tbuckley/cabot-search huggingface dataset:
Abstract 13643: Home Blood Pressure Monitoring in Pregnant Women and Women of Child-Bearing Age With Hypertension From 2009-2014
Authors: Ben Maxner, Stephanie C Lemon, Tiffany A Moore Simas, Sharina D PERSON, David D McManus, Stephen P Juraschek, Lara C Kovell
Journal: Circulation (2021)

Introduction: Hypertension (HTN) is a leading cause of maternal mortality, and HTN guidelines recommend home blood pressure monitoring (HBPM) to help achieve blood pressure (BP) control. Evidence suggests that HBPM be coupled with a care team to maximize its effectiveness. HBPM and provider counseling in pregnant women with HTN are unknown. Objective: To assess HBPM use and provider counseling in pregnant women and women of child-bearing age with HTN Methods: We used data from 3,614 women in the National Health and Nutrition Examination Surveys 2009-2014 to determine HBPM use and provider counseling for pregnant women and women of child-bearing age (20-50 years) with HTN. HBPM use and provider counseling were self-reported. Results: For pregnant women with HTN, the mean (SE) age was 33.3 (1.6) years, the mean (SE) BMI was 44.8 (6.3) kg/m 2 , and 47.5% were on BP medication (Table). Among pregnant women with HTN, 51.2% reported HBPM in the past year, and 46.3% used HBPM at least weekly. However, only 9.6% of pregnant women with HTN received provider counseling. Among women of child-bearing age with HTN, 49.6% reported HBPM in the past year and 40.4% received provider counseling. Conclusions: While over half of pregnant women with HTN have adopted HBPM, less than 10% of this population received provider counseling. This gap highlights a need and opportunity for providers to improve BP management by supporting a popular monitoring approach among pregnant women with HTN.
Plasticity in the Absence of NOTCH Uncovers a RUNX2-Dependent Pathway in Small Cell Lung Cancer
Authors: Deli Hong, Erik H. Knelson, Yixiang Li, Yavuz T. Durmaz, Wenhua Gao, Emily Walton, Amir Vajdi, Tran Thai, Maura Sticco-Ivins, Amin H. Sabet, Kristen L. Jones, Anna C. Schinzel, Rod T. Bronson, Quang-De Nguyen, Michael Y. Tolstorukov, Marina Vivero, Sabina Signoretti, David A. Barbie, Matthew G. Oser
Journal: Cancer Research (2021)

Abstract Neuroendocrine to nonneuroendocrine plasticity supports small cell lung cancer (SCLC) tumorigenesis and promotes immunogenicity. Approximately 20% to 25% of SCLCs harbor loss-of-function (LOF) NOTCH mutations. Previous studies demonstrated that NOTCH functions as a SCLC tumor suppressor, but can also drive nonneuroendocrine plasticity to support SCLC growth. Given the dual functionality of NOTCH, it is not understood why SCLCs select for LOF NOTCH mutations and how these mutations affect SCLC tumorigenesis. In a CRISPR-based genetically engineered mouse model of SCLC, genetic loss of Notch1 or Notch2 modestly accelerated SCLC tumorigenesis. Interestingly, Notch-mutant SCLCs still formed nonneuroendocrine subpopulations, and these Notch-independent, nonneuroendocrine subpopulations were driven by Runx2-mediated regulation of Rest. Notch2-mutant nonneuroendocrine cells highly express innate immune signaling genes including stimulator of interferon genes (STING) and were sensitive to STING agonists. This work identifies a Notch-independent mechanism to promote nonneuroendocrine plasticity and suggests that therapeutic approaches to activate STING could be selectively beneficial for SCLCs with NOTCH2 mutations. Significance: A genetically engineered mouse model of NOTCH-mutant SCLC reveals that nonneuroendocrine plasticity persists in the absence of NOTCH, driven by a RUNX2-REST–dependent pathway and innate immune signaling.
Five-Year Outcomes of Chronic Red Blood Cell Exchange Transfusion Program for Patients with Sickle Cell Disease, the Experience of University of Nebraska Medical Center
Authors: Omar Abughanimeh, Steven Ebers, Mahammed Khan Suheb, Julie Eclov, Robin High, Aleh Bobr, Scott A Koepsell, James Harper, Krishna Gundabolu, Alex Nester, Laxmi Narayana Buddharaju
Journal: Blood (2021)
RADT-23. RECURRENT OLIGODENDROGLIOMAS AFTER FIRST CHEMO-RADIATION THERAPY RESPONDED REMARKABLY TO RE-RADIATION
Authors: Fumi Higuchi, Takeo Uzuka, Keisuke Ueki
Journal: Neuro-Oncology (2021)

