tbuckley/cabot-search huggingface dataset:
Abstract 9977: Concerns Raised Around Adverse Event Reporting Associated with the Subcutaneous Implantable Cardioverter Defibrillator Device
Authors: Gene Hu, Anthony Lin, John M Mandrola, Bogdan Enache, Madris Tomes, Rita F Redberg
Journal: Circulation (2021)

Objective: To review adverse events reports for the subcutaneous implantable cardioverter defibrillator (S-ICD) device and understand challenges in its application. Background: The S-ICD is an increasingly popular alternative to transvenous ICD (TV-ICD) devices since FDA approval in 2012. Although we have the benefit of professional guidelines, there are no high-quality trials showing mortality benefit. There are concerns about higher rates of inappropriate shocks with use of S-ICD, which prompted a ‘Smartpass’ firmware upgrade in 2016. The impact of this upgrade on rates of inappropriate shocks remains ill-defined. Methods: Narrative reports of adverse events associated with the S-ICD reported to the FDA MAUDE database were reviewed for reason for reporting and outcomes. These were compared with the total number of devices found on shareholder reports as of October 2020. Results: Of 35,000 S-ICD devices in the US, 9,349 adverse events and 2,521 inappropriate shocks were reported in MAUDE. There were 108 deaths, 21 of which were due to a failure to convert a ventricular arrhythmia. Rates of inappropriate shocks comprised an increasing proportion of adverse events year over year with no decline following the ‘Smartpass’ upgrade. Conclusion: The multiple instances of death following S-ICD failure are alarming as these fatal events are thought to be rare for TV-ICDs. Additionally, even with the introduction of Smartpass, inappropriate shocks have not declined. These findings, taken in conjunction with the lack of data for mortality benefit of the S-ICD and safety concerns surrounding the recent lead recall, should be considered by clinicians in future decisions about S-ICD use.
Modeling the Development of <i>SRSF2</i> Mutated Myeloid Malignancies By CRISPR/Cas9 Mediated Genome Engineering of Primary Human Hematopoietic Stem and Progenitor Cells
Authors: Gabriel Pabst, Johannes Foßelteder, Angelika Schlacher, Lisa Auinger, Daniel Martinez-Krams, Asiri Ediriwickrema, Karl Kashofer, Christine Beham-Schmid, Hildegard T. Greinix, Albert Woelfler, Peter Schlenke, Heinz Sill, Armin Zebisch, Ravi Majeti, Andreas Reinisch
Journal: Blood (2021)
Abstract 13010: Aquaporin 4 Alleviates Myocardial Ischemia-reperfusion Injury By Inhibiting Cardiomyocyte Apoptosis
Authors: Qiong Jiang, Mingfang Ye, Yuanming Yan, Jun Fang, Yukun Luo
Journal: Circulation (2021)

Introduction: Myocardial injury caused by ischemia-reperfusion is the main pathological manifestation of coronary artery disease (CAD), which is characterized by high mortality and morbidity. Thus, there’s an urgent need to develop efficacious strategies and elucidate the underlying mechanisms to prevent or alleviate myocardial ischemia-reperfusion injury to improve the clinical outcomes. Hypothesis: Aquaporin 4 may alleviates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte apoptosis. Methods: In this study, we took advantage of a typical myocardial cell line of mice (HL-1) and cultured with or without an aquaporin 4 inhibitor (TGN-20 denoted as AQP4i) under normal conditions (NC), ischemia (IS) and ischemia reperfusion (IR), respectively. The cytomorphology, ultrastructure, cell vitality and expression pattern of apoptotic proteins were verified with scanning electron microscope (SEM), immunofluorescence staining, flow cytometry, quantitative real-time PCR and western-blotting analysis, respectively. Results: HL-1 under IS or IR condition revealed higher expression of Aquaporin 4 (Aqp4) compared to the NC group, whereas showed similarity in cytomorphology and ultrastructure. Aqp4 inhibition was sufficient to improve the apoptotic cells in HL-1 while showed minimal effects to the other cellular vitality. Furthermore, the expression pattern of apoptotic proteins and anti-apoptotic proteins together with proinflammatory factors in HL-1 was effectively rescued by Aqp4i treatment both at the mRNA level and protein level. Conclusions: Ischemia and ischemia reperfusion caused higher expression of Aqp4 and resultant increase of cardiomyocyte apoptosis. Myocardial ischemia-reperfusion injury of HL-1 was effectively alleviated by Aqp4 and apoptosis inhibition. Our findings provided new references for myocardial ischemia-reperfusion injury management via targeting Aqp4-mediated apoptosis of cardiomyocyte.
