tbuckley/cabot-search huggingface dataset:
SURG-11. TUMOR RECURRENCE PATTERNS AFTER SURGICAL RESECTION OF INTRACRANIAL LOW-GRADE GLIOMAS
Authors: Yoshihiro Muragaki, Yasukazu Fukuya, Soko Ikuta, Masayuki NItta, Taiichi Saito, Shunsuke Tsuzuki, Takashi Maruyama, Takakazu Kawamata
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis. METHODS Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years. RESULTS Early (within 2 years after primary surgery) and non-early ( &amp;gt; 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow ( &amp;gt; 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1-mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG. Follow-up MRI also showed same results. CONCLUSIONS Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.
IMMU-02. GENOMIC AND TRANSCRIPTOMIC CORRELATES OF IMMUNOTHERAPY RESPONSE WITHIN THE TUMOR MICROENVIRONMENT OF LEPTOMENINGEAL METASTASES
Authors: Christopher Alvarez-Breckenridge, Sanjay Prakadan, Samuel Markson, Albert Kim, Naema Nayyar, Benjamin Kuter, Joana Mora, Brian Shaw, Eudocia Quant Lee, Ugonma Chukwueke, Daniel Cahill, Ryan Sullivan, Scott Carter, Alex Shalek, Priscilla Brastianos
Journal: Neuro-Oncology (2021)

Abstract Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials utilizing either Pembrolizumab alone or the combination of Ipilimumab and Nivolumab. We investigated the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We isolated and sequenced 34,742 cells from both the malignant and immune compartment within CSF. Amongst the 19 patients included in the cohort, there were 13 pre-treatment and 24 post-treatment samples, and 9 patients were sampled across multiple timepoints. We detected dynamic changes in immune cell recruitment into the CSF and activation within 30 days of ICI, including increased effector T cell activation and IFN-gamma response pathways within T cells. Moreover, the overall level of IFN-gamma response and antigen processing within 30 days of ICI in malignant cells correlated with survival past clinical trial primary endpoint. Lastly, we observed evidence of longitudinal outgrowth of distinct immunogenic clones over the course of ICI. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and provides unique insights into the compartmental and temporal variation during the course of ICI. Moreover, our findings demonstrate the clinical utility of cell- free and single-cell genomic measurements for LMD research.
Abstract 10560: Reducing Cardiovascular Risk Among Participants in a Community Supported Agriculture Program
Authors: Martha J Biddle, Junghee J Kang, Dawn Brewer, Timothy A Woods
Journal: Circulation (2021)

Introduction: Eating a diet high in vegetables translates to lower risk for cardiovascular disease. Only 10% of Americans consume the recommended servings of vegetables per day. Community supported agriculture (CSA) programs support local farmers while promoting increased consumption of vegetables. At the University of Kentucky (UK), employees receive vouchers to encourage CSA program participation while giving financial support to local farms that allow them to operate in an economically sustainable manner. Our objective was to examine the effect of participation in a CSA voucher program on CVD risk factors as a new approach to CVD risk management. Methods: Participants self-selected in the UK employee Health and Wellness CSA voucher program. Biometric measurements (blood pressure, lipid levels, and noninvasive dermal carotenoid levels via Veggie Meter) and vegetable intake via six-question BRFSS were collected pre- and post- CSA program participation. Descriptive statistics, independent t-tests, paired t-tests and cluster analysis were used to analyze the data. Results: Among 204 eligible individuals, 85 enrolled pre-program and 52 completed post program for a 61.2% retention rate. Average participant age was 42 + 10 years, predominantly Caucasian females. Systolic blood pressure was significantly reduced from pre- to post program (125.8 compared to 120.6 mmHg, p = 0.012). Carotenoid levels significantly increased from pre- to post program (286.3 ± 110 to 295.9 ± 124,) while controlling for age and sex (p = &lt;0.001). Frequency of total vegetable, red/orange vegetables, dark green vegetables and other vegetable intake also increased from pre- to post- program while controlling for age and sex (p = 0.003, 0.004, 0.013, &lt; 0.001 and 0.011 respectively). Conclusion: Our data identifies participation in a CSA employer incentivized program can effectively reduce blood pressure and increase vegetable intake (dermal carotenoids) and self-reported quantity and variety of vegetable consumption thereby reducing CVD risk.
A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity
Authors: Murillo Silva, Yu Kato, Mariane B. Melo, Ivy Phung, Brian L. Freeman, Zhongming Li, Kangsan Roh, Jan W. Van Wijnbergen, Hannah Watkins, Chiamaka A. Enemuo, Brittany L. Hartwell, Jason Y. H. Chang, Shuhao Xiao, Kristen A. Rodrigues, Kimberly M. Cirelli, Na Li, Sonya Haupt, Aereas Aung, Benjamin Cossette, Wuhbet Abraham, Swati Kataria, Raiza Bastidas, Jinal Bhiman, Caitlyn Linde, Nathaniel I. Bloom, Bettina Groschel, Erik Georgeson, Nicole Phelps, Ayush Thomas, Julia Bals, Diane G. Carnathan, Daniel Lingwood, Dennis R. Burton, Galit Alter, Timothy P. Padera, Angela M. Belcher, William R. Schief, Guido Silvestri, Ruth M. Ruprecht, Shane Crotty, Darrell J. Irvine
Journal: Science Immunology (2021)

