tbuckley/cabot-search huggingface dataset:
INNV-38. COVID-19 INDUCED TELEMEDICINE LESSONS FOR CLINICIANS CARING FOR PATIENTS WITH PRIMARY BRAIN TUMORS
Authors: Edina Komlodi-Pasztor, Amy Brady, Stuart Grossman
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The COVID-19 pandemic triggered a rapid conversion from in-person to video-visits for new patient consultations and follow-up visits. Now with available vaccines and declining case rates efforts are underway to return to in-person visits as they provide more revenue and are viewed as best for patients and clinicians. This abstract reviews these assumptions. METHODS Electronic medical records from seven full-time faculty neuro-oncologists at Johns Hopkins Hospitals were retrospectively reviewed from 4/1/20 to 3/31/21 to examine the use of video visits over time and their patient demographics. RESULTS From 4/1/20 to 3/31/21, 279 new patients were seen (57% video-visits) with a median age of 52 years for both video and in-person visits. Patients came from 15 states for video and 17 states for in-person visits. There were also 2247 follow-up visits (85% video-visits) with a median age of 47 yrs for video and 50 yrs for in-person visits. Patients came from 28 states for video and 14 for in-person visits. No show visits were more frequent for in-person visits. During early months of the pandemic, few patients were seen in the clinics. Thereafter, video-visits rose sharply comprising 93% of follow-up visits in June 2020 and 62% of new patient consultations in September 2020. These rates have remained high (in March 2021, 72% of all follow-up visits and 59% of new patient consultations). CONCLUSIONS Despite reductions in COVID-19 infection rates, our neuro-oncologists continue to favor video-visits for new patient consultations and follow-up visits. Video-visits save patients and caregivers travel time, parking costs, and time away from work. They also allow an acceptable history and neurological exam, participation by many family members, easy sharing of MRI scans and laboratory data, and discussions unencumbered by face masks and shields. These advantages to video-visits remain significant even as the pandemic recedes.
Abstract 12019: Muscular Microcirculatory Dynamics During Lower Limb Strength Exercise Testing in Heart Failure With Preserved Ejection Fraction
Authors: Amanda Vale-Lira, Natalia Turri-Silva, Kenneth Verboven, JOAO LUIZ Quagliotti Durigan, Dominique Hansen, Gerson Cipriano
Journal: Circulation (2021)

Introduction: Muscular microcirculatory dynamic changes during muscle strength effort remain to be studied in different heart failure (HF) phenotypes and severities. This study compare the muscular microcirculatory responses during strength exercise testing in HF with preserved ejection fraction (HFpEF) with reduced ejection fraction (HFrEF) and disease severities. Hypothesis: HFpEF patients display worse microvascular function during strength exercise testing, particularly in those with more severe disease (according to Weber classification). Methods: Seventeen HF patients (HFpEF, n=10, HFrEF n=7, mean age 57±6 years) underwent muscular microcirculatory dynamics assessment by near-infrared spectroscopy (tissue saturation index, TSI, %; oxyhemoglobin, O 2 Hb, μM and deoxyhemoglobin concentration, HHb, μM) during concentric isokinetic strength exercise testing (20 repetitions at an angular velocity of 180°/s) and subsequent recovery. Patients were analyzed according to their phenotype and disease severity (Weber A+B and Weber C). Results: From HFpEF, Weber Class C patients presented a poor capability to achieve higher oxygen extraction during exercise than Class A and B. Among those with Weber C, while HFrEF patients presented lower oxyhemoglobin (O 2 Hb, μM) (-18.9±11.8 vs.-8.9±5.6, p=0.029) during exercise, HFpEF had lower O 2 Hb during the recovery period (-3.0±3.4 vs. 5.9±2.8, p=0.007). Figure 1 illustrates muscular oxygenation dynamics in heart failure phenotypes and severities. No differences for TSI and HHb, neither on O 2 Hb in between phenotypes on Weber A+B severity. Conclusions: Preliminary findings regarding muscular microcirculatory oxygen reduction during isokinetic muscle strength testing are present in HFpEF patients more severely impaired (Weber C), which helps explain exercise intolerance in Heart Failure, reinforcing a worst circulatory periphery environment in such phenotype.
