tbuckley/cabot-search huggingface dataset:
Abstract 10521: Frequency and Impact of Virtual Follow-Up Visits After Heart Failure Hospitalizations: Insights from Michigan
Authors: Mike P Thompson, Jessica Yaser, Thomas Cascino, Hari Nathan, Chad S Ellimoottil
Journal: Circulation (2021)

Introduction: Outpatient follow-up after heart failure hospitalization has been shown to reduce readmission and emergency department (ED) visits. Hypothesis: We sought to evaluate the use of virtual follow up-care heart failure hospitalizations in a commercially insured population. Methods: We queried the Michigan Value Collaborative multipayer claims database for heart failure hospitalizations in patients discharged to home or home health between 7/20-11/20. We identified follow-up visits as outpatient office visits within 30 days of discharge, and categorized each patient as having an in-person only, virtual-only (GT or 95 modifier code), both virtual and in-person, and no follow-up visit. Multivariable logistic and linear regression was used to evaluate the association between follow-up visit type and 30-day readmissions, ED visits, and price-standardized episode spending. Results: A total of 2415 patients were discharged alive after a heart failure hospitalization: 94 (3.9%) patients had a virtual-only follow-up visit, 258 (10.7%) had both in-person and virtual visits, 1551 (64.2%) had in-person only follow-up visits, and 512 (21.2%) had no follow-up within 30 days of discharge. Adjusted analyses revealed that patients receiving both virtual and in-person visits had similar rates of 30-day readmissions (aOR=0.73, 95% CI: 0.42, 1.27), ED visits (aOR=0.52, 0.26, 1.07), and episode spending (adjusted difference= -$1508, 95% CI: -$3835, $821; Table ). However, patients receiving only virtual visits or no follow-up had significantly higher 30-day readmissions (aOR=2.31, 95% CI: 1.21, 4.42) and episode spending (adjusted difference= $1974, 95% CI: $206, $3742) compared to in-person visits. Conclusions: Virtual follow-up visits occurred in nearly 15% of heart failure patients, but had mixed results on patient outcomes. More evidence is needed to support the role of virtual-only follow-up visits after heart failure hospitalizations.
Abstract 10131: Alarmingly Rising Burden of Cardiovascular Comorbidities and Risk of Major Adverse Cardiac and Cerebrovascular Events in Nationwide Admissions from Low Income Households (2017 vs. 2007)
Authors: Dipen Zalavadia, Ashish Nepal, Srija Shanker, Bansari Kalolia, Bushra Fatima, Tanvi Singla, Aamer Mohammad, Deepu Joseph, Mir Zeeshan Ali Khan, Rupak Desai
Journal: Circulation (2021)

Background: Social determinants of health have an important influence on health equity. Addressing them appropriately is essential to improve population health outcomes and decrease health care disparities. We aimed to compare data from two nationwide cohorts from the US to analyze the shift of cardiovascular risk burden and major adverse cardiac and cerebrovascular events (MACCE) in low-household income (LHI) groups. Methods: Adult admissions among patients from LHI (0-25th) quartile were identified from two cohorts in 2007 and 2017 using the National Inpatient Sample. Socio-demographics, and pre-existing cardiovascular/extra-cardiovascular comorbidities were compared between the cohorts and multivariable regression was performed to assess the risk of MACCE (all-cause mortality, acute myocardial infarction and cardiac arrest including ventricular tachyarrhythmias) in 2017 vs. 2007 cohort. Results: Hospitalizations among LHI quartile showed 12% relative increase in 2017 (N=10,680,030) as compared to 2007(N=9,510,877). The 2017 cohort was younger (mean age 57 to 54 years) and admissions among male patients increased from 39% to 43.6% between 2007 and 2017. Also, non-elective and Medicaid admissions increased from 74% to 81% and 21% to 32%, respectively in 2017. Traditional CVD risk factors and comorbidities in the LHI quartile increased in 2017 compared to 2007 cohort (Table 1). The risk of composite MACCE was higher in the 2017 cohort compared to 2007 cohort (7.2% vs 6.7%, adjusted OR 1.03, 95%CI:1.03-1.04, p&lt;0.001). Although the hospital stay was comparable (3 days), hospitalization charges increased in 2017. Conclusion: Comparative analysis of LHI admissions across a decade shows that increasingly younger, male, non-white patients get hospitalized for non-elective reasons and have a higher burden of CVD risk factors and MACCE in 2017 vs. 2007. This warrants preventive strides to curtail CVD burden in patients of the LHI and improve health outcomes.
