tbuckley/cabot-search huggingface dataset:
Abstract 14391: Transient Cell Cycle Induction in Cardiomyocytes is a Promising Approach to Treat Ischemia Induced Heart Failure
Authors: Riham Abouleisa, Qinghui Ou, Xian-liang Tang, Mitesh Solanki, Yiru Guo, Lindsey McNally, Pawel Lorkiewicz, Krishna Choudhary, Reuben Thomas, Hamzah Ruxshan Juhardeen, Aisha Siddique, Zainab Ifthikar, Abou Bakr Salama, Yu Huang, Kathryn N Ivey, Bradford Hill, Deepak Srivastava, Roberto Bolli, Tamer Mohamed
Journal: Circulation (2020)

Rationale: The regenerative capacity of the heart to repair itself after myocardial infarction (MI)is limited. Our previous study showed that ectopic introduction of Cdk1/CyclinB1 andCdk4/CyclinD1 complexes (4F) promotes cardiomyocyte proliferation in vitro and in vivo andimproves cardiac function after MI. However, its clinical application is limited due to the concernsfor tumorigenic potential in other organs. Objectives: To first, identify on a single cell transcriptomic basis the necessary reprogrammingsteps that cardiomyocytes need to undertake to progress through the proliferation processfollowing 4F overexpression, and then, to determine the pre-clinical efficacy of transient andcardiomyocyte specific expression of 4F in improving cardiac function after MI in small and largeanimals. Methods and Results: Temporal bulk and single cell RNAseq of mature hiPS-CMs treated with4F or LacZ control for 24, 48, or 72 h revealed full cell cycle reprogramming in 15% of thecardiomyocyte population which was associated with sarcomere disassembly and metabolicreprogramming. Transient overexpression of 4F specifically in cardiomyocytes was achievedusing non-integrating lentivirus (NIL) driven by TNNT2 (TNNT2-4F-NIL). One week after inductionof ischemia-reperfusion injury in rats or pigs, TNNT2-4F-NIL or control virus was injectedintramyocardially. Compared with controls, rats or pigs treated with TNNT2-4F-NIL showed a 20-30% significant improvement in ejection fraction and scar size four weeks after treatment, asassessed by echocardiography and histological analysis. Quantification of cardiomyocyteproliferation in pigs using a novel cytokinesis reporter showed that ~10% of the cardiomyocyteswithin the injection site were labelled as daughter cells following injection with TNNT2-4F-NILcompared with ~0.5% background labelling in control groups. Conclusions: We provide the first understanding of the process of forced cardiomyocyteproliferation and advanced the clinical applicability of this approach through minimization ofoncogenic potential of the cell cycle factors using a novel transient and cardiomyocyte-specificviral construct.
Abstract 15868: Title: Accuracy of Fetal Echocardiography in the Antenatal Diagnosis of Three Common Conotruncal Defects
Authors: Rose He, Jayani Abeysekera, Kim Haberer, Aisling Young, Luke Eckersley, Angela McBrien, Isabella C Adatia, Rishav Sharma, Michelle Rushfeldt, Lisa K Hornberger
Journal: Circulation (2020)