Abstract P430: VSMCs Increase Glutamine Utilization For Energy Metabolism During Obesity
Authors: Krystal M Roggerson, Sharon Francis
Journal: Circulation Research (2021)

Obesity increases the risk of developing cardiovascular disease through vascular remodeling though the underlying mechanisms are not entirely understood. However, metabolic fuel partitioning and mitochondrial flexibility during energy metabolism may play a critical role. We demonstrated serum and glucocorticoid-inducible kinase 1 (SGK-1) is up-regulated in the vasculature of diet-induced obese mice and that SGK-1 deletion is protective against obesity-induced vascular remodeling by metabolically reprogramming vascular smooth muscle cell (VSMC) energy metabolism towards oxidative phosphorylation (OXPHOS) and away from glycolysis. Mitochondrial substrate availability and utilization of the primary metabolic fuels glucose, long chain fatty acids (LCFAs) and glutamine can drive metabolic reprogramming. Therefore, alterations in fuel utilization may contribute to vascular remodeling during obesity. The purpose of this study was to examine SGK-1’s role in 1) fuel dependency: a cell’s reliance for a specific fuel and 2) fuel capacity: a cell’s ability to oxidize a specific fuel to meet cellular energy demand under low-fat and high-fat diet-induced obesity. Using the MitoXpress Oxygen Consumption assay which measures OXPHOS, primary VSMCs isolated from wildtype (WT) and SMC-specific SGK-1 knockout (smSGK-1 KO) mice fed a 10% kcal low-fat or 45% kcal high-fat diet for eight weeks were seeded in a 96-well plate at a density of 6x10 4 cells/well in culture medium. To assess fuel dependency, cells were treated with fuel pathway inhibitors UK5099, Etomoxir or BPTES to block glucose, LCFA or glutamine oxidation, respectively. To measure fuel capacity, VSMCs were treated with a combination of two pathway inhibitors simultaneously. Next, samples were overlaid with a fluorescent extracellular oxygen consumption reagent, sealed with high-sensitivity mineral oil, then signals were read at 1.5-minute intervals for 2 hours at Ex/Em= 380/650 nm. Our results show WT VSMCs are exclusively glucose-dependent for OXPHOS regardless of dietary conditions. However, SGK-1 deletion induces a dependency for all three fuels for OXPHOS in VSMCs under low- and high-fat conditions. Even though WT and smSGK-1 KO VSMCs preferentially oxidized glucose for OXPHOS under low-fat conditions; SGK-1 deletion resulted in a 2.2-fold increase in glutamine capacity. Alternatively, WT VSMCs exposed to obesogenic conditions preferentially oxidized glutamine whereas SGK-1 deletion induced a nearly equal partitioning of all three fuels during obesity suggesting elevated mitochondrial flexibility. Overall, this study suggests SGK-1 increases glucose dependency for energy metabolism under physiological and obesogenic conditions. Also, increased glutamine utilization for OXPHOS during obesity may be an underlying cause of VSMC dysfunction and subsequent vascular impairment.
Out-of-Pocket Costs for Colonoscopy After Noninvasive Colorectal Cancer Screening Among US Adults With Commercial and Medicare Insurance
Authors: A. Mark Fendrick, Nicole Princic, Lesley-Ann Miller-Wilson, Kathleen Wilson, Paul Limburg
Journal: JAMA Network Open (2021)

This economic evaluation examines whether adult patients in the US who have commercial or Medicare insurance pay out-of-pocket costs associated with follow-up colonoscopy within 6 months of a noninvasive stool-based test.
Abstract 10650: Artificial Intelligence Correlates with Expert Aortic Measurements in Presurgical CTA Evaluation for Transcatheter Aortic Valve Replacement
Authors: John P Lineberger, Megan Mercer, Gilberto Aquino, Nathan Leaphart, Brian Dean, Sophia Nance, Anand Mulji, Andrew Wortham, Jordan Chamberlin, Joseph Schoepf, Jeffrey Waltz, Jeremy R Burt
Journal: Circulation (2021)

Introduction/Hypothesis: Transcatheter aortic valve replacement (TAVR) requires pre-surgical planning via CTA. Our purpose is to compare pre-TAVR CTA expert measurements versus an AI in a pilot study. Methods: An AI model was created using Unett++ with a Resnet18 encoder, and was trained using transfer learning. A total of 52 randomized patients with a preTAVR CTA were identified for AI validation. The average diameter from 3 aortic segments was measured by AI: annulus, sinuses of Valsalva, and sinotubular junction. Of the original 52 subjects, 39 patients had expert measurements for comparison with AI results. Standard statistical analysis was performed. Results: Patients were 65% male and 88% Caucasian. The median age and BMI were 82 years and 28 kg/m2, respectively. A Sorensen-Dice coefficient of 0.93 was attained between the expert and AI measurements. Annulus (Pearson r = 0.911), sinuses of Valsalva (r = 0.919), and sinotubular junction (r = 0.874) average diameter measurements correlated with the experts’ (p&lt;0.001 in all cases). It was shown that there was no proportional bias and that the concordance between AI and expert measurements was good to excellent (intraclass correlation coefficients = 0.909 (95% CI 0.834-0.951), 0.899 (0.766-0.952) and 0.830 (0.694-0.908) for annulus, sinuses of Valsalva and sinotubular junction). Limitations include small pilot sample with uncharacterized generalizability. Conclusion: In this validation study, AI measurements of the aortic annulus, sinuses of Valsalva, and sinotubular junction correlate with expert measurements. There was high inter-relater reliability for all sites. Further study will include expanded patient cohorts and accurately streamlined preoperative assessment for TAVR. Figure. Pre TAVR CT angiogram images in orthogonal projection for aortic annulus (A), sinuses of Valsalva (B), and sinotubular junction (C). “Ground Truth” is expert segmentation and “Threshold 0.5” is AI segmentation.
