tbuckley/cabot-search huggingface dataset:
Abstract 12270: The Evolution of Tricuspid Regurgitation After Percutaneous Patent Ductus Arteriosus Closure in Ex-Preterm Infants Under 2 Kilograms
Authors: Salvador A Rodriguez Franco, Barry O’Callaghan, Jenny E Zablah, Gareth J Morgan
Journal: Circulation (2021)

Objective: To evaluate incidence and evolution of new tricuspid regurgitation (TR) after percutaneous patent ductus arteriosus (PDA) closure in preterm infants under 2 kg. Background: Multiple advances in techniques and technology in cardiac catheterization have facilitated percutaneous closure of neonatal PDAs. A higher rate of complications has been suspected in this setting, but robust scientific evidence concerning this association is not yet available. TR has been a recognized significant complication, gaining notoriety with the use of the Piccolo device over the last few years. Methods: We performed a single-center retrospective cohort study. We included 29 patients under 2 kg who underwent percutaneous PDA closure between January 2019 and December 2020. This cohort was then matched with a control group of sub 2 Kg patients who did not have percutaneous PDA closure at a ratio of 2:1 (n=58). Echocardiographic data points were collected prior to catheterization and at intervals up to 1-year post-procedure. To standardize the temporal change in TR, we measured the zone of convergence and normalized it with the body surface area related to time. Results: TR after percutaneous PDA closure was seen in 9 cases (31.1%), of which 8 cases were classified as mild-to-moderate (27.6%) and 1 case as severe (3.4%). At the end of follow-up, TR persisted in 5/9 cases (17.2%); however, no increases in TR, clinical complications, or need for reintervention were noted for these patients. In the control group of 58, we incidentally noted two patient with moderate to severe TR which diminished over time. Compared to the control group, our cohort did not present significant difference in terms of survival or weight gain characteristics. Conclusions: TR remains a worrying likely mechanical consequence of catheter and device manipulation in percutaneous preemie duct closure. We should strive to decrease such complications by technical and procedural improvement. Despite this, no patient in our cohort has required specific medical or surgical reintervention for TR, and the echocardiographic trend is tending towards a decreasing grade of TR over time.
Abstract 11629: Contributions of Socio-Economic Status, Lifestyle, and Biological Risk Factors to Ethnic Differences in Type 2 Diabetes Risk in a Multi-Ethnic Asian Population
Authors: Jowy Yi Hoong Seah, Xueling Sim, Wei Jie Seow, E Shyong Tai, Rob M. van Dam
Journal: Circulation (2021)

Introduction: There is no study that identified contributions of socio-economic status (SES), lifestyle, and biological risk factors to ethnic differences in T2D risk in Asia’s populous ethnic groups - Chinese, Malays and Indians. Methods: We used data of 7,427 participants from the Multiethnic Cohort, a population-based study of subjects aged ≥21 y. Information on SES and lifestyle were collected using standardized questionnaires. Biological risk factors were measured using validated methods. T2D cases were based on self-reported physician-diagnosed diabetes or a national medical registry, or fasting plasma glucose ≥7.0 mmol/L or HbA1c ≥6.5 %, after an average of 7.2 y (SD: 2.2 y). Multivariable logistic and linear regression models were used in association and mediation analyses. Results: In Model 1, Malays and Indians had a twofold higher risk of developing T2D compared with Chinese ( Table 2 ). In Model 2, only the association between Indians and Chinese remained. The higher T2D risk in Malays and Indians was largely mediated by BMI and HDL cholesterol ( Table 3 ). Adjusting for adiponectin concentrations widened the differences in T2D risk. We observed a larger mediation effect by HOMA-IR for Indians than Malays. Conclusion: The excess risk in Malays was completely explained by higher BMI. In contrast, neither adiposity nor SES and lifestyle could fully explain the higher T2D risk in Indians.
Abstract 9982: World Health Organization Cardiovascular Risk Score Correlates with Carotid Intima-Media Thickness, but Fails to Identify High Risk Black Patients Unlike the Framingham and Atherosclerotic Cardiovascular Risk Score Models
Authors: Amha M Weldehana, Abel Tenaw, Natnael Abegaz, Robel Amenu, Tigest Zewdie, Yodit Yaynishet, Eden Gidena, Abenezer Legesse, Tinsaye Shihur, Addisu melkie, Negussie Deyessa, george cotsonis, Yewondwossen Mengistu, Puja K Mehta
Journal: Circulation (2021)

