tbuckley/cabot-search huggingface dataset:
NCMP-03. ANATOMIC AND SURGICAL FACTORS PREDICT DEVELOPMENT OF LEPTOMENINGEAL DISEASE IN PATIENTS WITH METASTATIC MELANOMA
Authors: Stephen Lowe, Christopher Wang, Amanda Brisco, John Arrington, Kamran Ahmed, Michael Vogelbaum, James Liu
Journal: Neuro-Oncology (2021)

Abstract Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, portending a poor prognosis with an estimated median survival of 4-6 weeks if left untreated. Several reports have suggested surgical resection as a potential causative factor. Herein, we explore if surgical and anatomical factors are correlated with development of LMD in patients with melanoma brain metastases. METHODS: Patients treated at our institution between 1999-2019 for primary melanoma with brain metastasis were compiled into a database based on ICD9/10 coding. 1,079 patients with melanoma brain metastases and appropriate imaging were identified, and 834 patients with a minimum of 3 months’ follow up were included. Patients were dichotomized by development of LMD or lack thereof, and categorized into an overall cohort, and surgical and non-surgical cohorts. Anatomic factors and ventricular access during surgery were investigated as possible correlative factors for the development of LMD. RESULTS: In the overall cohort, female gender(p=0.033), presence of dural metastasis(p=0.018), presence of periventricular lesions(p&amp;lt; .001), presence of intraventricular lesions(p&amp;lt; .001), and ventricular access during surgery(p&amp;lt; .001) were significantly associated with LMD. Patients undergoing surgery, or those undergoing surgery without ventricular access, were not at higher risk of LMD. On multivariate analysis, female gender(p=.033), presence of periventricular lesions (p&amp;lt; .001), presence of intraventricular lesions(p&amp;lt; .002), and presence of dural metastasis(p=0.032) were significantly associated with development of LMD. In patients who had surgery, iatrogenic ventricular access(p&amp;lt; .001) was significantly correlated with LMD. In the group of patients without surgery, those with periventricular lesions had significantly higher odds of LMD(p&amp;lt; .001). CONCLUSIONS: In a retrospective cohort of patients with melanoma metastatic to the brain, surgical intervention does not increase odds of LMD; however, iatrogenic access to the CSF space during surgery is highly correlated with LMD development. Anatomic contact with the CSF space predicts LMD regardless of surgical status.
Abstract 9361: The Effect of Immune Checkpoint Inhibitors on the Right Ventricle and Pulmonary Vasculature: Autopsy/Biopsy and Echocardiographic Data
Authors: Carolyn G Ahlers, Olusola A Orimoloye, Jeffrey Annis, Kathryn Beckermann, Douglas Johnson, Javid Moslehi, Evan Brittain
Journal: Circulation (2021)

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can lead to cardiovascular toxicities including myocarditis which can present as left ventricular dysfunction. Little is known about the effect of ICIs on the right ventricle (RV) and pulmonary vasculature. Methods: We identified six patients at our institution with ICI-induced myocarditis and right ventricular dysfunction. We also compared pulmonary pressure estimates or tricuspid regurgitant velocity measurements in two independent cohorts of patients who had pre- and post-ICI treatment echocardiography (echo) data. The first cohort included 13 unselected patients with renal cell carcinoma (RCC) or melanoma treated with an ICI at this institution. The second cohort included 31 patients from an international registry who met European Society of Cardiology criteria for ICI myocarditis. Echo parameters pre- and post-ICI were compared using the Wilcoxon signed rank test. Results: Biopsy and autopsy results from the six patient case series revealed lymphocytic myocarditis affecting the interventricular septum and right ventricle (Table 1). All patients with autopsies had RV dilation, and five of the six patients had RV dysfunction on imaging during their hospitalization. In the melanoma/RCC cohort, tricuspid regurgitation velocity was significantly increased post-ICI versus pre-ICI [mean 2.42, SD 0.51 m/s vs. mean 2.16, SD 0.48 m/s, p=0.03]. Right ventricular systolic pressure (RVSP) pre-ICI [mean 24.00, SD 8.26 mmHg] was decreased compared to post-ICI [mean 31.93, SD 12.93 mmHg, p=0.05]. In the second cohort, RVSP was significantly increased post-ICI [median: 30.5, IQR: 26.7-38] as compared to pre-ICI [median: 27.5, IQR: 24.6-35, p=0.03]. Conclusion: ICIs may negatively affect RV and pulmonary circulatory function. More research is needed to understand whether ICIs increase the risk of RV dysfunction and pulmonary vascular disease.