An adjuvant composed of saponin and a TLR4 agonist acts by enhancing lymph flow and antigen entry into lymph nodes.
Abstract 11501: Morbid Obesity Eliminates the Obesity Paradox in Patients Hospitalized for Heart Failure
Authors: Jose S Aguilar-gallardo, Francisco ROMEO, Ashish A Correa, Johanna P Contreras
Journal: Circulation (2021)

Introduction: For reasons unclear, obesity has been paradoxically associated with reduced mortality in patients hospitalized for heart failure. In this study, we analyze if this paradox extends to patients with morbid obesity. Methods: This was a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included adult patients hospitalized with a primary diagnosis of heart failure. Patients with morbid obesity and non-morbid obesity were compared to those without obesity as a comorbidity. The primary outcome was mortality. Secondary outcomes included length of stay, total charges, and cardiogenic shock. Multivariate regression analysis was used to adjust for age, race, Charlson Comorbidity Index, and other relevant comorbidities with a p-value &lt;0.2 in univariate screen. Statistical analysis was performed using Stata 17.0. Results: A total of 1,248,490 (weighted) heart failure hospitalizations were included. Multivariate regression analysis revealed a trend for increased mortality in the morbidly obese with an odds ratio (OR) 1.10 (p=0.056). It also revealed paradoxically decreased mortality in patients with non-morbid obesity with an OR 0.73 (p=0.000), confirming the presence of the obesity paradox in this population. In the subgroup with reduced ejection fraction, morbid obesity was associated with increased mortality, with an OR 1.68 (p=0.029). Morbid obesity was also associated with increased length of stay and total hospitalization charges, but decreased incidence of cardiogenic shock. Conclusions: Morbid obesity eliminates, and in some cases reverses the obesity paradox in patients hospitalized for heart failure. More research is required to clarify the mechanisms behind this counterintuitive phenomenon.
EXTH-02. AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS OF HER2+ BREAST CANCER BRAIN METASTASIS
Authors: Dan Laks, Kenny Chen, Xiaoqin Ren, Ishan Shah, Usman Hameedi, Jenna Tocci, Timothy Fiore, Kyle Grant, Kelly Bales, Hasson Samuel
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND HER2+ tumors constitute approximately 20% of breast cancer patients and are characterized by overexpression of the growth factor receptor HER2 (ERBB2), a cell proliferation driver. Effective anti-HER2 therapies confer prolonged patient survival necessitating the need for transformative treatments targeting brain metastases, a major cause of mortality in ~30-50% of HER2+ metastatic breast cancer patients. HER2-directed antibody immunotherapy, while efficacious for peripheral disease, has limited central nervous system exposure (CNS). To overcome these challenges, we transduced CNS cells with a novel AAV vector carrying an anti-HER2 antibody payload. METHODS We assessed the biochemical equivalence and functional effectiveness of AAV vector-encoded antibodies using in vitro assays. After selecting promising vector-encoded antibody candidates, a novel, blood-brain barrier penetrant AAV capsid was administered via i.v. dosing to an orthotopic xenograft mouse model of HER2+ brain metastases. Bioluminescent imaging provided a longitudinal measure of brain tumor burden. At study termination, we measured antibody biodistribution in cerebrospinal fluid (CSF), serum, and brain homogenates with AlphaLISA assays. RESULTS Using HER2+ breast cancer cell lines, we determined that an antibody-dependent cell cytotoxicity (ADCC) enhanced anti-HER2 antibody was most effective and demonstrated that AAV-vector encoded forms of the antibody performed comparably to recombinant reference antibodies. Following i.v. administration of a HER2 antibody encoding AAV vector, we measured &amp;gt;1 ug/mL of the antibody in CSF. Importantly, AAV-mediated expression of the ADCC-enhanced HER2-directed antibody significantly abrogated tumor growth in orthotopic xenograft models. CONCLUSIONS Peripheral administration of an AAV vector was able to transduce brain tissue such that efficacious levels of HER2-directed antibodies were produced. This strategy was successful at preventing tumor growth in our physiologically relevant model of breast cancer brain metastases. Such a treatment modality should be further evaluated in patient derived PDX models to validate translational efficacy for human patients.
Abstract 11363: Pericardial Constriction-Like Echocardiographic Findings in Elite Athletes Following Mild Covid-19 Infection: A Propensity Score-Matched Analysis
Authors: Balint K Lakatos, Marton Tokodi, Alexandra Fabian, Zsuzsanna Ladanyi, Hajnalka Vágó, Liliána Szabó, Nora SYDO, Emese Csulak, Orsolya Kiss, Máté Babity, Anna Reka R Kiss, Zsofia Gregor, Andrea Szucs, Béla Merkely, Attila Kovacs
Journal: Circulation (2021)

