tbuckley/cabot-search huggingface dataset:
Abstract 13656: Outcomes of Vaccine Preventable Diseases and Heart Failure With Reduced Ejection Fraction
Authors: Juan Daniel Del Cid Fratti, Erwin Argueta
Journal: Circulation (2021)

Background: Over five million Americans suffer from Heart Failure (HF), and this is associated with multiple chronic comorbidities and recurrent decompensations. Currently, there is an increased incidence of vaccine-preventable diseases (VPDs). We aim to investigate the impact of VPDs on hospitalization outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Methods: A retrospective analysis from all hospital admissions from the 2016-2018 National Inpatient Sample (NIS) using the ICD-10CM codes for patients admitted with a primary diagnosis of VPDs with HFrEF and those without reduced ejection fraction. Outcomes evaluated were in-hospital mortality, length of stay (LOS), health care utilization, frequency of admissions, and in-hospital complications. Multivariate regression analysis was conducted to adjust for confounders. Results: Out of 317,670 VPDs discharges, we identified 12,130 (3.8%) patients with HFrEF as comorbidity. The most common admission diagnosis for VPDs was influenza virus (IV) infection (75.0% vs 64.1%; P:&lt;0.01), followed by Pneumococcal pneumonia (PNA) (13% vs 9.4%; P:&lt;0.01). After adjusting for confounders, patients with HFrEF had higher odds of being admitted due to a diagnosis of IV (aOR 1.42; P:&lt;0.01) and PNA (aOR 1.27; P:&lt;0.01). Patients with VPDs and HFrEF had significantly higher odds of mortality (aOR 1.76; P:&lt;0.01), LOS, respiratory failure requiring mechanical ventilation, and mechanical ventilation for less than 96 hours. Conclusion: Influenza and PNA were the most common VPDs admitted to the hospital in patients with HFrEF. They were associated with increased mortality and in-hospital complications.
Abstract 11207: Electronic Hookah Vaping with and Without Nicotine: Insights into Vascular Function and Plasma Fibrinogen
Authors: Mary Rezk-hanna, Chiao-Wei Cheng, Byron Bustos, Mary-Lynn Brecht
Journal: Circulation (2021)

Introduction: Electronic nicotine delivery systems (ENDS) are growing quickly in the United States, particularly among youth. Electronic (e-) hookahs are a new category of vaping devices in which the e-bowl is combined with and placed on a traditional waterpipe, allowing the flavored aerosol to pass through a water-filled base before being carried through the hose into the user’s mouth. E-hookah vaping with flavored nicotine acutely impairs endothelial function. However, the relative contribution of flavorings vs. nicotine on e-hookah vaping associated vascular dysfunction is unclear. Methods: In a randomized cross-over design study, we investigated the acute effect of flavored e-hookah with and without nicotine and sham vaping, among a cohort of 9 healthy young adult chronic hookah smokers (27±1 years, mean ±SE), on endothelial function, measured by brachial artery flow-mediated dilation (FMD). Fibrinogen, a major plasma protein coagulation factor, as well as smoking exposure biomarkers (plasma nicotine and expired carbon monoxide levels) were collected before and after the sessions. Results: Vaping e-hookah with nicotine induced an acute reduction in FMD (from 6.9±0.9 to 5.2±0.8%, pre- vs. post- vaping, p&lt;0.001), suggesting impairment in endothelial function and increased plasma fibrinogen (+14.5±4.1 mg/dL, p&lt;0.001). Though vaping e-hookah in the absence of nicotine did not significantly impair endothelial function (p = ns), it significantly induced an increase in plasma fibrinogen levels (+20.9±7.4 mg/dL, p&lt;0.001), higher than levels induced after vaping e-hookah with nicotine. Plasma nicotine concentrations increased 4-fold more after vaping e-hookah with nicotine, whereas no changes were observed after vaping e-hookah without nicotine or sham-vaping (p = ns). Exhaled CO levels did not change across all three vaping sessions. Conclusions: In healthy young adults, our findings to date suggest that while vaping e-hookah with nicotine induces an unfavorable effect on the vasculature, non-nicotine constituents generated from heating the flavored e-hookah aerosol cannot be ignored. Further plans are needed to elucidate the long-term vascular implications of vaping non-nicotine flavored constituents.
Extracorporeal Photopheresis Induces Netosis in Neutrophils Derived from Patients with Graft-Versus-Host Disease
Authors: Idan Goldberg, Galit Granot, Alona Telerman, Shirly Partouche, Moshe Yeshurun, Pia Raanani, Ofir Wolach, Vered Yahalom
Journal: Blood (2021)
Transcriptomic Profile Identifies Early Signatures of Immunoediting and a Potential Role for VISTA As a Molecular Target in Acute Myeloid Leukemia
Authors: Simona Pagliuca, Carmelo Gurnari, Tariq Kewan, Waled Bahaj, Keman Zhang, Minako Mori, Laila Terkawi, Ishani Nautiyal, Jaroslaw P. Maciejewski, Lily Wang, Valeria Visconte
Journal: Blood (2021)
Abstract 10710: Venous but Not Arterial Thrombus is Biologically Active: Cellular and Enzymatic Contributions
Authors: Matthew T Bender, Doran S Mix, Matthew Godwin, Anu Aggarwal, Leben Tefera, Joseph Campbell, Ihab haddadin, Michael Tong, Scott J CAMERON
Journal: Circulation (2021)

