tbuckley/cabot-search huggingface dataset:
Abstract 13887: Cardio-Oncology in a Dish: Cardiovascular Tissue Engineering Strategies for Modeling Cancer Therapy Related Cardiac Dysfunction
Authors: Caroline Bashai, Noam Kazma, Idan Haiim, Yaara Libai, Anastasia Nevo, Gil Arbel, Amira Gepstein, Oren Caspi
Journal: Circulation (2021)

Cardio-oncology in a dish: cardiovascular tissueengineering strategies for modeling cancer therapyrelated cardiac dysfunction.Over the recent years, there was a robust proliferation of oncological therapies leading to asignificant reduction in cancer related death. Unfortunately, there was a parallel increase in thenumber of patients developing cardiotoxicity &amp; heart failure making it the main cause of deathamong cancer survivors. Current strategies for predicting cardio-toxic side effects are limitedand robust pre-clinical, personalized platforms for assessing both harmful drugs and protectiveagents are lacking.In the current study by using human pluripotent stem cells technology, we developed a uniquehuman-engineered cardiac tissue (ECT) platform generated from cardiomyocytes, endothelialcells and authentic cardiac fibroblasts derived from the epicardial cell layer. Using this platform,we are examined the ability of the model to recapitulate the cardio-toxic effects of Doxorubicinand the cardio protective capabilities of Dexrazoxane and SGLT2i; a novel agent, that wasrecently shown to prevent heart failure in patients with diabetes and high risk forcardiovascular diseases.p&lt;0.001 Results: Paired, long-term, consecutive force evaluations of the ECTs demonstrated the cardio-toxiceffect of Doxorubicin resulting in a lower total active force for each preload compared toBaseline control. Moreover, concomitant exposure to Doxorubicin and the cardio-protectiveagents (Dexrazoxane and SGLT2 inhibitor ‘Empagliflozin’) resulted in considerable recovery ofthe active force generation compared to control. Conclusion: This report is an initial proof of concept demonstrating the ability of ECTs to serve as a modelfor functional evaluation induced by cardio toxic drugs as well as the effect of cardio-protective agents. High-throughput based on this platform may be used for identifying novel cardio-protective agents as well as for evaluating patient-specific cardio-toxic effects.
Digital symptom monitoring with patient-reported outcomes in community oncology practices: A U.S. national cluster randomized trial.
Authors: Ethan Basch, Deborah Schrag, Jennifer Jansen, Sydney Henson, Angela M. Stover, Patricia Spears, Mattias Jonsson, Allison Mary Deal, Antonia Vickery Bennett, Gita Thanarajasingam, Bryce Reeve, Claire Frances Snyder, Deborah Bruner, David Cella, Lisa A. Kottschade, Jane Perlmutter, Robert S. Miller, Jon F. Strasser, Dylan M. Zylla, Amylou C. Dueck
Journal: Journal of Clinical Oncology (2021)

349527 Background: Symptoms are common during cancer care but often go undetected. Digital systems that elicit patient-reported outcomes (PRO) surveys may detect symptoms early and prompt clinicians to intervene, thereby alleviating suffering and averting complications. Methods: In a cluster-randomized trial, U.S.-based community oncology practices were randomized 1:1 to digital symptom monitoring with PRO surveys, or to usual care control. Patients receiving systemic treatment for metastatic cancer were eligible. At PRO practices, participants were invited to complete a weekly survey via web or automated telephone system for up to one year, including questions about nine common symptoms, performance status, and falls. Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing longitudinal symptom data were available to oncologists at visits. Pre-specified secondary outcomes included impact on physical function, symptom control, and health-related quality of life (HRQL). The primary outcome of survival is not yet mature. Results: At 52 practices, 1,191 patients were eligible and enrolled (593 PRO; 598 control). Clinically meaningful benefits were experienced in physical function by 13.8% more patients with PRO versus control (P=0.009); symptom control by 16.1% (P=0.003); and HRQL by 13.4% (P=0.006). Mean changes from baseline were superior with PRO versus control for physical function (mean difference 2.47, 95% CI 0.41-4.53; P=0.02), symptom control (2.56, 0.95-4.17; P=0.002), and HRQL (2.43, 0.90-3.96; P=0.002). Patients completed 20,565/22,486 (91.5%) of expected weekly PRO surveys. Conclusions: Digital symptom monitoring during cancer treatment confers clinical benefits. Clinical trial information: NCT03249090.
