tbuckley/cabot-search huggingface dataset:
Abstract 14318: Sex Differences in Treatment Responses to NP-6A4, a Cardiomyopathy Drug With the FDA Designation, in Heart Disease Induced by Untreated Obesity
Authors: Lakshmi Pulakat, Abuzar Mahmood, Anthony Belenchia, Madhavi Gavini, PIe Liu, Brian Mooney, Yinian Tang, Alexander Mehm, Vincent G Demarco
Journal: Circulation (2021)

Introduction: Obesity affects 42% of the US population and exacerbates heart disease. Currently there are no effective treatments for obesity-induced cardiac pathology. We reported that NP-6A4, a peptide agonist of the Angiotensin receptor AT2R mitigates cardiac dysfunction and damage in male rats with untreated obesity. Since cardiac pathology of male and female rats with untreated obesity differ, we hypothesized that there can be differences in their cardiac response to NP-6A4. Methods and Results: Echocardiographic analysis was performed in 15-week old male and female healthy Wistar (N=8) or Zucker lean (N=7) rats treated with saline, and obese and pre-diabetic Zucker rats treated with saline or NP-6A4 (1.8-10mg/kg/day in saline) for four weeks (N=8/group for females, N=7/group for males; subcutaneous delivery). Compared to healthy males, obese males showed significant (P&lt;0.05) reduction in heart rate and increase in anterior wall thickness and left ventricular (LV) filling pressure (E/E’) suggesting concentric hypertrophy. Compared to healthy females, obese females showed significant (P&lt;0.05) reduction in relative wall thickness, heart rate, and ejection fraction (although preserved) and increase in LV internal diameter at both diastole and systole indicating eccentric hypertrophy. NP-6A4 treatment suppressed the pathologic changes in both obese males and females (P&lt;0.05). In another cohort of obese female rats NP-6A4 treatment from 13-to 17-weeks significantly (P&lt;0.05) reduced abnormal E/A ratio and isovolumic contraction and relaxation time, and improved myocardial radial strain. Treatment with AT2R antagonist PD123319 (N=8: 5mg/kg/day delivered subcutaneously) abolished NP-6A4 effects. Cardiac proteome analysis of 18 tissue samples from this cohort using data independent acquisition (DIA) resulted in a total proteome of 4520 proteins and 296 differentially expressed proteins that were significant (P&lt;0.01). Ingenuity pathway analysis predicted that inhibition of NP-6A4-mediated signaling by PD123319 may increase infection of cells (P=&lt;0.001). Conclusion: NP-6A4 attenuated cardiac pathology induced by untreated obesity by altering different cardiac parameters in male and female rats.
Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome
Authors: Kasey J Chaszczewski, Sarah Perelman, Christine B Falkensammer, Nahla Khalek, Chengcheng Pang, Zhiyun Tian, Jack Rychik
Journal: Circulation (2021)

Background: Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden. Methods: Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests. Results: SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS &gt; 6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy. Conclusions: Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.
Abstract 12214: Characterization of Iatrogenic Left Bundle Branch Block After Septal Myectomy for Hypertrophic Cardiomyopathy
Authors: William Gionfriddo, William Gionfriddo, Austin Burrows, Chockalingam Narayanan, Srijan Shrestha, Hassan Rastegar, Ann Garlitski, Jonathan Weinstock, Munther Homoud, Ethan J Rowin, Martin S Maron, Barry Maron, Christopher Madias
Journal: Circulation (2021)