INNV-25. RITUXIMAB MONOTHERAPY FOR TREATMENT OF RARE LOW GRADE PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; A CASE REPORT AND LITERATURE REVIEW
Authors: Grace Tobin, Elizabeth Neil
Journal: Neuro-Oncology (2021)

Abstract Primary central nervous system lymphoma (PCNSL) is a specific variant of non-Hodgkin's lymphoma confined to the brain, leptomeninges, spinal cord, and/or eyes. The majority of PCNSL is diffuse large B-cell lymphoma (DLBCL), however, a small percentage are categorized as low-grade lymphomas (LGL). Compared to high-grade and aggressive DLBCL, LGL are indolent; allowing for targeted and less neurotoxic first-line treatments. There is currently no consensus for LGL treatment. A patient at our institution was diagnosed with LGL without extra-CNS involvement 11/2018 and then, successfully treated with rituximab monotherapy. This 65 year-old, immunocompetent woman presented with one month of right leg weakness and numbness. Brain MRI demonstrated a subtly enhancing infiltrative left thalamic lesion extending into the left frontal lobe with surrounding edema. Flow cytometry on spinal fluid showed rare monotypic B-cells. Brain biopsy results showed an atypical predominantly perivascular lymphoid infiltrate. These atypical small lymphoid cells had mature-appearing nuclear chromatin, absent nucleoli, and uniformly expressed CD79a and CD20 with variable PAX-5 expression, lacked CD56 and CD117 expression, and had plasmacytic differentiation; thus consistent with marginal zone lymphoma, a type of indolent B-cell lymphoma. There was no evidence of extra-CNS involvement on PET scan, bone marrow biopsy, or ocular exam. She had normal cognitive functioning on neuropsychological testing. Interestingly, SPEP showed a monoclonal IgM immunoglobulin of kappa-light chain-type that became a monoclonal protein in the gamma fraction. Additionally, CT abdomen initially showed splenomegaly that resolved on repeat imaging a year later. Radiation therapy was deferred due to high risk. Weekly rituximab 500mg/m2 was initiated for 4 doses, then monthly for 4 doses. Therapy was well tolerated and she noted clinical improvement plus there was positive response on brain imaging. Repeat ophthalmology exam and CT body without any evidence of cancer. She is now 29 months progression-free since completing rituximab.
Abstract 13863: Incidence and Clinical Significance of Cardiac Arrhythmias During Labor
Authors: Nikhil Sharma, Kristie Coleman, Dillon Gurciullo, Rosaline Ma, Roland Hentz, Joanna Fishbein, Nirav Shah, Stavros Mountantonakis
Journal: Circulation (2021)

Introduction: Physiologic changes during pregnancy can predispose mothers to new-onset cardiac arrhythmia. Women with a history of cardiac arrhythmia are at increased risk of recurrence or worsening of previously identified conditions. Previous studies have demonstrated that women with heart disease are at increased risk of maternal morbidity and mortality. However, few studies have explored the prevalence and clinical significance of maternal arrhythmias specifically. Objectives: The objectives of this study are to define the prevalence of arrhythmias in pregnancy and labor, identify risk factors for having such arrhythmias in patients both with and without prior history of cardiac arrhythmia, and examine the association between cardiac arrhythmias and adverse maternal outcomes. Methods: The medical records of patients admitted for delivery to any of the 13 hospitals in Northwell Health utilizing the electronic medical records from Jan 2012 - Dec 2020 were reviewed to identify patients with a history or current diagnosis of cardiac arrhythmia. Outcomes including Cesarean section, length of stay (LOS), infant requiring care in the neonatal intensive care unit (NICU) were evaluated between the arrhythmia group and a subset of deliveries without arrhythmias (controls). Results: Out of 141,772 patients, 88 were identified with a history of and/or current SVT and 87 were compared with 334 controls. The sample had mean age 31.7 ± 5.2 years, median length of stay 3 days (IQR 2-3), and median parity 2 (IQR 1-2). When adjusting for age and parity, logistic regression showed SVT was significantly associated with C-section (OR 1.9, CI 1.1-3.1, AUC 0.69 p=0.01). Fisher’s exact test showed SVT was associated with admission to NICU (p=0.03). Cox proportional hazards regression found SVT was not associated with LOS (HR 0.8, CI 0.6-1.0, p=0.06) when adjusted for age and parity. Conclusion: A history of SVT and/or current SVT during labor was associated with C-sections and NICU admissions but was not associated with LOS. These findings may help guide treatment strategies for this patient population.