Background: Acute arterial thrombosis has devastating consequences, but urgency is rarely a factor in treating venous thrombosis, especially in the legs. Our goal was to determine the cellular content and enzymatic activity of catheter-extracted thrombus to gain insight into vascular remodeling. Methods: Catheter-extracted thrombosis in 27 patients with VTE (deep vein thrombosis [DVT, n=5], pulmonary embolism [PE, n=9]) and thrombotic stroke (AT, n=13) was evaluated by 2-dimensional electrophoresis, and immunoblotting (IB) for markers of platelets: (CD41), white blood cells (WBC, CD45), and red blood cells (RBC, CD235A ). Matrix metalloproteinase (MMP) isoforms were determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and confirmed by IB. Total MMP activity was determined by zymography, then isoform catalytic activity was validated using chromogenic substrates. Results: Protein concentration in 7mg thrombus was greater in VTE vs. AT (p=0,046). CD41 was similar in VTE vs. AT thrombus while CD45 (p=0.047) and CD235A (P=0.001) were greater in VTE. Only CD235A was greater in PE vs. DVT thrombus (P=0.002). Zymography identified enzymatic activity of many MMP isoforms. Of the 10 MMP isoforms assessed, only the following were identified in both VTE and AT: MMP 1,2,8,9,10,14. Protein content was greater in VTE vs. AT by IB for: MMP1 0.79±0.13 vs. 0.43±0.12, p=0.02, MMP2 (0.30±0.08 vs. 0.17±0.03, p=0.05), and MMP9 (1.3±0.38 vs. 0.26±0.06, p=0.009). MMP9 activity was far greater in thrombus from patients with VTE vs. AT (25 U±5.6 vs. 63±8.1 ng/mL.(μg protein) -1 protein, p=0.0008). Conclusion: Cellular composition of thrombus in different vascular beds varies, altering susceptibility to tissue plasminogen activator and the potential for thrombus to irreversibly remodel blood vessels. Thrombus-derived biomarkers driving decisions for catheter-extraction should be prospectively evaluated in patients with VTE.
NCOG-03. PREDICTORS OF NEUROLOGIC DEATH IN PATIENTS WITH BRAIN METASTASES
Authors: Alexander Reese, Nayan Lamba, Paul Catalano, Daniel Cagney, Patrick Wen, Ayal Aizer
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Neurologic death (ND), defined as intracranial disease progression with accompanying neurologic symptoms in the absence of life-threatening systemic disease, is the most serious consequence of intracranial disease among patients with brain metastases (BMs). Data indicating which factors are predictive of this outcome remain limited, however. Determining which patients are at increased risk of ND will guide improved care and further research aimed at preventing ND. METHODS We identified 1,218 patients with newly diagnosed BMs managed at Brigham and Women’s Hospital from 2008-2015. Demographic and tumor characteristics for patients experiencing ND, non-neurologic death, and who were alive at last follow up were analyzed by univariable and multivariable Fine and Gray competing risks regression to identify predictors of ND, with non-neurologic death serving as a competing risk. RESULTS In multivariable analysis, ND was associated with number of BMs (hazard ratio [HR] 1.01 per 1 metastasis increase, 95% CI 1.01-1.02, p&amp;lt; 0.001) and three primary tumor sites (with non-small cell lung cancer as the reference): melanoma (HR 4.67, 95% CI 3.27-6.68, p&amp;lt; 0.001), small cell lung cancer (HR 2.33, 95% CI 1.47-3.68, p&amp;lt; 0.001), and gastrointestinal cancer (HR 2.21, 95% CI 1.28-3.82, p=0.005). Additionally, among patients with breast primaries, HER2+ tumors displayed increased risk of ND relative to the reference subtype (HR+/HER2-) in univariable analysis (HR 2.41, 95% CI 1.00-5.84, p=0.05). A reduced risk of ND was found in patients with Karnofsky performance status of 90-100 versus 30-80 (HR 0.67, 95% CI 0.48-0.95, p=0.03) and progressive extracranial disease (HR 0.50, 95% CI 0.38-0.67, p&amp;lt; 0.001). CONCLUSION Patients with melanoma, small cell lung cancer, gastrointestinal, and HER2+ breast cancer primaries, in addition to those with greater intracranial versus extracranial disease burdens, are at increased risk of ND. Future research into novel intracranial approaches should focus on these groups of patients.
Oral status in patients with inherited epidermolysis bullosa: A multicentric observational study
Authors: Christine Chiaverini, Mathieu Marty, Sophie-Myriam Dridi, Sophie Caroline Campana, Thibault Canceill, Isabelle Bailleul-Forestier, Veroniek Verhaeghe, Dominique Declerck, Thomas Hubiche, Philippe Kémoun, Juliette Mazereeuw-Hautier, Clara Joseph
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 11165: Stimulated Release of Apoptosis- Induced Endothelial Microparticles in Patients with Diabetes and Coronary Artery Disease
Authors: Isra Marei, Chidiac Omar, Binitha Thomas, Jameesh Muhammed, Amin Jayyousi, Jassim M Al suwaidi, Charbel Abi Khalil
Journal: Circulation (2021)