Venous Thromboembolism Is Associated with Inferior Survival after Allogeneic Hematopoietic Cell Transplant
Authors: Lauren M. Granat, Lisa A. Rybicki, Mailey L. Wilks, Christina Ferraro, Matt Kalaycio, Ronald M. Sobecks, Navneet S. Majhail, Dana E. Angelini, Betty K. Hamilton
Journal: Blood (2021)
Transcriptome Based Classification Model and Co-Expression Networks Analysis Identify <i>CXCR4alt</i> Subtype and <i>Blnkaf</i> in B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Panxiang Cao, Mingyu Wang, Guangsi Zhang, Fang Wang, Xue Chen, Yang Zhang, Daijing Nie, Xiaoli Ma, Ming Liu, Hongxing Liu
Journal: Blood (2021)
Abstract 10113: Improving Safety of Direct Oral Anticoagulant Dosing in Patients with Advanced Chronic and End-Stage Renal Disease
Authors: Naman Upadhyay, Rahed Mohammed, Kirpal Kochar, Max Ruge, Sean Dikdan, yair lev
Journal: Circulation (2021)

Introduction: Direct oral anticoagulants have become a mainstay in therapy for venous thromboembolism as well as mitigation of stroke and systemic embolism risk in atrial fibrillation. Although guidelines have been put forth for dose reduction in renal impairment, significant inconsistency in dosing practices exists. No study has directly evaluated the dosing practice of apixaban and rivaroxaban in those with advanced chronic kidney disease (stage 4 and 5) and end-stage renal disease at a quaternary care institution. Methods: We screened 853 patients from 1/1/2017 to 3/21/2020 with advanced chronic kidney disease and end-stage renal disease and identified 312 patients on either apixaban or rivaroxaban. Clinical data collected include anticoagulation indication, dosing, serum creatinine, age, weight, and creatinine clearance (calculated by the Cockcroft-Gault equation). Results: A total of 312 patients were studied (268 apixaban, 44 rivaroxaban). Among all patients with advanced chronic kidney disease and end-stage renal disease, a total of 123 patients (46%) were incorrectly dosed with apixaban compared to 17 patients (38%) with rivaroxaban. Among those with advanced chronic kidney disease, 57 patients (41%) were dosed incorrectly with apixaban compared to 10 patients (27%) with rivaroxaban. Among those with end-stage renal disease, 66 patients (50%) were dosed incorrectly with apixaban. (Figure 1). Conclusion: We demonstrate that there is significant variance in the dosing practice of direct oral anticoagulants among patients with advanced chronic kidney disease and end-stage renal disease. We hope to develop a checklist within the electronic medical record to promote adherence to guidelines when determining whether a patient requires dose reduction in the setting of renal dysfunction. Further investigation is being carried out to determine differences in outcomes among those properly dosed and those incorrectly dosed.