A Completely Digital Workflow for Differentials in Bone Marrow Cytomorphology Supported By Machine Learning Provides Promising Results in Object Detection
Authors: Christian Pohlkamp, Niroshan Nadarajah, Inseok Heo, Dimitros Tziotis, Sven Maschek, Rudolf Drescher, Siegfried Hänselmann, Thomas Lörch, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
Journal: Blood (2021)
Abstract 10211: Longitudinal Changes in Clinical and Imaging Variables During Withdrawal of Heart Failure Therapy in Patients with Recovered Dilated Cardiomyopathy: An Analysis from TRED-HF
Authors: Brian P Halliday, Ruth Owen, John Gregson, Ali Vazir, Amrit S Lota, Zohya Khalique, Martin R Cowie, Dudley Pennell, John Cleland, Sanjay K Prasad
Journal: Circulation (2021)

Introduction: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed during withdrawal of therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal. Purpose: To profile the changes in clinical and imaging variables amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods: Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a crossover phase. Clinical variables were measured at each study visit and imaging variables were measured at baseline, 16 weeks and 6 months. Mean values and 95% CIs were calculated at each time point. Clinical variables were modelled using fractional polynomials. Results: Of 51 patients, 26 were assigned to continue therapy and 25 to withdraw therapy over the first 6 months. Of the former, 24 of 26 patients, withdrew therapy in the cross-over phase between 6-12 months. An increase in mean heart rate was noted within 4 weeks of beginning therapy withdrawal and was the earliest change observed. Heart rate and change in heart rate from baseline were closely associated with the occurrence of relapse in multivariable analysis. A rise in systolic and diastolic blood pressure was apparent by 8 weeks. A rise in mean log NT-pro-BNP was the latest change to occur and not observed until 6 months after starting therapy withdrawal. ( Figure 1 &amp; Table 1) . A rise in mean LV mass and LVEDV and a reduction in mean LVEF was seen by 16 weeks ( Figure 2 &amp; Table 1) . Conclusion(s): A rise in heart rate may be the earliest sign of relapse during withdrawal of medication. This is accompanied or closely followed by changes in LV structure and function, with changes in natriuretic peptide concentrations occurring later. This informs monitoring strategies in cases where it may be necessary to reduce heart failure therapy.
Abstract 13780: Aggressive Hydration and Contrast-Induced Acute Kidney Injury Following Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Randomized Controlled Study
Authors: Yong Liu, Jiyan Chen, Ning Tan, Jin Liu
Journal: Circulation (2021)

Objective: To evaluate the efficacy of aggressive hydration compared with general hydration for contrast induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Methods: The ATTEMPT study is an open-label, randomized controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 minutes, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/h for 6 hours after randomization. The primary endpoint is CI-AKI, defined as a &gt;25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48-72 hours after primary angioplasty. The safety endpoint is hydration relative acute heart failure. Results: From July 2014 and May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs. 31.1%; RR 0.78, 95% CI 0.61 to 0.98). Hydration relative acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (7.9% vs. 6.9%, RR 1.07, 95% CI 0.77 to 1.48). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants. Conclusions: Comparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.
