tbuckley/cabot-search huggingface dataset:
RADT-12. USE OF FDOPA PET FOR RADIATION THERAPY TARGETING IN GRADE 2 IDH MUTANT GLIOMA
Authors: James Cordova, Thomas Mazur, Timothy Mitchell, Gloria Perez-Carrillo, Qing Wang, Yong Wang, Maria Ponisio, Jiayi Huang
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Low-grade, IDH mutant (IDHmt) gliomas typically do not enhance on MRI complicating radiotherapy (RT) target delineation. Amino acid PET using 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) has demonstrated avidity in IDHmt gliomas and may assist in RT planning for non-enhancing tumors. This study aims to compare conventional and FDOPA-defined target volumes in grade 2 IDHmt gliomas. METHODS In a prospective pilot study, patients underwent MRI and FDOPA PET using a 3T MRI/PET system followed by standard therapy. Gross tumor volumes (GTV) included the T2/FLAIR abnormality and surgical cavity; clinical target volumes (CTV) included a 1 cm expansion constrained anatomically. Metabolic target volumes (MTVs) were generated using the FDOPA SUV &amp;gt; 1.5-fold normal brain isocurve. Union of GTV and MTV generated a fusion GTV (fGTV); expanding fGTV by 1 cm yielded the fusion CTV (fCTV). Target volumes were compared volumetrically with overlap (Dice coefficient) and surface metrics (Hausdorff distance). Medians are reported with ranges. RESULTS Four patients with grade 2 IDHmt glioma (3 1p/19q codeleted oligodendrogliomas, 1 non-codeleted astrocytoma) received MRI/PET before treatment. All oligodendrogliomas exhibited FDOPA avidity; the astrocytoma showed no avidity. GTV and CTV measured 16.1 cc (4.9 - 82.2 cc) and 76.7 cc (29.5 - 256.1 cc), respectively. The MTV volume outside of GTV was 0.8 cc (0.2 – 6.1 cc), but was covered in each case by the CTV. Addition of FDOPA increased fGTV and fCTV volumes by 5.4% and 17.5%, respectively. Dice coefficient and Hausdorff distances for GTV vs fGTV were 0.96 (0.95 - 0.99) and 11.2 mm (10.0 – 11.9 mm), respectively, and for CTV vs fCTV were 0.87 (0.81 – 0.95) and 10.2 mm (10.0 - 11.0), respectively. CONCLUSIONS FDOPA PET identified tracer-avid regions outside of MRI-defined GTVs in a group of IDHmt gliomas. FDOPA PET provides useful metabolic information for RT planning and warrants further investigation.
Abstract 11373: Computational Approach in Target Discovery and Its Validation: In Search for Inhibitors of Vascular Calcification
Authors: Takeshi Tanaka, Takaharu Asano, Takehito Okui, Shiori Kuraoka, Sasha A Singh, Masanori Aikawa, Elena Aikawa
Journal: Circulation (2021)

Introduction: Vascular calcification is cardiovascular disorder which has no therapeutic options. We previously reported that O-octanoyltransferase (CROT) suppression can inhibit calcification in vivo and in vitro through ameliorating mitochondrial function and fatty acid metabolism. Hypothesis: Small molecule compound inhibiting calcification via CROT-associated mechanisms will be excellent candidate for non-invasive treatment of vascular calcification. Here we used a computational approach to identify existing drugs that can inhibit vascular calcification through CROT. Methods: For screening of the compounds that reduce CROT expression, we utilized L1000 computational platform, which contains gene expression profiles in various cell lines and substances. We identified and tested 17 compounds in human primary smooth muscle cells (hSMCs) treated with calcification inducing osteogenic media. Niclosamide, an FDA-improved anthelminthic drug, inhibited calcification along with reduced CROT mRNA expression. To validate this compound in vivo , oral doses of Niclosamide (0 or 750 ppm admixed with diet) were given to Ldlr-deficient mice fed with high fat diet for 10 weeks. At sacrifice, the aortic calcification was visualized and quantified using optical molecular imaging employing near-infrared calcium tracer (Osteosense680) and then examined by histopathology. Samples from the aorta were collected to perform proteomics analysis at intermittent and terminal time points. Results: Molecular imaging and histological analyses of mouse aortas showed significant decrease of calcification after 10 weeks of Niclosamide treatment. Niclosamide improved fatty liver changes with decreased cholesterol levels in the liver along with decreased CROT expression, while plasma total cholesterol levels did not change. Proteomics analysis showed that lipid metabolism and transportation of fatty acid or cholesterol were increased with AMPK or Wnt pathways alteration. Conclusions: We identified a small molecule, which can inhibit calcification in vivo and in vitro with reduced CROT expression. Our computational strategy suggests that repurposing of an “old” drug could present novel treatment for vascular calcification.
