassweiler
Journal: European Urology (2021)