EPCO-30. MACHINE-LEARNING PREDICTIVE MODELS BASED ON DNA METHYLATION SIGNATURES DETECTED IN LIQUID BIOPSY SPECIMENS ACCURATELY PREDICT THE DIAGNOSIS AND PROGNOSIS OF MENINGIOMAS
Authors: Grayson Herrgott, Thais Sabedot, Ruicong She, Michael Wells, Karam Asmaro, Tathiane Malta, Maritza Mosella, Kevin Nelson, Ana deCarvalho, Laila Poisson, Adam Robin, Ian Lee, James Snyder, Tobias Walbert, Steven Kalkanis, Jack Rock, Houtan Noushmehr, Anavaleria Castro
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Detection of distinct epigenetic features in circulating cell-free DNA (cfDNA) of liquid biopsy specimens (e.g. blood) provides an opportunity to diagnose and prognosticate central nervous system (CNS) tumors. Utilization of distinctive cell-type genome-wide DNA methylation patterns allows for development of machine-learning (ML) models with the ability to predict tumor diagnosis and prognosis, and remains widely unexplored in meningiomas using LB. METHODS We profiled the cfDNA methylome (EPIC array) in serum specimens from patients with meningiomas, other CNS tumors and nontumor conditions (n= 63, 190 and 18, respectively) and harnessed internal and external meningioma tissue methylome data. For diagnostic model development, we identified “meningioma specific” signatures through comparison of meningioma and non-meningioma serum specimens (Wilcoxon rank-sum test) which exhibited tissue methylation similarities named Meningioma- epigenetic Liquid Biopsy (MeLB), and were then employed to develop and cross-validate a Random-Forest derived “MeLB” score to discriminate meningiomas from the other conditions. To predict recurrence risk (RR), we classified a meningioma tissue cohort as ‘favorable’ or ‘unfavorable’ (low and high RR, respectively), using a validated ML outcome model and identified outcome-specific methylation markers with serum subgroup specificities used as input to train a Random-Forest to predict RR in serum-based specimens. RESULTS Prediction models based on meningioma-specific methylation markers detected in the serum presented a high accuracy in classification of samples as meningioma or not (Accuracy: 89.6%, Sensitivity: 80%, Specificity: 93.8%). The prognostic model using tissue-serum matching methylation markers was validated across an independent tissue-based cohort (Accuracy: 88%, Sensitivity: 86%, Specificity: 88%) and allowed for classification of serum samples according to RR. CONCLUSIONS Machine-learning models using DNA methylation markers identified in the serum can accurately diagnose and predict prognosis in patients with meningioma. After validation in an external cohort, these approaches may improve presurgical diagnosis and therapeutic management of patients with this type of tumor.
BRMP-04. AI-based biomarker of the peritumoral region using tissue microstructure
Authors: Zahra Riahi Samani, Drew Parker, Ronald Wolf, Steven Brem, Ragini Verma
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Glioblastomas, the most common malignant brain tumor [BS1], infiltrate into peritumoral brain structures, making clinical management challenging. An unmet need is to develop a biomarker that reliably characterize infiltration in the peritumoral region, where surgical biopsy or resection may be hazardous. Diffusion tensor imaging (DTI) with multicompartment modeling can characterize extracellular free water, providing unique information of the tissue microstructure that is able to capture this heterogeneity. We propose a novel biomarker based on peritumoral tissue microstructure, using deep-learning on DTI-based free water map. METHOD Peritumoral regions were automatically segmented for 136 patients with brain tumors (86 glioblastomas and 50 metastases, ages 23–87 years, 65 females). We trained a Convolutional Neural Network (CNN) on free-water maps using automatically defined patches in the peritumoral area from glioblastomas and metastases, labeled as low free-water and high free-water to extract a microstructural index for each voxel. To extract the biomarker, we grouped peritumoral voxels into connected components (CCs) where adjacent voxels have high (&amp;gt;0.9) microstructural index values. Two independent test sets related to two clinically significant problems were evaluated: i) metastases vs. glioblastomas; ii) glioma patients categorized into short and long survival groups and the number of CCs were statistically compared. RESULT Two-sample t-tests showed significant group difference in the number of CCs between metastases and glioblastomas (p&amp;lt; 0.05), and short and long-survivals (p&amp;lt;0.05) with higher number of CCs in metastases and long-survivals, which suggests smaller number of voxels in CCs. CONCLUSION The proposed biomarker based on CCs of microstructural index captures the differences in infiltration of the peritumoral region, showing larger CCs in glioblastomas and short-survivals corresponding to higher infiltration. CLINICAL IMPORTANCE The proposed biomarker provides a novel insight into the peritumoral microenvironment and can be derived from clinically feasible DTI data, providing new possibilities for the diagnosis and treatment of glioblastoma.
