tbuckley/cabot-search huggingface dataset:
CNTM-05. Left hemisphere gliomas induce a plastic bi-hemispheric language network further characterized by lobe specific glioma data
Authors: Matthew Ramsey, Shashwat Tripathi, Mohit Saxena, Matthew Tate
Journal: Neuro-Oncology (2021)

Abstract Primary brain tumors are among the most burdensome diagnoses patients can receive as they often carry with them externally obvious and significant detriments to motor and speech. The stroke model is severely limited by the inherent nature of the insult to the brain: binary, relatively instantaneous and defined by vascular boundaries. We instead have chosen to study glioma-induced neuroplasticity in patients with gliomas as presentation is over a significantly longer time course with a gradient of insult to language activation areas instead of immediate ablation. Chart review was conducted on 545 patients who completed fMRI imaging from 2013–2019 while completing 1+ of the following language tasks: antonyms, reading comprehension, rhyming, word generation and picture naming. A total of 117 patients’ fMRI scans were included in the final analysis which entailed both a cluster-based analysis in FSL and a 34 gyral, mask-based analysis using FEATquery. Right hemisphere gliomas (RHG) were first established as a reliable control group by averaging anatomically significant voxels across all five language tasks (LT) yielding a core conserved network. Left hemisphere gliomas (LHG) were then directly compared to the RHG language tasks. We found LHG induced global reorganization of the conserved language network with little evidence for direct homologous recruitment of functional structures. Instead, a generalized right hemisphere recruitment is observed with 87% of non-zero masks shifting their laterality index to the right hemisphere. Furthermore, in each of the five LT, the LHG activates fewer total suprathreshold voxels in both the mask and cluster based analyses while having a higher peak intensity within the activated clusters. A preliminary analysis of frontal LHG compared to temporal LHG reveals increased contralateral recruitment in the frontal subgroup with more direct homologous recruitment. This nuanced understanding of existing mechanisms for neuroplasticity can aid in our future intentional manipulation for therapeutic benefit.
Abstract 10723: Fetal Echocardiographic Assessment of Right Ventricular and Tricuspid Valve Function in Hypoplastic Left Heart Syndrome: Correlation with Postnatal Outcomes
Authors: Sarah Lowenstein, Lindsay Edwards, Elizabeth Caris, Aarti Bhat, Jeff Conwell, Mark Lewin, Bhawna Arya
Journal: Circulation (2021)

Introduction: Hypoplastic left heart syndrome (HLHS) carries significant morbidity and mortality. Transthoracic echocardiogram (echo) assessment of right ventricular (RV) function and tricuspid regurgitation (TR) correlate with HLHS outcomes. There are limited reports on RV function and TR in fetal HLHS and postnatal outcomes. We aim to correlate RV function and TR on fetal-echo (F-echo) with transplant-free survival (survival), hospital length of stay after initial surgery (LOS), and timing of Glenn (BDG) in HLHS patients. Methods: Imaging and clinical data of fetuses diagnosed with HLHS between February 2014 and September 2020 at our institution were retrospectively reviewed. Measurements of RV myocardial performance index (MPI) and fractional area change (FAC) were made on initial F-echo. The RV shortening fraction (SF), presence/degree of TR, and RV size by diastolic short-axis dimension were recorded. Postnatal outcomes included survival, LOS and age at BDG. Early BDG was a repair at &lt;4 months. Mann-Whitney U test correlated F-echo measures and postnatal outcomes. Results: F-echo was available in 69 subjects; 22 excluded for termination/fetal demise, 9 for genetic syndromes, resulting in 38 subjects. Mean age at initial F-echo was 31.4±0.9wks, 11 referred &gt;30 weeks from regional cardiologists (adjusted mean age 23.1±0.4wks). Subject age at time of review ranged from 7 months to 6.5 years. Eight subjects died (median age 2 months) and 3 required transplant (median age 8 months). F-echo RV MPI was significantly higher (0.372±0.09;p=0.005) and RV FAC was significantly lower (43%±6.4%;p=0.016) in HLHS non-survivors versus survivors. Fetal RV size and presence of TR were not significantly different. Subjects with initial LOS &gt;30 days were more likely to have fetal TR (p&lt;0.001) and RV dilation (p=0.019), but no significant RV MPI and FAC difference. No fetal measures correlated with need for an early BDG. Conclusion: F-echo evaluation of RV MPI and FAC in HLHS correlates with transplant-free survival. Presence of fetal TR and RV dilation correlate with a longer LOS. F-echo measures of RV function and TR function may inform prenatal counseling and postnatal outcomes for fetal HLHS.
Abstract 11540: Charlson Comorbidity Index is an Effective Predictor of Hospital Outcomes in Takotsubo Cardiomyopathy
Authors: Jose S Aguilar-gallardo, Francisco ROMEO, Ashish A Correa, Johanna P Contreras
Journal: Circulation (2021)