Introduction: High endothelial microparticles (EMPs) levels could be used as a marker of vascular dysfunction. Hypothesis: The release of EMPs with apoptotic characteristics in the blood of patients with diabetes is different according to the presence of CAD, and further distinct between chronic CAD and ACS. Methods: A total of 80 participants were recruited and equally classified as: 1) healthy participants without diabetes, 2) healthy diabetics without micro or macro-vascular complications, 3) participants with T2D and chronic CAD, and 4) participants with T2D and ACS. MPs were isolated using ExoQuick-LP TM and analysed using flow cytometry of CD42 and CD31. CD62E was used to determine the apoptotic/activation state of the EMPs. MP content was extracted and profiled using angiogenesis array (R&amp;D systems). Results: Mean age of participants was 56 ±10. Levels of CD42- CD31+ EMPs were significantly increased in diabetics with acute ACS (257.5±35.58) when compared to healthy subjects (105.7±12.96, p&lt;0.01). There was no significant difference when comparing diabetics, with and without chronic CAD. The ratio of CD42-CD62+/ CD42-CD31+ EMPs was reduced in all diabetic groups, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analysed and revealed a significant differential expression of 5 factors in patients with ACS and diabetes: TGF-β1, PD-ECGF, platelet factor 4, serpin E1 and thrombospondin 1 (Figure 1). Ingenuity Pathway Analysis revealed of those 5 differentially expressed molecules, mainly TGF-β1, causes an inhibition of key pathways involved in normal endothelial function. Conclusions: Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of the presence of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that are indicative of vascular dysfunction.
INNV-15. PROTEIN TYPING AND MRNA ANALYSIS OF CIRCULATING EXOSOMES FOR GLIOBLASTOMA THERAPY USING PLASMONIC-ENHANCED INTEGRATED MAGNETO-ELECTROCHEMICAL SENSOR
Authors: Hsing-Ying Lin, Chen-Han Huang, Peng-Wei Hsu, Yu-Jen Lu, Peter C Y Chou, Hugo C H Chen, Vicky Y H Liu
Journal: Neuro-Oncology (2021)