Abstract 14033: Inhibition of the Prolyl Isomerase Pin1 Improves Endothelial Function and Attenuates Vascular Remodelling in Pulmonary Hypertension by Inhibiting TGF-β Signalling
Authors: Kondababu Kurakula, Quint Hagdorn, Diederik Van Der Feen, anton vonk noordegraaf, Peter Dijke, Rudolf A De Boer, Harm J Bogaard, Marie Jose Goumans, Rolf M Berger
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by obstructive pulmonary vascular remodelling ultimately leading to right ventricular (RV) failure and death. Disturbed transforming growth factor-β (TGF-β) / bone morphogenetic protein (BMP) signalling, endothelial cell dysfunction, increased proliferation of smooth muscle cells and fibroblasts, and inflammation contribute to this abnormal remodelling. Peptidyl prolyl isomerase Pin1 has been identified as a critical driver of proliferation and inflammation in vascular cells, but its role in the disturbed TGF-β/BMP signalling, endothelial cell dysfunction and vascular remodelling in PAH is unknown. Methods and Results: Pin1 expression is increased in cultured pulmonary microvascular endothelial cells (MVECs) and lung tissue of PAH patients. Pin1 inhibitor, juglone significantly decreased TGF-β signalling, increased BMP signalling, normalized their hyper-proliferative, and inflammatory phenotype. Juglone treatment reversed vascular remodelling through reducing TGF-β signalling in monocrotaline + shunt-PAH rat model. Juglone treatment decreased Fulton index, but did not affect or harm cardiac function and remodelling in rats with RV pressure load induced by pulmonary artery banding. Conclusions: Our study demonstrates that inhibition of Pin1 reversed the PAH phenotype in PAH-MVECs in vitro and in PAH rats in vivo, potentially through modulation of TGF-β/BMP signalling pathways. Selective inhibition of Pin1 could be a novel therapeutic option for the treatment of PAH.
EPCO-25. MULTI-OMICS DISEASE STRATIFICATION IN PATIENTS WITH IDH-WILDTYPE GLIOBLASTOMA: SYNERGISTIC VALUE OF CLINICAL MEASURES, CONVENTIONAL AND DEEP RADIOMICS, AND GENOMICS FOR PREDICTION OF OVERALL SURVIVAL
Authors: Anahita Fathi Kazerooni, Sanjay Saxena, Danni Tu, Erik Toorens, Vishnu Bashyam, Hamed Akbari, Elizabeth Mamourian, Chiharu Sako, Costas Koumenis, Russell T Shinohara, Stephen J Bagley, Arati Desai, Robert A Lustig, Donald M O’Rourke, Tapan Ganguly, Spyridon Bakas, MacLean Nasrallah, Christos Davatzikos
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Multi-omics data integration captures tumor characteristics at multiple scales [i.e., microscopic (genomics and epigenetics), macroscopic (radiomics), clinical manifestation], provides a more comprehensive assessment of patient’s risk, and facilitates personalized therapies. In this work, we investigated the synergistic value of such multiple data sources for risk stratification and prediction of overall survival in IDH-wildtype glioblastoma tumors. METHODS Quantitative conventional and deep radiomics were extracted from pre-operative multi-parametric structural MRI (T1, T1Gd, T2, T2-FLAIR) of 501 patients with newly diagnosed glioblastoma. 389/501 and 112/501 patients formed our discovery and replication cohorts, respectively. Conventional radiomics were extracted from CaPTk, and deep radiomics from a pre-trained VGG-19 model. Multivariate SVM classification was performed on the discovery cohort to stratify patients in high, medium, and low-risk groups, using recursive feature elimination and 5-fold cross-validation. This model was independently tested on the replication cohort, and a radiomic-based survival prediction index (SPIradiomics) was calculated for each patient. Multi-stage integration of omics data, i.e., clinical (age, gender, extent of resection (EOR)), SPIradiomics, epigenetics (MGMT promoter methylation), and genomics (27 clinically relevant gene mutations via next-generation sequencing (NGS)), was performed using multivariate Cox proportional hazards (Cox-PH) model for stratification of the risk in the replication cohort. RESULTS Cox-PH modeling resulted in a concordance index (c-index) of 0.65 (95% CI:0.6–0.7) for clinical data, 0.67 (95% CI:0.62–0.72) for clinical and epigenetics, 0.70 (95% CI:0.65–0.75) for clinical and radiomics, 0.72 (95% CI:0.68–0.77) for clinical, epigenetics, and radiomics, and 0.75 (95% CI:0.71 – 0.78) for the multi-omics combination of all data; highlighting the added value of each layer of information in prediction of the patient’s risk. CONCLUSION Our results reinforce the synergistic value of integrated diagnostic methods for improving risk assessment of patients with glioblastoma that may pave the path towards a more personalized treatment planning.