Introduction: LBBB results in impaired transseptal conduction and delayed posterolateral LV activation. Criteria for left bundle branch block (LBBB) vary across scientific organizations. Septal myectomy for hypertrophic cardiomyopathy (HCM) could serve as an iatrogenic anatomic model to characterize LBBB. Objective: To describe ECG features of LBBB after septal myectomy for HCM. Methods: ECG data were analyzed for 377 HCM patients (204 male) who developed post-operative LBBB after extended septal myectomy between 2004-2018. Results: Average age of the cohort at myectomy was 53 ± 14 years. Baseline QRS duration (QRSd) was 94 ± 10ms. The post myectomy QRSd was 152 ± 15ms, consistent with an average ΔQRSd of 58 ± 13ms. There was positive correlation between pre and post myectomy QRSd (r = 0.485; p &lt; 0.0001). The average LV end-diastolic diameter (LVEDd) pre and 2 months post myectomy was 40 ± 5.6mm and 46.2 ± 6.5mm, respectively. Positive correlation between post myectomy QRSd and post myectomy LVEDd was also observed (r = 0.340; p &lt; 0.0001). Females and males had pre myectomy QRSd of 93 ± 10ms and 95 ± 10ms respectively (p = 0.007) and post myectomy QRSd of 147 ± 13ms (120-184ms) and 157 ± 14ms (126-209ms) respectively (p &lt; 0.0001). ΔQRSd was less in females than males (54 ± 13ms vs. 62 ± 11ms; p&lt;0.0001). Only 13 females and 3 males had post myectomy QRSd &lt; 130ms. Only 23 males had QRSd &lt; 140ms. Conclusions: Surgical myectomy serves as a model to characterize LBBB. Following myectomy, QRSd correlated with LVEDd as well as pre-myectomy QRSd, and was longer in males due to delayed depolarization of larger hearts in men. Notably only 3 males and a minority of females had QRSd &lt; 130ms. These data provide important insights for the validation of electrocardiographic LBBB criteria.
CTNI-31. RESECTION AND SURGICALLY TARGETED RADIATION THERAPY FOR TREATMENT OF LOCALLY RECURRENT GBM IN 28 PROSPECTIVELY TREATED PATIENTS
Authors: Kris Smith, Peter Nakaji, Theresa Thomas, Dilini Pinnaduwage, Garrick Wallstrom, David Brachman
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Recurrent GBM is a diffuse disease and resection (R) alone does not routinely provide durable local control (LC) or prolonged overall survival (OS). We hypothesized R plus immediate radiation (RT) utilizing a novel brachytherapy device might achieve more durable LC and thereby secondarily improve OS. METHODS From 2/2013-2/2018, locally recurrent GBM were treated in a single arm trial (ClinicalTrials.gov, NCT#03088579) of R plus immediate implantation of a surgically targeted radiation therapy (STaRT) device utilizing Cs-131 in bioresorbable collagen tiles (GammaTile, GT Medical Technologies, Tempe AZ USA). RESULTS 28 patients (pts) were treated, 20 at first recurrence (range 1-3). Median age 58 (range 21-80), KPS 80 (60-100), female:male ratio 10:18. Median OS was 10.7 mo., radiographic LC 8.8 mo., and no first failure was local. MGMT, KPS, and sex were non-predictive. Post hoc analysis disclosed after R+STaRT, 17 pts (54%) received &amp;gt; 1 cycle of Sys (“Sys+”) and 13 (46%) did not (“Sys- “). Sys was given as adjuvant, salvage, or both, either alone or in combination. 15 pts received bevacizumab (BEV), 12 temozolomide (TMZ) and 8 lomustine (CCNU). Median OS (mo.) for Sys+ vs. Sys- was 15.1/6.5 (hazard ratio (HR) .38, p=.017); OS for BEV+ vs. BEV- was 16.7/4.5 (HR .38, p=.017), TMZ+ vs. TMZ- 17.5/6.7 (HR .40, p=.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, p=.25), respectively. LC was 11.4 mo. for Sys+ vs. 2.1 mo. for Sys- (HR .44; p=.16). Three attributed AE occurred, 1 wound infection requiring surgery and 2 radiation brain effects, managed medically. CONCLUSION Post hoc analysis suggests R+STaRT+Sys may have the potential to impact OS in locally recurrent GBM, possibly by allowing sufficient time for effective but biologically slower treatments to have an impact. FDA clearance was received in 2018 for recurrent intracranial neoplasms and in 2020 for newly-diagnosed malignant brain tumors.
Predicting Out-of-office Blood Pressure in United States Adults
Authors: B K Bellows, J Xu, J P Sheppard, J E Schwartz, D Shimbo, P Muntner, R McManus, A E Moran, K B Bryant, L P Cohen, A P Bress, J B King, J M Shikany, B Green, Y Yano, D Clark, Y Zhang
Journal: Circulation (2020)
Abstract 14250: Innovative Model-Based Algorithm for Non-Invasive Estimation of Pressure-Volume Loops in Patients With Cardiogenic Shock
Authors: Stefania Sacchi, Antonella Sabatini, ANGELA VENUTI, elena cinel, Bianca Gattari, Luca Baldetti, Francesco Calvo, Mario Gramegna, Vittorio Pazzanese, Alberto Maria Cappelletti
Journal: Circulation (2021)