Abstract Oligodendrogliomas with 1p/19q-codeletion are relatively slow progressive tumors that show good response to chemo-radiation therapy after resection. The median survival is about 15 years regardless of WHO grade, although recurrences are mostly inevitable and there is no standard treatment for recurrence. We experienced 5 oligodendroglioma cases who underwent re-radiation for recurrent tumors after chemo-radiation treatment. We retrospectively investigated those for response to re-radiation, the duration from first radiation to second radiation, and Karnofsky Performance Status (KPS) before and after the re-radiation. Patients were all male; the median radiation dose for primary tumor was 60Gy (54-60Gy), the median age at first radiation was 46 years (35-59), the median duration from the first radiation to re-radiation was 65 months (range 18-116 months), and the median follow-up period after re-radiation was 15 months (1-39 months). In all 5 cases, tumors showed good response to re-radiation. In 3 of the 5 cases, tumor recurred in corpus callosum and/or lateral side of cerebral hemisphere or basal ganglia contiguous with primary tumor sites and were radiated by IMRT (50Gy/25fr) . In 2 cases, tumors recurred around the fourth ventricle and posterior fossa and underwent conventional radiation (54Gy/30fr and 30Gy/10fr). In 2 of the 5 cases, the tumors re-recurred 24 months later after re-radiation, but the KPS were maintained until re-recurrence. For oligodendrogliomas, re-radiation therapy appears to be very effective to recurrent tumors after first chemo-radiation. Although evaluation for longer-term side effects is to be examined, re-radiation appears to be a good option for recurrent oligodendrogliomas after first chemo-radiation therapy.
Newly Diagnosed Multiple Myeloma: How Many Drugs Are Enough?
Authors: Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2021)

The treatment of multiple myeloma (MM) has evolved over the past decade, yet it remains a chronic disease. Several trials of 4-drug induction regimens have resulted in deepening of disease response. With the emergence of multidrug regimens, questions have arisen regarding the role of autologous stem cell transplant (ASCT) in MM therapy and available treatment options after ASCT. Clinicians have also continued to improve the efficacy of maintenance therapies. In transplant-ineligible patients, the phases of treatment are less distinct; however, several regimens have demonstrated efficacy in this clinical setting. Future research should focus on individualizing treatment approaches.
Abstract 10245: Egfr Calculation Without the Race Coefficient Obscures Obesity Related Glomerulopathy in Female Adolescents
Authors: Dana Bielopolski, Ohad S Bentur, Neha Singh, Roger D Vaughan, David M Charytan, Rhonda G Kost, Jonathan N Tobin
Journal: Circulation (2021)

Introduction: Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. Hypothesis: We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG). Methods: We created a cohort of women and girls ages 12-21 from the New York Metropolitan area using their longitudinal electronic health records (EHR). Glomerular filtration rate (GFR) was estimated in two ways: I) using the standard age recommended formulae, and II) eGFRr -without a race-specific coefficient. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of ≥135ml/min/1.73m 2 . Results: 7315 Black and 15,102 non-Black women and girls were evaluated for kidney function in parallel to body measures. Hyperfiltration was more frequent in Black compared to non-Black individuals when using standard eGFR but was lower after eliminating the race-specific coefficient. Black race was independently associated with hyperfiltration with standard eGFR calculation (OR=3.43, 95% CI 2.95-3.99) but the association was reversed when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Risk of hyperfiltration was higher for Black individuals across all BMI strata with standard eGFR estimates, but when estimated as eGFRr hyperfiltration risk was reduced for overweight (OR =0.70 95% CI 0.54-0.89) and obese (OR=0.47, 95% CI 0.37-0.60) black participants. Simultaneous removal of the race coefficient and adjustment to individual BSA provided the most accurate estimation of GFR compared to creatinine clearance. Conclusions: Estimated CKD prevalence among Black adolescents and young adults increases following removal of the race coefficient while fewer have evidence of ORG. Removing the race coefficient should be accompanied by adjustment to individual BSA in order to estimate more realistically GFR.
Splicing-Mediated Antigen Escape from Immunotherapy for B-cell Malignancies
Authors: Jessie Bourcier, Omar Abdel-Wahab
Journal: Blood Cancer Discovery (2021)