DDRE-27. METABOLIC SWITCHING AS A MECHANISM OF DRUG RESISTANCE AGAINST NAMPT INHIBITION IN GLIOMAS
Authors: Pratibha Sharma, Vinay Puduvalli
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Gliomas exhibit significant heterogeneity in treatment response and characteristically deploy resistance mechanisms that render conventional therapies ineffective. Recently, novel agents have been developed that target regulators of differential energy pathways specifically utilized by gliomas. We previously reported on the targeting of Nicotinamide Phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway and its essential role in glioma cell energy metabolism. Here, we determined the mechanisms by which glioma cells bypass blockade of energy metabolism and develop resistance to NAMPT inhibitors. METHODS Using isogenic parental and drug-resistant patient-derived glioma stem-like cells (GSCs), we examined adaptive changes after NAMPT inhibition in glycolysis, mitochondrial function (oxidative state, basal respiration rate, spare respiratory capacity, maximum respiration capacity and proton leak) and metabolite levels using Agilent Seahorse assay and targeted metabolomics. Cross reactivity across various NAMPT inhibitors was measured using Cell Titer Glo assay. RESULTS GSCs exposed for an extended period to sub-lethal doses of FK866, a potent NAMPT inhibitor, acquired drug resistance to the agent which were also cross-resistant to other NAMPT inhibitors. Drug-resistant GSCs showed a decrease in extracellular acidification rate and oxygen consumption rate compared to isogenic parental lines. Further, metabolomic analysis showed a high accumulation of glutamate, creatine and histidine metabolites in these cells. These results indicate a shift in metabolism of drug-resistant GSCs from carbon metabolism to nitrogen metabolism. CONCLUSIONS GSCs resistant to the NAMPT inhibitor, FK866 showed cross resistance to other NAMPT inhibitors indicating specificity of this effect. The resistance mechanism involves a shift of preferential energy generation from glycolysis to amino acid metabolism which allows the cells to use alternative methods to generate NAD. Additional results from ongoing studies to delineate the mechanisms of metabolic switch in the drug resistance lines will be presented that will help develop strategies to combat resistance to NAMPT inhibitors.
Abstract 14404: Developing a Frailty Score for Use in Children and Adolescents With Congenital Heart Disease
Authors: Sarah Studyvin, Brian F Birnbaum, Vincent Staggs, David A White
Journal: Circulation (2021)

Introduction: Frailty is a complex syndrome that is associated with morbidity and decreased quality of life. It consists of 5 constructs: slowness, weakness, fatigue, energy expenditure, and body composition. Although frailty has been investigated in geriatrics, there is little describing the association of a frailty score on health outcomes in children and adolescents with chronic disease. The purpose of the study is to create a frailty score for use in children and adolescents and evaluate its usefulness in predicting morbidity in those with congenital heart disease (CHD). Hypothesis: We hypothesize that a higher composite frailty score is associated with an increased incidence in poor clinical status. Methods: Participants (Fig 1A) were enrolled in a cross-sectional study comparing the 5 components of frailty to age and sex matched controls. Frailty measures were modified for children and adolescents (Fig 1B). Constructs were combined to form a composite frailty score, which was correlated to clinical status, characterized as number of hospitalizations, emergency room (ER) visits, number of heart failure medications, at 23-31 month follow up. Results: The association between composite frailty scores, individual frailty measures, and outcomes was evaluated using Pearson correlation coefficient (Fig 1B). A higher frailty score was not found to be significantly correlated with outcomes. However, all individual frailty measures excluding body composition were inversely associated with the outcomes, indicating worse outcomes with poor functional status. Conclusions: Although composite frailty score was not associated with clinical outcomes, individual constructs were associated with worse clinical status. Our study was limited by a small and heterogenous sample, and future studies should be done to validate a frailty score for use in the CHD population. A frailty tool can identify at risk patients in this vulnerable population prior to sentinel events.
