tbuckley/cabot-search huggingface dataset:
Abstract 11380: Undersizing Mitral Annuloplasty Acutely Eliminates Functional Mitral Regurgitation but Does Not Relieve Tethering Forces on the Mitral Valve Chordae Tendineae
Authors: Dongyang Xu, Samantha Zhan-Moodie, Kirthana Sreerangathama Suresh, Qi He, Muralidhar Padala
Journal: Circulation (2021)

Introduction: Functional mitral regurgitation (FMR) develops secondary to mitral valve (MV) geometric distortions such as isolated annular dilatation (AD), asymmetric tethering (Asym), and symmetric tethering (Sym). Undersizing mitral annuloplasty (UMA) has been religiously used to repair FMR with the notion that it can restore coaptation and relieve tethering forces, which has not been tested. Hypothesis: UMA does not relieve MV chordal tension in the setting of FMR from AD, Asym and Sym despite correcting regurgitation. Methods: In an ex vivo MV simulator ( Fig. A ), fresh pig MVs were mounted onto an adjustable annulus and two papillary muscle displacing rods ( Fig. B ), which are used to induce AD, Asym and Sym MV configurations. A 28mm annuloplasty ring was implanted ( Fig. C ) after the three MV geometries were established. MV hemodynamics were measured using electromagnetic flowmeters, leaflet kinematics were measured by 2D echocardiography, and chordal forces were measured using miniature C-ring force transducers. Results: Regurgitation fraction was significantly reduced in the Asym and Sym geometries after 28mm annuloplasty (Asym: 5.3±3.7% vs 1.6±1.2%, p=0.024; Sym: 12.8±5.6% vs 5.6±3.1%, p=0.006) ( Fig. D ). Tenting height was not significantly reduced after annuloplasty in all valve geometries, indicating persistent tethering despite annular downsizing ( Fig. E ). Neither anterior nor posterior leaflet mobility was improved after annuloplasty ( Fig. F-G ). The chordal forces in the anterior strut and posterior strut chordae tendineae were depicted in ( Fig. H1-4 ). The peak forces in the chordae slightly reduced after UMA, but the reduction in the peak forces did not reach statistical significance. Conclusions: UMA corrects FMR by forcing the leaflets together in the mitral valve orifice but does not improve leaflet mobility or relieve the tethering forces on the leaflets, which explains the mechanistic basis for high rates of recurrent FMR after UMA.
Abstract 9890: HFpEF with Normal Natriuretic Peptides: An Earlier Stage of Disease or Fundamentally Different Phenotype?
Authors: Hidemi Sorimachi, Kazunori Omote, Masaru Obokata, Yogesh Reddy, Barry A Borlaug
Journal: Circulation (2021)

Introduction: Many patients with heart failure with preserved ejection fraction (HFpEF) display normal N-terminal-pro-B type natriuretic peptide (NTproBNP)levels. Mortality and hospitalization rates are lower in this group compared to patients with high NTproBNP, but it remains unclear whether these patients represent a fundamentally different phenotype or an earlier stage of disease. Methods: 213 subjects with HFpEF defined by invasive hemodynamics underwent serial echocardiographic examinations &amp;gt;1 year apart. Clinical, cardiac structural, functional, and hemodynamic characteristics were examined. Results: Exam 2 was performed a median of 3.2 years (IQR 2.2-5.1) following Exam 1. From this cohort, 66 (33%) displayed normal NT-proBNP levels (≤125pg/ml, nBNP) and 147 (67%) displayed high NTproBNP (hBNP). Compared to hBNP, nBNP patients were younger (62±10 vs 71±9 years, p&amp;lt;0.0001) and more obese (35±8 vs 32±7 kg/m 2 , p=0.005). At Exam 1, approximately 50% of nBNP displayed left ventricular (LV) systolic dysfunction defined as LV longitudinal strain (GLS)&amp;lt;16% ( Figure A ) and LA dysfunction defined as left atrial (LA) reservoir strain&amp;lt;26% ( Figure B ), but right ventricular (RV) systolic function as relatively preserved ( Figure C ). At Exam 2, LV, LA, and RV strain decreased in both groups (Panels A-C), with no difference between nBNP and hBNP in the velocity of change (p&amp;gt;0.6 for all). More patients crossed the threshold definition for LV systolic and LA dysfunction in nBNP compared to hBNP ( Figure D and E ), but the prevalence of RV dysfunction increased more in hBNP ( Figure F ). Conclusions: In patients with HFpEF with normal NT-proBNP, biventricular systolic function and LA function deteriorate over time at similar pace. These data suggest that patients with HFpEF are not a fundamentally different disorder, but rather represent an earlier stage of disease that progresses from LV and LA dysfunction in early stages to RV dysfunction in advanced stages.
Microglia contribute to the propagation of Aβ into unaffected brain tissue
Authors: Paolo d’Errico, Stephanie Ziegler-Waldkirch, Vanessa Aires, Philippe Hoffmann, Charlotte Mezö, Daniel Erny, Laura Sebastian Monasor, Sabine Liebscher, Vidhya M. Ravi, Kevin Joseph, Oliver Schnell, Katrin Kierdorf, Ori Staszewski, Sabina Tahirovic, Marco Prinz, Melanie Meyer-Luehmann
Journal: Nature Neuroscience (2021)