Abstract MP207: A Precision Medicine Approach For Non-invasive, Longitudinal, And Quantitative Monitoring Of Cardiac Tissue-engineered Scaffolds
Authors: Carmen Gil, Connor Evans, Lan Li, Merlyn Vargas, Gabriella Kabboul, Travis Fulton, Remi Veneziano, Nick Nick, Holly Bauser-Heaton, Ryan K Roeder, Vahid Serpooshan
Journal: Circulation Research (2021)

3D bioprinting has revolutionized personalized and precision medicine by enabling the manufacturing of tissue constructs that precisely recapitulate the cellular and functional features of native tissues. In cardiac regenerative medicine, printed scaffolds have shown tremendous potential in repairing damaged heart, however, their clinical applications have been limited by the lack of precise noninvasive tools to monitor the patch function following implantation. By integrating state-of-the-art 3D bioprinting and photon-counting computed tomography (PCCT), this study introduces a new approach for bioengineering defect-specific scaffolds and monitoring their function. We prepared distinct CT-visible bioinks containing a variety of molecular or nanoparticle (NP) contrast agents, including iodine and gadolinium molecules, Au NPs, Gd 2 O 3 NPs, and iodine-loaded liposomes ( Fig 1A-B ). In vitro release experiments showed relatively rapid diffusion-controlled depletion of molecular contrast agents from scaffolds. In contrast, NP agents showed more stable encapsulation and only a partial, degradation-mediated release for up to 3 weeks of incubation ( Fig 1C-D ). Next, PCCT imaging was performed on various scaffold geometries printed using bioinks laden with Gd 2 O 3 or Au NPs. Results demonstrated CT visibility with differential contrast between different patch regions that corresponded to the designed geometries ( Fig 1E ). Finally, we evaluated the in vivo CT imaging of bioprinted patches after their subcutaneous implantation in a mouse model. CT images demonstrated adequate signal from implanted grafts ( Fig 1F ). Together, these results establish a novel precision medicine platform for non-invasive monitoring of medical devices which can open new prospects for a broad range of tissue engineering applications. Figure 1. 3D Bioprinting of CT-visible cardiac patches. A-B: Design of bioinks functionalized with molecular (left) and nanoparticle (right) CT contrast agents ( A ) and their bioprinting ( B ). C-D: In vitro release of contrast agents from printed patches. E: CAD design (left), CT image (middle), and PCCT material decomposition (right) for multi-contrast bioprinted scaffolds. F: In vivo CT imaging of printed patch, laden with Au NPs, implanted subcutaneously into a mouse torso.
Abstract 14418: Epigenetic Landscapes of Stroke Risk Haplotypes Suggest Genetic Risk Operates Through Fibroblasts
Authors: Kerry E Poppenberg, Cathleen Kuo, Muhammad Waqas, Adnan H Siddiqui, James N Jarvis, Vincent M Tutino
Journal: Circulation (2021)

Introduction: Genome-wide association studies (GWAS) in stroke have identified many single nucleotide polymorphisms (SNPs). However, the mechanisms behind how these SNPs confer genetic risk is unknown. Hypothesis: Stroke variants confer genetic risk by affecting non-coding DNA elements, specifically enhancers, that modulate gene expression in certain cell types. Methods: We analyzed 26 stroke risk SNPs that were validated across multiple studies. We mapped these SNPs to the associated linkage disequilibrium (LD) blocks and used chromatin immunoprecipitation-sequencing data to examine the presence of enhancer-associated histone marks (H3K27ac, H3K4me1, H3K9ac) in each block. This was performed using data for cells of the circulating blood and the vascular tissue (significant enrichment was determined by empirical p-value calculation). In cells with significant enhancer marks, HiC data was used to identify topologically associated domains (TADs) encompassing the LD blocks, which contain genes potentially affected by altered enhancer activity. Disease and biological function term enrichment was performed in Ingenuity Pathway Analysis to investigate the biological significance of these genes. Results: Fibroblasts and smooth muscle cells demonstrated significant enrichment of enhancer-associated histone marks in stroke-associated LD blocks (p&lt;0.05). Bioinformatics analysis on TAD genes reflected enrichment of vessel development (e.g., Angiogenesis, Vasculogenesis) and fibroblast turnover (e.g., Proliferation of Fibroblast Cell Lines, Apoptosis of Fibroblast Cell Lines). Conclusion: Stroke-associated genetic variants confer risk through the vessel wall rather than circulating immune cells. Further studies are needed to experimentally confirm function of these enhancers and identity of causal variants.
