tbuckley/cabot-search huggingface dataset:
Abstract 11183: A Classificatory Analysis of Right Heart Geometry and Dysfunction Provides Prognostic Stratification in Heart Failure of Any Left Ventricular Ejection
Authors: Mattia Casati, Francesca Bursi, Giulio M Mondellini, Gloria Santangelo, Andrea Santamaria, Francesca Rusconi, Federica Valli, Giulia Ferrante, DANIELA TORTA, Laura Massironi, Diego Tarricone, Carugo Stefano, Marco Guazzi
Journal: Circulation (2021)

Introduction: The prognostic role of the left heart dysfunction is established in heart failure (HF). However, focusing only on left ventricular ejection fraction (LVEF) may be reductive as HF with preserved ejection fraction (HFpEF) yields to poor outcomes, similarly to HF with reduced ejection fraction (HFrEF). Hypothesis: We investigated the prognostic role of the right ventricle (RV) phenotype through a classification based on RV end diastolic diameter (RVEDD) and tricuspid annulus systolic excursion (TAPSE) in chronic HF of any LVEF. Methods: We retrospectively examined two well-defined population of ambulatory patients with chronic HF: severe HFrEF (LVEF≦35%) and HFpEF (LVEF≧55%), all receiving optimal guideline-directed medical and device therapy, followed at a dedicated outpatient HF clinic. Patients were categorized by echocardiography based on RVEDD (cut-off 42 mm) and TAPSE (cut-off 17 mm) into four groups (above and below cut-offs): not dilated and not hypokinetic (NDNH), dilated and not hypokinetic (DNH), not dilated and hypokinetic (NDH) and dilated and hypokinetic (DH). Results: Among 256 patients (mean age 67±12 years, 75% men, 75% HFrEF, 60% ischemic), RVEDD and TAPSE were available for 202. Distribution of NDNH, NDH, DNH and DH is reported in the figure. Over a median follow-up of 4 years, 62 deaths occurred; KM-survival curves are shown in figure. After multivariable adjustment for age, HFpEF/HFrEF, and ischemic etiology, patients with DNH and DH showed increased risk of mortality (HR 2.4 95%CI 1.1-5.1 p=0.024; and 3.4 95%CI 1.7-6.7 p&lt;0.001 respectively) compared to NDNH, with NDH showing comparable risk (HR 1.6 95%CI 0.9-3.7 p=0.232). Conclusions: In chronic HF receiving optimal medical and device therapy, a simple and easy to use RV classificatory analysis is worth of consideration out of LVEF categorization. RV dimensions rather than motility drive the mortality rate independently of age, HFpEF/HFrEF phenotype and HF etiology.
А New Combination of Prognostic Markers in Follicular Lymphoma That Influences the Choice of Therapy
Authors: Ekaterina S. Nesterova, Nataliya A. Severina, Bella V. Biderman, Andrey B. Sudarikov, Tatiana N. Obukhova, Alla M. Kovrigina, Sergey K. Kravchenko, Eduard G. Gemdzhian, Valery G. Savchenko
Journal: Blood (2021)
Abstract 12013: Procollagen Type 1 N-terminal Propeptide, a Collagen Synthesis Biomarker, is Associated With Adverse Clinical Outcome in Patients With Suspected Acute Coronary Syndrome
Authors: Thomas Andersen, Dennis W Nilsen, Heidi Grundt, Harry Staines, Thor Ueland, Pal Aukrust, Frederic P Kontny
Journal: Circulation (2021)