IMMU-36. B CELL-VACCINE ELICITS LONG TERM IMMUNITY AGAINST GLIOBLASTOMA VIA ACTIVATION AND DIFFERENTIATION OF TUMOR-SPECIFIC CD8+ MEMORY T CELLS
Authors: David Hou, Brandyn Castro, Mark Dapash, Aida Rashidi, Peng Zhang, Yu Han, Aurora Lopez-Rosas, Maciej Lesniak, Jason Miska, Catalina Chang
Journal: Neuro-Oncology (2021)

Abstract While immunotherapy is used clinically to treat many cancers, its translation into brain tumors remains elusive. The importance of B cells in cancer immunity has become increasingly clear, and we previously developed a B cell-based cellular vaccine (BVax) against glioblastoma (GBM) by further activating 4-1BBL+ B cells with CD40 agonism and IFNγ. BVax were characterized as professional antigen-presenting cells (APCs) that promote CD8+ T cell migration and persistence in murine tumor-bearing brains. This study seeks to understand the mechanisms underlying BVax-induced CD8+ T cell fitness in the tumor microenvironment. Initial transcriptomic analysis highlighted that Bvax express high levels of IL15Rα, indicating their potential ability to trans-present IL15. Considering IL15 trans-presentation is fundamental in T-cell memory differentiation, we used BVax to induce T cell activation in the presence of exogenous IL15. BVax were better capable of activating antigen-specific CD8+ T cells and promoting a memory phenotype when compared to other professional APCs such as dendritic cells (DCs). T cell receptor (TCR) CDR3β sequencing showed that BVax expanded a number of TCR clones in-vitro that were found in brains of CT2A tumor-bearing mice in-vivo. These BVax-activated CD8+ T cells displayed a stronger antigen recall response and unique metabolic profile compared to DC-activated CD8+ T cells as shown by metabolomic analysis of tumor-infiltrating CD8+ T cells. When comparing the anti-tumor effects of CD8+ T cells activated by various APCs, BVax with exogenous IL15 promoted CD8+ T cells that displayed the most potent cytotoxicity against GBM cells in-vitro. Collectively, this study suggests that the IL15/IL15Rα axis and interactions with CD8+ T cell are key factors of BVax therapy in promoting a robust survival benefit and long-term immunologic memory against GBM in preclinical models. Additionally, the development of T cell therapies based on B cell licensing can be a promising future approach for glioblastoma therapy.
Abstract 14158: Cardiac Leaflet Enhancement (CARLEN) Treats Functional Mitral Regurgitation While Preserving the Native Valve Dynamics
Authors: Kirthana Sreerangathama Suresh, Dongyang Xu, Qi He, Hirschel Nambiar, Muralidhar Padala
Journal: Circulation (2021)

Introduction: Interventional repair of functional mitral regurgitation (FMR) is rapidly replacing traditional surgical correction as surgery is contraindicated in most FMR patients. Current treatments reduce FMR acutely but unfavorably alter mitral valve (MV) geometry resulting in MR recurrence over time and are restricted to use in specific anatomies. We developed a new focal leaflet augmentation approach ( Fig. 1A ) that augments a single leaflet to correct FMR without the disturbing MV dynamics. Hypothesis: We hypothesize that Cardiac leaflet enhancing (CARLEN) implant can effectively correct regurgitation in different geometries seen clinically in FMR patients. Methods: CARLEN was laser cut from a thin sheet of nitinol and shape set to form a 3D structure with two arms that grasp the leaflet and a balloon like section that enables leaflet enhancement ( Fig. 1B ). A trans-septal delivery system was developed and the feasibility of deployment was tested in a swine model ( Fig. 2 ). CARLEN functionality was tested and compared to Edge-to-Edge repair (EE) in an in-vitro left heart simulator with an isolated pig MV (n=6) in different valve geometries seen in FMR patients: a) Annular dilation (AD) alone (aFMR), b) AD+asymmetric tethering (iFMR), and c) AD+symmetric tethering (dFMR). Results: CARLEN consistently and significantly decreased FMR in all geometries (aFMR: 14.79±3.11% vs 6.79±1.90%; iFMR: 20.52±2% vs 6.64±2.16%; dFMR: 21.93±7.2% vs 7.12±2.83%, p&lt;0.05). However, significant reduction after EE was seen only in iFMR and dFMR ( Fig. 3 ). CARLEN did not perturb leaflet kinematics whereas leaflet mobility was significantly decreased after EE ( Fig. 4 ) in all geometries. Conclusion: Focal leaflet enhancement with CARLEN can effectively correct regurgitation in all clinically relevant valve geometries associated with FMR, potentially expanding the opportunity for transcatheter repair to a larger patient population.