Introduction: The prenatal diagnosis of conotruncal defects (CTDs) has improved over the past decade, particularly with inclusion of outflow tract imaging at routine ultrasound. Appropriate prenatal counseling for CTDs demands an accurate diagnosis, as even more subtle cardiac pathology could complicate clinical outcomes. We sought to determine the anatomical accuracy of fetal echocardiography in evaluating common CTDs and factors that contribute to accuracy. Methods: All cases of tetralogy of Fallot(TOF), double outlet right ventricle(DORV) and truncus arteriosus(TA) encountered in our institution from 2007-2018 were reviewed. Discrepancies in anatomical findings between prenatal (most accurate exam) and postnatal (echo/surgery) or autopsy exams were categorized as: C1) no difference C2) minor difference with no impact on outcome (e.g.aberrant right subclavian artery), C3) minor difference that could make a minor difference to the delivery plan or surgery (e.g.branch pulmonary artery stenosis), C4) major difference that changes the course of the pregnancy, delivery or surgical planning (e.g.ductal dependency). Results: Of the 255 CTD cases, 162 had prenatal and postnatal and/or autopsy data available. Of the 162, 107(65.6%) fit C1, 35(21.5%) C2, 12(7.4%) C3, and 8(5.5%) C4. The greatest accuracy was observed in TOF, with 69/71(97.2%) in C1 and C2 versus 56/69(81.2%) in DORV and 16/22(72.7%) in TA(p=0.003). Excluding 5 cases at 10-16weeks, there was a tendency towards a greater proportion in C1 and C2 when examined at 17-23 weeks (60/64, 93.4%) versus 24-32 weeks (50/57, 87.7%) and &gt;32 weeks (28/36, 77.8%) (p=0.06). Era of assessment also revealed a difference with 43/55(78.2%) of studies performed from 2007-2011 in C1 and C2 versus 99/107(92.5%) from 2012-2018 (p=0.01).When we compared pregnancies with one versus serial exams, we observed a lower proportion of C4 cases from 9.6% to 2.7%, respectively. In those with serial exams, 20% had achieved C1 or C2 only at serial exam. Conclusions: The diagnostic accuracy of fetal echocardiography in CTDs is generally high, especially for TOF and when performed at 17-24weeks. There has been significant improvement in accuracy since 2011. Serial exams potentially improve diagnostic accuracy.
Abstract 13214: Underuse of Combination Pharmacotherapy for Management of Dyslipidemia versus Diabetes and Hypertension Among Patients With Atherosclerotic Cardiovascular Disease (ascvd): Insights From the Getting to an Improved Understanding of Low-density Lipoprotein-cholesterol and Dyslipidemia Management (gould) Registry
Authors: Ali M Agha, Mikhail N Kosiborod, James A De Lemos, Robert S Rosenson, Qi Gao, Katie Mues, Shushama Alam, Deepak L Bhatt, Christopher P Cannon, Christie M Ballantyne
Journal: Circulation (2020)

Introduction: Cardiovascular disease prevention entails treatment of multiple risk factors, including diabetes (DM), hypertension (HTN), and hyperlipidemia (HLD), based on guidelines that promote the use of combination therapy when monotherapy does not achieve treatment goals. The purpose of this study is to determine how frequently combination pharmacotherapy is employed to manage these disorders among patients with atherosclerotic cardiovascular disease (ASCVD), based on the GOULD registry. Methods: The multicenter, observational GOULD registry describes low-density lipoprotein cholesterol (LDL-C) treatment patterns over time in adults with clinical ASCVD in the United States. Patients were enrolled into 3 cohorts: 1) Currently on PCSK9 inhibitor (PCSK9i), or not on PCSK9i with 2) LDL-C 70-99 mg/dL, or 3) LDL-C ≥100 mg/dL. We determined the prevalence of DM and HTN within this registry, the classes of medications used to treat these disorders, and how frequently patients were on two or more medications to treat these disorders at baseline, 6, 12, 18, and 24 months, respectively. Results: Among 5,006 patients in this cohort on lipid-lowering therapy (LLT), 35.2% had DM and 86.0% had HTN at baseline. Of those receiving treatment, 47.6% and 71% were receiving two or more medications for management of DM and HTN, respectively. In contrast, only 19.5% of patients were receiving two or more LLT medications (51.9% among PCSK9i subjects, 15.4% among LDL-C subjects) (Figure). There was a modest increase in combination lipid therapy from 19.5% at baseline to 25.6% at 24 months. Conclusions: Despite recent guidelines supporting the use of combination therapy in patients with high risk ASCVD with an LDL-C above threshold after statin therapy, this high-risk group continues to be managed mostly with statin monotherapy in contrast to the widespread use of combination therapy for the treatment of DM and HTN.
Association of Display of Patient Photographs in the Electronic Health Record With Wrong-Patient Order Entry Errors
Authors: Hojjat Salmasian, Bonnie B. Blanchfield, Kelley Joyce, Kaila Centeio, Gordon B. Schiff, Adam Wright, Christopher W. Baugh, Jeremiah D. Schuur, David W. Bates, Jason S. Adelman, Adam B. Landman
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Wrong-patient order entry (WPOE) errors have a high potential for harm; these errors are particularly frequent wherever workflows are complex and multitasking and interruptions are common, such as in the emergency department (ED). Previous research shows that interruptive solutions, such as electronic patient verification forms or alerts, can reduce these types of errors but may be time-consuming and cause alert fatigue. <h3>Objective</h3> To evaluate whether the use of noninterruptive display of patient photographs in the banner of the electronic health record (EHR) is associated with a decreased rate of WPOE errors. <h3>Design, Setting, and Participants</h3> In this cohort study, data collected as part of care for patients visiting the ED of a large tertiary academic urban hospital in Boston, Massachusetts, between July 1, 2017, and June 31, 2019, were analyzed. <h3>Exposures</h3> In a quality improvement initiative, the ED staff encouraged patients to have their photographs taken by informing them of the intended safety impact. <h3>Main Outcomes and Measures</h3> The rate of WPOE errors (measured using the retract-and-reorder method) for orders placed when the patient's photograph was displayed in the banner of the EHR vs the rate for patients without a photograph displayed. The primary analysis focused on orders placed in the ED; a secondary analysis included orders placed in any care setting. <h3>Results</h3> A total of 2 558 746 orders were placed for 71 851 unique patients (mean [SD] age, 49.2 [19.1] years; 42 677 (59.4%) female; 55 109 (76.7%) non-Hispanic). The risk of WPOE errors was significantly lower when the patient's photograph was displayed in the EHR (odds ratio, 0.72; 95% CI, 0.57-0.89). After this risk was adjusted for potential confounders using multivariable logistic regression, the effect size remained essentially the same (odds ratio, 0.57; 95% CI, 0.52-0.61). Risk of error was significantly lower in patients with higher acuity levels and among patients whose race was documented as White. <h3>Conclusions and Relevance</h3> This cohort study suggests that displaying patient photographs in the EHR provides decision support functionality for enhancing patient identification and reducing WPOE errors while being noninterruptive with minimal risk of alert fatigue. Successful implementation of such a program in an ED setting involves a modest financial investment and requires appropriate engagement of patients and staff.
Abstract 13534: Reduced Hospitalizations, Emergency Room Vists and Death Among Patients Seen Once in a Heart Failure Bridge Clinic (HFBC) Program
Authors: Addison Upton, Laura Sleater, Kaitlyn Bankieis, LaVone Smith, Benjamin Trichon, Vinay Thohan
Journal: Circulation (2020)

