tbuckley/cabot-search huggingface dataset:
Abstract 9959: Narrowing the Survival Gap: Trends in Survival in Individuals with Down Syndrome with and without Congenital Heart Defects Born 1979 - 2018
Authors: Lydia K Wright, Erin B Stallings, Janet D Cragan, Laura J Pabst, Matthew E Oster
Journal: Circulation (2021)

Introduction: Congenital heart defects (CHD) affect nearly 50% of children born with Down syndrome (DS) and have been shown to affect both early (&lt;1 year) and late mortality. In the non-DS population, survival with CHD has improved greatly over the last 40 years. We aim to evaluate if these changes have narrowed the survival gap between those with DS + CHD and those with DS alone over recent decades. Methods: Individuals with DS born in metropolitan Atlanta between 1979 and 2018 were identified through the Metropolitan Atlanta Congenital Defects Program, a population-based surveillance system maintained by the Centers for Disease Control and Prevention. Survival analysis was performed to evaluate predictors of mortality for those with DS + CHD and DS alone. Results: Cohort included 1,668 individuals with DS, 764 individuals of whom had a CHD. There were 150 deaths at a median age of 0.4 years (interquartile range (IQR) 0.1 - 4.5 years). In a multivariable model evaluating survival through 10 years, CHD, birthweight &lt;2500g, birth before 2000, and maternal Black race were associated with mortality. Ten-year survival in DS + CHD improved steadily from the 1980s to 2010s (82% to 93%, p=0.01) but remained stable (96% to 95%, p=0.97) in those with DS alone; presence of CHD was not significantly associated with mortality for those born in the most recent decade (HR 1.65 [95% CI 0.60 - 4.51], Figure). In multivariable analysis conditioning on surviving to 1 year, presence of CHD (HR 3.04 [95% CI 1.79-5.18]) remained significantly associated with long-term mortality. Conclusions: Early survival among children with DS + CHD has significantly improved over the last 4 decades, such that the survival gap between those with DS + CHD and those with DS alone has disappeared in the most recent decade. It remains to be seen whether these improvements will translate into improved long-term survival; CHD continues to be a risk factor for late mortality for those born in earlier decades.
Health protocol compliance integrated monitoring system to inform public health actions during the COVID-19 pandemic in Indonesia
Authors: Dewi Nur Aisyah, Thifal Kiasatina, Gayatri I Gusti, Wiku Adisasmito, Logan Manikam, Zisis Kozlakidis
Journal: The Lancet (2021)

BackgroundThe Indonesia National Task Force for the Acceleration of COVID-19 Mitigation has developed an integrated monitoring system to measure community compliance with the health protocol Bersatu Lawan COVID-19. The current study aims to evaluate compliance with the health protocol in Indonesia through the Bersatu Lawan COVID-19 digital mobile application.MethodsData was collected from the National Task Force between Oct 1, 2020, and May 2, 2021. A total of 437 093 front-line public order forces (eg, police and the military) and Behavioural Change Ambassadors reported real-time community compliance on mask wearing and physical distance keeping at public places such as markets, malls, schools, offices, and worship places. Individuals who did not comply were reprimanded and educated.FindingsAs of May 2, 2021, more than 165 million reports were gathered, with 469 million people were monitored in 514 districts or cities across 34 provinces in Indonesia. The overall national figures show a compliance of 322 736 010 (85·9%) of 375 711 304 people in mask wearing, and of 315 973 207 (84·1%) of 375 711 304 people in keeping physical distance, as a cumulative estimate. The results showed the variation of compliance rates among districts and cities in provinces. An analysis of data gathered in the week of April 26 to May 2, 2021, showed that mask wearing compliance was low (defined as observed by less than 75% of people) in 103 (29·6%) of 348 districts and cities across Indonesia, and that physical distance compliance was low in 99 (28·4%) of 348 districts and cities. The temporal pattern analysis estimated that compliance decreased in November and December, 2020 (before the peak of the second wave of the pandemic), and that it increased between January and May, 2021 (during and after the second wave). 321 million people were reprimanded and educated on the importance of adherence to the health protocol.InterpretationThis paper discusses an example of the use of the Bersatu Lawan COVID-19 application in Indonesia, the most populous country in southeast Asia. We report the first time that an application for digital health, introduced nationally, produced data that could be analysed on a real-time basis, thus enabling central and local government to strengthen enforcement of the health protocol to stop the potential transmission of COVID-19 in public places.FundingNo funding to declare.
Abstract 9681: Guideline Directed Lipid Therapy Prescribing Patterns Contrasted by Achievement in Optimal Lipid Levels in Patients Following Acute Coronary Syndrome
Authors: Maxwell Ambrosino, Sydney Emerson, Patricia Hernandez, Douglas Jacoby
Journal: Circulation (2021)

