tbuckley/cabot-search huggingface dataset:
Abstract 11225: Comparison of Coronary Artery Calcium Scores in South Asians and Other Racial-Ethnic Groups
Authors: Suvasini Lakshmanan, Suraj Dahal, April Kinninger, Venkat Manubolu, Jairo Aldana, Sion Roy, Matthew Budoff
Journal: Circulation (2021)

Introduction and Hypothesis: There is a disproportionately higher incidence of atherosclerotic cardiovascular disease (ASCVD) and associated adverse outcomes in South Asians (SA), compared to other races. SA ancestry has been identified as a risk enhancer in the US cholesterol guidelines. Coronary artery calcium (CAC), a validated marker of sub clinical atherosclerosis offers a robust assessment of CVD risk. We sought to compare the distribution of CAC scores as a marker of CVD risk, across various age groups in SA and other races/ethnicities. Methods: Our analyses included 33,663 individuals (517 SA, 24,060 whites, 1,509 African Americans (AA), 3,759 Hispanics, 3,818 Asians), who underwent CAC scoring at our center. CAC scores were stratified by age, across various races/ethnic sub-groups. Age groups were classified into quartiles as follows: &lt;51 years, 51-59 years, 59-67 years and &gt;67 years of age. Differences in median CAC across races/ethnicities were tested with the Kruskal-Wallis Test, by age quartiles as described. Results: Mean (SD) age was 59 (11.6) years and 63% were men in the entire cohort. SA over 67 years of age, had significantly higher median CAC score 354.0, Interquartile Range (IQR) 36 - 1476, compared to other race/ethnicities (Median CAC (IQR): whites, 195, (21-762), Hispanics 167.5, (19-779), Asians 144, (14-642), AA 159 (8.5-676) (P=0.0019). In age groups from 50-67 years of age, median CAC scores were not significantly different between these groups (Figure 1). Conclusions: In older age groups, SA have higher median CAC scores compared to whites and other racial/ethnic groups including AAs, Hispanics and other Asians. The observed differences in atherosclerotic burden provide mechanistic insights to higher CVD risk, in the vulnerable SA groups. Future studies should explore the effects of CAC screening on treatment strategies, such as initiation of statins and prognosis in SA.
DDRE-28. IDENTIFICATION OF SYNERGISTIC DRUG COMBINATIONS FOR THE THERAPY OF IDHmut GLIOMA
Authors: Rolf Warta, Florian Stammler, Andreas Unterberg, Christel Herold-Mende
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE Isocitrate Dehydrogenase (IDH) mutation in glioma results in a multitude of biological differences with consequences for survival and therapy response. Therefore, IDH mutated (IDHmut) and wildtype (IDHwt) tumors are regarded as separate entities with the need for adjusted therapy like the combination of procarbazine, CCNU and vincristine (PCV). However, as vincristine has often severe side effects like neuropathy new effective therapy options are required. Therefore, we searched for combinations of FDA-approved drugs which effectively inhibit the growth of IDHmut cells in vitro. METHODS We tested different drug combinations of a drug library consisting of 146 FDA-approved drugs on two established IDHmut GSC lines. Based on a previous single agent drug screen, six drugs were selected (Idarubicin, Ixazumib, Ponatinib, Neratinib, Romidepsin) to be combined with all 146 drugs of the library. Cell viability was assessed by the CellTiterGlo 3D assay (Promega) in 96 well plates, while Caspase-Glo 3/7 3D assay was used to measure induction of apoptosis. RESULTS Out of 1460 drug combinations tested altogether 21 synergistic drug combinations could be identified and validated. The combination with the highest blood-brain-barrier permeability score was further investigated. Finally, drug-concentrations elucidating the highest synergistic effect on proliferation was further studied in a 8-point dose-response matrix followed by validation in additional four IDHmut GSC lines. CONCLUSION This work can lay the foundation for future improvements of the therapy of patients suffering from LGGs.