Introduction: Procollagen type 1 N-terminal Propeptide (P1NP) is a precursor protein of collagen type 1, a major component of cardiac extracellular matrix. The association of P1NP to clinical outcome in patients with suspected acute coronary syndrome (ACS) has so far not been investigated. The objective of the present study was to assess the predictive value of P1NP concerning adverse clinical outcome in patients admitted for suspected ACS. Methods: Plasma P1NP was measured with an enzyme immune assay in samples taken upon admission from patients enrolled in the Risk markers in Acute Coronary Syndrome (RACS) study (NCT00521976), a Norwegian single center study including patients with suspected ACS from November 2002 to September 2003. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year. Additional analyzes included the composite and its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. Associations between quartiles of P1NP and the endpoints were assessed in both univariate analyzes and in stepwise multivariable Cox regression analyzes fitted with significant clinical variables, past medical history, medication, TnT, BNP, and eGFR before P1NP was introduced. Results: Samples were available from 813 patients (Mean age 69.6 years, 61.4 % males, 52.9% elevated TnT). Mean P1NP levels was 46.2 ng/mL (CI 44.8-47.6). In multivariable Cox analyzes, P1NP was found to be significantly associated with the composite of all-cause mortality, MI, or stroke at 1 year (HR [Q4vsQ1] 1.82, CI 1.12-2.98; p=0.017). This association did not remain significant beyond 1 year. No association was seen for any of the individual components, or cardiac death, at any timepoint, or in patients with elevated TNT (p&gt;0.05 for all). Conclusions: This first study on P1NP in suspected ACS revealed a significant association with adverse clinical outcome (all-cause death, MI, or stroke) at 1 year. However, no predictive value was found concerning outcome for the individual components of the primary endpoint, or cardiac death, at any timepoint, or in patients with elevated TNT.
Clinicopathological Features and Outcomes of EBV Positive and Negative DLBCL: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)
Authors: Denisse Castro, Brady E Beltran, Luis Villela, Efreen Montaño Figueroa, Ana Florencia Ramirez-Ibarguen, Myrna Candelaria, Guilherme Fleury Perini, Ana Carolina Oliver, Humberto Martinez-Cordero, Henry Idrobo, Rosa Oliday Rios, Fabiola Valvert, Sally Rose Paredes, Carolina Cristina Pellegrino, Yusaima Rodriguez, Francisco Lopez, Victoria Irigoin, Maria Gabriela De Galvez, Jorge J. Castillo, Bryan Valcarcel, Luis Malpica Castillo
Journal: Blood (2021)
An end-to-end approach to segmentation in medical images with CNN and posterior-CRF
Authors: Shuai Chen, Zahra Sedghi Gamechi, Florian Dubost, Gijs van Tulder, Marleen de Bruijne
Journal: Medical Image Analysis (2021)

Conditional Random Fields (CRFs) are often used to improve the output of an initial segmentation model, such as a convolutional neural network (CNN). Conventional CRF approaches in medical imaging use manually defined features, such as intensity to improve appearance similarity or location to improve spatial coherence. These features work well for some tasks, but can fail for others. For example, in medical image segmentation applications where different anatomical structures can have similar intensity values, an intensity-based CRF may produce incorrect results. As an alternative, we propose Posterior-CRF, an end-to-end segmentation method that uses CNN-learned features in a CRF and optimizes the CRF and CNN parameters concurrently. We validate our method on three medical image segmentation tasks: aorta and pulmonary artery segmentation in non-contrast CT, white matter hyperintensities segmentation in multi-modal MRI, and ischemic stroke lesion segmentation in multi-modal MRI. We compare this with the state-of-the-art CNN-CRF methods. In all applications, our proposed method outperforms the existing methods in terms of Dice coefficient, average volume difference, and lesion-wise F1 score.
Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for Hospitalised Patients with Mild or Moderate COVID-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomised Controlled Trial
Authors: Asad Charania, Nikhil Vergis, Rachel Phillips, Victoria Cornelius, Alexia Katsarou, Taryn Youngstein, Lucy Cook, Willicombe Michelle, Clio Pillay, Tina Shturova, Melanie Almonte, Richard Turner, Onn Min Kon, Graham Cooke, Mark Thursz, Svetlana Cherlin, James Wason, Dragana Milojkovic, Andrew J. Innes, Nichola Cooper
Journal: Blood (2021)
Abstract 12286: Pregnancy Outcomes in Pulmonary Hypertension With Congenital Heart Disease: A Multicenter Experience From 2220 Cases
Authors: Qian Zhang
Journal: Circulation (2021)

Background: Cardiovascular disease is a global burden for women’s health. Pregnancy with pulmonary hypertension associated with congenital heart disease (CHD-PH) is related to prohibitive maternal mortality. According to the latest AHA scientific statement, their pregnancies are contraindicated, regardless of their CHD diagnosis and PH severity. Considering the emerging population of CHD-PH reaching the child-bearing age, how to balance the maternal risk and patients’ reproductive rights remains understudied and under-recognised. Hypothesis: We assessed the hypothesis that if the mild CHD-PH patients have better pre-pregnancy cardiac situation, their pregnancies shouldn’t all be contraindicated. Methods: Patients were retrospectively included before March 2017 and 205 cases were prospectively collected after that time. Pregnancy with CHD-PH was subdivided into two subgroups based on the estimated SPAP measured by non-invasive echocardiography (30-50 mmHg as mild and &gt;50 mmHg as moderate-to-severe). Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 729 women had CHD-PH (398 mild CHD-PH). Of PH patients, the main CHD diagnosis is shunt lesion (70.92%) and only 26.89% were surgically repaired. The mortality and incidence of heart failure were 2.60% and 21.81%, respectively. No dead case happened in mild CHD-PH. Independent risk factors of maternal cardiac events included brain natriuretic peptide level, NYHA class, ejection fraction (EF), unrepaired CHD, strict supervision, late antenatal visit, without MDT and the severity of PH(except for mild CHD-PH). Furthermore, after propensity score matching analysis, the no-PH and mild PH groups have no significant difference in the maternal and offspring outcomes. Consistency Analysis indicated that mild CHD-PH had lower cardiac incidence than level IV of the modified WHO, except when they were associated with NYHA III-IV or EF&lt;50%. Conclusion: To conclude, pregnancy in women with CHD-PH continues to be associated with significant morbidity, although their mortality is relatively low. If the mild CHD-PH patients have better pre-pregnancy cardiac situation (EF&gt;50% and NYHA I-II), their pregnancies shouldn’t all be contraindicated.
Abstract 14149: Access to Neurology and Telestroke Services in Rural America
Authors: Sara Machado, Robin Ulep, Andrew M Southerland, Muthiah Vaduganathan
Journal: Circulation (2021)

Introduction: Stroke and other neurologic diseases may disproportionately affect persons in rural areas, and stroke-related mortality in rural counties has increased in recent years. Little is known about distribution and trends in neurologists and telestroke services in rural vs urban counties in the US. Methods: Volume and age distribution of neurologists in each county were determined using the AMA Physician Masterfile for each year 2010-2018. Neurologist density (per 100,000 persons) was estimated based on county-level population data. Telestroke units per county were identified using Area Health Resource files. Counties were classified as large metropolitan, medium or small metropolitan, or rural based on CDC WONDER designations. Results: From 2010-2018, mean (SD) neurologist density in rural counties decreased from 6.3 (21.6) to 5.9 (18.7) per 100,000 persons. A majority of rural counties experienced little to no change (0-5 per 100,000) in neurologist density over time. In contrast, neurologist density increased in large metropolitan counties from 31.1 (42.7) to 37.8 (52.1) per 100,000 and in medium/small metropolitan counties from 29.3 (67.8) to 32.2 (74.9) per 100,000. Over time, 42% of large metropolitan and 27% of medium/small metropolitan counties experienced &gt;10 per 100,000 longitudinal increases in neurologist density. The proportion of younger neurologists (&lt;35 or 35-44 years) appeared to increase in urban counties, while the proportion of older neurologists (≥65 years) relatively increased in rural counties. In 2018, telestroke units were available in 51%, 37%, and 18% of large metropolitan, medium/small metropolitan, and rural counties, respectively. Conclusions: Neurologist density has decreased in rural counties in the US, with a relative aging of existing neurologists in these settings. Four out of 5 rural counties do not have telestroke units. These data underscore the need to improve access to neurology in rural areas.
