tbuckley/cabot-search huggingface dataset:
Abstract 12362: Association Between GP130 Signaling, Microtubule Regulation, and RV Function in Porcine RV Pressure Overload
Authors: Megan Eklund, Rajat Kalra, Cindy M Martin, Kurt W Prins
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a rare but lethal disease, which results in rightventricle (RV) failure. Unfortunately, there are no available therapies to directly combat RV failure and improvesurvival in PAH. We previously showed antagonism of the GP130 signaling pathway prevents microtubuleremodeling and enhances RV function in rat PAH. However, rodent models does not always recapitulatehuman physiology, which may limit translatability of our finding. Therefore, we examined the relationshipsbetween GP130 activation, microtubule regulation, t-tubule structure, and RV function in porcine RV pressureoverload. Methods: Pulmonary artery banding (PAB) was performed on old Yorskhire piglets and animals wereevaluated 4 weeks after. Immunoblots of RV extracts were probed with GP130, STAT3, phosphorylatedSTAT3, α-tubulin, β-tubulin, and detyrosinated α-tubulin primary antibodies to quantify GP130 activation andmicrotubule remodeling respectively. T-tubule architecture was examined using confocal microscopy. Finally,cardiac MRI quantified RV structure and function. Results: PAB pigs exhibited induction of GP130 signaling with higher levels of GP130, STAT3, andpSTAT3. Additionally, there was evidence of microtubule remodeling with elevated expression of α-, β-, anddetyrosinated α-tubulin. Confocal microscopy revealed t-tubule derangements in PAB pigs. Cardiac MRIshowed PAB pigs had significantly increased RV end systolic volume, reduced RV ejection fraction, andimpaired RV-pulmonary artery coupling. Finally, GP130 and tubulin expression levels were inverselyassociated with RV ejection fraction and RV-pulmonary artery coupling. Conclusion: Increased expression of GP130 and tubulin is associated with lower RV ejection fraction andworse RV-PA coupling. Future studies are needed to determine if GP130 antagonism enhances RV function inporcine RV pressure overload.
Virtual Care Mitigates Pain and Drug Errors After Surgery
Authors: Anita Slomski
Journal: JAMA (2021)

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Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial
Authors: Kazunori Murai, Hiroshi Ureshino, Takashi Kumagai, Hideo Tanaka, Kaichi Nishiwaki, Satoshi Wakita, Koiti Inokuchi, Toshihiro Fukushima, Chikashi Yoshida, Nobuhiko Uoshima, Toru Kiguchi, Masayuki Mita, Jun Aoki, Satoshi Kimura, Kaori Karimata, Kensuke Usuki, Joji Shimono, Yoshiaki Chinen, Junya Kuroda, Yasufumi Matsuda, Kensuke Nakao, Takaaki Ono, Katsumichi Fujimaki, Hirohiko Shibayama, Chisaki Mizumoto, Tomoharu Takeoka, Katsuhiro Io, Takeshi Kondo, Masatomo Miura, Yousuke Minami, Takayuki Ikezoe, Jun Imagawa, Ayako Takamori, Atsushi Kawaguchi, Junichi Sakamoto, Shinya Kimura
Journal: The Lancet Haematology (2021)
RADT-27. EFFECTIVENESS ANALYSIS OF RADIOTHERAPY FOR INTRACRANIAL RECURRENT EPENDYMOMA
Authors: Qingjun Hu, Mingyao Lai, Juan Li, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE There is no standard treatment for recurrent ependymoma. This study aimed to investigated the role of radiotherapy in recurrent ependymoma. METHODS Retrospective analysis was performed on 49 cases of recurrent ependymoma diagnosed in Guangdong Sanjiu Brain Hospital from January 2008 to July 2020. Overall survival (OS) was calculated by Kaplan-Meier method and tested by Log-rank test. P &amp;lt; 0.05 was considered statistically significant. RESULTS The median age was 7 years (range:1-57 yrs). Nineteen patients were with ependymoma WHO grade II while 30 were with grade III, respectively. Recurrence treatment: 14 cases received re-surgery, 23 cases received radiotherapy, among them 16 cases received re-radiotherapy. To May, 2021, the median follow-up time was 35 months (range 3-153). Median PFS time was 17 months after initial diagnosis, median PFS time was 8 months after treatment to recurrence disease, Median OS time is 39 months, and median OS time is 20 months after recurrence. The median survival time for recurrence was 48 months vs. 11 months (P =0.001) in the radiotherapy group vs. non-radiotherapy group,res; Re-radiotherapy combined with chemotherapy vs reradiotherapy alone (0.194); RRT combined with anti-angiogenesis therapy vs. RRT alone (0.688). CONCLUSION Radiotherapy can prolong the survival time of recurrent ependymoma, and concurrent therapy as chemotherapy or anti-angiogenesis therapy with RT does not seem to improve the prognosis. Therefore, radiotherapy can be used as the main treatment for recurrent ependymoma.