Abstract 14028: N-formyl Peptide Receptor 2 Activation via Annexin A1 Up-Regulates Hematoma Resolution After Germinal Matrix Hemorrhage
Authors: Jerry J Flores, Prativa Sherchan, Jiping Tang, John Zhang
Journal: Circulation (2021)

Introduction: Germinal matrix hemorrhage (GMH) is one of the leading causes of morbidity and mortality in preterm infants in the United States with little progress made in its clinical management. Survivors are often afflicted with long-term neurological sequelae, which include cerebral palsy, mental retardation, and post-hemorrhagic hydrocephalus. Blood clots disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage are key contributors towards post-hemorrhagic hydrocephalus development. n-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been associated with the activation of scavenger receptor CD36. CD36, a transmembrane glycoprotein, plays an essential role in microglia phagocytic blood clot clearance after GMH. Currently, FPR2’s role in blood clot clearance after hemorrhagic stroke is unknown. Hypothesis: We hypothesize that FPR2 activation by Annexin A1 will enhance hematoma resolution via upregulation of the CD36 signaling pathway, thereby improving short- and long-term neurological outcomes. Methods: Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in male and female P7 rat pups to induce GMH. Annexin A1 and FPR2 Inhibitor (Boc2) were given at 1-hour post-GMH via intranasal administration. Short-term neurobehavior were assessed using negative geotaxis test. Hematoma volume was assessed using hemoglobin assay. Protein expression was assessed using western blots. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests. Nissl staining was conducted on long-term samples to calculate ventricular dilation. Results: We have demonstrated that Annexin A1 treatment decreased hemoglobin content and improved neurobehavior at 72 hours post-ictus. Annexin A1 attenuated post-hemorrhagic hydrocephalus and neurological deficits 4 weeks post-ictus. Lastly, treatment increased FPR2 and CD36 protein expression. Conclusions: This present study demonstrates that FPR2 agonism via Annexin A1 enhances blood clot clearance, thereby improving outcomes after GMH.
Abstract 10518: Impact of Managing Provider Type on Severe Aortic Stenosis Referral and Treatment Patterns: An Optum Electronic Medical Records Analysis
Authors: Patricia A Pellikka, Ratnasari Padang, Christopher Scott, Todd J Brinton, Shannon M Murphy, Rosalind Fabunmi, Jeremy J Thaden
Journal: Circulation (2021)

A significant proportion of patients diagnosed with symptomatic severe aortic stenosis (ssAS) do not receive treatment with aortic valve replacement (AVR) despite current ACC/AHA guidelines. Delayed care leads to increased hospitalizations, worsening heart failure and death. Timely referral to a cardiac specialist is a critical step in the treatment pathway. We sought to identify the impact of managing provider type on follow-up care for newly diagnosed patients with severe aortic stenosis (sAS). We analyzed Optum® electronic medical records to identify adults with a new outpatient sAS echo diagnosis in the pre-COVID era (1/2017 - 3/2019). We identified integrated delivery network patients alive 1d post echo excluding those with missing data or AVR within 3d of echo, then selected those managed by a primary care provider (PCP) or a cardiologist (n=5,683). Baseline characteristics were used for covariate-adjusted Cumulative Incidence Function and Fine-Gray subdistribution hazard models. We estimated the impact of managing provider type on the specialist follow-up visit rate (cardiologist, interventional cardiologist and/or cardiothoracic surgeon) for all sAS patients and of surgical or transcatheter AVR for ssAS patients within 1 year of diagnosis. Within 90d of sAS diagnosis, 47% of PCP- vs. 73% of cardiologist-managed patients had a follow-up visit (1-year rates: PCP, 69% vs. cardiologist, 90%; Hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.49-0.59, p&lt;0.0001). Within 1 year of diagnosis, 36% of PCP- vs. 51% of cardiologist-managed ssAS patients underwent AVR (HR=0.72, CI: 0.63-0.82, p&lt;0.0001) (Figure). Analysis suggests lower referral rates for PCP- than cardiologist-managed patients. In ssAS, 1-year AVR rates were low, particularly for PCPs. These data underscore the importance of timely follow up of all severe AS patients for symptom assessment and appropriate treatment, presenting an opportunity for initiatives to drive behavior change.