Real-World Evidence on Treatment Utilization in Lower-Risk Myelodysplastic Syndromes: Findings from a Medical Record Review in the United States
Authors: Ulrich Germing, Ravi K. Goyal, Aylin Yucel, Rohan C. Parikh, Maria Jimenez, Martina Sluga-O'Callaghan, Derek Tang, Christina Hughes, Maria Diez-Campelo
Journal: Blood (2021)
CTIM-11. PHASE 2 STUDY OF SL-701, A NOVEL IMMUNOTHERAPY, IN ADULTS WITH RECURRENT GBM: A HIGH PARAMETER FLOW CYTOMETRY ANALYSIS OF CD8+ T CELLS AND POTENTIAL IMPLICATIONS FOR PATIENT ENRICHMENT STRATEGIES
Authors: David Peereboom, Ross Lindsay, Michael Badruddoja, L Burt Nabors, Priya Kumthekar, Frank Lieberman, David Tran, Surasak Phuphanich, David Schiff, Jonathan Sherman, Nicholas Butowski, Erin Dunbar, Karen Fink, Fabio Iwamoto, Christopher Moertel, Michael Schulder, Tobias Walbert, Nassir Habboubi, Krzysztof Grzegorzewski, Christopher Brooks, David Reardon
Journal: Neuro-Oncology (2021)

Abstract Treatment of glioblastoma (GBM) remains a critical challenge and unmet medical need due to limited treatment options. SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit a target-specific anti-tumor immune response against the GBM antigens IL-13Rα2, ephrinA2, and survivin. A multicenter, 2-stage, phase 2 clinical trial (NCT02078648) that evaluated the safety and efficacy of SL-701 in 74 adults with recurrent GBM was previously reported. This report describes preliminary data to suggest a correlation of immunocompetence to clinical outcome. In stage 2 (SL-701 + bevacizumab + poly-ICLC) the overall survival at 12 months was 50%. Two of 28 patients enrolled in stage 2 achieved CR (duration of response: 7.8 and 8.8 months) and 2 achieved PR (duration of response: 7.9 and 8.8 months). In a preliminary analysis to assess CD8+ T-cell responses, long-term survivors were comprised largely of subjects with an SL-701-induced target-specific CD8+ T-cell response, indicating a potential correlation of immunocompetence to clinical outcome. By week 24, SL-701-induced target-specific CD8+ T cells expressing IFNg were detected in 8 of 27 patients (30%) who had sufficient samples, with co-expression of PD-1, TIM3, and LAG3 detected in 4 patients. To further understand the T-cell response to SL-701, deep sequencing of target-specific CD8+ T cells using whole transcriptome-based molecular cytometry and high parameter (25+ color) flow cytometry is currently underway and updated data will be reported.
Abstract 12202: Pandemic-Related Diminished Pollution and ST-elevation Myocardial Infarctions
Authors: Sidney Aung, Eric Vittinghoff, Gregory M Marcus
Journal: Circulation (2021)

Introduction: The reason for the reduction in ST-elevation myocardial infarctions (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic remains a mystery. Increased particulate matter 2.5 (PM 2.5) is a known risk factor for ST-elevation myocardial infarctions (STEMI), although evidence of the reciprocal relationship (decreased PM 2.5 associated with decreased STEMI incidence) has not been shown. We sought to perform a natural experiment to determine if decreased PM 2.5 during the COVID-19 pandemic was associated with a decrease in STEMIs. Methods: We abstracted daily STEMI events between January 1, 2019 to April 30, 2020 (shelter-in-place [SIP] orders began in March) from the National Emergency Medical Services (EMS) Information System (NEMSIS) database. Incidence rates (events per 10,000 person-years) were calculated using US Census population denominators by US Census Divisions We abstracted average daily PM 2.5 data from across the US from the Environmental Protection Agency (EPA) website. Negative binomial regression models were used to estimate the relationship between levels of PM 2.5 and STEMI rates, adjusting for US Census Division, calendar day of week, calendar month, and calendar year. Results: There were 60,722 total STEMI events recorded during the study period. After multivariable adjustment, there were 6% less STEMIs per each 10 μg/m 3 reduction in PM 2.5 (rate ratio 0.94, 95% CI 0.90-0.99, p = 0.016; Figure ). Using the same multivariate adjustment, there were 373.8 less STEMIs per 10,000 person-years for each 10 μg/m 3 decrease in PM 2.5 (95% CI 69.4-678.1). Conclusions: Pandemic-related declines in PM 2.5 levels were associated with significantly less STEMIs across the US. While more pollution is known to increase STEMI risk, this demonstration of the reciprocal relationship provides the most direct evidence that efforts to reduce ambient pollution can prevent the most severe forms of myocardial infarctions.