Introduction: Cardiogenic shock (CS) pathophysiology may be well explained through the left ventricular pressure-volume (PV) loops. Hypothesis: We developed an innovative model-based algorithm to derive non-invasive left ventricular PV loops and we assessed its ability to provide information in CS patients. Methods: We conceived and implemented a simple, intuitive and practical model-based algorithm for the non-invasive left ventricular PV loop diagram visualization and analysis. This model is based on the quantitative numerical calculation of the product of two time-varying curves, namely the LV volume V(t) multiplied by the time varying LV elastance function, in order to obtain the time varying LV pressure curve, according to the well-known relation: P(t) = E(t) * V(t) [formula F1] [Seeman et al. 2019]. The algorithm works as follows: 1) Input parameters: HR, EDV, ESV, Estimated LV elastance value for healthy (control) and for pathologic subjects. 2) Picked qualitative illustrations exhibiting time-varying dynamics of:a. Normal LV Elastance b. Normal LV Volume 3) Digitized, appropriately scaled, and adapted to input, curves in step (2).4) P(t) obtained by applying formula (F1) in Excel spreadsheet.5) Construction of the PV Loop diagram in Excel spreadsheet. Results: To test the algorithm, non-invasive input parameters were collected in a patient with CS due to acute myocarditis and in a normal subject. In the CS patient, HR, ESV, EDV were 83bpm, 228 ml and 200 ml, respectively; while in the normal subject, they resulted as 86 bpm, 110 ml, and 45 ml, respectively. In the CS patient, the non-invasive derived PV diagram was significantly different from that assessed in the control subject and exhibited an abrupt reduction of ventricular contractility. Conclusions: This novel model-based algorithm provides reliable non-invasive left ventricular PV diagrams in CS patients.
Disparity Analysis and Prognostic Value of Pretreatment Whole Blood Epstein-Barr Virus DNA Load and EBER Status in Lymphomas: A Retrospective Multicenter Study in Huaihai Lymphoma Working Group
Authors: Ziyuan Shen, Lingling Hu, Jianlin Qiao, Linyan Xu, Kailin Xu, Hao Zhang, Wei Sang
Journal: Blood (2021)
TMOD-22. DIFFERENTIAL DRUG SENSITIVITY ANALYSIS IN PAIRED PATIENT-DERIVED CELL LINES OF GLIOBLASTOMA
Authors: Dena Panovska, Aniket Shetty, Marleen Derweduwe, Annelies Claeys, Marine Van der Voordt, Tina Smets, Matthias Versele, Giovanni Monaco, Bart De Moor, Patrick Chaltin, Paul Clement, Keith Ligon, Steven De Vleeschouwer, Raf Sciot, Jon Pey, Asier Antoranz, Frederik De Smet
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) remains the most aggressive adult brain tumour with dismal prognosis. Even when treated by the most optimal standard-of-care modalities, disease progression remains consistently inevitable. Understanding how tumours evolve from a newly diagnosed to a recurrent setting is therefore critical, but research models to functionally test how therapeutic interventions evolve accordingly remain scarce. Here, we describe our efforts to develop paired models including newly diagnosed and recurrent GBM cell lines derived from the same patients. Overall, we collected 50 tumour samples originating from 24 patients at different time points in their treatment scheme. This resulted in the generation of 27 models overall, from which 18 originated from 9 patients at different timepoints. The latter were subsequently investigated extensively. First, using genomic profiling, we consistently observed an increase in mutational burden and chromosomal aberrations in the recurrent samples, while transcriptomic profiling showed that tumour subtypes evolved in a very patient-specific way. A large fraction of the recurrent models showed resistance to temozolomide (TMZ), which coincided with a downregulation of DNA repair (MMR) pathways or mutations. Half of the tested models also acquired resistance to radiation therapy. Next to standard-of-care therapy, we investigated several small molecule inhibitors that are currently in clinical evaluation, which also showed differential sensitivity. Overall, the developed paired cell lines recapitulate the most important features related to tumour recurrence, and offer the opportunity for more elaborate dependency screening efforts.
Assessment of 4 Doses of SARS-CoV-2 Messenger RNA–Based Vaccine in Recipients of a Solid Organ Transplant
Authors: Nassim Kamar, Florence Abravanel, Olivier Marion, Raphaelle Romieu-Mourez, Chloé Couat, Arnaud Del Bello, Jacques Izopet
Journal: JAMA Network Open (2021)