Abstract 11097: Radiation Doses to Interventional Echocardiographers During Percutaneous Structural Heart Interventions
Authors: David A McNamara, Rajus Chopra, Jeffrey Decker, Michael McNamara, Stacie VanOosterhout, Duane Berkompas, Musa Dahu, William Merhi, Jessica L Parker, Ryan D Madder
Journal: Circulation (2021)

Background: The use of transesophageal echocardiography during percutaneous left atrial appendage closure (LAAO) and transcatheter edge-to-edge repair of the mitral valve (TEER) requires an interventional echocardiographer (IE) to stand near the radiation source. The occupational radiation exposure of IEs remains understudied. Hypothesis: IE experience higher radiation doses than interventional cardiologists and sonographers. Methods: Prospective, blinded radiation doses were collected by dosimeters worn by IEs, interventional cardiologists, and sonographers during 30 consecutive LAAO and 30 TEER structural heart cases at a tertiary care center. Measured personal dose equivalents per case were compared among the three groups. Results: Over the 60 procedures, the median radiation dose per case was 5-fold higher for IEs than interventional cardiologists (10.6 [4.2, 22.4] μSv versus 2.1 [0.2, 8.3] μSv, p&lt;0.0005). During TEER, IEs received a median radiation dose of 10.5 [2.3, 20.9] μSv, which was 11-fold higher than interventional cardiologists (0.8 [0.0, 12.1] μSv, p = 0.0005). During LAAO procedures, the median radiation dose was 10.8 [5.9, 24.6] μSv among IEs and 3.6 [1.4, 6.5] μSv among interventional cardiologists, representing a 3.0-fold greater radiation dose to echocardiographers (p&lt;0.0001). Compared to IEs, sonographers exhibited low radiation doses during both LAAO (0.2 [0.0, 1.6] μSv, p&lt;0.001) and TEER (0.03 [0.00, 0.15] μSv, p&lt;0.0001). Conclusions: During LAAO and TEER procedures, IEs were exposed to 3-fold and 11-fold higher radiation doses than interventional cardiologists, respectively. These comparatively higher radiation doses indicate an important occupational risk faced by IEs, which has implications for the rapidly expanding structural heart team.
A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects with B-Cell Malignancies
Authors: Michael Dickinson, Nada Hamad, Christian E Bryant, Gautam Borthakur, Chitra Hosing, David Shook, Joanne Tan, Kanya Rajangam, Hongtao Liu, Glen A Kennedy, Peter A. McSweeney, Brian T. Hill
Journal: Blood (2021)
Abstract 9209: Type 1 Brugada Syndrome Diagnosed in a Patient With an Unaffected Identical Twin
Authors: CODY SCHWARTZ, Neeraj Jain
Journal: Circulation (2021)

Introduction: Brugada syndrome is a rare arrhythmia disorder due to a cardiac channelopathy with a predisposition to ventricular arrhythmias or SCD. It is characterized by an ECG pattern of complete or incomplete right bundle branch block and ST segment elevation in leads V1-V3. It is normally inherited in an autosomal dominant pattern however environmental factors such as viral infections and inflammation may create myocardial cell damage that may induce an ECG pattern consistent with the diagnosis of Brugada syndrome. Case: A 39-year-old male with no significant past medical history presented to the hospital for two weeks of intermittent dizziness and nocturnal symptoms of being “jolted” awake. ECG on admission was suggestive of a Type 2 Brugada pattern. He denied a family history of first-degree relatives with cardiac disease, SCD or unexplained syncope but did note that he had an identical twin brother. Given symptoms and ECG findings, he was given 400 mg of oral flecainide for a sodium blockade challenge. Four hours after administration of flecainide he developed an overt Type 1 Brugada pattern. Due to issues with the MRI, a cardiac CTA was performed to assess for ARVD. Cardiac CTA showed a mild amount of fat in the apex of the right ventricular wall but was otherwise unremarkable. He was discharged with a wearable external defibrillator and outpatient follow up with EP. During outpatient follow up he reported resolution of symptoms. Interrogation of the defibrillator did not reveal any arrhythmias. An ECG was done on his identical twin brother which did not show evidence of a Type 1 Brugada pattern. He completed a cardiac MRI that showed normal morphology and motion of the right ventricle without evidence of fat dysplasia or late gadolinium enhancement. Given resolution of his symptoms with a normal cardiac MRI and an unremarkable ECG from his identical twin, he was diagnosed with an acquired Brugada syndrome likely due to a viral myocarditis. Conclusion: While Brugada syndrome is normally an inherited genetic disorder, there are instances of acquiring the syndrome through environmental factors. As demonstrated by our case of identical twin brothers with the same genetic makeup, one was diagnosed with Brugada syndrome while the other had an unremarkable ECG.