QOLP-13. RETROSPECTIVE REVIEW OF HOSPICE CARE UTILIZATION IN GLIOBLASTOMA PATIENTS IN A TERTIARY CARE CENTER
Authors: Sushant Puri, David Heron, Martin NIcholas, Michael Huber, Jason Tuite, Sushant Puri
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma is a highly aggressive grade IV tumor of the brain. Standard of care is maximal safe resection followed by radiation therapy and chemotherapy. Despite optimal management, majority recur, and the median survival is 2-3 years. Hospice is a philosophy of care to alleviate end-of-life suffering, and it can also relieve caregiver fatigue. METHODS This is a retrospective chart review in a tertiary care center. IRB approval was obtained from the Office for the Protection of Research Subjects. ICD-10 code for malignant gliomas C71.9 was used to query EMR at UIC from 2015-2020. Patients with primary glioblastoma that had their entire neuro-oncologic care at UIC were included in the data analysis. Patient’s age &amp;lt; 18 years, unknown date of death, or those who transitioned to a different facility were excluded. Data included were demographic (including marital status as a proxy for social support), insurance, ethnicity, tumor characteristics, and treatments provided. End-of life quality measure assessed were (1)no chemotherapy &amp;lt; 2w, (2)hospice status &amp;lt; 7 days, (3)no hospital admission &amp;gt; 30 days (4)no ICU admission &amp;lt; 14 days. RESULTS 48 patients with primary glioblastoma were identified and out of those, a total of 35 patients received entirety of neurooncological care at our center. Date of death was available for 13 patients. 9 patients had been referred to hospice and 4 were not. Demographic variables were similar except social support – patients referred to hospice were more likely to be married. End-of-life quality measures were met in all patients in hospice group (9/9) but only in half of those not referred to hospice (2/4). DISCUSSION Social support has an impact on enrollment of hospice care. Including goals of care discussion earlier in the treatment would require a multi-disciplinary team with additional involvement of supportive care, nurses, and social workers.
Abstract P391: Inhalation Of Airborne Particulate Matter Alters Cardiovascular Function Of Alzheimer-prone Mice
Authors: Devin R O'Piela, Ty A Saldana, David M Aslaner, Matthew W Gorr, Amy R Mackos, Loren E Wold
Journal: Circulation Research (2021)

Air pollution has detrimental effects on cardiovascular and lung function, and the extent of its pathological consequences continues to be uncovered. Recently, air pollution has been implicated in the development of Alzheimer Disease (AD) progression. AD and heart failure are common co-morbidities, giving reason to believe that cardiovascular dysfunction may contribute to AD. A known contributor to cardiovascular dysfunction-particulate matter (PM 2.5 , &lt; 2.5 μm diameter)—is a critical component of air pollution and is considered a risk factor for heart failure and AD development. This co-morbidity pattern and shared environmental risk factor prompted the hypothesis that PM 2.5 contributes to cardiovascular dysfunction in a transgenic mouse model of AD. We tested our hypothesis by subjecting 6-month-old transgenic (APP) and non-carrier wildtype (WT) male mice to filtered air (FA) or PM 2.5 for 5 days/week, 6 hours/day for 3 months (n = 34). Following exposure, echocardiography, pressure-volume (PV) loops, and respiratory mechanics were performed to detect cardiac and pulmonary changes associated with genotype and exposure conditions among the 3-month group. Echocardiography revealed left ventricular anterior wall thickness in systole was significantly elevated among PM-exposed APP mice compared to FA-exposed APP controls. PV data demonstrated significant reduced end-systolic elastance in PM-exposed mice compared to FA-exposed mice in both WT and APP mouse models, demonstrating impaired contractility. PV loops also showed that the time constant of isovolumetric relaxation was increased in PM-exposed compared to FA-exposed WT mice. APP mice experienced higher lung resistance and central airway resistance with an increasing dose of methacholine. Taken together, these findings indicate airborne particulate matter exposure causes cardiac and pulmonary dysfunction in a transgenic mouse model of AD.