Introduction: The Charlson Comorbidity Index (CCI) is a recognized predictor of clinical outcomes that has been studied in diverse clinical settings. In this study, we evaluate its utility for prediction of outcomes in Takotsubo cardiomyopathy. Methods: This is a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included patients admitted with a primary diagnosis of Takotsubo syndrome. Outcomes were mortality, length of stay, total hospitalization charges, and cardiogenic shock. Multivariate regression analysis was performed adjusting for patient age, race, gender, severe sepsis, cardiogenic shock, tobacco use, atrial fibrillation, 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 7,970 weighted patients were hospitalized with Takotsubo syndrome, with a mean age of 66.5 years. Incidence of primary outcomes was gradually higher with an increasing Charlson Comorbidity Index. On multivariate regression analysis, each one-point increase in Charlson score was associated with 64% increased odds of inpatient mortality (odds ratio 1.64, p= 0.000). The odds of cardiogenic shock was also increased (odds ratio 1.24, p=0.000), as well as the mean length of stay and total hospitalization charges. Conclusions: The Charlson Comorbidity Index is an effective predictor of hospital outcomes in Takotsubo cardiomyopathy.
EXTH-13. LOCAL DELIVERY OF AN IL-15 SUPERAGONIST USING A REPLICATING RETROVIRUS SIGNIFICANTLY IMPROVES SURVIVAL AND LYMPHOCYTE INFILTRATION IN POORLY IMMUNOGENIC MURINE GLIOBLASTOMA MODELS
Authors: Alexander Haddad, Jordan Spatz, Megan Montoya, Sara Collins, Sabraj Gill, Elaina Wang, Polly Chuntova, Jacob Young, Noriyuki Kasahara, Manish K Aghi
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) leads to severe systemic and local immunosuppression, and immunotherapies have had limited clinical success. Here, we evaluated the treatment efficacy of RLI, a superagonist of T-cell activator IL-15, delivered to tumor cells using a tumor-selective retroviral replicating vector (RRV) in the syngeneic murine SB28 and Tu2449 GBM models, which are both engineered to be poorly immunogenic with low-mutational burden and known resistance to immunotherapy, and hence more accurate biomimetic models of human GBM. RRV-RLI replicated and spread effectively in cultured murine GBM cells with robust production of functional RLI (165.4 ± 5.3 ng/mL). Stereotactic injection of RRV-RLI into pre-established intracerebral SB28 tumors significantly reduced tumor growth on bioluminescent imaging, and increased median survival compared to control mice (55 vs. 19 days, p=0.002), leading to long-term survival in 12% of treated mice. In the Tu2449 model, imaging results showed complete eradication of intracerebral tumors after RRV-RLI treatment, with long-term survival (median not reached) in &amp;gt; 85% of treated mice, compared to a median survival of 12.5 days in control mice (p=0.001). RRV-RLI treated tumors showed significantly increased CD8 T-cell infiltration, without altering immunosuppressive cell populations. Similarly, broad anti-tumor inflammatory changes, including increased expression of genes involved in T-cell activation and killing, were observed in the NanoString nCounter platform using a 770-gene panel representing various immune cell types. Notably, RLI was not detected in the blood of treated mice, and tumor-localized RRV-RLI gene delivery showed no adverse systemic immune effects in either model. In summary, RRV-mediated RLI immunotherapy results in immunostimulatory and pro-inflammatory changes to the tumor microenvironment and achieves a significant survival benefit in two poorly immunogenic syngeneic murine models of GBM. This tumor-localized immunomodulatory gene therapy has the potential to safely reverse the T-cell depleted immunophenotype of GBM.
Abstract 10784: Circulating Obesity Associated Pro-Fibrotic Protein Promotes Fibrosis in Liver and Heart
Authors: Yung-ting Hsiao, Ippei Shimizu, Yohko Yoshida, Goro Katsuumi, Tohru Minamino
Journal: Circulation (2021)