Abstract 11323: Role of Mir-6236 on Skeletal Muscle Angiogenesis
Authors: Arul Murugan Mani, Isaac L Eigner-Bybee, Madhu V Singh, Ayotunde O Dokun
Journal: Circulation (2021)

Peripheral arterial disease (PAD) affects more than 200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no medical treatments available and in severe cases, PAD may lead to critical limb ischemia requiring amputation. The pathophysiology of PAD is characterized by marked changes in gene expression and reduced angiogenesis. Although many studies have investigated the molecular mechanisms involved in PAD, less is known about the role of microRNAs (miRNA) in the pathogenesis of the disease. MiRNAs are important regulators of gene expression that bind to specific target mRNA and repress their expression. Using a mouse model of PAD, we investigated miRNAs induced by ischemia using RNAseq analysis of ischemic and non-ischemic hind limb tissue. Our data showed 77 miRNAs were upregulated and 40 miRNAs were downregulated in ischemic mouse hind limbs versus non-ischemic controls. Among these miRNAs, miR-6236 was significantly upregulated suggesting a possible role in post ischemic adaptation. We validated miR-6236 expression by qPCR (Ischemic 2.04±0.39 vs Non-Ischemic 1.0±0.11; n=5-6; p&lt;0.05). In vitro, using primary mouse microvascular endothelial cells (MVECs), ischemia induced miR-6236 expression in a time dependent manner up to 72 hrs. At the same time, ischemia caused decrease in proliferation (Ischemia (Isch) 0.12±0.03 vs Normoxia (Norm) 0.23±0.02; n=4-6; p&lt;0.05), migration (Isch 46.7±0.52 vs Norm 72.02±2.74; n=6; p&lt;0.05) and tube formation (Isch 31.5±3.58 vs Norm 82.12±6.5; n=8; p&lt;0.05), and increased apoptosis (Isch 0.94±0.05 vs Norm 0.59±0.02; n=4-5; p&lt;0.05). Treatment of mouse MVECs with miR-6236 inhibitor (miRINH, 100 nM) prior to ischemia decreased miR-6236 expression by 50% and improved proliferation (miRINH + Isch 0.21±0.01 vs Isch 0.12±0.03; n= 4; p&lt;0.05), migration (miRINH + Isch 63.71±2.08 vs Isch 46.7±0.52; n=6; p&lt;0.05), tube formation (miRINH + Isch 50±5.92 vs Isch 31.5±3.58; n=8; p&lt;0.05) and decreased ischemia-induced apoptosis (miRINH + Isch 0.64±0.04 vs Isch 0.94±0.05; n=4-5; p&lt;0.05). We conclude that miR-6236 serves as a critical regulator of endothelial cell function in ischemic skeletal muscle and can be a promising target for therapeutic skeletal muscle angiogenesis.