In this issue of Blood Cancer Discovery, Zheng and colleagues identify that alternative RNA splicing of CD22 within B-cell acute lymphoblastic leukemia can result in antigen escape from CD22-targeted immunotherapies. Drug-resistant isoforms of CD22 exist within leukemic cells pretreatment and can influence response to the CD22-directed antibody-drug conjugate inotuzumab ozogamicin, the immunotoxin moxetumomab pasudotox, as well as anti-CD22 chimeric antigen receptor T cells. See related article by Zheng et al., p. 103 (7).
Abstract 12451: Monocytes Enhance Inflammatory Responses to Soluble Matrilin-2 in Human Aortic Valve Interstitial Cells via the Interaction of β2-integrin With ICAM-1
Authors: Zichao Luo, Peijian Zhang, Qingzhou Yao, Yufeng Zhai, Lihua Ao, Qingchun Zeng, David Fullerton, Xianzhong Meng
Journal: Circulation (2021)

Calcific aortic valve disease (CAVD) is a slow progressive disease. Chronic inflammation plays a crucial role in CAVD progression. Monocyte infiltration and macrophage accumulation are found in cal...
<i>Longitudinal Next Generation Sequencing Reveals the Clonal Hierarchy of IDH Mutated Clones and Impact on Survival in NPM1 Mutated AML</i>
Authors: Curtis Lachowiez, Courtney D. DiNardo, Kiyomi Morita, Ken Furudate, Feng Wang, Tomoyuki Tanaka, Sa A Wang, Tapan M. Kadia, Naval Daver, Nicholas J. Short, Joseph D. Khoury, Keyur Patel, L. Jeffrey Medeiros, Marina Konopleva, Farhad Ravandi, Koichi Takahashi, Sanam Loghavi
Journal: Blood (2021)
Abstract 12959: Clonal Hematopoiesis of Indeterminate Potential Predicts Incident Venous Thromboembolism in the UK Biobank Cohort
Authors: Ozan Dikilitas, Seyedmohammad Saadatagah, Benjamin Satterfield, Iftikhar J Kullo
Journal: Circulation (2021)

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) refers to the formation of genetically distinct subpopulations of blood cells due to somatic mutations. CHIP is associated with a variety of adverse outcomes, including hematological cancers, cardiovascular disease, and death. We sought to investigate the association of CHIP with incident venous thromboembolism (VTE). Methods: We analyzed exome sequence data from 200,628 individuals in the UK Biobank cohort using Mutect2 to identify a prespecified list of somatic mutations in DNMT3A, TET2, and ASXL1, which are known genetic drivers of CHIP. CHIP was defined as harboring a somatic mutation at a variant allele fraction (VAF) ≥10% and individuals with VAF &lt;2% were deemed as non-carriers. VTE was ascertained using verbal interview data and diagnostic/procedural codes and defined as a composite of the following: thrombophlebitis of deep veins of lower limbs, embolism/thrombosis of vena cava, pulmonary embolism, venous thrombectomy of lower limb veins or IVC filter insertion. We implemented a nested case-control design with incidence density sampling to identify incident cases and controls matched (1:8 ratio) for sex, smoking status, and history of malignancy at baseline. Conditional logistic regression analysis adjusted for age, BMI, and genetic ancestry was performed to assess the association between CHIP and incident VTE. Results: Among 200,628 individuals, we identified 3,885 individuals with CHIP at baseline and 748 incident VTE events during a median follow-up of 9.2 years. In 748 incident cases and 5984 matched controls, CHIP was associated with increased risk of incident VTE independent of conventional risk factors for VTE, namely, age, sex, BMI, smoking, and history of malignancy (incidence rate ratio [95% confidence interval]; 1.60 [1.04-2.46], p=0.032). When we restricted the cases to individuals with incident pulmonary embolism (n=441), we observed a stronger association with CHIP (1.80 [1.08-3.05], p=0.025). Conclusions: CHIP is associated with increased risk of VTE independent of history of malignancy and other conventional risk factors. The pathophysiological basis for this association needs further investigation.
Abstract 12780: TBX20 Improves Contractility and Mitochondrial Function During Direct Cardiac Reprogramming From Human Fibroblasts
Authors: Yang Zhou, Yawen Tang, Rui Lu, Jianyi Zhang
Journal: Circulation (2021)

Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). We thus sought to identify potential missing factors for human direct reprogramming. Methods and Results: By comparing the transcriptome differences between human iCMs and functional cardiomyocytes (CMs), we identified T-box transcription factor TBX20 as the top CM gene that is not activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significant activation of contractile proteins, such as αActinin (38.31±2.54% vs 23.30±1.32%, P &lt; 0.0001) and cardiac troponin I (79.65±1.47% vs 48.42±1.88%, P &lt; 0.0001) when compared with MGT133+EV control transduction. Meanwhile, iCMs produced with MGT133+TBX20 more frequently demonstrated beating in co-culture with pluripotent stem cell derived CMs (32.50±4.61% vs 2.29±1.52%, P &lt; 0.0001). Furthermore, addition of TBX20 led to increased mitochondrial amount determined by MitoTracker staining (~3.1 fold, P &lt; 0.0001) and qPCR amplification of mitochondrial genome copy number (~2.9 fold, P &lt; 0.0001). TBX20-transduced iCMs also showed higher mitochondrial respiration, suggesting TBX20 as a potent activator on metabolic maturation of iCMs. Mechanistically, TBX20 directly bound on the enhancers of under-expressed cardiac genes, such as MYBPC3 , MYH7 and KCNH2 , to activate gene expression. We also found that TBX20’s binding on MGT-regulated cardiac loci could further boost activation of contractile genes, such as ACTC1 , SCN5A and MYOM2, for cardiac fate conversion. Conclusions: Our findings demonstrate that TBX20 promotes cardiac cell fate conversion and enhances functional acquisition of iCMs by direct targeting contractility genes.
Abstract 11474: Ti <sub>3</sub> C <sub>2</sub> T <sub>x</sub> MXene Nanosheets for Immunomodulation and Prevention of Allograft Vasculopathy
Authors: Weiang Yan, Alireza Rafieerad, Keshav Narayan Alagarsamy, Abhay Srivastava, Rakesh C Arora, Sanjiv Dhingra
Journal: Circulation (2021)

Allograft vasculopathy is an aggressive form of accelerated atherosclerosis that manifests uniquely in transplanted hearts, lungs and kidneys. Activated blood vessel endothelial cells (ECs) stimulate alloreactive CD4 + and CD8 + T-lymphocytes to result in sustained inflammation. MXenes, an emerging class of transition metal carbides, have recently been shown to have unique immunomodulatory properties that may be leveraged to treat allograft vasculopathy. In this study, we present the synthesis, characterization and application of novel two-dimensional titanium carbide MXene (Ti 3 C 2 T x ) nanosheets for immunomodulation. MXene nanosheets (MNSs) were selectively etched from bulky Ti 3 AlC 2 MAX phase using hydrofluoric acid. The resultant MNSs are 2 to 5 μm in size and are surface modified with carboxyl, hydroxyl and amine functional groups for biological interactions. Using an in vitro co-culture system, we found that MNSs interact with activated human ECs to reduce activation and pro-inflammatory Th1 polarization of allogeneic CD4 + lymphocytes. Mechanistically, we showed that treatment with MNSs significantly decreased expression of the co-stimulatory molecule CD86 and altered the ratio of endothelial surface co-stimulatory to co-inhibitory molecules. Furthermore, when applied in an in vivo rat model of allograft vasculopathy, treatment with MNSs reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted vessel segments. Taken together, these findings suggest that these novel MNSs have potential as an effective treatment to prevent allograft vasculopathy.
Abstract 10288: Reduced Pulmonary Artery Distensibility: A Predictor of Persistent Pulmonary Hypertension and 2-Year Mortality Post-Transcatheter Aortic Valve Replacement in High-Risk Patients with Severe Aortic Stenosis
Authors: Valery Turner, Eva Maret, Juyong B Kim, A Claire C Watkins, William F Fearon, Francois Haddad, Martin J Willemink, Dominik Fleischmann
Journal: Circulation (2021)