Abstract 12587: In Postmenopausal Women With Cardiovascular Disease Hypomagnesaemia May Exacerbate Dyslipidemia and Inflammatoty Syndrome
Authors: Ioan A Gutiu, Anton I Gutiu
Journal: Circulation (2021)

Introduction: We proposed to study the relationships between the serum magnesium level (Mg) and the presence of atherosclerosis risk factors and inflammatory syndrome (C reactive protein -CRP-, serum fibrinogen, dental state appreciated by missing teeth, -MT- as consequence of periodontosis and/or periodontitis, etc.) in postmenopausal women with cardiovascular disease (CVD). Methods: We studied 675 postmenopausal women: mean age 63.7±9.5 years, mean interval from menopause beginning – 9.3 years. Cardiovascular disease was presented such as: old myocardial infarction (34%), angina pectoris (31%), peripheral arterial disease (5%), ischemic cardiomyopathy (5%), stroke (10%), atrial fibrillation (15%). Mean serum cholesterol was 221±52 mg%, smoking index 106±226, systolic arterial pressure 159±25 mmHg, mean MT 16±10, high CRP level in 35.4%, Fibrinogen 418 ±105 mg%, serum magnesium 2.10±0.30 mg%. Results: The comparison of the women with normal (565 patients) or reduced levels of serum (Mg&lt;1.8mg%-110 patients), shown: age 61±8 years in normal Mg group, versus 63.7±9 years in reduced Mg group (P&lt; 0.004); BMI 29.7+/-14.1 versus 26.8+/-5.8 Kg/m2 (P&lt;0.03); Triglicerides: 149.7+/-105.1 versus 175.7+/-151.4 mg (P&lt;0.025); serum Glucose 104.7+/-32.3 versus 133.4+/-61.49 mg (P&lt;0.001); HDL-Cholesterol 49.9+/-14.0 versus 42.6+/-11.9 mg (P&lt;0.001); LDL-Cholesterol: 141.8+/-45.1 versus 159.3+/-58.2 (P&lt;001). Concerning inflammation: high CRP level in 26%, versus 44% ,(P&lt;0.002); Fibrinogen 408.2+/-103.4 versus 460.9+/-111.5 mg% (P&lt;0.001); MT 15.03+/-9.01 versus 17.46+/-9.47 (P&lt;0.009). Conclusions: Hypomagnesiaemia may intervene in CVD mainly by alteration of membrane ions exchange, endothelium functionality, insulin resistance, inflammation mechanism. In menopausal women, Mg deficit may be important and is found in women more aged, with more low BMI, with dyslipidemia and with the presence of some inflammatory markers: CRP, Fibrinogen, MT. The explanations and consequences of these findings will be discussed.
Abstract 10540: Worsening Racial Disparity in Waitlist Mortality for Pediatric Heart Transplant Candidates Since the 2016 Pediatric Heart Allocation Policy Revision
Authors: Lydia K Wright, Robert J Gajarski, Christina Phelps, Timothy M Hoffman, Irene Lytrivi, Defne Magnetta, Fawwaz R Shaw, Consuela Thompson, Molly Weisert, Deipanjan Nandi
Journal: Circulation (2021)

Introduction: The US Pediatric Heart Allocation Policy was recently revised with the goal of lowering waitlist mortality. Effective March 2016, these rules significantly changed the requirements for priority status. We evaluated the hypothesis that this change, which has led to an increase in status exceptions, has worsened known racial disparities in waitlist outcomes. Methods: Children in the Pediatric Heart Transplant Study database listed at a US center from January 2012 - June 2020 were included and stratified by listing before (Era 1) or after (Era 2) allocation policy change on March 22, 2016. Competing risk survival analysis was performed to evaluate endpoint of death or deterioration on the waitlist with transplant treated as a competing risk. Results: Compared with white children (n=2,648), non-white children (n=1,441) were more likely to have an underlying diagnosis of cardiomyopathy (49% vs. 39%, p&lt;0.001), be currently hospitalized (81% vs. 71%, p=0.007) and supported with a ventricular assist device (VAD) (12% vs 9%, p=0.005) at the time of listing. Waitlist mortality was similar in white and non-white children in Era 1, but worse for non-white children compared to white children in Era 2 (Figure). In multivariable analysis controlling for diagnosis, age and severity markers, non-white children had a significantly higher waitlist mortality only if listed after the policy change (Era 1: sHR 1.18 [95%CI 0.88 - 1.59] vs. Era 2: sHR 1.52 [95%CI 1.14 - 2.02]). Hispanic ethnicity was not associated with waitlist mortality in either period when controlling for other risk factors. Conclusions: Widening racial disparities in waitlist mortality may be an unintended consequence of the 2016 Pediatric Heart Allocation Policy revision. Additional analyses may help the transplant community understand the degree to which this policy (i.e. prioritized listing status and exceptions) vs. unrelated changes in care differentially contribute to these disparities.