Introduction: Correlation between various cardiovascular risk models and carotid intima-media thickness (CIMT) in the black population is not well described. To risk stratify patients in Ethiopia, three scores are used: Non-laboratory World Health Organization (nWHO) score, used for Sub-Saharan countries, ACC/AHA atherosclerotic cardiovascular risk score (ASCVD), and Framingham risk score (FRS). We compared these three scores and determined their relationship with a marker of subclinical atherosclerosis such as CIMT. Methodology: 336 patients (ages 40-79) with no atherosclerotic cardiovascular disease were randomly selected in Ethiopia’s largest tertiary hospital and underwent CIMT measurement read by blinded readers. Participants were stratified into low, intermediate, and high-risk groups based on the three scores. Pearson correlations and Freedman’s comparisons were used. Results: The three risk scores and mean CIMT were moderately correlated (Figure 1). There were strong positive correlations between ASCVD and FRS (n=284, r=0.71, CI: 0.65-0.77, p&lt;.0001), ASCVD and nWHO (n=279, r =0.73, CI: 0.67-0.78, p&lt;.0001), as well as FRS and nWHO risk scores (n=331, r=0.76, CI: 0.71-0.78, p&lt;.0001). However, there was significant disagreement in their risk categorization (Figure 2). Conclusion: Non-laboratory WHO risk score fails to identify high-risk patients stratified by ASCVD or FRS despite having similar correlations with CIMT. The use of nWHO score may underestimate risk in the Ethiopian population, compared to ASCVD and FRS scores. These findings have therapeutic implications for primary prevention.
CTNI-23. A FIRST-IN-HUMAN PHASE 0/1 CLINICAL TRIAL OF 5-AMINOLEVULINIC ACID SONODYNAMIC THERAPY IN RECURRENT GLIOBLASTOMA
Authors: Nader Sanai, An-Chi Tien, Artak Tovmasyan, Yu-Wei Chang, Tigran Margaryan, Kristin Hendrickson, Jennifer Eschbacher, Wonsuk Yoo, Jocelyn Harmon, Christopher Quarles, Lea Alhilali, Igor Barani, Shwetal Mehta, Zaman Mirzadeh
Journal: Neuro-Oncology (2021)

Abstract 5-Aminoleveulinic acid sonodynamic therapy (5-ALA SDT) is a drug-device strategy that exploits the metabolic liabilities of cancer. Following systemic administration of 5-ALA, aberrant tumor metabolism leads to accumulation of protoporphyrin-IX (PpIX). Activation of PpIX by non-invasive, non-ablative magnetic resonance-guided focused ultrasound (MRgFUS) induces reactive oxygen species and tumor cell death. This first-in-human Phase 0/1 study investigates the feasibility, safety, and biological effects of 5-ALA SDT in recurrent glioblastoma (GBM) patients. Six hours prior to SDT, adult patients with recurrent GBM are administered Sonala-001 (10mg/kg), an IV formulation of 5-ALA. In a Dose-Escalation Arm, 9-18 patients are assigned to one of three ascending acoustic energy doses of MRgFUS (200J/400J/800J, measured at transducer surface), followed by a four-day interval to planned tumor resection. In each patient, half the tumor volume, including Gadolinium-enhancing and nonenhancing tumor, is targeted with MRgFUS and the other half serves as an internal control. Using tumor pharmacodynamic endpoints, the Minimum Biological Dose (MBD) associated with 5-ALA SDT response is identified. In a subsequent Time-Escalation Arm, 12 patients are treated at the MBD and assigned to one of two time-intervals between SDT and resection. As of May 1, accrual to the 200J dose level (n=3) is complete without significant drug- or device-related adverse events. No cellular or radiographic changes to non-targeted tissue were detected. The median Cmax for 5-ALA and PpIX were 307 µM and 319 nM, respectively. The oxidative stress biomarkers 4-hydroxynonenal, glutathione, cysteine, and thiol were significantly elevated in treated tissue vs. control. Similarly, the apoptosis biomarker cleaved caspase-3 was increased in treated tumor vs. control (median, 48.6% vs. 29.6%, p=0.05). This first-in-human experience with a new therapeutic modality for recurrent glioblastoma patients demonstrates that 5-ALA SDT is safe at 200J. Sonodynamic therapy leads to targeted oxidative stress and tumor cell death in human glioblastoma tissue.
Abstract 12309: Effects of Sex and Age on Plasma Fatty Acids as Measured by Gas Chromatography/Mass Spectrometry in a Very Large Population Analysis
Authors: Margaret R Diffenderfer, Nandani Rajapakse, Ericka Pham, Lihong He, John R Nelson, Ernst J Schaefer
Journal: Circulation (2021)