Introduction: Multidisciplinary clinics established in the care of heart failure patients are particularly impactful after hospital discharge. Clinical pharmacist integration with HFBC allows focused attention to optimizing guideline directed medical therapies (GDMT). The clinical impact of pharmacist inclusive HFBC requires further evaluation. Hypothesis: Patients with a HFBC encounter within 30 days after index heart failure hospitalization have reduced recurrent hospitalization, emergency room visits and mortality. Methods: All patients with left ventricular ejection fraction (LVEF) less than 40% obtained within 90 days prior to hospital discharge from Mission Memorial Hospital between 8/2018 and 7/2019 were screened. Patients included in the HFBC arm had a clinic encounter within 30 days of hospital discharge and the remainder of patients comprised the control arm. Electronic and manual chart abstraction was used to assess and follow patients. Baseline characteristics were compared for differences using descriptive statistics. HFBC included clinical assessment, detailed heart failure education, medication reconciliation and adjustment with an emphasis on optimization of GDMT. Patients were followed for 90 day for the primary endpoints of hospitalization, emergency room visit and death Results: A total of 1,463 patients (HFBC 307, Control 1156) comprised our final cohort. After accounting for baseline variables associated with endpoints the cumulative rates of hospitalization, emergency room visit or death still favor HFBC compared with controls at 90 days (HFBC 26% vs Control 32%, p=0.03). The 30 and 90 day frequencies of individual endpoints are represented in figure 1. Conclusions: Clinical pharmacist integrated HFBC program allows for focused medication review and optimization is associated with 19% risk reduction in hospitalization, emergency room visit and death at 90 days.
Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study
Authors: Patricia J Rodriguez, D Allen Roberts, Julianne Meisner, Monisha Sharma, Morkor Newman Owiredu, Bertha Gomez, Maeve B Mello, Alexey Bobrik, Arkadii Vodianyk, Andrew Storey, George Githuka, Thato Chidarikire, Ruanne Barnabas, Magdalena Barr-Dichiara, Muhammad S Jamil, Rachel Baggaley, Cheryl Johnson, Melanie M Taylor, Alison L Drake
Journal: The Lancet Global Health (2020)

Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence.In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective.Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine).Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis.WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.
Abstract 16035: Socioeconomic Status and 1-year Mortality Among Patients With Heart Failure in China: Findings From the China-PEACE Prospective Heart Failure Study
Authors: YILAN Ge, Yan Gao, Bin Wang, Jing Li, xin zheng
Journal: Circulation (2020)

Introduction: Socioeconomic status (SES) has been shown to affect the survival of patients with heart failure (HF) in the developed countries. However, the association between SES with mortality has been scarcely investigated in China. Methods: We studied a national sample of 4717 patients admitted to 52 hospitals for HF who had SES record and were discharged alive from the China PEACE-Prospective Heart Failure Study. SES were obtained through questionnaires during hospitalization, and were measured by self-reported employment status (employed, retired, never work), education level (low educational attainment defined as primary school or below; intermediate educational attainment defined as junior high school; high educational attainment defined as senior high school or above) and partner status (having a partner, no partner). We assessed the association between SES and 1-year all-cause mortality using Cox models. Results: The median age of study population was 67 (57,76) years, 37.6% were women.17.6% of patients had a job, 72.5% retired and 9.9% never worked. The proportions of patients who had low, intermediate and high educational attainment were 43.0%, 29.0% and 28.0%,respectively. Additionally, 80.8% of patients had a partner. In unadjusted analysis, compared with patients who had a job, who had high educational attainment and who had a partner, respectively, currently no work status (retired group: HR 2.08, 95%CI 1.64 to 2.63; never work group: HR 2.23, 95%CI 1.78 to 3.22), low educational attainment (HR 1.52, 95%CI 1.28 to 1.81) and no partner (HR 1.31, 95%CI 1.12 to 1.54) were all associated to higher mortality. After adjusting for patient characteristics, medication use at discharge and mutually adjusting for socioeconomic status, education level and partner status were not associated with mortality, However, patients without work currently (retired group: adjusted HR 1.52, 95%CI 1.17 to 1.97; never work group: adjusted HR 1.60, 95%CI 1.15 to 2.22) were still more likely to die within 1 year. Conclusions: In a national Chinese cohort of patients hospitalized for HF, currently no work status was associated with higher 1-year mortality risk, while the education level and partner status were not correlated with mortality.
Abstract 15827: Views of Patients and Family Members in Nicaragua and Pakistan Regarding Pacemaker Reutilization
Authors: Palaniappan Muthappan, Timir Baman, Naila Baig-Ansari, Abdul Bari-Khan, Kim Eagle, Fayez Jawed, Qingmei Jiang, Rolando Jiron, Christian Machado, Thomas Crawford
Journal: Circulation (2013)

Introduction: Many patients in developing nations have neither the financial resources nor insurance to pay for a pacemaker for the treatment of symptomatic bradycardia. Reprocessed, resterilized p...
Balloon-assisted endoscopic sclerotherapy: a novel technology
Authors: Xuecan Mei, Xi Wang, Wenyue Wu, Yi Xiang, Yi Han, Derun Kong
Journal: Endoscopy (2020)

Endoscopic injection sclerotherapy is an effective method for treating esophageal variceal hemorrhage [1] [2]. However, owing to the rapid loss of the sclerosing agent, the overall effect of sclerotherapy is weakened. Therefore, increasing the residence time of the sclerosing agent remains a focal point of current investigations. The present study reported a case treated with a novel technology termed balloon-assisted endoscopic sclerotherapy.
Abstract 14338: Prevalence, Associations and Outcomes of Double Orifice and Parachute Mitral Valve
Authors: uzoma obiaka, Anna Chow, Jen Lie Yau, Valeria Matto Morina, Shubhika Srivastava
Journal: Circulation (2020)