Abstract 13174: Female Sex is Not Associated With Subsequent Heart Failure in Adult Patients Treated With Anthracyclines
Authors: Gabriel Pajares Hurtado, Andrea Nathalie Rosas Diaz, Cole Turissini, Sujithraj Dommaraju, Sarah Warack, Michelle J Keyes, Jordan B Strom, Aarti Asnani
Journal: Circulation (2021)

Introduction and Hypothesis: Female sex has long been considered a risk factor for anthracycline-associated cardiotoxicity, based largely on data in childhood cancer survivors. However, preclinical experiments suggest that female sex hormones present in adulthood may protect against doxorubicin cardiotoxicity. We therefore hypothesized that female sex would be associated with a decreased odds of heart failure in adult patients treated with anthracyclines. Methods: We conducted a retrospective cohort study of 871 adult patients (44% women and 56% men) at our medical center with no prior history of heart failure who were treated with anthracyclines for non-hormone-dependent malignancies including lymphoma, leukemia, and sarcoma. Patients who expired during the study period were excluded. The presence or absence of heart failure within five years of initiation of anthracyclines was assessed using ICD-9/10 codes. Logistic regression models were used to assess odds ratios based on self-reported sex and other covariates, adjusting for age. Results: Baseline characteristics were similar in men and women, including age, total cumulative anthracycline dose, and prevalence of cardiovascular comorbidities such as hypertension, diabetes, and coronary artery disease. The odds of heart failure increased modestly with age (OR: 1.02; 95% CI: 1.01 to 1.03, p = 0.001). In an age-adjusted model, female sex was not associated with subsequent heart failure (OR: 1.03, 95% CI 0.72 to 1.47, p = 0.88), including after stratification by age ≤ 50 years or &gt; 50 years as a surrogate for menopausal status. Conclusions: In this retrospective cohort study, female sex was not associated with heart failure in adult patients treated with anthracyclines for non-hormone-dependent tumors. These findings diverge from prior reports suggesting an increased risk of cardiotoxicity in women. Future studies will assess the competing risks of cancer and cardiovascular disease/death in men versus women treated with anthracyclines.
Noninvasive respiratory support following extubation in critically ill adults: a systematic review and network meta-analysis
Authors: Shannon M. Fernando, Alexandre Tran, Behnam Sadeghirad, Karen E. A. Burns, Eddy Fan, Daniel Brodie, Laveena Munshi, Ewan C. Goligher, Deborah J. Cook, Robert A. Fowler, Margaret S. Herridge, Pierre Cardinal, Samir Jaber, Morten Hylander Møller, Arnaud W. Thille, Niall D. Ferguson, Arthur S. Slutsky, Laurent J. Brochard, Andrew J. E. Seely, Bram Rochwerg
Journal: Intensive Care Medicine (2021)
3D biplane versus conventional 2D ultrasound imaging for internal jugular vein cannulation
Authors: Harm J. Scholten, Michael I. Meesters, Leon J. Montenij, Erik H. M. Korsten, R. Arthur Bouwman, Joris van Houte, Cecile H. Kicken, Renee J. C. van den Broek, Leontien ter Horst, Veerle Piot
Journal: Intensive Care Medicine (2021)
Lung transplantation for acute respiratory distress syndrome: a retrospective European cohort study
Authors: Jens Gottlieb, Philipp M. Lepper, Cristina Berastegui, Beatriz Montull, Alexandra Wald, Jasvir Parmar, Jesper M. Magnusson, Felix Schönrath, Tanel Laisaar, Sebastian Michel, Hillevi Larsson, Robin Vos, Assad Haneya, Tim Sandhaus, Erik Verschuuren, Jérôme le Pavec, Jussi Tikkanen, Konrad Hoetzenecker
Journal: European Respiratory Journal (2021)

Background The published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres. Methods We conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of “ARDS/pneumonia” were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed. Results 55 centres (81%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015–2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977–55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation. Conclusions Lung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging.