Abstract Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infiltration. Manipulation of microglia function reduced Aβ deposition within grafts. Furthermore, in vivo imaging identified microglia as carriers of Aβ pathology in previously unaffected tissue. Our data thus argue for a hitherto unexplored mechanism of Aβ propagation.
NIMG-02. 18F-FLUCICLOVINE POSITRON EMISSION TOMOGRAPHY TO DISTINGUISH TUMOR PROGRESSION FROM RADIATION NECROSIS FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASIS: A QUALITATIVE ANALYSIS
Authors: Timothy Smile, Martin Tom, Nancy Obuchowski, Frank DiFilippo, Stephen Jones, John Suh, Erin Murphy, Jennifer Yu, Alireza Mohammadi, Gene Barnett, Steve Huang, Guiyun Wu, Scott Johnson, Manmeet Ahluwalia, David Peereboom, Glen Stevens, Samuel Chao
Journal: Neuro-Oncology (2021)

Abstract PURPOSE/OBJECTIVE(S) To assess the ability of 18F-Fluciclovine PET/CT to distinguish radiation necrosis (RN) from tumor progression (TP) among patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) in a prospective pilot study. MATERIALS/METHODS Adults with post-SRS BM presenting with follow-up brain MRI equivocal for RN versus TP underwent 18F-Fluciclovine PET/CT within 30 days of equivocal MRI. PET images were reconstructed using a point-spread-function algorithm. Three physician reviewers independently performed qualitative analyses of each lesion using a three-point visual score relative to PET-avidity of blood pool and parotid. Quantitative metrics for each lesion were documented. Reference standard was clinical follow-up with brain MRI until tumor board consensus or tissue confirmation. Nonparametric estimates of area under the receiver operating characteristic curve (AUC) for clustered data were estimated, with diagnostic performance based on visual score. RESULTS In 15 subjects with 20 lesions, final diagnosis was RN in 16 (80%) lesions and TP in 4 (20%). Visual score significantly correlated with final diagnosis (AUC range 0.836-0.906 [p≤0.037]). A threshold score of 2 (lesion 18F-fluciclovine uptake above blood pool to parotid) and higher produced sensitivities and specificities of 75-100% and 38-56% respectively among the reviewer majority. Conversely, a threshold of 3 (uptake higher than parotid) produced sensitivities and specificities of 50-75% and 100% respectively. CONCLUSION In this prospective pilot, basic visual analysis of 18F-Fluciclovine PET/CT provided high sensitivity and specificity in detection of TP in post-SRS BM based on different threshold scores, suggesting room for visual threshold optimization. A low TP event rate limited the ability to estimate sensitivity/specificity and to perform combined qualitative/quantitative analyses. Further study to refine interpretation criteria is ongoing.
Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer
Authors: Joao V Alessi, Biagio Ricciuti, Stephanie L Alden, Arrien A Bertram, Jessica J Lin, Mustafa Sakhi, Mizuki Nishino, Victor R Vaz, James Lindsay, Madison M Turner, Kathleen Pfaff, Bijaya Sharma, Kristen D Felt, Scott J. Rodig, Justin F. Gainor, Mark M. Awad
Journal: Journal for ImmunoTherapy of Cancer (2021)