Introduction: Persistent pulmonary hypertension (PH) post-TAVR is a better predictor of poor outcome than pre-TAVR PH, possibly due to longstanding vascular damage involving loss of pulmonary artery (PA) elasticity. In this study we sought to evaluate whether PA distensibility (D PA ) measured on pre-procedural ECG-gated CTA is associated with persistent-PH and 2-year mortality after TAVR. Hypothesis: Reduced D PA is a predictor of persistent-PH and mortality post-TAVR. Methods: 336 patients undergoing TAVR between July 2012 and March 2016 were retrospectively included. All patients underwent retrospectively ECG-gated CTA of the chest, with reconstruction of 10 phases over the cardiac cycle (0%- 90% of the R-R interval) prior to TAVR. Patients were followed for all-cause mortality. Main pulmonary artery (MPA) area was measured at 20% (area-MPA 20 ) and 80% (area-MPA 80 ) of the R-R interval. D PA was calculated as follows: [(area-MPA 20 -area-MPA 80 )/area-MPA 20 ]%. Persistent-PH was defined as pre-TAVR RVSP&gt;35mmHg which persisted &gt;35mmHg in post-TAVR echocardiography. 2 groups were compared based on D PA &lt;8% (specificity of 70% for persistent-PH). Kaplan-Meier, Cox proportional-hazard and logistic regression analyses were performed. Results: Median follow-up time was 413 (interquartiles 339-757) days. A total of 68 (20%) patients died within 2 years after TAVR and 183 (54%) had persistent-PH. Those with D PA &lt;8% had significantly more atrial fibrillation (50% vs 35%, p&lt;0.001), 2-year deaths (28% vs 15%, p=0.006) and persistent-PH (67% vs 47%, p&lt;0.001), compared to those with D PA &gt;8%. Multivariable regression analyses adjusted for age, sex, STS-score, cardiac risk, frailty≥2 and NYHA≥III, showed that D PA &lt;8% was independently associated with two-year mortality (HR 2.91 [95%-CI 1.5-5.8], p=0.002) and persistent-PH (OR 2.10 [95%-CI 1.3-4.5], p=0.007). Kaplan-Meier analysis showed that mortality of patients with D PA &lt;8% was significantly higher compared to patients with D PA ≥8% (mortality 28% vs 15%; log-rank p=0.003). Conclusion: D PA on pre-procedural CTA is independently associated with persistent-PH and two-year mortality in patients who undergo TAVR and could be a valuable parameter for risk stratification of TAVR candidates.
Prognosis Value of Measurable Residual Disease By Multiparameter Flow Cytotometry in Patients with Acute Myeloblastic Leukemia Prior to Allogeneic Hematopoietic Cell Transplantation
Authors: Teresa Caballero, Olga Pérez-López, Ana Yeguas Bermejo, Eduardo Rodriguez Arbolí, Enrique Colado Varela, Maria Desamparados Sampere Talens, María Belén Vidriales, Covadonga Quirós Caso, Marta Reinoso Segura, Concepción Prats-Martín, Pau Montesinos, Jose A. Perez-Simon
Journal: Blood (2021)
Abstract 13427: Identification of Patients Who Can Safely Undergo Same Day Discharge Following Atrial Fibrillation Ablation: Lessons Learned in the COVID-19 Era
Authors: Nicolle S Milstein, Matthew T Saberito, Dan L Musat, Advay G Bhatt, Mohammadali Habibi, Mark Preminger, Tina C Sichrovsky, Suneet Mittal
Journal: Circulation (2021)

Background: Historically, pts have been admitted for overnight observation following atrial fibrillation (AF) ablation. The COVID-19 pandemic ushered the need to consider same day discharge (SDD). It remains unclear how to identify pts who can safely undergo SDD. Objective: To evaluate acute (within 4 hrs) and subacute (within 24 hrs) safety of SDD post AF ablation; we also sought to identify predictors of safe discharge. Methods: All pts undergoing AF ablation at our center following the end of the COVID imposed lockdown were enrolled. In each pt, ICE guided single transseptal puncture using the VersaCross® (Baylis) system was performed. Following ablation, protamine was not administered; all femoral venous access sites were closed with Vascade™ (Cardiva Medical) closure devices. Pts ambulated after 2 hrs of bedrest. Pts who had SDD were compared to those who stayed for overnight observation. Results: The cohort included 226 pts (65 ± 10 yrs, 157 [69%] male, 118 [52%] PAF, CHA 2 DS 2 -VASc 2.4 ± 1.7). Cryo PVI was performed in 193 (85%) pts; 34 (15%) pts had a redo procedure. SDD was attempted in 126 pts and successfully accomplished in 115 (91%) pts at 251 + 72 minutes from procedure end. The most common reason for failed SDD attempt was access site oozing necessitating additional bedrest. No SDD pt had a major complication. Overnight observation was performed in 100 (44%) pts, most commonly due to physician/pt preference. Compared to pts who had SDD, these pts were older and more likely to have heart failure and history of TIA/stroke. Oozing within the first 4 hrs was observed at a similar rate to SDD pts. A minor complication was seen in 1 pt each in SDD and overnight stay group between 4 and 24 hrs of ablation (Figure). Conclusions: Our study shows that when attempted, SDD after AF ablation can be accomplished in &gt;90% of pts. Venous access site oozing was the greatest hinderance to pts going home. However, if pts had no issue 4 hrs after AF ablation, they had an uneventful course over the next 24 hrs.
Prevalence of Stroke and Cognitive Impairment in Patients with Hereditary Thrombotic Thrombocytopenic Purpura
Authors: Azra Borogovac, Erika Tarasco, Johanna A. Kremer Hovinga Strebel, Kenneth D. Friedman, Adam S. Asch, Sara K. Vesely, Calin I. Prodan, James N. George
Journal: Blood (2021)