Abstract P399: Endothelial Myc Deletion Reduces Doxorubicin-induced Cardiac Dysfunction And Remodeling
Authors: Jacqueline F Machi, Alejo A Morales, Yue Qi, Nikole Q Mendez, Augusto F Schmidt, Claudia O Rodrigues
Journal: Circulation Research (2021)

Cardiotoxicity is the most common complication in patients undergoing chemotherapy, and the leading cause of death in long-term cancer survivors. Anthracyclines are highly effective drugs broadly used in cancer treatment, but with limited use due to cardiotoxicity. Currently, there is no effective treatment for anthracycline-induced cardiotoxicity. Recent studies have shown the role of endothelial cells in cardioprotection after anthracycline exposure, though mechanisms involved remain elusive. In the present study, we provide supporting evidence that endothelial Myc plays a role in anthracycline-induced cardiotoxicity. Myc is a stress sensor and master regulator involved in multiple cellular functions. Deregulated Myc expression has been linked to multiple pathological conditions. Using a conditional knockout model, we tested the hypothesis that loss of endothelial c-Myc is cardioprotective. Control (CT) and endothelial knockout (KO) juvenile mice were exposed to 15mg/kg cumulative dose of doxorubicin administered in 6 doses every 2-days along 2-weeks. Echocardiography was performed 3-days after last dose. Doxorubicin had a significant sex-specific impact in cardiac function as previously reported. In CT males, doxorubicin caused significant decline in stroke and diastolic volume, without changes in ejection fraction. In CT females, doxorubicin caused significant increase in heart rate, decline in ejection fraction, and increase in diastolic volume. KO animals showed attenuated response to these doxorubicin-induced alterations in both males and females. Pathology analysis of the heart 3-months after doxorubicin exposure showed significant decline in CT and KO male cardiac mass and collagen content, both of which were attenuated in KO animals. Doxorubicin did not show any impact on mass and collagen content in females. RNAseq analysis suggested modulation of distinct pathways in CT and KO hearts associated with inflammation, DNA damage and repair, cell death and fibrosis. Cdkn1a and TP53 were top upstream regulators predicted to be activated in CT and let-7 in KO hearts. Our findings support the potential targeting of endothelial Myc in doxorubicin-induced cardiotoxicity.
SARS-CoV-2 infection and return to play in junior competitive athletes: is systematic cardiac screening needed?
Authors: Luna Cavigli, Michele Cillis, Veronica Mochi, Federica Frascaro, Nicola Mochi, Arnel Hajdarevic, Alessandra Roselli, Massimo Capitani, Federico Alvino, Silvia Giovani, Corrado Lisi, Maria Teresa Cappellini, Rosa Anna Colloca, Giulia Elena Mandoli, Serafina Valente, Marta Focardi, Matteo Cameli, Marco Bonifazi, Flavio D'Ascenzi
Journal: British Journal of Sports Medicine (2021)

Background SARS-CoV-2 infection might be associated with cardiac complications in low-risk populations, such as in competitive athletes. However, data obtained in adults cannot be directly transferred to preadolescents and adolescents who are less susceptible to adverse clinical outcomes and are often asymptomatic. Objectives We conducted this prospective multicentre study to describe the incidence of cardiovascular complications following SARS-CoV-2 infection in a large cohort of junior athletes and to examine the effectiveness of a screening protocol for a safe return to play. Methods Junior competitive athletes suffering from asymptomatic or mildly symptomatic SARS-CoV-2 infection underwent cardiac screening, including physical examination, 12-lead resting ECG, echocardiogram and exercise ECG testing. Further investigations were performed in cases of abnormal findings. Results A total of 571 competitive junior athletes (14.3±2.5 years) were evaluated. About half of the population (50.3%) was mildly symptomatic during SARS-CoV-2 infection, and the average duration of symptoms was 4±1 days. Pericardial involvement was found in 3.2% of junior athletes: small pericardial effusion (2.6%), moderate pericardial effusion (0.2%) and pericarditis (0.4%). No relevant arrhythmias or myocardial inflammation was found in subjects with pericardial involvement. Athletes with pericarditis or moderate pericardial effusion were temporarily disqualified, and a gradual return to play was achieved after complete clinical resolution. Conclusions The prevalence of cardiac involvement was low in junior athletes after asymptomatic or mild SARS-CoV-2 infection. A screening strategy primarily driven by cardiac symptoms should detect cardiac involvement from SARS-CoV-2 infection in most junior athletes. Systematic echocardiographic screening is not recommended in junior athletes.