Background: Studies have documented the beneficial effects of omega-3 fatty acids, specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as found in oily fish and/or fish oil capsules, on cardiovascular disease (CVD) risk reduction. JELIS using purified EPA 1800 mg/day and REDUCE-IT using EPA 4 g/day reported significant reductions in CVD endpoints in statin-treated subjects versus controls. Median plasma EPA levels increased from 97 to 166 μg/mL in the treatment group in JELIS and from 26 to 169 μg/mL in REDUCE-IT. Reductions in CVD endpoints were related to EPA levels. No benefit on CVD risk was observed in STRENGTH, when subjects were given 4 g/day of a carboxylic acid formulation containing both EPA and DHA. Objective: We aimed to ascertain interrelationships of sex and age with plasma fatty acids, especially omega-3 fatty acids, in a very large clinical population. Methods: Plasma fatty acids were measured by gas chromatography/mass spectrometry after lipid extraction in 1,169,621 fasting United States subjects (56.2% female; median age 58.2 yr). Results: Plasma fatty acid indices (median±IQR), expressed as percentage of total fatty acids, were 31.5±1.5% for saturated fatty acids (sum of 14:0, 16:0, and 18:0); 21.4±2.2%, monounsaturated fatty acids (sum of 16:1n7- cis and 18:1n9- cis ); 0.45±0.23%, trans fatty acids (sum of 16:1n7- trans and 18:1n9- trans ); 42.4±3.0%, omega-6 fatty acids (sum of 18:2n6, 20:3n6, and 20:4n6); and 2.55±0.80%, omega-3 fatty acids (sum of 20:5n3 and 22:6n3). EPA plasma levels were 22.0±9.6 μg/mL (median±IQR), significantly lower than levels ≥150 μg/mL required for significant CVD risk reduction in randomized trials. Females had significantly ( P &lt;0.0001) lower indices of monounsaturated (-4.31%) and trans fatty acids (-9.30%) and significantly higher indices of omega-6 (+2.79%) and omega-3 fatty acids (+6.82%) than males. Older subjects (≥65 years of age) had a significantly ( P &lt;0.001) higher median omega-3 fatty acid index (+29.68%) and higher plasma EPA levels (+57.05%) than younger subjects (&lt;30 years of age). Conclusion: In one of the largest US population studies looking at fatty acids, we found sex and age specific differences. Plasma EPA levels were very low in all groups.
Rate of Clonal Hematopoiesis in Patients with Venous Thromboembolism
Authors: Tamanna Haque, Arletta Lozanski, Tzyy-Jye Doong, Ying Huang, Rui Li, Abigail Bartosic, Gerard Lozanski, John C. Byrd, Tzu-Fei Wang
Journal: Blood (2021)
Abstract 12504: The Gender-Based Outcome in the Patients Undergoing Percutaneous Left Atrial Appendage Occlusion With the Watchman Device: A Longitudinal Nationwide Inpatient Sample Analysis
Authors: Neel Patel, Birendra Amgai, Chakraborty Sandipan, Adrija Hajra, Zeel Patel, Aryal Binit, mazin Khalid, Prodip Kumar Paul, Wilbert S Aronow
Journal: Circulation (2021)

Introduction: Compared to men, women have an increased risk of having a stroke, cardiovascular disease, and death. It requires continuous anticoagulation use based on CHA 2 DS 2 -VASc scores for stroke prevention. The Watchman device is indicated for patients with non-valvular AF at high risk of stroke who have contraindications to long-term anticoagulation use. We sought to determine the periprocedural outcome difference based on gender in the patients undergoing watchman device implantation. Methods: National Inpatient Sample databases from 2016 to 2018 were utilized using Stata 16.0. NIS databases are the ICD-10-CM code-based largest publicly available all-payer inpatient database. Patients with atrial fibrillation who underwent the watchman procedure were identified; later divided and compared based on gender. Multivariate logistic regression, linear regression, and student t-t-tests were used for analysis. Data were further analyzed after greedy propensity matching for accuracy. Results: Out of 33,825 patients who had the procedure, 14,105 (41.8%) were female, and 19,690 (58.2%) were male. The mean age for women and men were 76.5±7.5 and 75.6±8.1 respectively. Co-morbidities such as DM, CAD, CKD, PVD, and history of CABG were more in men, whereas anemia and pulmonary hypertension were more in women. Mortalities in women were 30 whereas it was 26 in men. There was no difference in mortality on multivariate logistic regression analysis. Complications such as pericardial drain and major bleeding requiring blood transfusion were higher in women. There was no difference in pericardial complications, ischemic stroke, hemorrhagic stroke, and AKI. The overall mean LOS and cost per hospitalization were higher in women. Conclusions: Patients undergoing watchman procedure showed no difference in periprocedural mortality between men and women; however, women had high events of pericardial drainage and major bleeding requiring blood transfusion.
Abstract 10505: S100a12 Aggravates Acute Myocardial Infarction Injury Through Excessive Neutrophil Extracellular Trap Formation
Authors: Xi Zhang, Xiaolin Zhang, Yujie Zhang, Yi Cai, Dan Liu, Xiaoxiang Tian, Chenghui Yan, Han Yaling
Journal: Circulation (2021)