NIMG-24. RANO CRITERIA DETECTS EARLY PROGRESSION SOONER THAN MODIFIED RANO CRITERIA IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Gilbert Youssef, Mary Jane Lim-Fat, Camden Bay, Omar Arnaout, Wenya Linda Bi, Daniel Cagney, Matthew DeSalvo, L Nicolas Gonzalez Castro, Jeffrey Guenette, Eudocia Quant Lee, J Ricardo McFaline-Figueroa, Christopher Potter, David Reardon, Timothy Cloughesy, Benjamin Ellingson, Rifaquat Rahman, Raymond Huang, Patrick Wen
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Accurate response criteria are crucial for determining treatment efficacy. The response assessment in neuro-oncology (RANO) criteria was developed to standardize response assessment in neuro-oncology. Modified RANO (m-RANO) criteria were recently proposed to address some limitations of the initial criteria including the use of a post-radiation baseline and an additional scan to confirm progression. We sought to identify differences in the association of progression-free survival (PFS) and overall survival (OS) using RANO and m-RANO criteria. METHODS We conducted a retrospective review of newly diagnosed glioblastoma (GBM) patients treated at Dana-Farber Cancer Institute from January 2013 until December 2019. Patients with available clinical and imaging data obtained before initiation of treatment, after radiation completion and at intervals of 1 to 3 months were included. MRIs were evaluated by two independent readers, and PD dates determined using RANO and m-RANO criteria. RESULTS 552 patients were included. 97.1% of the tumors were IDH wild-type. MGMT promoter was unmethylated in 51.4%, methylated in 35.1% and undetermined in 8.5%. Median OS among patients was 18.1 months. 72 patients (13%) did not have PD at the end of the study. 83 patients had treatment change while being clinically stable and without a confirmation scan and were excluded from the final analysis. PFS was 8.2 months with RANO and 8.4 months with mRANO. Difference in PD dates between RANO and m-RANO was detected in 76 patients (14%), where PFS was 3.5 months with RANO and 5.1 months with m-RANO. These patients had a worse median OS than those with identical RANO and m-RANO PD dates (15.2 vs. 22.4 months, p&amp;lt; 0.0001). CONCLUSION RANO and m-RANO criteria resulted in identical PFS for most patients. 14% of patients had discordant PD dates and a worse prognosis. These patients progressed early, and their PD was identified sooner with RANO criteria.
Abstract 10308: Rural-Urban Differences in Health Characteristics and Health Behaviors in 14,955 US Stroke Survivors
Authors: Ryan Bailey, Natalie Miner
Journal: Circulation (2021)

Introduction: Rural residence is associated with increased CVD risk, including incident stroke. Less is known about the association of rurality on health characteristics and health behaviors among stroke survivors. The purpose of this study was to determine the presence and magnitude of rural/urban differences in health characteristics and health behaviors among stroke survivors. Methods: Data from 14,599 stroke survivors were available from the 2017 &amp; 2019 Behavioral Risk Factor Surveillance System, an annual health survey of non-institutionalized US adults. Inclusion criteria included history of self-reported stroke and age ≥65 years. Respondents with missing data regarding rural vs. urban dwelling status were excluded from analysis. Respondents provided self-reported data on sociodemographics (sex, race, marital status, education, and income), health characteristics, and health behaviors (see table for characteristics and behaviors). Logistic regression was used to compute odds ratios and 95% CI’s to examine the association among rural/urban status and health characteristics and health behaviors. Results: Prevalence of health characteristics and health behaviors, and computed adjusted odds ratios, are presented in the table. Although the prevalence of disability, poor general health, and insufficient physical activity were higher among rural-dwelling stroke survivors, odds ratios adjusted for sociodemographic and health characteristics demonstrated no association among rurality, health characteristics, and health behaviors. Conclusions: Although no differences in health characteristics and behaviors were found between rural and urban-dwelling stroke survivors, prevalences of many CVD risk factors were high, which increase risk for recurrent stroke, secondary conditions, and chronic disease. Interventions for improving risk factors and health behaviors in this health disparate population are needed.