Introduction: Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Obesity contributes inflamed visceral adipose tissue secretes pro-inflammatory adipokines that is causal for systemic metabolic disorders. Despite its importance, the mechanism of NASH in the presence of morbid obesity related adipokines from BAT remains unclear. Hypothesis: Various kinds of white adipokines are known in obesity. However, brown adipokines still remain to be explored. Methods: To identify the function of obesity associated pro-fibrotic protein (OAFP), we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine systemic OAFP knockout (KO) model. We also conducted functional in vitro studies with differentiated brown adipocytes. Results: Analyzing two sets of DNA microarray data with bioinformatics, we identified a secreted form OAFP expressed in dysfunctional brown adipose tissue (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of NASH patients or aged individuals. We generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and found that OAFP is produced predominantly by BAT. In this model, we also found that OAFP increased in plasma. For this reason, we generated a murine systemic OAFP knockout (KO) model and found that liver fibrosis ameliorated in OAFP-KO model. In addition, vaccination therapy also inhibited liver fibrosis. In contrast, liver fibrosis augmented in OAFP gain of function (GOF) model, and these results suggested that OAFP has causal role for the progression of fibrotic response in liver. In the obese NASH model, we found that cardiac fibrosis also developed and this ameliorated in OAFP-KO model, indicating that OAFP may have pathological roles for heart failure with preserved ejection fraction (HFpEF) related with age-related disorders. In vitro studies with differentiated brown adipocytes showed that OAFP was upregulated through by PERK/JNK/c-fos/AP1 pathways. Conclusions: Our results suggest that OAFP contributes for the progression of fibrotic responses in obese or aged models. Inhibition of OAFP may become a therapy for NASH or HFpEF.
Prevention and management of thrombosis in hospitalised patients with COVID-19 pneumonia
Authors: Jean-Louis Vincent, Marcel Levi, Beverley J Hunt
Journal: The Lancet Respiratory Medicine (2021)

A proportion of people infected with SARS-CoV-2 develop moderate or severe COVID-19, with an increased risk of thromboembolic complications. The inflammatory response to SARS-CoV-2 infection can cause an acute-phase response and endothelial dysfunction, which contribute to COVID-19-associated coagulopathy, the clinical and laboratory features of which differ in some respects from those of classic disseminated intravascular coagulation. Understanding of the pathophysiology of thrombosis in COVID-19 is needed to develop approaches to management and prevention, with implications for short-term and long-term health outcomes. Evidence is emerging to support treatment decisions in patients with COVID-19, but many questions remain about the optimum approach to management. In this Viewpoint, we provide a summary of the pathophysiology of thrombosis and associated laboratory and clinical findings, and highlight key considerations in the management of coagulopathy in hospitalised patients with severe COVID-19, including coagulation assessment, identification of thromboembolic complications, and use of antithrombotic prophylaxis and therapeutic anticoagulation. We await the results of trials that are underway to establish the safety and benefits of prolonged thromboprophylaxis after hospital discharge.
Abstract 9941: Coronary Artery Calcification Score is Associated with Left Ventricular Diastolic Function in Patients Without Coronary Artery Disease
Authors: Katsuomi Iwakura, Toshinari Onishi, Yasushi Koyama, ATSUNORI OKAMURA, MUTSUMI IWAMOTO, Satoshi Watanabe, Koji Tanaka, Hiroyuki NAGAI, Yuko Hirao, Nobuaki Tanaka, Akinori Sumiyoshi, Masato Okada, Kota Tanaka, Satoshi Suzuki, Hirokazu Tanaka, Shinichi Harada, Kenshi Fujii
Journal: Circulation (2021)