Introduction: S100A12 represents a novel biomarker and therapeutic target that regulates cardiovascular disease after its release from myeloid cells. However, the role of S100A12 in the etiology of Acute Myocardial Infarction (AMI) is not well understood. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of AMI and in the externalization of some S100 family members. Here, we investigated the effect of S100A12 on neutrophils’ function and myocardial injury after AMI. Methods and Results: Since S100A12 is a human specific molecule and not expressed in mice, we constructed transgenic (TG) mice expressing S100A12 in myeloid cells. By left anterior descending artery ligation and flow cytometry, we found that S100A12 markedly increased neutrophil infiltration and myocardial injury in TG mice compared to WT mice. Within the infarct zone, more neutrophil extracellular traps (NETs) were observed in TG mice, whereas intraperitoneal injection of DNase I decreased the damage effect of NETs. We used the overexpressing plasmid of S100A12 and observed that S100A12 enhanced the level of NETosis. Whereas, siRNA-mediated S100A12 silencing reduced the production of NETs. By ChIP and dual-luciferase reporter assay we found that Hypoxia-inducible factor-1α (HIF1α) directly bound to the promoter of the S100A12 gene and regulated S100A12 expression. We next used tandem mass tag (TMT) labeling quantitative proteomic technology and discovered that annexin a5 (ANXA5) was a receptor with significantly different expression level in TG compared with WT mice. Finally, we demonstrated that S100A12 increased NETs formation via receptor RAGE and ANXA5. Conclusions: Our findings reveal a critical role of S100A12 in regulating neutrophil activation and NETs formation, resulting in aggravated myocardial injury after AMI. In such a process, S100A12 regulates NETosis via the Hif1α-S100A12-ANXA5/RAGE pathway. S100A12 is a useful molecular marker and possible target for treatment for AMI.
RADT-20. SINGLE INSTITUTION REVIEW OF LARGE VOLUME HIGH GRADE GLIOMA PATIENTS TREATED WITH RADIOTHERAPY
Authors: Vishal Manik, Angela Swampillai, Omar Al-Salihi, Kazumi Chia, Lucy Brazil
Journal: Neuro-Oncology (2021)

Abstract AIM Not uncommonly, we come across significantly large high grade glioma cases (HGGs). With standard delineation protocols, we end up irradiating a large volume of normal brain. Emami &amp; QUANTEC data define normal brain tolerance doses, however they are often of limited use in clinic practice. Thus, we reviewed our patients with significant tumor volumes to derive a safe dose/ volume level for brain. METHODOLOGY Patients with HGGs over the last 3 years were extracted from Mosaiq™ information system. The output was sorted with respect to clinical target volumes from lowest to highest. The top 25 percentile i.e. patients with a CTV of &amp;gt; 412cc (n=53) were identified for this study. Data was collected with respect to clinical, tumor characteristics and radiotherapy parameters. RESULTS Median age of population was 53 and majority (n=38) were males. Nine patients had multi-focal tumors while six had bilateral extension. Majority of the study group had Glioblastoma Multiforme (n=44), whereas 6 had Grade 3 tumors. Most of the patients could only have a biopsy (n=27). Molecular profile showed 42 were Isocitrate-Dehydrogenase negative and 26 were unmethylated tumors. Stupp’s &amp; Perry’s regimen were the commonly used protocols, however patients (n=7) with significant volumes near critical structures were treated with doses in the range of 50.4 – 55Gy in 30 fractions. The CTV volumes in the population ranged from 412 – 1223 cc while total brain volume range was 1112 – 1667 cc. Median of 43.5% of brain volume was covered in the PTV, while median of 5% of brain volume outside the PTV was treated to BED2 of 100Gy. Median survival was 12.4 months. CONCLUSION Our study shows reasonable tolerance of radiotherapy doses of &amp;gt; 50 Gy to larger volumes of brain. We propose a multi-center collaborative study to derive a new standardized dose volume tolerance.
Coagulopathy Following Chimeric Antigen Receptor T Cell Therapy in R/R Adult B Cell Malignancies: A Single Center Experience
Authors: Safia Belbachir, Jean Jacques Tudesq, Sylvain Lamure, Pierre Rocanieres, Elena Properzi, Patrice Ceballos, Nathalie Fegueux, Eve Gehlkopf, Franciane Paul, Emmanuelle Tchernonog, Alexandre Theron, Anne-Charlotte Teyssier, Isabelle Diaz, Aguilar-Martinez Patricia, Charles Herbaux, Guillaume Cartron
Journal: Blood (2021)
Abstract 12520: Thirty-Day Readmission Rates and Causes Among Patients Admitted With Acute Myocarditis: Insights From the Nationwide Readmissions Database
Authors: Amandeep Goyal, Shubham Lahan, Tarun Dalia, Sagar Ranka, Prakash Acharya, Suveenkrishna Pothuru, Siva Taduru, Ioannis Mastoris, Andrew J Sauer, Nicholas Haglund, Andrija Vidic, Zubair Shah
Journal: Circulation (2021)