Abstract 10958: Ability of Machine Learning Algorithms to Predict Stage 2 Hypertension Using Health Examination Data from Japanese General Population
Authors: Shin Kawasoe, Takuro Kubozono, Satoko Ojima, Takeko Kawabata, Anwar A Salim, Hironori Miyahara, Koichi Tokushige, Mitsuru Ohishi
Journal: Circulation (2021)

Introduction: There is a large amount of specific health examination data in Japan. Efforts to utilize these data to predict the future onset of cardiovascular diseases are important from the perspective of improving prognosis and QOL as well as medical economy. We evaluated the prediction ability of machine learning algorithms for newly developed 5-year hypertension. Methods: Among those who underwent examinations from 2008 to 2018, individuals whose baseline (year X), 1 year later (year X+1), and 5 years later (year X+5) data were available were included. Hypertension was defined as &gt; 140/90 mmHg or under treatment with antihypertensive drugs. Those with hypertension in year X or X+1 were excluded. Three different machine learning algorithms, Support vector machine (SVM), Logistic regression (LR), and Multilayer perceptron (MLP) to predict hypertension on year X+5 from single-year data (year X) or consecutive 2 years data (year X and X+1) were assessed, and the predictive ability was compared. Anthropometric measurements, blood pressure and pulse rate, laboratory measurements, and lifestyle related indices were included as explanatory variables. Results: A total of 24,652 participants (age 48.0±10.1 years, male 47.5%) were included and 3,596 individuals (14.6%) had hypertension in year X+5. The indices of predictive ability from single-year data were as follows: SVM, AUC 0.80, accuracy 0.71, precision 0.94; LR, AUC 0.80, accuracy 0.86, precision 0.87; MLP, AUC 0.80, accuracy 0.86, precision 0.86. Those from multi-year data were as follows: SVM, AUC 0.85, accuracy 0.75, precision 0.95; LR, AUC 0.85, accuracy 0.87, precision 0.88; MLP, AUC 0.84, accuracy 0.87, precision 0.89. The variables with the highest importance features were systolic blood pressure (0.49), diastolic blood pressure (0.26), waist circumference (0.13), and body mass index (0.06). Conclusions: The ability to predict new onset of hypertension was better when using data from two consecutive years than when using data from a single year. The AUCs ranged from 0.84 to 0.85 and were generally better than previously reported risk models using statistical methods. Anthropometric measures, along with blood pressure levels, have been identified as major contributors.
SURG-04. THE CLINICAL COURSE AND ROLE OF SURGERY IN PEDIATRIC MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A DATABASE STUDY
Authors: Victor Lu, Shelly Wang, David Daniels, Robert Spinner, Allan Levi, Toba Niazi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Malignant peripheral nerve sheath tumors (MPNST) are rare tumors found throughout the body, with their clinical course in children still to be completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this demographic from a large national database. METHODS All MPNST patients aged ≤18 year in the U.S. National Cancer Database (NCDB) between 2005-2016 were retrospectively reviewed. Data were summarized and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS A total of 251 pediatric MPNST cases were identified. Overall, mean age at diagnosis was 13.1 years (range, 1-18) with there being 132 (53%) females and 119 (47%) males. There were 84 (33%) MPNSTs located in extremities, 127 (51%) less than 1cm in size, and 22 (9%) have metastasis at diagnosis. In terms of treatment, surgery was pursued in 187 (74%) patients, chemotherapy in 116 (46%) patients, and radiation therapy in 129 (61%) patients. Five-year overall survival was estimated to be 52% (95% CI, 45-59%), and with median survival of 64 months (range, 36-136). Multivariate regression revealed older age (HR 1.10, P&amp;lt; 0.01), with metastases at time of diagnosis (HR 2.14, P=0.01), and biopsy only (HR 2.98, P&amp;lt; 0.01) all significantly and independently predicted shorter overall survival. Chemotherapy and radiation therapy were not statistically significant. CONCLUSIONS Pediatric MPNSTs are rare malignant entities, and only approximately half of patients will survive to five years. There remains a clear survival benefit in pursuing maximal safe resection in these patients. As such, judicious workup with meticulous surgical resection by an expert team should then be considered the standard of care for these tumors in children.