Introduction: The cardiovascular effects of COVID-19 in elite athletes is still a matter of intense scientific debate. Hypothesis: We sought to perform a comprehensive echocardiographic characterization of post-COVID athletes by comparing them to a non-COVID athlete cohort. Methods: 107 elite athletes with COVID-19 were prospectively enrolled (P-CA; 23±6 years, 23% female) 107 healthy athletes were selected as a control group using propensity score matching (N-CA). All athletes underwent 2D and 3D echocardiography. Left (LV) and right ventricular (RV) end-diastolic volumes (EDVi) and ejection fractions (EF) were quantified. To characterize LV longitudinal deformation, 2D global longitudinal strain (GLS) and the ratio of free wall versus septal longitudinal strain (FWLS/SLS) were also measured. To describe septal flattening (SF - frequently seen in P-CA), LV eccentricity index (EI) was calculated. Results: P-CA and N-CA athletes had comparable LV and RVEDVi (P-CA vs N-CA; 77±12 vs. 78±13mL/m2; 79±16 vs 80±14mL/m2). P-CA had significantly higher LVEF (58±4 vs 56±4%, p&lt;0.001), while LVGLS values did not differ between P-CA and N-CA (-19.0±1.9 vs -18.8±2.2%). EI was significantly higher in P-CA (1.13±0.16 vs 1.01±0.05, p&lt;0.001), which was attributable to a distinct subgroup of P-CA with a prominent SF (n=35, 33%), further provoked by inspiration. In this subgroup, the EI was markedly higher compared to the rest of the P-CA (1.29±0.15 vs 1.04±0.08, p&lt;0.001), LVEDVi was also significantly higher (80±14 vs 75±11 mL/m2, p&lt;0.001), while RVEDVi did not differ (82±16 vs 78±15mL/m2). Moreover, the FWLS/SLS ratio was significantly lower in the SF subgroup (91.7±8.6 vs 97.3±8.2, p&lt;0.01). P-CA with SF experienced symptoms less frequently (1.4±1.3 vs. 2.1±1.5 symptom during the infection, p=0.01). Conclusions: COVID-19 infection might be frequently associated with a constriction-like physiology in elite athletes.
Abstract 10895: Biomarkers of Physical Frailty in Heart Failure
Authors: Quin E Denfeld, Jonathan Q Purnell, Christopher S Lee, Samuel A Camacho, Mary Roberts Davis, Shirin O Hiatt, Kerri Winters-Stone, William R Woodward, Beth A Habecker
Journal: Circulation (2021)