Abstract Monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem. Glioblastomas shed large quantities of exosomes into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Recently, we develop a highly sensitive and rapid analytical technique for profiling circulating exosomes directly from serum plasma of patients with glioblastoma. Exosomes are labeled with target-specific metal nanoparticles and detected by a miniaturized integrated magneto-electrochemical sensing system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate GBM exosomes from nontumor host cell–derived exosomes. We also show that circulating GBM exosomes can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.
A Real World Study of Venetoclax Combined with Azacitidine in 64 Chinese Patients Newly Diagnosed Acute Myeloid Leukemia
Authors: Jiejing Qian, Jieyu Xu, Qing Hong, Yinjun Lou, Liping Mao, Weilai Xu, Min Yang, Wenjuan Yu, Haitao Meng, Wenyuan Mai, Xiujing Ye, Honghu Zhu, Jie Jin
Journal: Blood (2021)
Functional hydrogels as therapeutic tools for spinal cord injury: New perspectives on immunopharmacological interventions
Authors: Ciara M. Walsh, Jacek K. Wychowaniec, Dermot F. Brougham, Dearbhaile Dooley
Journal: Pharmacology & Therapeutics (2021)

Spinal cord injury (SCI) is a complex medical and psychological challenge for which there is no curative therapy currently available. Despite major progress in pharmacological and surgical approaches, clinical trials for SCI patients have been uniformly disappointing thus far as there are many practical and biological issues yet to be resolved. Neuroinflammation is a critical event of the secondary injury phase after SCI, and recent research strategies have focused on modulating the immune response after injury to provide a more favorable recovery environment. Biomaterials can serve this purpose by providing physical and trophic support to the injured spinal cord after SCI. Of all potential biomaterials, functional hydrogels are emerging as a key component in novel treatment strategies for SCI, including controlled and localized delivery of immunomodulatory therapies to drive polarization of immune cells towards a pro-regenerative phenotype. Here, we extensively review recent developments in the use of functional hydrogels as immunomodulatory therapies for SCI. We briefly describe physicochemical properties of hydrogels and demonstrate how advanced fabrication methods lead to the required heterogeneity and hierarchical arrangements that increasingly mimic complex spinal cord tissue. We then summarize potential SCI therapeutic modalities including: (i) hydrogels alone; (ii) hydrogels as cellular or (iii) bioactive molecule delivery vehicles, and; (iv) combinatorial approaches. By linking the structural properties of hydrogels to their functions in treatment with particular focus on immunopharmacological stimuli, this may accelerate further development of functional hydrogels for SCI, and indeed next-generation central nervous system regenerative therapies.
NOX1 mediates metabolic heart disease in mice and is upregulated in monocytes of humans with diastolic dysfunction
Authors: Lifen Xu, Melania Balzarolo, Emma L Robinson, Vera Lorenz, Giacomo Della Verde, Lydia Joray, Michika Mochizuki, Beat A Kaufmann, Gideon Valstar, Saskia C A de Jager, Hester M den Ruijter, Stephane Heymans, Otmar Pfister, Gabriela M Kuster
Journal: Cardiovascular Research (2021)

Microvascular inflammation plays an important role in the pathogenesis of diastolic dysfunction (DD) and metabolic heart disease. NOX1 is expressed in vascular and immune cells and has been implicated in the vascular pathology of metabolic disease. However, its contribution to metabolic heart disease is less understood.NOX1-deficient mice (KO) and male wild-type (WT) littermates were fed a high-fat high-sucrose diet (HFHS) and injected streptozotocin (75 mg/kg i.p.) or control diet (CTD) and sodium citrate. Despite similar weight gain and increase in fasting blood glucose and insulin, only WT-HFHS but not KO-HFHS mice developed concentric cardiac hypertrophy and elevated left ventricular filling pressure. This was associated with increased endothelial adhesion molecule expression, accumulation of Mac-2-, IL-1β-, and NLRP3-positive cells and nitrosative stress in WT-HFHS but not KO-HFHS hearts. Nox1 mRNA was solidly expressed in CD45+ immune cells isolated from healthy mouse hearts but was negligible in cardiac CD31+ endothelial cells. However, in vitro, Nox1 expression increased in response to lipopolysaccharide (LPS) in endothelial cells and contributed to LPS-induced upregulation of Icam-1. Nox1 was also upregulated in mouse bone marrow-derived macrophages in response to LPS. In peripheral monocytes from age- and sex-matched symptomatic patients with and without DD, NOX1 was significantly higher in patients with DD compared to those without DD.NOX1 mediates endothelial activation and contributes to myocardial inflammation and remodelling in metabolic disease in mice. Given its high expression in monocytes of humans with DD, NOX1 may represent a potential target to mitigate heart disease associated with DD.
Abstract 14006: Cardiovascular Health Benefits of Theobromine in Cacao and Chocolate
Authors: Joshua Hahn, Hafeez Ul Hassan Virk, Zhen Wang, Wai Hong W Tang, Chayakrit Krittanawong
Journal: Circulation (2021)