This case series study assesses whether a fourth dose of a SARS-CoV-2 messenger RNA (mRNA)–based vaccine is associated with improved anti–SARS-CoV-2 antibody response in solid organ transplant recipients in France.
QOLP-24. COMBATING EMOTIONAL DISTRESS AND SOCIAL ISOLATION IN PEDIATRIC BRAIN TUMOR FAMILIES: A CASE STUDY OF A NATIONAL NONPROFIT’S IMPLEMENTATION OF A PEER INTERVENTION TO IMPROVE QUALITY OF LIFE
Authors: Kathy Riley
Journal: Neuro-Oncology (2021)

Abstract Interpersonal and emotional support issues present some of the deepest and most pervasive challenges for patients and families. In the Pediatric Brain Tumor Foundation’s 2018 Community Health Needs Assessment report (n=900), family survey respondents cited patient anxiety and depression as the greatest challenge patients face in nearly one in three cases, with isolation lagging not far behind. Beyond patients, interpersonal and emotional issues represent the dominant category of challenges for families as well. Many parents stated they felt guilty thinking about their problems, as the patient’s suffering far exceeded their own, and nearly half reported often neglecting their own well-being at considerable personal cost. To combat these interpersonal and emotional support issues, the Pediatric Brain Tumor Foundation launched a national intervention in 2020 titled the Peer to Peer Mentoring Program. The program matches patients or family members with trained mentor volunteers who have experience facing the challenges that come with a pediatric brain tumor diagnosis. The theoretical framework used to design the intervention is the Social Support theory. This theory is based on the work of House (1981) who defines social support as the functional content of relationships and categorizes four broad types of supportive behaviors: emotional support, instrumental support, informational support and appraisal support (Glanz, Rimer &amp; Viswanath, 2008). The case study explores the technology platform employed to track matches; how matches are made; how mentors are recruited and trained; how mentees are recruited; and how mental health support is provided to mentors. Analysis of peer meeting logs elucidates key themes that emerge in peer encounters as well as key program challenges and how they are being overcome. This theoretical and practical presentation will define the interpersonal and emotional support issues families face, describe the peer intervention’s goals and objectives, and report on insights gained and outcomes achieved.
Abstract 11451: Use of Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from the PROGRESS-CTO Registry
Authors: Judit Karacsonyi, Karen Deffenbacher, Keith H Benzuly, James D Flaherty, Khaldoon Alaswad, Farouc A Jaffer, Paul Poomipanit, Jaikirshan Khatri, Mitul Patel, Robert Riley, Abdul Sheikh, Jason R Wollmuth, Ethan Korngold, Barry F Uretsky, Robert W Yeh, Raj H Chandwaney, R M Wyman, Srinivasa Potluri, Anthony Doing, Ahmed M Elguindy, Khalid Tammam, Nidal Abi Rafeh, Christian Schmidt, Evangelia Vemmou, Ilias Nikolakopoulos, Spyridon Kostantinis, Iosif Xenogiannis, Bavana V Rangan, Imre Ungi, Emmanouil S Brilakis, Daniel R Schimmel
Journal: Circulation (2021)