Abstract P319: SARM1 NAD Hydrolase Deficiency Protects Hearts Against Diabetic Cardiomyopathy
Authors: Christine Light, Chi Fung Lee
Journal: Circulation Research (2021)

NAD depletion is associated with the pathogenesis of diseases such as heart failure. Strategies to replenish cellular NAD levels by activating NAD synthesis pathways have shown promises to treat heart disease. However, how NAD consumption mechanisms lead to NAD depletion are less understood. SARM1 is a novel intracellular NAD hydrolase that degrades NAD and promotes axonal degeneration in neurons. We recently showed that NAD redox imbalance and depletion promote the progression of diabetic cardiomyopathy. Therefore, we hypothesized that SARM1 deficiency might protect hearts against diabetic cardiomyopathy. 16-week diabetic stress initiated by streptozotocin (STZ) injections was applied to wild-type C57BL/6 (WT) and whole-body SARM1-KO mice. Cardiac function was measured after 8-week or 16-week of diabetic stress, and cardiac tissue and plasma samples from these mice were harvested after 16 weeks of diabetes. SARM1 mRNA or protein levels were suppressed in SARM1-KO hearts. STZ induced similar hyperglycemia (~600 mg/dL) in both WT and SARM1-KO male mice after 16 weeks. Chronic diabetic stress led to progressive decline in systolic function (Baseline fractional shortening: 50%; 16-week diabetes: 35%; P&lt;0.05; n=5) in WT male mice, which was ameliorated in SARM1-KO male mice (16-week diabetes: 48%; P&lt;0.05; n=5). Progressive decline in diastolic function induced by chronic diabetes (Baseline WT E’/A’: 1.53; WT 16-week diabetes: 1.12; n=5) was also improved in diabetic SARM1-KO mice (KO E’/A’ ratio at 16-week diabetes: 1.5; P&lt;0.05; n=5). Heart weights were similar in diabetic WT or diabetic SARM1-KO hearts. A similar study is on-going in a female cohort. Despite loss of SARM1 expression, no compensatory changes in expressions of other NAD hydrolases (i.e. Cd38 or Bst1) were observed in diabetic SARM1-KO hearts, while expression levels of genes related to NAD consumption and synthesis pathways were mostly unchanged except Qprt and Haao. Cardiac fibrosis was induced in diabetic WT hearts and were suppressed in diabetic SARM1-KO hearts after 16-week diabetic stress, but these changes were not observed in tissues harvested after 8-week diabetic stress. The results suggest fibrosis is a later event in the progression of diabetic cardiomyopathy. WT and SARM1-KO mice have also been challenged with high fat diet feeding (HFD) for 16 weeks, and increased fasting glucose levels and body weights were similarly observed in HFD-WT and HFD-SARM1-KO mice. Longitudinal cardiac function analyses are on-going. Our data thus far support the protective role of SARM1 deficiency in metabolic stress-induced cardiomyopathy, while pathogenic mechanisms of SARM1 in diabetic hearts remain to be determined.