Abstract 11075: Unearthing the Gaps in Targeted Medical Therapy in Chronic Heart Failure
Authors: Lotos Galison, Akshyaya Pradhan, Rishi Sethi, Sharad Chandra, pravesh vishwakarma, Gaurav Chaudhary, Monika Bhandari, Akhil Kumar Sharma, prachi sharma, Abhishek Singh, Ayush Shukla, SK Dwivedi
Journal: Circulation (2021)

Introduction: Despite recent advancement in management of Heart failure (HF), the accessibility and affordability of this treatment is still an issue in developing countries. Hypothesis: We aimed to assess etiological and pharmacological profile of heart failure patients in our study. Methods: The study population consisted of 407 patients with chronic heart failure aged &gt;18 years attending as outpatient. Acute Heart Failure and patients hospitalized for Acute Heart Failure within 4 weeks were excluded. The diagnosis of heart failure was made in accordance with 2016 ESC guidelines for the Heart failure. Patients were stratified into those with reduced ejection fraction(HFrEF: when EF &lt; 40%), preserved ejection fraction (HFpEF: when EF &gt; 50%), and those with mid-range ejection fraction (HFmrEF; when EF = 40-50%). Results: The mean age of the cohort was 58.8 years &amp; 64.4% (n = 262) were males. The overall mean left ventricular ejection fraction (LVEF) of the cohort was 38.47±9.24%. Heart failure with reduced ejection fraction (HFrEF) was seen in 58.5% of patients. The two most prevalent etiologies of HF were ischemic heart disease (IHD) (53.6%; n = 218),) and idiopathic cardiomyopathy (34.2%; n = 133).The percentage of patients who received diuretics, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), aldosterone antagonists, ARNI and Beta blockers as treatment were 93.12%, 71.99%, 8.11%, 82.31% , 6.63 % and 90.42 % respectively.The most commonly prescribed ACEI was ramipril (68.8%), Betablocker was carvedilol (45.7%) and MRA was Spironolactone (82.33%).Guideline directed medical therapy (beta-blocker,RAAS blocker and MRA-all 3) was prescribed in 63.88 % of patients. The median dose of ramipril was 2.86 mg (28% of target),carvedilol was 6.4 mg (12.8% of target), ARNI was 88.89mg (44.4% of target ) &amp; spironolactone was 49.3mg (98.6% of target). Conclusions: Ischemic Heart Disease is the most common etiology of HF in the region.Despite the encouragement to follow the ESC Heart Failure Guidelines, only 63.88 % of patients were on prescribed guideline based therapy. Even among those getting drug, majority drugs failed to reach even 50% of the target doses with the exception of MRA.
INNV-43. MORE THAN WHAT MEETS THE EYE: ETMR AN UNDER RECOGNISED ATYPICAL BRAINSTEM PRIMARY. A RARE BRAIN TUMOR CONSORTIUM (RBTC) STUDY
Authors: Sara Khan, Palma Solano-Paez, Jordan R Hansford, Mei Lu, Salma Al-karmi, Lydia Leung, Ashley Plant-Fox, Melina La Spina, Eden Andrew, Christopher Dunham, Joanna Phillips, Rita Ridola, Spyros Sgouros, Lili-Naz Hazrati, Mary Shago, Lindsey Hoffman, Cynthia Hawkins, Ute Bartel, Jean Mulchay, Rajeev Vibhakar, Nicolas Andre, Eric Bouffet, Annie Huang
Journal: Neuro-Oncology (2021)

Abstract 10% of all pediatric brain tumors arise in the brainstem. Amongst these gliomas are the most common while other entities are rare and infrequently described in the literature. In this study we investigated the prevalence of non-gliomatous tumors in the brainstem. Amongst the 1323 embryonal tumours received at the RBTC, we identified 17 cases of ETMRs (17/165) that presented as brainstem primaries. Previously grouped within CNS-PNETs, ETMR, is a new WHO diagnostic entity, characterized by C19MC alterations. ETMR is a disease of infancy, the clinical spectrum of which is poorly understood. ETMRs arise at multiple CNS locations including cerebrum being most common (60%,) followed by cerebellum (18%) and midline structures (6%); notably 10% were brainstem primaries, mimicking DIPG radiologically. All patients presented with a short history of progressive neurological symptoms, with most common signs and symptoms of cranial neuropathies, long tract signs and gait disturbance. Median age at diagnosis was 27 months (range 16-75months) with a male to female ratio of 0.9:1. Predominantly localized (M0-94%, M2-3 -6%) majority of patients underwent upfront biopsy or partial resection (15/17:88%), while complete tumor resection was achieved in 2 cases. All patients received heterogenous combination of chemotherapy with and without radiotherapy. Majority of patients progressed rapidly with median time to progression of 4 months and overall survival of &amp;lt; 13 months. The only long-term surviving patient had complete resection dose intensified chemotherapy and radiation (OS 202months). Primary ETMRs in the brainstem are under recognised entities and carry a dismal prognosis. Although rapidly progressive, prompt recognition, maximal resection and management with multimodal adjuvant therapy should be considered in cases with brainstem disease.
Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial
Authors: Craig Haifer, Sudarshan Paramsothy, Nadeem O Kaakoush, Aiasha Saikal, Simon Ghaly, Tao Yang, Laurence Don Wai Luu, Thomas J Borody, Rupert W Leong
Journal: The Lancet. Gastroenterology & hepatology (2021)
QOLP-35. PEDIATRIC POST-MORTEM TISSUE DONATION DURING A PANDEMIC: A MODEL OF COLLABORATION
Authors: Esteban Uceda, Cindy Campbell, Sheila McThenia, Melanie Degliuomini, Yasmin Khakoo, David J Pisapia, Jeffrey Greenfield
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Obtaining post-mortem tissue from pediatric oncology patients is not only critical to research, but studies show that participating in the process can also help grieving families heal. Since 2019, the national Gift from a Child program — a multi-institutional effort to increase the rate of rapid autopsies for pediatric CNS tumor patients — has made significant progress. Collecting high-quality post-mortem tissue has advanced research through cell line generation and genomic analyses. Unfortunately, some autopsy programs temporarily shut down during the COVID-19 pandemic. METHODS We retrospectively reviewed autopsies of four patients treated at Memorial Sloan Kettering (MSK) who underwent limited brain post-mortem examination at Weill Cornell Medicine College (WCMC) from June 2020 to June 2021. We collected patient demographics; DNR status; time of death and procedure; restrictions due to the COVID-19 pandemic; and results of the tissue analysis. Each case presented unique challenges and the timing of securing parental consent varied. RESULTS Three of four specimens were processed within 12 hours of the time of death. Two Spanish-speaking families required interpreters services to obtain consent. In all cases tumor aliquots were flash frozen for further study. All specimens contained viable tumor and cell line generation was successful in one case. All families/caregivers expressed gratitude for the opportunity to participate and for the handling of the procedures. DISCUSSION Despite the sensitive nature of these cases, clinicians should offer the option of a rapid autopsy to caregivers of pediatric patients based on the scientific need and the positive effect it has on grieving families. This paper outlines the logistical efforts required for these donations to take place and provides a framework for providers to offer rapid autopsy as an option for families through this program.
Dermatologic surgery opioid prescribing recommendations in practice
Authors: Surya A. Veerabagu, Arianna F. Yanes, Brian Cheng, Jeremy R. Etzkorn, Christopher J. Miller, Thuzar M. Shin, Joseph F. Sobanko, H. William Higgins, Stacy L. McMurray, Joanna L. Walker, Cerrene N. Giordano
Journal: Journal of the American Academy of Dermatology (2021)
NCOG-49. UNMET NEEDS AND WISH FOR SUPPORT OF FAMILY CAREGIVERS OF PRIMARY BRAIN TUMOUR PATIENTS
Authors: Lucy Pointon, Robin Grant, Sharon Peoples, Sara Erridge, Paula Sherwood, Martin Klein, Florien Boele
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it may lead to significant burden. To develop support it is therefore vital to distinguish between unmet needs, and an actual wish for support. Study aims: 1) identify the presence and magnitude of caregivers’ unmet needs; 2) examine associations between unmet needs and wish for support; 3) evaluate perceived usefulness of caregiver needs screening in clinical practice. METHODS Family caregivers of primary brain tumour patients were recruited and asked to complete an adapted version of the Caregiver Needs Screen (CNS) which consisted of 33 common issues in neuro-oncology caregiving (scale 0-10), and the wish for support (yes/no). Participants ranked (0-7) their experience of using the CNS with a study-specific evaluation questionnaire. Descriptive and correlational analyses were applied. RESULTS Caregivers (N=79) reported between 1-33 unmet needs (M=17.20, sd=7.98) but did not always wish for support (range 0-28, M=4.71, sd=6.63). Most distressing items were changes in patient’s memory or concentration (M=5.75, SD=3.29), followed closely by patient’s fatigue (M=5.58, SD= 3.43), and recognising signs of disease progression (M=5.23, SD= 3.15). A weak correlation was found between the total number of unmet needs and wish for support (r=0.296, p=0.014). Caregivers most often wished for support with recognising disease progression (N=24, 34.78%), and least often with managing spiritual issues (N=0, 0%). Caregivers evaluated the CNS tool positively (mean item scores ranging 4.19-6.21 out of 7). CONCLUSIONS Family caregivers experience distress resulting from many neuro-oncology specific needs, but this is not directly related to a wish for support. Caregiver needs screening could be useful to tailor support to suit caregivers’ preferences in clinical practice.