Introduction: Left ventricular (LV) diastolic dysfunction is a strong predictor of cardiovascular events, and it shares several risk factors with coronary artery disease (CAD). It is not well elucidated whether coronary atherosclerosis could affect LV diastolic function even in patients without CAD. Hypothesis: Coronary artery calcification (CAC) score by computer tomography (CT) might be associated with LV diastolic function even in non-ischemic patients. Methods: We enrolled non-ischemic patients who underwent CT coronary angiography (CTA) and echocardiography, using the following inclusion criteria; (1) age ≥65 years (2) no history of ischemic events, coronary revascularization or mitral valve operation, (3) no significant stenotic lesion on CTA, and (4) regular sinus rhythm at echocardiography study. We measured CAC score on CT and diastolic parameters including median E/e’ ratio on echocardiogram. Continuous variables were expressed as median [interquartile range] and were compared using Kruskal-Wallis rank sum test. Results: We enrolled consecutive 242 patients for the present study (72 [68, 77] years, male; 56.2%). We divided them based on CAC score, as no (N: score 0, n=61), low- (L: 1-99, n=86), and high (H: ≥100, n=95) CAC group. There was difference in gender and history of diabetes among the groups, but not in age, BMI, hypertension and dyslipidemia. Significant difference was observed in E/e’ ratio among 3 groups (N: 8.1[6.9,9.9], L:8.7 [7.3,10.8], H: 9.1 [7.5,11.0], p=0.035), and the H-group had higher E/e’ than the N-group (p=0.036). There were also difference in left atrial volume (N: 35.2ml [26.8, 44.0], L:41.6 ml [30.5, 55.5], H: 42.5 [34.5 ,58.3], p=0.002) and in LV mass index (N: 82.7 g/m 2 [71.2, 93.3], L:84.1 g/m 2 [75.4, 97.7], H: 95.2 g/m 2 [80.8, 109.9], p=0.0004), and those in the H-groups were higher than those in the N-group. No difference was observed in LV ejection fraction or in E/A ratio. CAC score could detect E/e’ ratio ≥14 with 57% sensitivity and 63% specificity, using 71.0 as the cutoff value (AUC 0.64). Conclusions: High CAC score was associated with impaired LV diastolic function, implying the relationship between coronary artery atherosclerosis and LV diastolic dysfunction in patients without CAD.
Abstract 13677: Thirty-Day Readmissions After Transcatheter Aortic Valve Replacement in the United States
Authors: Muhammad U Khan, Muhammmad Zia Khan, Salman Zahid, Sudarshan balla
Journal: Circulation (2021)

Introduction: Transcatheter Aortic Valve replacement (TAVR) has revolutionized the treatment of severe aortic stenosis and is now considered the standard of care in prohibitive surgical risk population. Post procedure re-admission is associated with increased morbidity and mortality. Hypothesis: To evaluate the 30 day hospital re-admission presentations of patients who underwent recent TAVR. Methods: We used National readmission database year 2018 to identify all patients who underwent TAVR using ICD-10 codes (02RF3) Results: Of a total of 31,252 patients undergoing TAVR, 9102 (29.1%) patients were re-admitted at least once during the next 30 days. Of these 3475 (38.2%) patients had acute congestive heart failure, 1303 (14.3%) had pulmonary complication, 774 (8.5%) a GI complication, 443 (4.9%) vascular complication, 237 (2.6%) a neurological complication and 119 (1.3%) patients had prosthetic valve dysfunction for re-admission Conclusions: Re-admission rates after TAVR remains a significant challenge, with varying presentations, however, acute heart failure remains the leading re-admission diagnosis.
Abstract 13716: Significance of Time in Use of Manual Thrombus Aspiration in Patients Undergoing Primary PCI for Achieving TIMI 3 Flow
Authors: DILEEP KUMAR, Tahir Saghir, Jawaid Sial, Afzal Hussain, Kamran Ahmed Khan, SHAHZAD KHATTI, Umamah Yasin, Nadeem Qamar
Journal: Circulation (2021)