Introduction: Initiation of guideline directed lipid therapy (GDLT) for patients following acute coronary syndrome (ACS) is a well-established secondary prevention. Despite this, variable prescriber adherence to GDLT has been observed and it is not well understood how this impacts achievement of optimal LDL across gender and racial groups. Hypothesis: Gender and racial disparities in GDLT and subsequent achievement of LDL &lt;70 mg/dL exist. Methods: A cross-sectional study was employed across University of Pennsylvania Health System from 2018 to 2019. Electronic medical records were queried for all admitted patients diagnosed with ACS. Data was collected for age, gender, race, and prescribed lipid medication at both discharge and up to 1-year post-discharge. Results: We identified 3386 patients of which 66.8% were male and 33.1% were female. The majority was white (63.5%), followed by 21.2% Black, &lt;4% Asian, &lt;3%, &lt;2% East Indian, and &lt;1% American Indian. Discharge compared to post-discharge percentages of prescribed GDLT are as follows: 78.0% to 62.9% all patients; 75.2% to 60.8% White, 82.6% to 72.4% Black, 78.1% to 49.1% Asian, 85.8% to 64.7% Hispanic, 77.1% to 58.3% East Indian, 85.7% to 57.1% American Indian. At post-discharge, patients with LDL &lt;70 mg/dL are as follows: 50.7% all patients, 55.5% male, 41.2% female, 53.9% White, 41.1% Black, 54.0% Asian, 44.4% Hispanic, 37.9% East Indian, and 80% American Indian. Non-statin therapy was only prescribed to 13.3% of all patients. Conclusions: Disparities were observed among gender and racial groups in both prescribed GDLT and sustained LDL levels &lt; 70 mg/dL. The first step in overcoming disparities is through recognition. An improved holistic understanding of the existing disparities through further investigation will allow for targeted improvements in care and outcomes.
Abstract 14046: Psychosocial Impact of Risk Mitigation Strategies and Shielding From COVID-19 in Adults and Children With Early-Onset Neuromuscular Disease and Their Families
Authors: Lydia Spurr, Hui-leng Tan, Ruth Wakeman, Michelle Chatwin, Anita Simonds
Journal: Circulation (2021)

Introduction: Patients with early-onset neuromuscular diseases (NMDs) were considered clinically vulnerable to COVID-19 due to assumptions that treatments e.g. corticosteroids, or complications e.g. pre-existing respiratory failure or cardiac disease would increase risk. In the UK, most were advised to ‘shield’ and strictly limit social contact, however it is poorly understood how patients and families approached and responded to this. Methods: In-depth questionnaires specifically designed to meet research aims were completed by telephone between September 17 th and December 31 st 2020 by NMD patients or their parent. Open and closed questions enabled a) quantitative analysis and b) thematic analysis to evaluate reasoning and psychosocial impact. Results: 40 questionnaires were completed: patients were 70% male, aged 2 to 48 years with NMDs e.g. muscular dystrophies, spinal muscular atrophy. 80% (n=32) had long-term non-invasive or tracheostomy ventilation; 20% (n=8) had cardiac involvement. Strict adherence to shielding was initially reported: this included temporary cessation or reduction in external care support in 68% (n=27), leading to increased parental care. Shielding measures were often relaxed due to 1) official guidance, 2) evidence of less severe outcomes in children and NMDs, and 3) unsustainability of limited social contact. Anxiety, fear and worry were the most frequently reported emotions, but level and pervasiveness fluctuated. 75% (n=30) remained “extremely” or “very” worried about risk of COVID-19 to the patient’s health. Concern about hospital attendance during the pandemic and anxiety regarding perceived lack of capacity or access to Intensive care were common. Virtual healthcare access, experienced by 97.5% (n=39), was seen as positive, largely as an interim measure, but was less useful where examination or tests were required. Conclusions: Measures to reduce transmission of COVID-19 have disproportionately affected NMD patients and their families. For most, negative psychosocial impacts have and will continue to improve, particularly due to the success of the vaccination programme. Patients and carers require access to support and up-to-date information to minimise risk of infection and psychological burden.
Abstract 13774: Comparison of His Bundle Pacing and Bi-Ventricular Pacing in Heart Failure Patients With Atrial Fibrillation Who Need Atrial-Ventricular Node Ablation: The ALTERNATIVE Study
Authors: Weijian Huang, Lan Su, Songjie Wang, Shengjie Wu, Rujie Zheng
Journal: Circulation (2021)