An elevated peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is a negative prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving chemotherapy and immune checkpoint inhibitors. Whether dNLR is also associated with clinical outcomes to first-line pembrolizumab among patients with NSCLC and a programmed cell death ligand 1 (PD-L1) Tumor Proportion Score (TPS) of ≥50% is uncertain. How dNLR relates to the tumor immune microenvironment is also unclear.In two participating academic centers, we retrospectively analyzed the dNLR (defined as the absolute neutrophil count/white cell count - absolute neutrophil count) prior to initiation of first-line pembrolizumab in patients with metastatic NSCLC and a PD-L1 TPS ≥50% and lacking genomic alterations in EGFR and ALK. An unbiased recursive partitioning algorithm was used to investigate an optimal dNLR cut-off with respect to objective response rate (ORR). Multiplexed immunofluorescence for CD8+, FOXP3+, PD-1+, and PD-L1 was performed on a separate cohort of NSCLCs to determine the immunophenotype associated with dNLR.A total of 221 patients treated with first-line pembrolizumab were included in this study. The optimal dNLR cut-off to differentiate treatment responders from non-responders was 2.6. Compared with patients with a dNLR ≥2.6 (n=97), patients with dNLR <2.6 (n=124) had a significantly higher ORR (52.4% vs 24.7%, p<0.001), a significantly longer median progression-free survival (mPFS 10.4 vs 3.4 months, HR 0.48, 95% CI 0.35 to 0.66, p<0.001), and a significantly longer median overall survival (mOS 36.6 vs 9.8 months, HR 0.34, 95% CI 0.23 to 0.49, p<0.001). After adjusting for age, sex, tobacco use, performance status, histology, serum albumin level, oncogenic driver status, and PD-L1 distribution (50%-89% vs ≥90%), a dNLR <2.6 was confirmed to be an independent predictor of longer mPFS (HR 0.47, 95% CI 0.33 to 0.67, p<0.001) and mOS (HR 0.32, 95% CI 0.21 to 0.49, p<0.001). Among advanced NSCLC samples with a PD-L1 TPS of ≥50%, those with a dNLR <2.6 had significantly higher numbers of tumor-associated CD8+, FOXP3+, PD-1 +immune cells, and PD-1 +CD8+T cells than those with a dNLR ≥2.6.Among patients with NSCLC and a PD-L1 TPS ≥50%, a low dNLR has a distinct immune tumor microenvironment and more favorable outcomes to first-line pembrolizumab.
NCOG-31. GIANT PITUITARY ADENOMA (GPA) SCORE: A NOVEL SCORING SYSTEM TO PREDICT POSTOPERATIVE OUTCOMES OF GIANT PITUITARY ADENOMAS
Authors: Syed Ather Enam, Fauzan Alam Hashmi, Sanam Mir Ghazi, Ahsan Ali Khan, Muhammad Bilal Tariq, Muhammad Shahzad Shamim, Muhammad Faraz Raghib
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Giant pituitary adenomas (GPA) are uncommon and highly variable in morphology and extension. There is no scoring system that considers all the dimensions of adenoma invasion. We developed a new Giant Pituitary Adenoma score and report our surgical experience and evaluate outcomes after resection of these tumors in accordance with the preoperative score. METHODS We developed a novel scoring system for classifying giant pituitary adenomas, and 11-year data of GPA surgery at our center was collected retrospectively, based on this scoring system. GPA Score considered tumor’s parasellar extension, encasement of cavernous internal carotid artery (ICA), suprasellar extension &amp;gt; 2 cm, suprasellar extension &amp;gt; 4cm and retrosellar extension. Maximum possible score was 9. The scoring system was applied to 53 patients of GPA who underwent surgical resection between January 1, 2006, and December 2017. The Lundin-Pederson (ABC/2) method was used to calculate the tumor volume both pre- and post-resection and linear regression was used to assess the relationship between extent of tumor resection and GPA score. RESULTS The median age of the study population was 42.08 ± 16.49 years. The mean maximum diameter of the pituitary adenomas was 5.0 cm (range 4.0 cm-8.5cm) while the mean volume of the adenomas was 27.3 cm3 (range 10 cm3-149 cm3). There were 3 cases of score 2, 5 cases of score 3, 13 cases of score 4, 20 cases of score 5, 9 cases of score 6 and 3 cases of score 7. The range of tumor volumes of tumors for scores from 2-7 was 17.3 cm3 to 65.8 cm3 and GPA score was correlated with the percent residual tumor using linear regression that was statistically significant (p= 0.001). CONCLUSION GPA Score is a reliable scoring system to predict the extent and subsequent difficulty in tumor resection in GPA.
Abstract 10104: Sex and Ethnic Disparities in Heart Failure-Related Mortality Rates Among the Young
Authors: Abdul Minhas, Ahmed H Qavi, Safi U Khan, Sourbha Dani, Richard Krasuski, Erin Michos, Stephen J Greene, Marat Fudim
Journal: Circulation (2021)