Introduction: Physical frailty is highly prevalent and associated with worse outcomes among adults with heart failure (HF). However, the biological mechanisms underlying physical frailty in HF are poorly understood. The aim was to identify biomarkers associated with physical frailty in HF using a multimarker strategy to reflect multiple physiological processes. Hypothesis: We hypothesized that biomarkers of neurohormonal activation, inflammation, insulin resistance, and adipose and skeletal muscle dysfunction would differentiate physically frail from non-physically frail adults with HF. Methods: We collected data and plasma samples from adults with New York Heart Association Functional Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria. Plasma biomarkers assayed were: N-terminal pro-B-type natriuretic peptide, norepinephrine, dihydroxyphenolglycol, soluble tumor necrosis factor alpha receptor 1, adiponectin, insulin, glucose, insulin-like growth factor-1, and myostatin. Comparative statistics and multivariate linear regression were used. Results: The average age of the participants (n = 113) was 63.5±15.7 years, half (48%) were women, and most had a non-ischemic etiology of HF (73%). Physical frailty was identified in 42% of the sample and associated with female gender, higher body mass index, more comorbidities, and HF with preserved ejection fraction. After adjusting for Seattle HF Model projected survival scores, comorbidities, body mass index, and gender, those physically frail had significantly lower plasma adiponectin, lower insulin-like growth factor-1, and lower myostatin compared with those non-physically frail (all p &lt; 0.05). There were no significant differences in other biomarkers between physical frailty groups. Conclusions: Biomarkers involved in adipose tissue and skeletal muscle development, maintenance, and function were significantly different between those physically frail and non-physically frail. Physical frailty in HF may be, in part, underpinned by dysfunctional peripheral processes involving the adipose tissue and skeletal muscle.
OCEAN (OP-103): Melflufen Plus Dexamethasone (Dex) Versus Pomalidomide (Pom) and Dex in Relapsed Refractory Multiple Myeloma (RRMM) - Renal Impairment (RI) Analysis
Authors: Tadeusz Robak, Sosana Delimpasi, Ludek Pour, Tamas Masszi, Ivan Spicka, Wojciech Legiec, Pieter Sonneveld, Marcus Thuresson, Kajsa Larsson, Johan Harmenberg, Fredrik H. Schjesvold
Journal: Blood (2021)
Abstract 9727: Predictive Value of Machine Learning on Adenosine Stress Single Photon Emission Computed Tomography for Multivessel Coronary Artery Stenosis
Authors: Masato Shimizu, Hiroko Miyazaki, shummo cho, Yoshiki Misu, Ryo Tateishi, Masao Yamaguchi, Yosuke Yamakami, Hiroshi Shimada, Tomoko Manno, Ami Isshiki, Shigeki Kimura, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2021)