Introduction: Cardiac resynchronization therapy typically is attempted with biventricular pacing (BVP). As an alternative to BVP, his bundle pacing (HBP) can maintain electrical and mechanical synchrony in patients with atrial fibrillation (AF) and atrioventricular node ablation (AVNA). However, there is still a lack of prospective randomized studies to compare BVP and HBP. Hypothesis: For patients with heart failure (HF) and AF who need AVNA, HBP is not inferior to traditional BVP. Methods: ALTERNATIVE is a prospective multicenter randomized single blind crossover study. Fifty consecutive AF patients who received BVP or HBP in conjunction with AVNA between March 2016 and February 2019 were enrolled in 6 centers. Patients were implanted with a right apical pacing lead, left ventricular lead, and HBP lead. After successful implant, patients were randomized in single patient-blinded fashion to either HBP or BVP. After 9 months, patients were crossed over to the other pacing modality and followed for another 9 months. Pacing parameters, echocardiographic measurements were obtained at baseline and at each follow-up. Results: Fifty patients were enrolled from 6 centers in this study. 25 received BVP and 25 HBP at first stage. Thirty-eight patients completed the crossover analysis at 18 months. LVEF were significantly improved for both pacing modes compared with baseline (30.93±7.27% vs. 51.29±10.79%, p&lt;0.001 in HBP; 33.43±9.40% vs. 51.94±10.97%, p&lt;0.001 in BVP). HBP was superior to BVP in terms of post-implant QRS duration (103.33±12.00 ms vs. 132.42±15.25 ms). Moreover, HBP can lead to greater improvement in cardiac function than BVP (p&lt;0.001 in LVEDd; p&lt;0.001 in LVEF). Conclusions: HBP can be used as a favorable alternative to BVP in patients with HF and AF after AVNA whose QRS complex is less than 120 ms. Further long-term and large studies are warranted to compare the outcomes between HBP and BVP.
TAMI-52. NEURONAL MECHANISMS OF BRAIN TUMOR INVASION
Authors: Varun Venkataramani, Yvonne Yang, Marc Schubert, Carlo Beretta, Michael Botz, Laura Fankhauser, Svenja Tetzlaff, Julia Wagner, Luciano Garofano, Alexander Freudenberg, Martin Slowik, Dimitar Tanev, Leif Döring, Antonio Iavarone, Wolfgang Wick, Thomas Kuner, Frank Winkler
Journal: Neuro-Oncology (2021)

Abstract Incurable gliomas are characterized by their infiltration into the whole brain. Recently, we described tumor microtubes as a novel structure contributing to glioma cell invasion and uncovered synaptic contacts on glioma cells that drive brain tumour progression. However, the exact effects of neuronal activity on glioma cell motility are yet unclear. Here, we show how a recently described neuronal-like cellular transcription state of glioblastoma cells is correlated to glioma cell invasion in vivo. To unravel the details of neuronal features of glioma invasion in space and time, we established a novel approach of intravital imaging for brain tumor cells with a membrane-bound GFP combined with deep learning algorithms that are used to track glioma cell processes with a high temporal resolution over several hours. This approach uncovers how invading tumor microtubes use Levy-like movement patterns indicative of efficient search patterns often employed by animal predators searching for scarce resources such as food. Neuronal activity is able to accelerate the tumor microtube dynamics, accelerate the Levy-like movement patterns and increase the overall invasion speed of glioma cells. These processes are mediated by local calcium transients in glioma cell somata and tumor microtubes. In accordance, genetic manipulation and pharmacological perturbation of AMPA receptors reduces tumor microtube length, number and branching points by interfering with intracellular calcium transients. All in all, the work here uncovers novel neuronal activity-mediated mechanisms of glioma cell invasion, a hallmark of this yet fatal disease.
Abstract 11729: Elevated Procoagulant Platelets Predict Myocardial Infarction or Cardiac Death at 10 Months in Symptomatic Carotid Stenosis
Authors: Mohamad Khattab, Calin I Prodan, Chao Xu, George L Dale, Angelia Kirkpatrick
Journal: Circulation (2021)