NIMG-49. A PROSPECTIVE, MULTI-CENTRE TRIAL OF FET-PET IN GLIOBLASTOMA PATIENTS - THE TROG 18.06 FIG STUDY: KEY ASPECTS OF IMAGING AND RADIATION ONCOLOGY CREDENTIALING
Authors: Eng-Siew Koh, Roslyn J Francis, Martin Ebert, Hui Gan, Sze Ting Lee, Eddie Lau, Alisha Moore, Andrew Grose, Alana Rossi, Sweet Ping Ng, June Yap, Tam Ly, Peter Lin, Mark B Pinkham, Stanley Ngai, Christopher Yu, Peter Gorayski, Hien Le, Ian D Kirkwood, Wilson Vallat, Farhan Syed, Dayanethee Krishna, Shahroz Khan, Suki Gill, Elizabeth Thomas, Michael Back, Elizabeth H Barnes, Bradford A Moffat, Fiona Scott, Lucas Adda, Farshad Foroudi, Richard De Abreu Lourenco, Anna K Nowak, Dale L Bailey, Andrew M Scott
Journal: Neuro-Oncology (2021)

Abstract The FIG study is a prospective non-randomised study now recruiting up to 210 newly diagnosed GBM participants across ten Australian sites. Study outcomes will address the role of [18F] fluoroethyl-L-tyrosine positron emission tomography (FET-PET) in radiotherapy (RT) planning, evaluation of post-treatment changes versus disease progression and prognostication. We describe here the methodology and preliminary outcomes for site credentialing. Eligible participants with GBM undergo FET-PET imaging at three time-points: FET-PET1-post-operative pre-chemo-RT, FET-PET2 acquired one month post-chemo-RT and FET-PET3 (+/-FDG-PET) triggered when clinical and/or radiological (MRI) progression is suspected. Dynamic and static FET-PET images are analysed qualitatively and quantitatively. Radiotherapy is as per standard care with the treating Radiation Oncologist (RO) blinded to FET-PET1. Site nuclear medicine (NM) physicians are required to delineate a biological target volume (BTV) based on FET-PET1 with hybrid RT volumes derived post-hoc. Pre-trial NM quality assurance comprises certification from the Australasian Radiopharmaceutical Trials Network encompassing FET-PET radiochemistry Quality Control and PET camera calibration. Site and central integrated workflows incorporating multi-modality image registration, target volume/region of interest contouring and analysis have been developed. NM benchmarking involves delineation of FET-PET BTVs in 3 cases with another 3 cases addressing response criteria interpretation harmonized across FET-PET, FDG-PET and MRI. Site ROs complete 3 cases involving standard and hybrid target volume delineation based on pre-derived FET-PET volumes. All NM and RO credentialing cases undergo central expert review. To date, of six sites which have submitted full credentialing data, 19/21 RO and 6/6 planning cases were passed. Of 72 NM cases, 18/72 (25%) required resubmission, primarily related to ensuring standardisation of background regions and time activity curve interpretation. The FIG study will be pivotal in establishing the role of FET-PET in GBM management. The robust NM and RO credentialing program will build capacity and expertise in FET-PET production, acquisition and image interpretation.