Abstract 13860: Prognostic Implication of Biventricular Global Longitudinal Strain in Patients Undergoing Tricuspid Valve Surgery for Severe Isolated Tricuspid Regurgitation
Authors: Dae-Young Kim, Jiwon Seo, Iksung Cho, Geu-Ru Hong, Jong-Won Ha, Chi Young Shim
Journal: Circulation (2021)

Introduction: Isolated tricuspid valve (TV) surgery can be performed for patients with symptoms due to severe isolated tricuspid regurgitation (TR), preferentially before the onset of significant right ventricular (RV) dysfunction. In patients with severe TR, chronic RV volume overload may mask intrinsic myocardial dysfunction. Ultimately, RV dysfunction promotes LV underfilling, which can lead to left ventricular (LV) mechanical dysfunction. Hypothesis: Pre and postoperative biventricular global longitudinal strain (GLS) would give prognostic information in patients with isolated severe TR. Methods: In 117 patients who underwent TV surgery with severe isolated TR in a single tertiary center, we comprehensively assessed LV, RV, and biventricular global longitudinal strain (GLS) by speckle tracking echocardiography before and at least 1 month after TV surgery. Biventricular GLS was defined as a summation of LV-GLS and RV free wall strain. Patients with a history of open-heart surgery, severe left-side valve disease, reduced LV ejection fraction, and who underwent concomitant coronary artery bypass surgery were not included. Primary outcomes were defined as a composite of death, heart failure hospitalization, re-do TV surgery, and heart transplantation. Results: During a mean of 4.3 ± 3.9 years after TV surgery, 26 patients (22.2%) had experienced primary outcomes. In patients with primary outcomes, a previous history of diabetes mellitus and atrial fibrillation were more common, and
Abstract 11123: Racial and Ethnic Disparities Exist in Economic Stability and Healthcare Access and Utilization Among U.S. Children with Heart Conditions, National Survey of Children’s Health 2016-2019
Authors: Ashley Judge, Karrie F Downing, Matthew Oster, Wendy N Nembhard, Sherry Farr
Journal: Circulation (2021)

Racial disparities exist in mortality among children with heart conditions, but less is known about disparities in upstream determinants of health. Our objective was to assess differences in economic stability, access to care, and healthcare utilization by race/ethnicity among children with heart conditions. Using caregiver-reported data on 0- to 17-year-olds from the 2016-2019 National Survey of Children’s Health, we calculated prevalence estimates for family economic stability (caregiver educational attainment and work status), child’s healthcare access (insurance type, usual place of care, and problems paying for child’s care), and child’s healthcare utilization (receipt of preventive care, specialty care, and 1 and ≥2 emergency room (ER) visits in the past 12 months) by race/ethnicity (Hispanic, non-Hispanic (NH) Black, and NH White), accounting for complex sampling and weighted to produce national estimates. We used the predicted marginal approach to multivariable logistic regression to generate adjusted prevalence ratios (aPRs) controlling for child’s age and sex. Of 2,596 children with heart conditions, 65.5% were NH White and 52.2% were male. Compared to NH White children, Hispanic and NH Black children, respectively, were 0.9 to 0.8 times less likely to have caregivers who were employed or had more than a high school education. Hispanic and NH Black children were more likely to have public insurance (respective aPRs 1.8, 2.1) and less likely to have a usual place of care (aPRs 0.9, 0.8). Hispanic children were less likely than NH White children to have visited the ER once in the past 12 months, whereas NH Black children were more likely to have visited the ER once (aPR 1.4) and twice or more (aPR 2.5). Among U.S. children with heart conditions, racial/ethnic disparities were seen in indicators of economic stability, access to care, and healthcare utilization.