Background: Symptomatic carotid stenosis is associated with elevated myocardial infarction (MI) risk. Better risk prediction and intervention targets may help reduce adverse cardiac events. Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, predict stroke recurrence in symptomatic carotid disease, but the association with MI risk is unknown. Here we assess whether coated-platelets predict MI or sudden cardiac death (SCD) in symptomatic carotid stenosis. Methods: Patients with symptomatic ≥50% carotid artery stenosis were enrolled and coated-platelet levels assayed within 92 hours of stroke onset. Demographics, comorbidities and interventions were recorded. MI (4 th universal definition) and SCD (death from MI or arrhythmia) were determined by chart review and confirmed by blinded adjudication. The Area Under the Curve (AUC) was calculated for coated-platelet levels for predicting MI or SCD and the most sensitive and specific cutoff identified using Youdon’s Index. Predictors of MI or SCD were determined by Cox Proportional Hazards analysis. Results: We enrolled 179 patients (mean age 67, 85% male, 43% diabetic, 44% smokers, 45% with coronary disease, 26% with carotid revascularization at discharge). Eleven MI’s (5 fatal) and 4 SCD’s without MI (8.4%) occurred over 10.1±3.6 months. Baseline coated-platelets ≥54.6% were associated with risk of MI or SCD (AUC, 0.687±0.0842, p=0.0265, 53% sensitivity, 85% specificity). Age (HR=1.074, p=0.0187) and the interaction between elevated coated-platelets and carotid revascularization at discharge (HR=37.6, p=0.0182) were retained as significant on multivariate analysis. Conclusions: Our findings revealed a 37.6 increased hazard of MI or SCD among revascularized symptomatic carotid stenosis patients with ≥54.6% coated-platelets. A high rate of often fatal MI was also noted after revascularization, supporting the need to optimize cardiovascular risk management. Our results suggest a role for coated-platelets as biomarkers of perioperative cardiovascular risk and as potential novel treatment targets to reduce perioperative adverse cardiac events in symptomatic carotid stenosis.
Abstract 14388: Efficacy of Intravenous Procainamide for Treatment of Tachyarrhythmia in Children
Authors: Robert Przybylski, Elizabeth S DeWitt, Esther Chu, Kimberlee Gauvreau, John K Triedman, John N Kheir, Audrey Dionne
Journal: Circulation (2021)

Introduction: The safety and efficacy of IV procainamide is well established in adults, however data in pediatrics is more limited. Methods: Prospective cohort study including children &lt;18 yrs old who received IV procainamide for supraventricular tachycardia (SVT) or junctional ectopic tachycardia (JET) from June 2020 to May 2021. A severity of arrhythmia score (SAS, table), including arrhythmia density score (ADS), hemodynamic severity and need for adjunctive antiarrhythmic therapy was calculated pre and post procainamide. Full success was defined as decrease of the ADS to 0 and partial success as decrease by ≥50%. Results: Fifty-three patients (6.9 [IQR 1.2-34.9] months) received IV procainamide for treatment of SVT (n = 25, 47%) or JET (n = 28, 52%), including 44 (83%) with congenital heart disease (CHD) and 39 (74%) following cardiac surgery. Fifty (93%) patients were given a bolus (median 5 mg/kg, range 2.5-13 mg/kg) and 52 (96%) received an infusion (median 20 mcg/kg/min, range 10-30 mcg/kg/min). Full success was observed in 28 (53%) patients, partial success in 13 (25%) and failure in 12 (23%); 7 (19%) patients required adjunctive IV antiarrhythmic therapy. Median SAS decreased from 6 (IQR 4-8) to 1 (IQR 1-5) following procainamide. Procainamide bolus &gt;5 mg/kg was associated with greater decrease in SAS (median decrease 5 [4-6] vs 2 [0-4], p = 0.04). Children with CHD (median decrease 1 [IQR 0-4] vs 4 [IQR 4-5], p = 0.04), those in the early post-operative period (median decrease 2 [IQR 0-4] vs 4 [IQR 4-5], p = 0.03) and those with JET (median decrease 2 [IQR 0-4] vs 4 [IQR 2-5], p = 0.04) had less improvement in SAS score with procainamide. Conclusions: IV procainamide is effective for treatment of SVT and JET in children, and associated with decreased SAS even in patients without complete rhythm control. Higher procainamide bolus dose should be considered for increased efficacy. Future studies are needed to identify optimal doses in pediatrics.
Integrating engineered macro vessels with self-assembled capillaries in 3D implantable tissue for promoting vascular integration in-vivo
Authors: Lior Debbi, Barak Zohar, Margarita Shuhmaher, Yulia Shandalov, Idit Goldfracht, Shulamit Levenberg
Journal: Biomaterials (2021)