Abstract 11786: Heart Transplant in Congenital Heart Disease: Trends in Mortality With Ventricular Assist Devices
Authors: Alicia M Kamsheh, Danielle Burstein, Xuemei Zhang, Steve Ampah, Jonathan Edelson, Kimberly Lin, Matthew J O'Connor, Chitra Ravishankar, Carol Wittlieb-Weber, Katsuhide Maeda, Muhammad Nuri, James W Gaynor, Jonathan Chen, Stephanie M Fuller, Joseph Rossano
Journal: Circulation (2021)

Introduction: Patients with congenital heart disease (CHD) may require cardiac transplantation for either primary management or failed surgical palliation. This study describes 1-year mortality of patients with CHD listed for transplant, trends in 1-year mortality over three decades, and use of mechanical support in this population. Methods: The United Network for Organ Sharing database was queried to identify patients aged 0-30 years with CHD listed for transplant from 1990 to 2019. VAD status at listing and 1-year mortality after listing were examined using the Cochran-Armitage trend test. Results: Overall, 9327 patients with CHD aged 0-30 years were listed for transplant between 1990 and 2019 with a total 1-year mortality rate of 26% (n=2466). For non-survivors to 1-year after listing, 66% (n=1619) died before transplant and 34% (n=847) after transplant. Patients &lt;1 year of age were the most frequent age group listed for transplant (n=3678, 39%) and experienced the highest 1-year mortality after listing (n=1264, 34%). The 1-year overall mortality decreased over the study period (1990-1999: 33% vs 2000-2009: 30% vs 2010-2019: 19%, p&lt;0.0001), including in infants &lt;1 year of age (1990-1999: 41% vs 2000-2009: 37% vs 2010-2019: 26%, p&lt;0.0001). Overall, few patients were supported with VAD at listing (3.1%). However, VAD use increased (1990-1999: 1.0% vs 2000-2009: 2.8% vs 2010-2019: 5.0%, p&lt; 0.0001) and the 1-year mortality for patients with VAD at listing decreased over time (1990-1999: 57% vs 2000-2009: 35% vs 2010-2019: 20%, p&lt;0.0001). Conclusions: Survival after listing for heart transplant is improving, however mortality amongst infants remains high. While there has been &gt;50% improvement in survival in patients of all ages with CHD supported with a VAD at listing, VADs are used rarely in patients with CHD. Further study is needed to understand which patients may benefit from mechanical circulatory support, especially among infants.
TAMI-38. TUMOR-ASSOCIATED NEUTROPHILS IN GLIOBLASTOMA PROMOTE THE PERIVASCULAR GLIOMA STEM-LIKE CELL NICHE VIA OSTEOPONTIN SECRETION
Authors: Angad Beniwal, Saket Jain, Sumedh Shah, Sabraj Gill, Garima Yagnik, Alan Nguyen, Harsh Wadhwa, Aaron Diaz, Manish K Aghi
Journal: Neuro-Oncology (2021)

Abstract Among clinical analyses, elevated neutrophil-lymphocyte ratio has been correlated with poor outcomes of glioblastoma patients independent of other prognostic factors. Additionally, our flow cytometric studies of primary patient samples found neutrophil percentage to be significantly higher in higher-grade glioma versus lower-grade glioma. Tumor-associated neutrophils (TANs) comprise less than 2% of the glioblastoma microenvironment. While TANs were initially considered passive bystanders due to their short-lived nature, investigation of TANs in other cancers revealed distinct pro-tumoral roles. Therefore, we transcriptomically characterized glioblastoma TANs and defined their oncologic effects. Transcriptomic analysis of patient-matched TANs versus peripheral blood neutrophils revealed that functionally quiescent circulating neutrophils infiltrate IDH1-wild type glioblastoma via leukotriene B4 chemoattraction, where tumor cells morphologically and transcriptomically activate them to become TANs. Single-cell RNA-sequencing of patient-matched TANs and peripheral blood neutrophils revealed a subset of tumor-activated neutrophils which adopt a pro-tumoral secretory phenotype, marked by activation of the IL-17 signaling pathway and high osteopontin production. Using immunofluorescence stains of primary patient glioblastoma sections, we demonstrated that activated, myeloperoxidase-positive TANs reside in the perivascular niche of glioblastoma in close proximity to glioblastoma stem-like cells (GSCs) and CD31-positive endothelial cells. Further analysis in culture demonstrated that TAN-secreted osteopontin drives the formation, self-renewal, and proliferation of GSC-containing neurospheres. These results were validated using a syngeneic stem cell-derived IDH1-wild type murine glioblastoma model in vivo. Thus, while TANs are rare in glioblastoma, their enrichment in the glioblastoma perivascular niche uniquely positions them to support the GSCs that are crucial to therapeutic resistance of GBM.