Abstract 11605: Analysis of 10-yr MACE Risk of LDL-C ≥160-189 Mg/dL Compared to <160 Mg/dL in Young Adults (ages 20-39) in an Integrated Healthcare System
Authors: Viet T Le, Jeffrey L Anderson, Peter Calderone, Ana C Perez, Stacey Knight, Heidi T May, Benjamin D Horne, Joseph B Muhlestein, Kirk U Knowlton
Journal: Circulation (2021)

Introduction: Adults <40-yrs (20-39) may have elevated cardiovascular risk based on higher LDL-C (e.g., ≥160 mg/dL). We sought to compare the risk of MACE (all-cause death, MI, ischemic stroke, hea...
Novel Mechanisms of Acalabrutinib Resistance in Patients with Chronic Lymphocytic Leukemia By Whole Genome Methylome Sequencing
Authors: Kathleen Burke, Barrett Nuttall, Daniel L. Karl, Megan Callahan, Kerrin Mendler, Steven Criscione, Sergey Naumenko, Elena Bibikova, Andrew Bloecher, Brian Dougherty, J. Carl Barrett, Maurizio Scaltriti, Pablo Cingolani, John C. Byrd, Richard Furman, Jennifer R. Brown, Andrew Mortlock, James Hadfield, Veerendra Munugalavadla
Journal: Blood (2021)
Abstract 10597: Epidural Sympathetic Afferent Blockade by Resiniferatoxin Reverses Vagal Dysfunction Following Myocardial Infarction
Authors: Jonathan D Hoang, Mohammed A Swid, Ki-Woon Kang, Zulfiqar A Lokhandwala, Christopher A Chan, Neil R Jani, Marmar Vaseghi
Journal: Circulation (2021)

Introduction: Myocardial infarction (MI) induces sympathovagal imbalance, predisposing for ventricular tachyarrhythmias (VT). Thoracic epidural anesthesia reduces VT burden through sympathetic blockade. However, it is unknown if sympathetic afferent activation may cause vagal dysfunction, and if blockade of these spinal afferents can improve vagal function and reduce VT burden. Methods: Chronic MI was percutaneously created in Yorkshire pigs (n=8). In terminal experiments 6 to 8 weeks post MI, an epidural catheter was placed at the C7-T1 epidural space. After sternotomy, a 56 electrode sock was placed over the ventricles to record activation recovery intervals (ARI, surrogate of action potential duration). Effective refractory periods (ERP) were assessed via extra-stimulus pacing and left ventricular (LV) pressure monitored via a pressure catheter. Vagal function was assessed by baroreflex sensitivity (BRS) after phenylephrine (3 μg/kg, IV). ARIs, ERP, LV function, and BRS were checked before and after epidural RTX (0.6 μg/kg/ml). VT inducibility was assessed by endocardial extra-stimulus pacing from the right ventricular apex. Results: Epidural RTX led to a modest hemodynamic response peaking at 10.2 ± 4.2 min post-RTX with stabilization by 118 ± 15 min, characterized by increased LV systolic pressure (121±5.6 to 133±9.7 mmHg; p =ns) and contractility (1411±74 to 1514±163 mmHg/s; p =ns). While ARI and atrial/ventricular ERP did not change significantly, BRS was significantly augmented by 2 hrs (2.1±0.6 to 4.3±0.8 ms/mmHg, p &lt;0.01). 9/9 animals in our chronic MI model were inducible for VT by extra-stimulus pacing whereas only 1/6 were inducible for VT after epidural RTX ( p &lt;0.001). Conclusion: Blockade of nociceptive spinal sympathetic afferents by RTX augments reflexive vagal function without altering basal cardiac function. Blockade of nociceptive afferents and restoration of parasympathetic function alone may be sufficient to suppress VT.