Introduction: Myocarditis is a serious inflammatory process that can result in acute and chronic cardiomyopathy. Data on patient characteristics, predictors and national readmission rates related to myocarditis are limited. We sought to evaluate the causes and predictors of 30-day readmission rate of patients admitted with acute myocarditis. Methods: Using the Nationwide Readmission Database, we included adult patients (age&gt;18 years old) who were hospitalized between January 2016 to November 2018 for acute myocarditis. Thirty-day readmission rates, causes, and predictors of readmission were assessed. Results: We analyzed 9482 patients who were discharged alive with a primary diagnosis of acute myocarditis, without requiring advanced therapies (HTX or LVAD) during the index admission. Within 30 days, 641 (6.8%) were readmitted and half of the readmissions occurred in the first 10 days. The readmitted patients were older (mean age of 50 ± 19 vs 41 ± 17, p =&lt;0.001) and were more females (49 % vs 35%, p= &lt;0.001). Using multivariate logistic regression (Fig 1A) , the odds of 30-day readmission was higher in diabetics (OR 1.47: 95% CI 1.05-2.04), smokers (OR 1.39: 95% CI 1.05-1.84), prior MI (OR 2.17: 95% CI 1.36-3.44), chronic lung disease (OR 1.55: 95% CI 1.16-2.07) and renal failure (OR 1.97: 95% CI 1.31-2.96). Recurrent myocarditis (15%), and heart failure (15%) were the most common causes of readmission (Fig 1B) . Conclusions: The readmission rate among acute myocarditis patients is high and is driven by recurrent myocarditis and heart failure. Early identification of patients at increased risk for readmission may help develop prevention strategies and improve outcomes in acute myocarditis.
TAMI-50. PATHWAYS ACTIVATION IN GL261 MICE GLIOMA CELLS BY HIV-1 GLYCOPROTEIN GP120
Authors: Gabriel Valentín Guillama, Lilia Kucheryavykh
Journal: Neuro-Oncology (2021)

Abstract Patients infected with human immunodeficiency virus type 1 (HIV-1) are more prone to developing cancers, including glioblastomas (GBMs). The median survival for GBM patients with HIV is significantly shorter than for HIV-negative GBM patients, even though they receive the same treatments. This difference indicates that HIV infection is associated with more aggressive tumor behavior and with treatment resistance. Earlier we demonstrated that gp120, a main glycoprotein in the HIV shell, stimulates glycolysis and protein synthesis in glioma cells. The purpose of this study was to evaluate the underlying gp120 dependent signaling mechanism in glioma cell. Mouse glioma cells GL-261 were continuously cultured for 7 days in medium with and without soluble gp120 Bal III (100ng/ml) and collected for Western blot and Cell cycle assays. Western blot analysis presented an increase in phosphorylation of Proline-rich tyrosine kinase (Pyk2(Y402)), p38(YT100/Y182) and p70s6(T421/S424), the key proteins of the Pyk2 pathway, along with the increased levels of Akt(S473) and Glycogen Synthase Kinase 3b (GSK3b (S9)) phosphorylation. Flow cytometry analysis of Cell Cycle revealed an increase of G2/M phase in cells cultured in gp120 Bal III when compared to control cells. Furthermore, GL-261 cells with knock-out of Pyk2 via CRISPR Cas 9 gene editing showed no significant change in cell cycle regulation when cultured with gp120 Bal III.Overall, these results demonstrate that gp120 triggers activation of Pyk2/MAPK and Akt/GSK3b pathways and alter cell cycle regulation in GBM. This research was made possible by NIH grant number 1SC1GM122691.