Background: Primary percutaneous intervention is a life-saving procedure to open the occluded coronary artery. Most of these patients have either total occlusion of artery or have high thrombus burden.Therefore, timely use of thrombus aspiration catheters have a significant importance in terms of morbidity and mortality. Purpose: To assess the effect of timing of manual thrombus aspiration in patients undergoing Primary PCI on post procedure TIMI 3 Flow and in hospital outcomes of a tertiary care hospital. Methods: In this prospective observational study, patients with acute STEMI who underwent primary PCI and have totally occluded coronary artery (TIMI 0 flow) after passing the wire were selected. Time from the onset of chest pain to the use of export catheters (Export time) was calculated in these patients and subsequently in-hospital outcome was monitored. Results: 251 patients were enrolled Cut off value for optimal timing of thrombus aspiration was determined to be 315 minutes with a sensitivity of 68% and specificity of 50%. 117 patients reached in 315 minutes in which Export was used, they achieved post procedure TIMI III flow in 87.2% of patients and 75.4% in which Export was used after 315 minutes. Conclusion: Export time is a significant parameter that achieved better coronary intervention results in terms of post procedure TIMI III flow with the short Export time. Therefore, timely thrombus aspiration should be done for the maximum benefit.
Corrigendum to “Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)” [Eur Urol 77 (2020) 713–24]
Authors: Timothy J Wilt, Tien N Vo, Lisa Langsetmo, Philipp Dahm, Thomas Wheeler, William J Aronson, Matthew R Cooperberg, Brent C Taylor, Michael K Brawer
Journal: European Urology (2021)
Abstract 10757: Patient-Reported Quality of Life Outcomes in Hypertrophic Cardiomyopathy Patients
Authors: Samantha Xu, Wynne Zheng, Natalie M Szpakowski, Barbara Bittel, Susan Ospina, Nicholas G Smedira, Harry M Lever, Zoran B Popovic, Scott Frank, Milind Y Desai
Journal: Circulation (2021)

Background: Few studies have systematically assessed quality of life (QOL) in hypertrophic cardiomyopathy (HCM) patients not meeting the septal reduction therapy (SRT) threshold, but require avoiding isometric exertion and weightlifting. We prospectively studied a newly developed QOL instrument to examine the associations between patient characteristics and self-reported QOL scores in HCM patients not anticipated to undergo SRT for at least 6 months. Methods: A single-center, prospective sample of 51 adult HCM patients (54±14 years, mean interventricular septum thickness = 1.7±0.4cm, 65% with left ventricular outflow tract (LVOT) obstruction, mean provokable LVOT gradient 65±42 mmHg, 59% men) completed a baseline 70-item QOL instrument, adapted from validated QOL questionnaires. All patients signed informed consent. Results: Mean self-reported QOL scores (on a 5-point Likert scale with higher scores indicating higher QOL) were as follows: physical function (3.5±1), depression (3.7±1), anxiety (3.6±1), post-traumatic stress disorder (PTSD) (3.7±1), social function (4.1±1), spiritual acceptance of diagnosis (3.8±1), self-efficacy (4±1), and resilience (4±1). Men vs. women reported higher physical function (3.9±1 vs. 2.9±1), less depression (4±1 vs. 3.3±1), less anxiety (3.8±1 vs. 3.3±1), and higher social function (4.3±0.7 vs. 3.8±1) (all p&lt;0.05). Patients with obstructive HCM reported lower physical function scores (3.3±0.8) vs. non-obstructive HCM (3.8±0.8), p=0.03. Symptomatic patients reported lower physical function (3.2±0.8 vs. 4.3±0.5), social function (3.8±0.8 vs. 4.5±0.6) and worse depression (3.5±0.7 vs. 4.3±0.6), anxiety (3.4±0.8 vs. 4.1±0.7) and PTSD (3.5±0.8 vs. 4.3±0.9) scores (all p&lt;0.01). Presence of an implantable cardioverter defibrillator (ICD) was associated with lower vs. higher physical (2.9±0.4 vs. 3.5±1) and social function (3.6±1 vs. 4.1±1) (all p&lt;0.05). Conclusion: In HCM patients not requiring SRT, higher physical function scores were significantly associated with a better self-perceived overall health. Being a woman, having LVOT obstruction, presence of a defibrillator and presence of symptoms was significantly associated with worse perceived physical and social function.
T regulatory cells from atopic asthmatic individuals show a Th2‐like phenotype
Authors: Kirstin Jansen, Pattraporn Satitsuksanoa, Oliver F. Wirz, Stephan R. Schneider, Willem van de Veen, Ge Tan, Milena Sokolowska, Simon D. Message, Tatiana Kebadze, Nicholas Glanville, Patrick Mallia, Cezmi A. Akdis, Marcin Moniuszko, Sebastian L. Johnston, Kari Nadeau, Mübeccel Akdis
Journal: Allergy (2021)

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