Introduction: The use of mechanical circulatory support (MCS) in complex percutaneous coronary intervention (PCI) is the subject of ongoing investigation, but the role of MCS in chronic total occlusion (CTO) PCI is not well studied. Methods: We analyzed the patient and angiographic characteristics and procedural outcomes of 7,171 CTO PCIs performed between 2012 and June 2021 at 35 international centers. Results: Mean patient age was 64.5±10 years, mean left ventricular ejection fraction was 50 ± 13 % and 82% were men. MCS was used in 4.5% of the overall cases, MCS use was elective in 78.7% and urgent in 21.3%. The most common type of MCS was Impella CP (55.5%) followed by intra-aortic balloon pump (14.8%), Tandem Heart (10.0%) and Impella 2.5 (8.7%). Diabetes mellitus (51.0% vs. 42.4%, p=0.003), prior congestive heart failure (60.6% vs. 27.9%, p&lt;0.001) and prior myocardial infarction (52.3% vs. 45.3%, p=0.020) were more common in MCS patients. Left ventricular ejection fraction was lower in the patients with MCS use compared to patients without (Mean±standard deviation, 51.0 ± 12 vs. 34.0 ± 15 %, p&lt;0.001). Cases in which MCS was used were more complex with higher J-CTO score compared with cases without MCS (2.94 ± 1.19 vs. 2.39 ± 1.27, p&lt;0.001). Cases performed with MCS had lower technical (81.6% vs. 86.7%, p=0.011) and procedural (71.3% vs. 85.6%, p&lt;0.001) success rates with higher rates of periprocedural major cardiac adverse events compared to no MCS use (12.6% vs. 1.68%, p&lt;0.001). Conclusions: In a contemporary, multicenter registry MCS was used in 4.5% of CTO PCI. Cases where MCS was used were associated with lower technical and procedural success with higher periprocedural major complication rates. Further investigation is required to see if elective use of MCS can improve outcomes in patients with increased comorbidities and higher lesion complexity.
Some ways to tackle overprescribing
Authors: Peter Selley, Roger Stephenson
Journal: BMJ (2021)

Mir and colleagues suggest that £2m is wasted annually on unnecessary and potentially harmful prescriptions.1 Recent studies show that a third of people over 80 in England take eight or more drugs2 and that 11.5 million adults in England were prescribed one or more addictive drugs in 2017-18.3 While prescribing increases, life expectancy in deprived areas falls.4

Twenty …
Abstract 12513: Post-GWAS Functional Analysis of the CDKN2A/B Locus Identifies CUX1 as a Regulator of Endothelial Senescence by Modulating the CAD-Associated p16 <sup>INK4A</sup> Expression
Authors: Gang Li
Journal: Circulation (2021)

Introduction: Genome-wide association studies (GWAS) have validated a strong association of the CDKN2A/B locus with more than 10 different age-related diseases including atherosclerosis and its complications. Hypothesis: The CDKN2A/B locus is one of the most complicated genetic loci that harbors p16INK4a, one of the markers for cellular senescence. As a single locus associates with multiple different age-related diseases, this region may contribute to the progression of these diseases by promoting aging itself, perhaps through modulating cellular senescence. Methods: By coupling regulatory element-sequencing (Reel-seq) with SNP-specific DNA competition pulldown-mass spectrometry (SDCP-MS), two techniques recently developed in our lab, the disease-associated functional SNPs (fSNP) on the CDKN2A/B locus and the fSNP binding proteins were identified. The mechanism underlying the contribution of an atherosclerosis-associated fSNP rs1537371 to the pathogenesis of, and the susceptibility to atherosclerosis was revealed by contemporary techniques. Results: We demonstrate that the homeodomain transcription factor CUX1 specifically binds to the atherosclerosis-associated fSNP rs1537371 within the CDKN2A/B locus. Although it binds at a considerable distance (&gt; 100 kb), CUX1 is shown to regulate the CDKN2A/B encoded genes p14 ARF , p16 INK4A , p15 INK4B and ANRIL in endothelial cells (ECs). In-depth analysis demonstrates that endothelial CUX1 expression correlates with telomeric length and is induced by both DNA-damaging agents and oxidative stress. Moreover, induction of CUX1 expression triggers both replicative and stress-induced premature senescence via activating p16 INK4A expression. Consistent with these findings, we also detect elevated expression of CUX1 and p16 INK4A in the plaques of patients with carotid artery disease. Conclusions: CUX1 is a transcriptional regulator of p16 INK4A expression. It regulates p16 INK4A -dependent endothelial senescence via binding to the atherosclerosis-associated fSNP rs1537371.
A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury
Authors: He Shen, Bai Xu, Chao Yang, Weiwei Xue, Zhifeng You, Xianming Wu, Dezun Ma, Dan Shao, Kam Leong, Jianwu Dai
Journal: Biomaterials (2021)