Background: The incidence of congenital mitral valve disease is 0.4%; Double Orifice Mitral Valve (DOMV) and Parachute Mitral Valve (PMV) are two morphologic pathologies that may result in mitral valve dysfunction. The objectives of this study are 1) To describe valve function and progression and 2) To define factors contributing to disease progression. Methods: Retrospective database review. Fyler codes for DOMV, PMV and text search was performed. Echocardiographic images, echo reports, and chart review were used to identify mitral regurgitation (MR), mitral stenosis (MS), morphology, and associated lesions. Results: 39 patients with DOMV and 76 patients with PMV were identified. In the DOMV cohort, 51% were male, median age at diagnosis was 0.17 years (IQR 0.01, 3.88); median follow-up of 5.92 years (IQR 0.46, 10.22). In the PMV cohort, 44% were male, median age at diagnosis at was 0.01 years (IQR 0, 0.34); median follow-up of 2.56 years (IQR 0.25, 9.55). 41% of DOMV and 23% of patients with PMV had normal valve function at initial visit. DOMV was associated with MR (p=0.04), and PMV with MS (p&lt;0.0001). 23% of patients in the PMV cohort had progressive MS compared to 5% of patients in the DOMV cohort (p&lt;0.0001). There was no significant difference in MR progression between both groups (p=0.02). Papillary muscle (PM) morphology was evaluated in 37 (excluding canals) of 76 patients in the PMV cohort. 5 had true PMV (single PM), 32 had variant PMV with two PM groups of which 62.5% had dominant posterior medial PM. 67% of those with posterior medial PM dominance had progressive MS irrespective of association with Shone’s complex. The anterolateral PM muscle group dominant PMV were not associated with Shone’s complex and progressive MS. Conclusion: DOMV are more likely to have MR while PMV are more likely to have MS. DOMV has non progressive MR and MS. Posterior medial PM dominance in PMV is more likely to have progressive MS.
Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial
Authors: Paula Dakin, Alan J Kivitz, Joseph S Gimbel, Nebojsa Skrepnik, Stephen J DiMartino, Chetachi A Emeremni, Haitao Gao, Neil Stahl, David M Weinreich, George D Yancopoulos, Gregory P Geba
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To study the efficacy and safety of fasinumab in moderate-to-severe, chronic low back pain (CLBP). Methods In this phase II/III, double-blind, placebo-controlled study, patients with CLBP aged ≥35 years with inadequate pain relief/intolerance to acetaminophen, non-steroidal anti-inflammatory drugs and opioids were randomised to fasinumab 6 or 9 mg subcutaneous every 4 weeks (Q4W), 9 mg intravenous every 8 weeks (Q8W) or placebo. Primary endpoint was change from baseline to week 16 in average daily low back pain intensity (LBPI) numeric rating score. Key secondary efficacy variables included Roland-Morris Disability Questionnaire (RMDQ) and Patient Global Assessment (PGA). The results are based on a modified intent-to-treat analysis of 563/800 planned patients when enrolment was stopped early given emerging signals of joint risk in other osteoarthritis (OA) studies at doses being tested here. Results Significant placebo-adjusted LBPI reductions at week 16 were observed for fasinumab 9 mg Q4W and Q8W (least squares mean (standard error) −0.7 (0.3); both nominal p&lt;0.05), but not 6 mg (–0.3 (0.3); p=0.39). RMDQ and PGA improvements to week 16 were greatest for fasinumab 9 mg intravenous. Numerically greater efficacy occurred in patients with, versus those without, peripheral OA (pOA) over 16 weeks. Treatment-emergent adverse events (AEs) occurred in 274/418 (65.6%) patients in the combined fasinumab groups and 94/140 (67.1%) placebo patients. Joint AEs, mostly rapid progressive OA type 1, were more frequent in the combined fasinumab groups (19 events in 16 patients (3.8%) vs 1 event in 1 patient (0.7%) for placebo); all except one occurred in pOA patients. Conclusions Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit–risk.
Do malignant cells sleep at night?
Authors: Luis Enrique Cortés-Hernández, Zahra Eslami-S, Antoine M. Dujon, Mathieu Giraudeau, Beata Ujvari, Frédéric Thomas, Catherine Alix-Panabières
Journal: Genome biology (2020)

Abstract Biological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that internal and external ecological variations induced by biological cycles also influence or are exploited by cancer cells, especially by circulating tumor cells, the key players in the metastatic cascade. We then discuss the possible clinical implications of the effect of biological cycles on cancer progression, and how they could be exploited to improve and standardize methods used in the liquid biopsy field.