Abstract 13196: Highly Active Antiretroviral Therapy-related Complications And Associated Genetic Susceptibility Variants In Hiv-infected Patients With Pre-existing Heart Failure: A 7-year Prospective Cohort Study
Authors: Kevin Sheng-Kai Ma
Journal: Circulation (2021)

Introduction: HAART-associated metabolic syndromes have been reported, without such risk and genetic markers in patients with pre-existing heart failure (HF) being addressed. Hypothesis: We hypothesize that compared with HIV-infected patients without HF undergoing HAART, patients with pre-existing HF are at higher risk of long-term HAART-related metabolic complications, which is associated with genetic variants. Methods: In this prospective cohort study 172 HIV-infected patients were recruited and followed-up since 2013. Demographic and medical records such as weight, BMI, drug use, lab data of blood and urine, HAART regimens, Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) CVD risk scores, were recorded. Multivariate regression model was used to derive risk of adverse outcomes following HAART in HF patients, compared to matched-patients without HF. GWAS was conducted in HF patients to investigate genetic variants associated with adverse events susceptibility. Results: After matching on baseline, HAART was effective for both patients with or without HF, at a similar viral load (r=0.001, P=0.69) and CD4 count (r=-0.06, P=0.48). D:A:D (R) (r=0.002, P=0.97) and D:A:D (F) (r=0.04, P=0.62) CVD risk scores were comparable in patients with and without HF. Patients with HF presented with higher risks of subsequent T2DM (r = 0.24, P=0.01) and increased total cholesterol (r=0.23, P=0.006), LDL (r=0.18, P=0.04), and uric acid (r=0.35, P=0.004), compared to those without HF. Four independent SNPs in ABCG2 (rs717620), PNPLA3 (rs738409), CYP2A6 (rs28399433), and CYP2B6 (rs2279345) reached genome-wide significance for their associations with HAART-related complications in patients with HF, including ABCG2 for subsequent advanced stages CKD (eGFR &lt; 30), PNPLA3 for increased HDL levels, CYP2A6 for increased BUN levels, and CYP2B6 for hematuria. Conclusions: HAART was equally effective for HIV management in HF patients, and did not result in more subsequent cardiotoxicities, compared with those without HF; however, increased risk of T2DM, and increased levels of CHO, LDL, and uric acid during follow-ups, were observed. Genetic susceptibility variants associated with HAART-related complications in HF patients were demonstrated.
IMMU-41. NEOADJUVANT PD-1 BLOCKADE INDUCES T CELL AND CDC1 ACTIVATION BUT FAILS TO OVERCOME THE IMMUNOSUPPRESSIVE TUMOR ASSOCIATED MACROPHAGES IN RECURRENT GLIOBLASTOMA
Authors: Alexander Lee, Lu Sun, Aaron Mochizuki, Jeremy Reynoso, Joey Orpilla, Frances Chow, Jenny Kienzler, Richard Everson, David Nathanson, Linda Liau, Timothy Cloughesy, Willy Hugo, Robert Prins
Journal: Neuro-Oncology (2021)

Abstract In a small phase I clinical trial, neoadjuvant anti-PD-1 (neo-aPD1) improved survival in glioblastoma patients (GBM) and was associated with increased interferon-γ-related gene expression and an associated decrease in cell cycle-related gene expression in the tumor. Despite this, neo-aPD1 was not curative. To better understand how neo-aPD1 alters the GBM tumor microenvironment and to discover new therapeutic axes, we used CyTOF and single-cell RNAsequencing to analyze the tumor-infiltrating immune populations of 70 GBM patients, 20 of whom had received neo-aPD1. In patients treated with neo-aPD1 the proportion and number of tumor-infiltrating T cells increased and these T cells had increased expression of the cytokines CCL5 and XCL1, which promote dendritic cell migration. Among the infiltrating T cells was a population of progenitor exhausted CD8+ T cells expressing the genes TCF, SLAM6, CCR7, IL7R, and GZMB. Single-cell TCR analysis revealed that these CD8+ T cells arose from a population of early activated, cytotoxic T cells that had expanded in the peripheral blood and trafficked into the tumor. Within the tumor-infiltrating myeloid cells, we found that neo-aPD1 upregulated genes in the interferon-γ response pathways; namely genes related to T cell trafficking and immune suppression, such as CD274 (PD-L1), TREM2, GPNMB, and IL10, indicating a maladaptive response by some myeloid cells to the immune response triggered by neo-aPD1. Finally, we identified a new migratory and interferon-γ activated tumor-infiltrating conventional dendritic cell population that was increased with neo-aPD1 and that notably expressed XCR1, the receptor for XCL1. Additionally, our results provide future basis to study if modalities that enhance the T cell:DC axis or that inhibit the inhibitory myeloid populations may improve survival in patients with GBM when used in conjunction with neo-aPD1. In sum, we characterized the immune landscape in GBM and how it changes with neo-aPD1 at single cell resolution.