Abstract 10480: Comparison of Left Atrial Feature Tracking Strain and Rapid Long Axis Strain for Predicting Arrhythmia Recurrence After Atrial Fibrillation Ablation
Authors: Luuk H Hopman, Mark J Mulder, Anja M van der Laan, Pranav Bhagirath, Ahmet Demirkiran, Bob B von Bartheld, Michiel J Kemme, Albert C van Rossum, Cornelis P Allaart, Marco J Gotte
Journal: Circulation (2021)

Introduction: Global left atrial (LA) strain is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Recently, novel rapid LA long axis strain has been introduced. Currently, it is unknown whether this fast and simple strain approach can predict AF recurrence after PVI and hence may be a simple alternative for the cumbersome LA feature tracking (FT) strain analysis. Hypothesis: Rapid LA strain is a fast and simple alternative for predicting AF recurrence after PVI as compared to LA FT strain. Methods: A total of 58 AF patients (78% paroxysmal AF, 64% male, mean age 61±7 years) undergoing first PVI ablation were included. Prior to PVI, all patients were in sinus rhythm during cardiac magnetic resonance imaging. LA rapid strain, LA FT strain and LA volumes were derived from 2-chamber and 4-chamber cine CMR images (Figure A). All patients were routinely followed up for arrhythmia recurrence. Results: At one year follow-up, arrhythmia recurrence was observed in 21 patients (36%). Both, rapid LA strain and FT strain were significantly reduced in patients with AF recurrence compared to patients without AF recurrence (rapid strain: -19.96 ± 11.03% vs. -28.18 ± 9.93%, P=0.005; FT strain: -12.54 ± 4.16% vs. -15.94 ± 3.50%, P=0.002, Figure B, and C) while maximal LA volume index (LAVImax) was not different between both groups (16.98 ± 3.70ml/m2 vs. 15.04 ± 2.47ml/m2, P=0.11, Figure D). ROC analysis identified LA FT strain as having the highest area under the curve (AUC) for predicting AF recurrence after PVI (AUC: 0.75 for LA FT strain, 0.71 for LA rapid strain, 0.62 for LAVImax, figure E). Conclusions: Both rapid LA strain and LA FT strain are predictive of AF recurrence after index PVI in AF patients. Moreover, LA mechanical function (strain) may be a more useful marker for predicting AF recurrence than LA volume. Therefore, LA rapid strain can be a more convenient and reproducible parameter for the assessment of LA performance in clinical practice.
Abstract 12195: Racial and Ethnic Disparities in Reperfusion Interventions and Stroke Center Care in California
Authors: Kori S Zachrison, Margaret Samuels-Kalow, Sijia Li, Mathew J Reeves, Renee Y Hsia, Lee H Schwamm, Carlos A Camargo
Journal: Circulation (2021)

Background: There is significant hospital-level variation in quality of acute stroke care delivery. As a result, patients’ access to disability-reducing reperfusion interventions and stroke center care depends on the initial hospital of presentation and interhospital transfer. Our objective was to examine racial and ethnic disparities in access to reperfusion interventions, and whether interhospital patient transfer mitigates disparities in access to stroke center care. Methods: Using statewide administrating data including all emergency department and hospital discharges in California from 2010-2017, we identified acute ischemic stroke patients and outcomes of interest: thrombolytic therapy, endovascular thrombectomy (EVT) receipt, interhospital transfer, and discharge from primary or comprehensive stroke center hospital. We used hierarchical logistic regression modeling to identify the relationship between race/ethnicity and outcomes after accounting for important patient- and hospital-level factors. Results: Of 336,247 ischemic stroke patient encounters during the study period, 186,444 (55.4%) were non-Hispanic white, 66,016 (19.6%) Hispanic, 34,596 (10.3%) non-Hispanic Black and 35,784 (10.6%) non-Hispanic Asian/Pacific Islander. Relative to non-Hispanic white patients, adjusted odds of thrombolytic receipt were lower for Hispanic, non-Hispanic Asian/Pacific Islander, and non-Hispanic Black patients (Figure). Adjusted odds of EVT were lower for Hispanic and non-Hispanic Black patients. Adjusted odds of interhospital transfer were lower among Hispanic and non-Hispanic Asian patients. Adjusted odds of discharge from a stroke center hospital was similar across racial/ethnic groups. Conclusions: There are racial/ethnic disparities in receipt of reperfusion interventions among stroke patients in California. Configuration of the stroke system of care, hospital resources, and transfer patterns may contribute.