SURG-03. FUNCTIONAL OUTCOMES OF LASER INTERSTITIAL THERMAL THERAPY (LITT) VERSUS RESECTION IN THE TREATMENT OF LESIONS IN OR NEAR THE PRIMARY MOTOR CORTEX
Authors: Ethan Srinivasan, Emily Lerner, Ryan Edwards, David Huie, Peter Fecci
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This study compares the functional outcomes of LITT vs resection (RS) for lesions in or near the primary motor cortex (PMC). METHODS Retrospective review was performed of patients treated for PMC lesions by LITT or RS. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-LITT/RS. RESULTS 36 patients were identified with median follow-up of 194 days (IQR 72-503), age 64 years (57-72), and estimated baseline KPS 80 (80-90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) RS; all RS were performed with intra-operative motor mapping while LITT were not. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of RS patients (p&amp;lt; 0.01). LITT patients trended towards smaller lesions (1.9 cm vs 2.7 cm, p=0.03) and were more likely to show RN (67% vs 5%, p&amp;lt; 0.01) and be discharged home (87% vs 52%, p=0.04), with shorter ICU (0 vs 1 day, p&amp;lt; 0.01) and hospital stays (1 vs. 2 days, p&amp;lt; 0.01). At 30 days, 89% of surviving patients who received RS had stable or improved symptoms, compared to 46% of the LITT cohort (p=0.02). At 90 days, the difference was 88% to 50% (p=0.07), and at 180 days 100% to 80% (p=0.2941). CONCLUSIONS In the short term (30 days), patients with PMC lesions have better functional outcomes when treated with RS compared to LITT, while those who survive to the 180-day timepoint experience similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and RS.
Abstract 10834: Novel Biomarkers and Machine Learning Models for the Prediction of 30-Day Readmission Following Pediatric Congenital Heart Surgery
Authors: Likhita Sree Thiriveedi, Allen D Everett, Devin Parker, Meagan Stabler, Jeremiah R Brown
Journal: Circulation (2021)

Introduction: Hospital readmissions after congenital heart surgery (CHS) are common in pediatric patients and are linked to higher risks of complications, mortality, and increased treatment costs. Accurate prediction of 30-day readmission after CHS could help clinicians identify high risk patients and enable tailored care. Hypothesis: Novel biomarkers alone enhance prediction of readmission risk using XGBoost model and augmenting clinical features to the Society of Thoracic Surgeons (STS)-risk model improves predictions of 30-day readmissions. Methods: The prospective cohort included children of 18 years or younger who underwent congenital heart surgery at Johns Hopkins Hospital. Of the 162 patients, 159 survived discharge and were therefore included in the study. We used pre- and post-operative biomarkers ST2, Galectin-3, NT-proBNP and GFAP as features for the biomarker model, covariates from the STS CHS Database Mortality Risk Model for the STS-risk model and augmenting clinical features to STS-risk variables for clinical model. We implemented the XGBoost model and compared the biomarker model and clinical model performance to the STS-risk model. Results: Readmissions within 30 days of surgery occurred among 9% of pediatric patients. Using XGBoost, the STS-risk model derived an AUROC of 0.978 (95% CI: 0.955-1.0). The biomarker model performed better than the STS-risk model with AUROC of 0.982 (95% CI: 0.959-1.0, p=0.8). The augmented clinical model outperformed the STS-risk model with an AUROC of 0.997 (95% CI: 0.99-1, p=0.1). Conclusions: Novel biomarkers alone perform better compared to the STS- risk model in predicting 30-day readmission risk. XGBoost model improves risk prediction when adding additional clinical features to the existing STS-risk model which outperformed the STS-risk model. Depending on healthcare systems clinical resources and data availability, an optimized XGBoost model can improve the readmission risk prediction outcome.