Abstract 11124: Mitral Annular Calcification Mitral Stenosis: Obstruction is in the Tunnel
Authors: Evan Friend, Kinnari Murthy, Salima Qamruddin, Gregg S Pressman
Journal: Circulation (2021)

Background: Mitral annular calcification (MAC) is an increasingly encountered cause of mitral stenosis. As opposed to rheumatic disease, in MAC the commissures are typically open. In some cases the leaflet tips remain freely mobile while in others they are restricted. We sought to determine if mean mitral valve gradient (MVG) is associated with the minimal area in the MAC tunnel or the area at the leaflet tips. Methods: High quality 3D TEE datasets were acquired in 10 subjects with severe bulky MAC. Custom 2D cut planes were created at the mitral valve inlet, the narrowest portion of the MAC tunnel, and at the leaflet tips (figure 1), and compared with MVG by continuous wave Doppler. Results: Area at the annular inlet ranged from 5.4 - 11.0 cm 2 (mean 8.2). The smallest area within the tunnel ranged from 1.3 - 4.0 cm 2 (mean 2.4) while the smallest area at the leaflet tips ranged from 1.0 - 2.6 cm 2 (mean 1.6). MVG ranged from 3 - 14 (mean 8) mm Hg. As annular inlet area decreased MVG increased (r 2 = 0.49, p = 0.024). Similarly, as minimum tunnel area decreased MVG increased (r 2 = 0.54, p = 0.015; figure 2). There was a no significant relation between MVG and smallest leaflet area (r 2 = 0.17, p = 0.23). There was also no association between degree or distribution of MAC, and MVG or smallest tunnel area. Conclusions: In subjects with severe MAC and a resting gradient across the valve, obstruction to flow occurs at the annular inlet and within the calcium tunnel. In contrast to rheumatic mitral stenosis, valve area at the leaflet tips does not appear to determine the MVG.
Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial
Authors: Zelalem Temesgen, Charles D Burger, Jason Baker, Christopher Polk, Claudia R Libertin, Colleen F Kelley, Vincent C Marconi, Robert Orenstein, Victoria M Catterson, William S Aronstein, Cameron Durrant, Dale Chappell, Omar Ahmed, Gabrielle Chappell, Andrew D Badley, Meghan Lewis, Linda Sher, Michael Bowdish, Noah Wald-Dickler, Subarna Biswas, Lydia Lam, Khang Vo, Roy Poblete, May M. Lee, Douglass Hutcheon, Roberto Patron, John Gharbin, Caitlin Moran, Sheetal Kandiah, Valeria Cantos, Paulina Rebolledo, Carlos del Rio, Jeffrey Lennox, Carmen Polito, Anandi Sheth, Anup Patel, Homero Paniagua, Seife Yohannes, Alpesh Amin, Richard Lee, Miki Watanabe, Lanny Hsieh, Martin Cearras, Amay Parikh, Jason Sniffen, Wilfred Onyia, Michael Boger, Lisa Davidson, Kiran Gajurel, Michael Leonard, Lewis McCurdy, Nestor Quezada, Mindy Sampson, Zainab Shahid, Stephanie Strollo, David Weinrib, Sara Zulfigar, Cheryl McDonald, John Hollingsworth, John Burk, Joshua Berg, Daniel Barbaro, Andrew Miller, Lakshmi Sambathkumar, Stuart McDonald, Obinna Okoye, Juan Pulido, Jennifer Fulton, William Gill, Richard Zuckerman, Lionel Lewis, Chaitanya Mandapakala, Matthew Robinson, Brian Metzger, Maqsood Alam, Chrisoula Politis, Anne Frosch, Linh Ngo, Fernando Carvalho Neuenschwander, EstevÃo Figueiredo, Gualter CanÇado, Gustavo Araujo, Lucas GuimarÃes, Ricardo Diaz, Natalia Bacellar, Celso Silva, Paulo Ferreira, Marina Andrade Lima, Caroline Uber Ghisi, Camila Anton, Ricardo Albaneze, Daniel Wagner de Castro Lima Santos, Ana Caroline Iglessias, Marianna Lago, Paula Pietrobom, Maysa Alves, Juvencio José Duailibe Furtado, Leopoldo Trevelin, Valeria Telles, Francini Correa, Fabiano Ramos, Marina de A. R. Da Silva, Rebeca C. Lacerda Garcia, Ana Elizabeth G. Maldonado, Ana Carolina M. Beheregaray, Ana Maria T. Ortiz, Kleber Luz, Eveline Pipolo Milan, Janine Soares de Castro, Matheus José Barbosa Moreira, Renata Bezerra Onofre, TÁcito do Nascimento JÁcome, Victor Barreto Garcia, Victor Matheus Rolim de Souzafrom, Felipe Dal Pizzol, Cristiane Ritter, Marcelo B. Vinhas, Adilson Joaquim Westheimer Cavalcante, Julia Minghini, Loni Dorigo, Marina Salgado Miranda, Martti Anton Antila, Rebeca Brugnolli, Henrikki Antila
Journal: The Lancet Respiratory Medicine (2021)