A functional multi-scale vascular network can promote 3D engineered tissue growth and improve transplantation outcome. In this work, by using a combination of living cells, biological hydrogel, and biodegradable synthetic polymer we fabricated a biocompatible, multi-scale vascular network (MSVT) within thick, implantable engineered tissues. Using a templating technique, macro-vessels were patterned in a 3D biodegradable polymeric scaffold seeded with endothelial and support cells within a collagen gel. The lumen of the macro-vessel was lined with endothelial cells, which further sprouted and anastomosed with the surrounding self-assembled capillaries. Anastomoses between the two-scaled vascular systems displayed tightly bonded cell junctions, as indicated by vascular endothelial cadherin expression. Moreover, MSVT functionality and patency were demonstrated by dextran passage through the interconnected multi-scale vasculature. Additionally, physiological flow conditions were applied with home-designed flow bioreactors, to achieve a MSVT with a natural endothelium structure. Finally, implantation of a multi-scale-vascularized graft in a mouse model resulted in extensive host vessel penetration into the graft and a significant increase in blood perfusion via the engineered vessels compared to control micro-scale-vascularized graft. Designing and fabricating such multi-scale vascular architectures within 3D engineered tissues may benefit both in vitro models and therapeutic translation research.
Abstract 11751: Long Term Quality of Life Improvement After Peripheral Vascular Intervention- Insights From the Liberty 360 Study
Authors: Mohsin Chowdhury, Kim G Smolderen, Carlos Mena-hurtado, John Spertus, Robert W Yeh, Eric A Secemsky
Journal: Circulation (2021)

Background: Improving patients’ quality of life (QoL) is a primary indication for peripheral endovascular intervention (PVI) for peripheral arterial disease (PAD). Little is known about the long-term improvement in QoL following PVI or predictors of those who may experience the greatest benefit. Methods: We studied 1204 patients enrolled in LIBERTY 360 Study, a prospective, multicenter study that evaluated clinical outcomes in symptomatic PAD patients undergoing lower extremity PVI. Patient reported QoL measures were assessed at 30 days, 12 months and 36 months using EuroQol and VascuQol-25. Multivariable regression was used to identify significant predictors of improved quality of life at 12 months. Results: For claudication patients (Rutherford 2-3), the baseline VascuQol total score was 4.3±1.3 and EuroQol composite score indicated that 21.5% had no/slight functional problems (NSFP). Health status significantly improved by 30 days, with VascuQol score 5.4±1.3 and 48.2% with NSFP), and persisted through 3 years (1 year: VascuQol score 5.3±1.3, 46.3% with NSFP; 3 years: VascuQol score 5.3±1.4, 46.9% with NSFP). For patients with critical limb ischemia (CLI; Rutherford 4-6), baseline VascuQol total score was 3.8±1.4 and 16.6% had NSFP. Health status significantly improved by 30 days, with VascuQol score 4.7±1.4 and 29.9% with NSFP, and persisted through 3 years (1 year: VascuQol score 5.0±1.4, 35.0% with NSFP; 3 years: VascuQol score 5.0±1.4, 38.0% with NSFP). In multivariable regression, baseline symptom severity, disease severity, BMI, gender, history of PVI, target lesion residual stenosis and renal disease were significant predictors of QoL improvement post-intervention (Figure 1). Conclusions: Endovascular intervention is associated with significant, long-term improvement in QoL measures across different disease severity. Baseline symptom severity and comorbidities were strong predictors of QoL improvement 1 year after intervention.