Introduction: Theobromine is a naturally occurring substance found in cocoa products. Theobromine may have beneficial cardiovascular effects through various mechanisms. We used the NHANES database to analyze associations between theobromine consumption and cardiovascular health outcomes. Methods: The NHANES database represents a nationally representative population which was used to construct the study population from 1996-2016. We assessed multiple demographic factors and compared differences amongst those who consumed various amounts of theobromine to those who did not. The primary outcome measures were hypertension and lipid profiles. Results: Among 42,038 NHANES survey participants, 37569 and 4469 of the participants reported never consuming theobromine and consuming theobromine, respectively. Table 1 demonstrates baseline characteristics of those reporting no theobromine consumption in comparison to the theobromine consuming participants (100-400md/g and 400-850mg/d). Moderate to high amounts of theobromine consumption was observed in participants who were older with higher BMI and more education and were more likely to be tobacco users in comparison to those with no theobromine consumption (all p-values &lt;0.05). Moderate to high theobromine consumption was also observed to be associated with a higher hemoglobin level, higher LDL cholesterol, lower HDL cholesterol, and prevalence of hypertension (all p-values &lt;0.05). Conclusions: We observed that individuals who consumed moderate to high amounts of theobromine had associated improvements in lipid profile parameters as well as reduced blood pressure. Theobromine may represent a complementary non-pharmacologic supplementation to typical lifestyle modifications to improve cardiovascular outcomes. Further prospective studies are needed to better clarify this potential association.
Clinical and Genomic Characterization of Secondary Acute Myeloid Leukemia with Mixed Phenotype
Authors: Pallavi Galera, Alexander Chan, Andriy Derkach, Ying Liu, Jeeyeon Baik, Christopher Famulare, Allison Sigler, Maria E. Arcila, Douglas A Mata, Ahmet Dogan, Martin S. Tallman, Ross L. Levine, Yanming Zhang, Mikhail Roshal, Jacob L Glass, Wenbin Xiao
Journal: Blood (2021)
EXTH-40. MULTIDIMENSIONAL INTERROGATION OF GLIOBLASTOMA MICROENVIRONMENT TREATMENT RESPONSE IN EXPLANT CULTURES
Authors: Tala Shekarian, Ewelina Bartoszek-Kandler, Carl Zinner, Christian Schuerch, Gregor Hutter
Journal: Neuro-Oncology (2021)

Abstract The immune tumor microenvironment (iTME) of glioblastoma (GBM) contains microglial, macrophage, other myeloid cell populations and as adaptive immune cells. Recent therapeutic strategies for GBM aim at targeting iTME components to induce antitumoral immunity. A patient-tailored, ex vivo drug testing and response analysis platform would facilitate personalized therapy planning, provide insights into treatment-induced immune mechanisms in the iTME, and enable the discovery of biomarkers of response and resistance. Here, we generated patient-derived, live 3D GBM bioreactors from different tumor regions to assess iTME treatment responses to microglia modulators and immune checkpoint inhibitors. Intact GBM tissue specimens from the tumor center and periphery were cultured for 7 days in the presence or absence of anti-PD1, anti-CD47 antibodies or their combination. Tissues were analyzed by CODEX highly multiplexed microscopy using an immune-centered 54-marker panel, and changes in cytokine and chemokine levels in culture supernatants were investigated. A computational pipeline for integrative therapy response assessment was implemented. Explant cultures from n=8 IDH wt GBM were subjected to this integrative personalized analysis. Tissue integrity after 3D bioreactor cultures was comparable to tissue taken directly after surgery. FFPE CODEX workflow was feasible with adequate staining quality in bioreactor cultures. 850'000 single cells were segmented and clustered. Cellular composition between tumor center and the peripheral invasion zone differed significantly in immune phenotypes, cytokine profile and response to innate, adaptive or combinatorial local immunotherapies. Multiplexed cytokine analysis revealed IFNγ response signatures in a subset of center samples, whereas the peripheral invasion zone displayed a blunted cytokine response. This cytokine signature corresponded to cellular composition shifts within specific cellular neighborhoods. CD4 and CD8 T cells were invigorated and left their vascular niche. Our study demonstrates that local immunotherapies enable an active antitumoral immune response within the tumor center, and provides a multidimensional personalized framework for immunotherapy response assessment.