Introduction: Adenosine stress single photon emission computed tomography (SPECT) is utilized to detect coronary artery stenosis, but the diagnostic performance is recognized not to be enough in patients with multivessel disease (MVD). Estimation of left ventricular (LV) dysfunction on electrocardiography gated SPECT including LV dissynchrony was reported to be valuable to predict MVD, but prognostic value of machine learning of those data was not studied. Hypothesis: Machine learning of gated SPECT data has high diagnostic performance for MVD. Methods: We enrolled consecutive 256 patients (78±11 years, 188 male) who underwent adenosine stress gated SPECT (99mTechnesium) and coronary angiography in one month. LV function and myocardial perfusion score were evaluated by Heart Risk View (Nihon Medi-Physics Co.,Ltd.). First, multivariate logistic regression analysis underwent with minimum Akaike’s information critetion by stepwise regression. Propensity score (PS) was calculated with the selected predictors, and receiver operation characteristics (ROC) curve analysis was performed to evaluate the predictive value. Next, we constructed prediction model for MVD by machine learning (random forest method and deep learning). Results: Thirty-five cases (14%) showed MVD. Stepwise regression with AIC showed 7 predictors as the Figure. Their accuracy and area under ROC were in 0.527-0.809, 0.599-0.689, respectively. PS of the 7 predictors showed the accuracy 0.691 and AUROC 0.758. Random forest method and deep learning built prediction models, and their accuracy and AUROC were 0.840 and 0.788, 0.846 and 0.760, respectively. The top two feature importance of random forest were SD od TES on stress and Phase SD on stress, which indicate the degree of LV dyssynchrony. Conclusions: Machine learning of adenosine stress gated STECT had powerful predictive value for MVD, and the degree of LV dyssynchrony on stress played essential role in the prediction.
EFFECTIVENESS OF NON-PHARMACOLOGICAL INTERVENTIONS IN SYSTEMIC SCLEROSIS: A SYSTEMATIC REVIEW
Authors: L.M. Willems, J.E. Vriezekolk, A.A. Schouffoer, J.L. Poole, T.A. Stamm, C. Bostrom, T.P.V. Vlieland, C.H. van den Ende
Journal: Annals of the Rheumatic Diseases (2014)
Navigating the social identity of long covid
Authors: Julie Van de Vyver, Ana C. Leite, Nisreen A. Alwan
Journal: BMJ (2021)

Long covid is an urgent global public health problem.In the UK alone, experiencing it for a year or more is estimated to affect 405,000 people, with higher prevalence in deprived groups.Medical research into the pathophysiology of long covid, and how it can be treated is urgently needed, but it is also essential to consider social factors that may be implicated in the recovery of the millions of people with long covid across the world.It is not possible to holistically understand any individual's experiences, without understanding their connection and place within the broader community around them.Research shows that social connections and belonging are essential determinants of health and wellbeing.
CTNI-28. VOLUMETRIC AND DOSIMETRIC PATTERNS OF FAILURE ANALYSIS OF A PHASE II CLINICAL TRIAL OF 18F-DOPA-PET DIRECTED DOSE ESCALATED RADIOTHERAPY FOR GLIOBLASTOMA
Authors: William Breen, S Keith Anderson, Deanna Pafundi, Timothy Kaufmann, Christopher Hunt, Val Lowe, Diane Vogen, Elizabeth Yan, Jann Sarkaria, Paul Brown, Sani Kizilbash, Joon Uhm, Michael Ruff, Mark Zakhary, Yan Zhang, Maasa Seaberg, Abdou Abdel Rehim, Hok Seum Wan Chan Tseung, Jing Qian, Brian Kabat, Bradley Kemp, Nadia Laack, Debra Brinkmann
Journal: Neuro-Oncology (2021)

Abstract While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( &amp;gt;95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 &amp;gt; 7.8cc, MRI-defined GTV76 &amp;gt; 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p&amp;lt; 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 &amp;gt; 2.17 cc who had biopsy only (median PFS 3.2 months, p&amp;lt; 0.001). Patients with 18F-DOPA-PET-defined GTV51 &amp;gt; 50 cc had the highest risk of grade 3+ radionecrosis (p&amp;lt; 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.
A Phase II Study of a Novel Conditioning Regimen of Bendamustine and Melphalan Followed By Autologous Stem Cell Transplant for Patients with Multiple Myeloma
Authors: Alexandra Gomez-Arteaga, Tomer M Mark, Danielle Guarneri, Paul J Christos, Usama Gergis, June Greenberg, Jingmei Hsu, Sebastian A. Mayer, Ruben Niesvizky, Roger Pearse, Adrienne A. Phillips, Adriana C. Rossi, Morton Coleman, Koen Van Besien, Tsiporah B. Shore
Journal: Blood (2017)