Introduction: Heart failure (HF) accounts for significant morbidity, mortality, and economic suffering. The aim of this study was to examine the trends in HF-related deaths among the young population in the United States from 1999 to 2019. Methods: We used the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) to access National Vital Statistics System data from 1999 to 2019. HF-related deaths among individuals aged 15-44 years were identified from multiple causes of death and were represented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to examine changes in trends and annual percentage change (APC) overall, and then stratified by sex and ethnicity. Results: Overall, AAMR related to HF remained stable from 1999(2.36) to 2012(2.23) (APC -0.3[95% CI, -0.8 to 0.2]) and then gradually increased until 2019(3.16) (APC 5.0[95% CI, 3.6 to 6.3]). AAMR was higher in men (3.04) than women (1.87). AAMR was highest in non-Hispanic Black (NHB) (6.77) followed by Hispanic (1.51), non-Hispanic White (NHW) (1.91) and lastly non-Hispanic Asian or Pacific Islander (NH-API) (1.11) ethnic groups. After initial decline, APC in AAMR increased in women (5.2) starting in 2012. AAMR did not change significantly in men from 2005 to 2011 and subsequently increased from 2011 to 2019 (APC 4.9). After initially remaining stable, AAMR increased among NHW (APC 4.6) and NHB (APC 4.3) persons from 2012 to 2019. After initial decline, APC in AAMR increased among Hispanic persons (7.2) from 2012 to 2019. APC in AAMR increased in NH-API persons (2.4) during the entire study period (Figure). Conclusion: HF-related mortality in young adults has increased over the last decade. Stratification by sex and ethnicity reveals significant disparities. Mortality in NHBs has been growing at a faster rate than any of the other groups and the gap between mortality in NHBs and NHWs is large and widening.
Helping Cancer Survivors Return to Work
Authors: Amye J. Tevaarwerk
Journal: Journal of the National Comprehensive Cancer Network (2021)

Work limitations due to health problems can range from mild or transient limitations to persistent, long‐term dysfunction and can lead to employment instability, underemployment, and even loss of employment. In fact, compared with a healthy matched control population, cancer survivors are 1.37 times more likely to be unemployed. Because patients with metastatic disease are particularly vulnerable, proactive discussion regarding the potential impact of treatment on employment and work outcomes may be beneficial. However, employment and financial toxicity are not topics that clinicians are necessarily trained to address. Financial counselors or patient navigators may be better able to offer a personalized approach and help survivors navigate the complex resources that are involved. Additional research into cancer‐related work outcomes is needed.
Abstract P485: Loss Of Acta2 In Cardiac Fibroblasts Does Not Prevent The Myofibroblast Differentiation Or Affect The Cardiac Repair After Myocardial Infarction
Authors: Yuxia Li, Chaoyang Li, Qianglin Liu, Leshan Wang, Adam X Bao, Jangwook P Jung, Joseph Francis, Jeffery Molkentin, Xing Fu
Journal: Circulation Research (2021)

In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair in the infarcted area. One of the most widely accepted markers of myofibroblast differentiation is the expression of Acta2 which encodes smooth muscle alpha-actin (SMαA) that is assembled into stress fibers. However, the requirement of Acta2 / SMαA in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair remained largely unknown. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse line. Surprisingly, mice that lacked Acta2 in cardiac fibroblasts had a normal survival rate after MI. Moreover, Acta2 deletion did not affect the function or overall histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT and Acta2 -null cardiac myofibroblasts. It was identified that Acta2 -null cardiac myofibroblasts had a normal total filamentous actin level and total actin level. Acta2 deletion caused a unique compensatory increase in the transcription level of Actg2 and an increase in the protein level of sarcomeric actin isoform(s). In addition, the specific muscle actin isoforms that were upregulated in Acta2 -null cardiac myofibroblasts varied between individual cells. Moreover, the formation of stress fibers by cytoplasmic actin isoforms, especially the cytoplasmic gamma-actin, was enhanced in Acta2 -null cardiac myofibroblasts despite their unchanged RNA and protein expression. In conclusion, the deletion of Acta2 does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increased expression and stress fiber formation of non-SMαA actin isoforms and the functional redundancy between actin isoforms are able to compensate for the loss of Acta2 in cardiac myofibroblasts.
Abstract 11417: Association Between Community-Level Violent Crime and Cardiovascular Mortality in Chicago - A Longitudinal Analysis
Authors: Lauren A Eberly, Howard Julien, Eugenia South, Ashwin S Nathan, Elias Dayoub, Peter W Groeneveld, Sameed Ahmed A Khatana
Journal: Circulation (2021)