Abstract 11722: Assessing Disparity of Performance Measure by Door-to-Balloon Time Between Rural and Urban Area for Management of Patients with ST-Segment Elevation Myocardial Infarction -Insights from the Nationwide Japan Acute Myocardial Infarction Registry-
Authors: Kento Fukui, Jun Takahashi, Kiyotaka Hao, Satoshi Honda, Sunao Kojima, Misa Takegami, Yasuhiko Sakata, Tomonori Itoh, Tetsu Watanabe, Morimasa Takayama, Tetsuya Sumiyoshi, Kazuo Kimura, Satoshi Yasuda
Journal: Circulation (2021)

Background: Door to balloon time (D2B) ≤90 minutes is a key indicator of quality of care for ST-segment elevation myocardial infarction (STEMI). The development of standardized management for STEMI may narrow the performance gap between rural and urban hospitals. However, there are few studies to explore the disparity of D2B and outcomes between rural and urban areas. Methods and Results: The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide, real-world registry study. We retrospectively analyzed 17,938 STEMI patients (68±13 years, female 22.4%) treated with percutaneous coronary intervention, who were divided into the following two groups according to population density of 1147 persons/km 2 ; patients hospitalized in rural area and those in urban area. Overall, the median D2B was 72 mins and 73% achieved the target D2B ≤90 mins. Patients with D2B ≤90 mins had a lower in-hospital mortality compared with those with D2B &gt;90 mins (4.7% vs. 8,4%, P&lt;0.001). Rural patients were characterized by higher age, more accumulation of coronary risk factors and a higher prevalence of Killip class ≥2 at presentation compared with urban patients. The median D2B was longer (70 mins vs. 62 mins, P&lt;0.001) and achievement rate for D2B ≤90 mins was lower (70% vs. 75%, P&lt;0.001) in rural group than urban group ( Figure A ). In-hospital mortality tended to be higher in rural group (6.1% vs. 5.5%, P=0.06), whereas the benefit in shortening of D2B was noted equally in both groups ( Figure B ). Conclusions: The real-world nationwide study of JAMIR demonstrated that shortening of D2B time was significantly associated with survival benefit of STEMI in both rural and urban area.
Abstract 10885: Decreased Hydraulic Force Contributes to Diastolic Dysfunction and Associates with Survival Beyond Conventional Measures of Diastolic Dysfunction
Authors: Dhnanjay Soundappan, Angus Fung, Daniel Loewenstein, David Playford, Geoff Strange, Rebecca Kozor, James Otton, Martin Ugander
Journal: Circulation (2021)

Introduction: Decreased hydraulic force has recently been identified as a mechanism contributing to left ventricular (LV) diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF). However, it is unclear if hydraulic forces are independently associated with survival. Hypothesis: Decreased diastolic hydraulic force, estimated as the atrioventricular area difference (AVAD), is associated with survival independent of conventional diastolic dysfunction measures. Methods: Patients (n=37947, median [interquartile range] 4.9 [2.9-8.0] years follow-up, 6103 events) were selected from the National Echo Database Australia based on the presence of relevant transthoracic echocardiographic measures, LV ejection fraction (LVEF) ≥ 50%, heart rate 50-100 beats/minute, the absence of moderate or severe valvular disease, pericardial disease or mitral annular calcification, and no prior cardiac surgery. AVAD was calculated as the cross-sectional area difference between the LV and left atrium (LA) using circular approximation of LV end-diastolic diameter and LA end-systolic diameter. LV diastolic dysfunction grading was performed according to 2016 guidelines. Results: In multivariable linear regression, AVAD was weakly associated with E/e’, e’, peak tricuspid regurgitation velocity, and LVEF (global adjusted R2=0.11, p&lt;0.001), but not associated with left atrial volume index (p=0.83). In multivariable Cox regression, there was an association with survival for both AVAD (chi-square 279, hazard ratio (HR) [95% confidence interval] 1.23 [1.20-1.26], p&lt;0.001) and diastolic dysfunction grading (chi-square 1217, HR 3.21 [3.00-3.42], p&lt;0.001). In a separate multivariable model, there was an association with survival for both AVAD (chi-square 371, HR 1.27 [1.24-1.30], p&lt;0.001) and E/e’ (chi-square 1020, HR 1.39 [1.36-1.42], p&lt;0.001). Conclusions: Decreased hydraulic force, estimated as AVAD, is associated with diastolic dysfunction, and provides prognostic information beyond conventional measures used to grade diastolic dysfunction. This suggests that increased LA size relative to LV size is a potential therapeutic target in HFpEF.