Abstract 10296: Outcomes of Transcatheter Mitral Valve Repair in Patients with Acute Kidney Injury-A US National Inpatient Sample Analysis
Authors: Salman Zahid, Abdul Baqi, Madeeha Shafaqat, Fnu Salman, Abid Nawaz Khan Adil, Waqas Ullah, AAMER UBAID, Sakina Abbas, Hamza Muhammadzai, Muhammad Atif Khan, Arslan Inayat, Mian Tanveer Ud Din, Muhammmad Khan, Muhammad U Khan
Journal: Circulation (2021)

Introduction: Data on outcomes of transcatheter mitral valve repair (TMVR) in patients with acute kidney injury (AKI) remains limited. Hypothesis: AKI is associated with worse outcomes in patients undergoing TMVR Methods: We utilized the United States National Inpatient Sample database from the year 2015 to 2018 to evaluate outcomes of TMVR in AKI. Results: A total of 21,505 weighted hospitalizations were included in the analysis. Of the patients who underwent TMVR 3350 (15.6%) developed acute kidney injury. The mean age of patients undergoing TMVR was higher for patients with AKI compared to patients who did not develop AKI was 77 and 76 years respectively. A logistic regression model adjusted for age, gender and baseline comorbidities was developed for predictors of AKI. On adjusted comparison liver disease (OR 2.4 95% CI, 2-2.9), peripheral vascular disease (1.35, 95% CI 1.2-1.53), congestive heart failure (2.76 95% CI, 2.34-3.26) and history of weight loss (1.92 95% CI 1.64-2.25) were significant predictors of AKI. In-hospital mortality was higher for patients with AKI versus no AKI (10.1% vs. 0.7%, p&lt;0.01). Length of stay (13 vs 3 days) and cost of stay ($80787 vs. $ 44086) was significantly higher for patients with AKI versus those who did not develop AKI. Conclusions: AKI is associated with increased in hospital mortality and increased health care resource utilization in patients undergoing TMVR.
Abstract 11259: Promoting Discharges in Pediatric Patients with Congenital Heart Disease on Ventricular Assist Device Support: An ACTION Quality Improvement Project
Authors: David W Bearl, Hari Tunuguntla, Chloe Connelly, Jennifer Conway
Journal: Circulation (2021)

Introduction: Discharge of pediatric ventricular assist device (VAD) patients is lagging behind adults, especially pediatric patients with concurrent congenital heart disease (CHD). This quality improvement project aimed to increase discharge rates and decrease time to discharge for pediatric patients with CHD on VAD support. Methods: Patients with CHD implanted with HeartWare HVAD or HeartMate 3 at participating Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers were included. Baseline demographics and outcomes including explant, transplant, or death, and time to outcome was collected from April 2018 until October 2019. QI interventions (VAD Flight Plan and Discharge Journey Map) were initiated in November 2019. Percentage discharged on VAD as well as time to outcome were compared before and after intervention. Results: Twenty-six patients with CHD (18 single ventricle physiology) were identified (14 pre-intervention and 12-post). The mean age was 16 years old with 27% implanted as Intermacs profile 1. Mortality on device was high at 38%. There were 77% (n=20) considered discharge eligible (alive on device &gt; 30 days) while 42% (n=11) achieved discharge (Table 1). Mean length of stay post-implant for discharged patients was 33 days. A higher percentage of biventricular physiology were discharged (63%) compared to univentricular (33%). QI interventions did not change discharge rate (43% vs 42%), mean time to discharge (46.3 vs 43.4 days), transplant before discharge (17% vs 21%), or death before discharge (42% vs 43%) in the post-intervention group. Conclusion: Discharging CHD patients on VAD support from the hospital remains a challenge largely due to the complex and heterogenous nature of this population at the time of implant. Interventions to address optimal timing of VAD implantation and patient selection could impact outcomes.