Introduction: Prior studies suggest an association between neighborhood crime levels and cardiovascular (CV) risk factors and disease but have been limited by cross-sectional designs. We investigated whether longitudinal changes in violent crime are associated with CV mortality at the community level in a large US city - Chicago. Methods: Chicago is divided into 77 community areas. Using the Illinois Department of Public Health Division of Vital Records, we obtained age-adjusted mortality rates by community area for heart disease, stroke, and coronary artery disease deaths from 2000-2014 aggregated at 5-year intervals. Annual violent crime data were obtained from the City of Chicago Police Data Portal and were geocoded to the community area level. Violent crime was defined as assault, battery, criminal sexual assault, robbery, and homicide. Using a two-way fixed effects estimator, a robust longitudinal estimation method that accounts for measured or unmeasured time-invariant confounders, we assessed the association between longitudinal changes in violent crime and CV mortality after accounting for changes in demographic (proportion of racial/ethnic minorities) and economic (household income, unemployment, housing vacancy, education attainment) variables for each community area. Results: Between 2000 and 2014, the median violent crime rate in Chicago decreased from 3620 per 100,000 [IQR 2256, 7777] in the 2000-2004 period to 2390 [IQR 1507, 5745] in the 2010-2014 period (p=0.005 for trend). In the fixed effects model, after accounting for changes in demographic and economic variables, a 1% increase in community-area violent crime was independently associated with a 0.21% (95% CI 0.09, 0.33) increase in heart disease deaths (p=0.0006) and a 0.19% (95% CI 0.04, 0.33) increase in deaths from coronary artery disease (p=0.01). There was no significant association between change in violent crime and stroke deaths [0.17% (95% CI -0.08, 0.42; p=0.017)]. Conclusions: From 2000 to 2014, an increase in violent crime at the community level was associated with an increase in heart disease and coronary artery disease deaths in Chicago. Detecting rises in community-level violent crime may identify areas with worsening CV health independent of other factors.
NIMG-13. RESPONSE ASSESSMENT IN GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL-BASED IMMUNOTHERAPY: A COMPARATIVE ANALYSIS OF MACDONALD, RANO, MRANO, IRANO AND VOLUMETRIC MEASUREMENTS
Authors: Johanna Heugenhauser, Malik Galijasevic, Stephanie Mangesius, Johanna Buchroithner, Friedrich Erhart, Josef Pichler, Georg Widhalm, Matthias Preusser, Guenther Stockhammer, Sarah Iglseder, Christian Freyschlag, Stefan Oberndorfer, Karin Bordihn, Gord von Campe, Thomas Czech, Birgit Surboeck, Tadeja Urbanic Purkart, Christine Marosi, Thomas Felzmann, Martha Nowosielski
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Response assessment in the treatment of glioblastoma (GB) based on MR-imaging is still challenging, in particular for immunotherapeutic strategies. Several assessment tools have been proposed. In this post-hoc analysis we compared response assessment criteria (MacDonald, RANO, mRANO, Vol.-mRANO, iRANO) in newly diagnosed GB patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression free survival (PFS) and overall survival (OS). METHODS 76 patients with newly diagnosed GB enrolled in a multicenter randomized phase II trial receiving standard of care (SOC, n= 40) or SOC + Audencel vaccine (n= 36) were included. Tumor volumes were calculated by semiautomatic segmentation. To detect differences in PFS among the assessment criteria Kruskal-Wallis-test, for correlation analysis Spearman test was used. RESULTS There was a significant difference in median PFS based on the different assessments (mRANO 8.55 months [9.10-14.03], Vol.-mRANO 8.61 months [9.72-14.92] compared to MacDonald 4.04 months [5.21-8.75] and RANO 4.16 months [5.28-8.61]. For the vaccination arm only, median PFS by iRANO was 5.95 months [5.70-11.54]). There was no difference in PFS between SOC and SOC + Audencel using the different response criteria. The best correlation between PFS and OS was detected for mRANO (r= 0.65, p&amp;lt; 0.001) and Vol.-mRANO (r= 0.69, p&amp;lt; 0.001). At an 8-month landmark, the impact of progressive disease on median OS was best shown for mRANO (13.70 months [13.13-18.98], and Vol.-mRANO 12.03 months [12.51-17.94]) compared to MacDonald 17.97 months [15.45-20.92], RANO 17.97 months [15.92-20.95] and iRANO 17.34 months [14.99-22.73]. CONCLUSION When comparing different response assessments in GB patients treated with dendritic cell-based immunotherapy the best correlation between PFS and OS was observed for mRANO and Vol.-mRANO. Overall, no difference in PFS and OS was seen between the two treatment arms. iRANO was not superior for predicting OS in patients treated with Audencel.