Abstract 13214: Coping With Heart Failure: Association Between Coping Strategies and Health Outcomes in Patients With Heart Failure
Authors: Mohammed O Alanazi, Pallav Deka, Charles Given, Gwen Wyatt
Journal: Circulation (2021)

Introduction: Coping is an essential element of self-management in chronic conditions such as heart failure (HF) where patients experience poor physical and emotional health outcomes. Coping strategies (problem-focused, active, and avoidant) often determine patients’ well-being. Although multiple factors are known to be associated with the selection of coping strategies in HF, the evidence is limited and inconclusive. Specifically, clarity on the association between HF patients’ demographics (age, sex, education, income), disease duration, and symptom severity with coping strategies is needed. Research Questions: This in-progress study seeks answers to the following questions: 1) Identify the association between demographics, disease duration, and symptom severity and coping strategies (problem-focused, active and avoidant); 2) Examine the association between the three types of coping strategies and physical and emotional health status outcomes; 3) Describe the mediating effect of coping strategies on the relationship between the reported symptom severity and subsequent physical and emotional health outcomes. Conceptual framework: This study is guided by the Stress and Coping model that consists of three components: antecedents of stress, coping strategies, and adaptational outcomes. Methods: This in-progress study uses a cross-sectional descriptive design examining associations and potential mediators. A total of 112 HF patients will be recruited online using ResearchMatch , a secure online tool that aims to match researchers with target participants, and in-person from cardiovascular clinics in Michigan. The inclusion criteria are: 1) HF diagnosis, 2) a New York Heart Association classification ≥ II; 3) aged over 18; 4) speak and read in English. The Brief COPE and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) will be used to measure coping strategies and health outcomes, respectively. A mediation model was proposed to illustrate the mechanism in which coping mediates the influence of symptom severity on health status outcomes. Conclusion: This study will provide insight into coping strategies utilized by HF patients and highlight the influence of demographics, disease duration, and symptom severity on coping.
Abstract 11301: Comparing All-Cause to Procedure-Related Mortality in Cardiac Implantable Electronic Device (CIED) Lead Removals: A Systematic Review
Authors: Josh E Herman, Deborah Somanader, Laith Ishaq, Ahmed Abdelaal, Vrati Mehra, Rayoun Ramendra, Andrew Morris
Journal: Circulation (2021)

Introduction: Infection is a serious complication in patients with cardiac implantable electronic devices (CIEDs). Infection of the generator pocket, systemic bacteremia and lead-related or suspected endocarditis are absolute indications for device removal. While previous studies have reported infection as a major risk factor for mortality, it is unclear what proportion is related to complications of infection or the CIED lead removal procedure itself. Objective: We have conducted a systematic review looking at all-cause in-hospital mortality, intraprocedural, and procedure-related mortality in CIED lead removals and have done a subanalysis specifically exploring removals for infectious indications. Methods: A search was performed of studies published between January 1, 2000-August 29, 2019 indexed on Medline, EMBASE and Cochrane. Inclusion criteria were: (a) transvenous removal of ICD, pacemaker or CRT device leads, (b) Age≥18, (c) n&gt;100 patients. Exclusion criteria were: (a) generator only procedures, (b) planned surgical extractions, (c) data prior to 2000. From these studies, we further selected papers containing mortality data in which all subjects had infectious indications for removal, or papers with infectious only cohorts of n&gt;100 with mortality data. Outcomes: All-cause mortality during index hospitalization, intraprocedural mortality, procedure related mortality. Results: 2307 abstracts were screened after de-duplication resulting in 164 papers for full text review. Of these 164, 8 papers were selected for analysis based on our inclusion criteria. 7 reported periprocedural/mortality during index hospitalization which ranged from 1.47-7.20%; median 4.98% (IQR 2.74-5.69%). 4 studies reported intraprocedural mortality which ranged from 0-0.69%; median 0.10% (IQR 0.00-0.32%). and 6 reported procedure related death which ranged from 0-0.72%; median 0.50% (IQR 0.10-0.67%). Conclusions: Mortality after CIED lead removal is high in patients presenting with infection, however intraprocedural mortality and death directly related to the removal procedure remains low.