Anti-CCR9 CAR-T Cells for T Acute Lymphoblastic Leukemia
Authors: Paul M Maciocia, Patrycja Wawrzyniecka, Nicola C Maciocia, Amy Burley, David O'Connor, Theresa E. Leon, Tanya Rapoz-D'Silva, Thaneswari Karpanasamy, Martin Pule, Marc R. Mansour
Journal: Blood (2021)
Abstract 9996: Clinical Features and Predictors of Non-Cardiac Death in Patients Hospitalized for Acute Myocardial Infarction
Authors: Kohei Wakabayashi, Toshiro Shinke, Satoshi Higuchi, Seita Kondo, Katsumi MIYAUCHI, Hideki Miyachi, Hiroshi Iwata, Ryosuke Ito, Hiroyuki Tanaka, Mike Saji, Masao Yamasaki, Jun Yamashita, Mikio Kishi, Kaito Abe, Takaaki Mase, Kazuyuki Yahagi, Taku Asano, Shun Minatsuki, Yuya Mitsuhashi, Takeshi Yamamoto, Ken Nagao, Morimasa Takayama
Journal: Circulation (2021)

Introduction: Patients with acute myocardial infarction (AMI) commonly have multiple co-morbidities, and some of these patients die in the hospital from causes other than cardiac complication. However, limited information is available on the mode of death in patients with AMI. Therefore, the present study was performed to determine the incidence, clinical characteristics and predictors of in-hospital non-cardiac death in patients with AMI, using Tokyo Cardiovascular Care Unit (CCU) network registry. Methods: Tokyo CCU network registry included 33,780 consecutive patients with AMI admitted to CCU between 2010-2018. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. Results: The incidence of all-cause in-hospital mortality was 7.1% (n = 2382), and the incidence was 16% (n = 381) and 84% (n = 2001) for non-cardiac and cardiac causes, respectively. The primary diseases responsible for non-cardiac deaths are shown in Figure. Old age was associated with in-hospital non-cardiac death, with a 29% increase in the risk per decade [odds 1.29, 95%CI (1.17-1.43), p &lt; 0.001]. AMI onset in hospital [odds 2.78, 95%CI (1.98-3.92), p &lt; 0.001], high grade of Killip class [odds 1.92, 95%CI (1.75-2.11), p &lt; 0.001], no PCI [odds 1.76, 95%CI (1.32-2.34), p &lt; 0.001] and history of maintenance haemodialysis [odds 2.13, 95%CI (1.38-3.30), p = 0.003] were associated with in-hospital non-cardiac death. Conclusions: The incidence of in-hospital non-cardiac death was significant in patients with AMI, accounting for 16% of all in-hospital deaths in the Tokyo CCU network registry. Thus, the prevention and management of non-cardiac complications are vital to reduce acute-phase mortality in patients with AMI, especially those with predictors of in-hospital non-cardiac death.
NCOG-38. PREDICTORS OF COGNITIVE PERFORMANCE IN PATIENTS WITH PRIMARY BRAIN TUMORS: AN ANALYSIS OF BRAIN FITNESS CENTER (BFC) AT WALTER REED NATIONAL MILITARY MEDICAL CENTER
Authors: Ian Robertson, Brett Theeler, Wendy Law, Katherine Sullivan, Maddie Hartman
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Although developed initially for patients with traumatic brain injury (TBI), cognitive rehabilitation training (CRT) has expanded its use to include patients suffering from a variety of neurocognitive disorders including neurologic malignancies. The Brain Fitness Center (BFC) at Walter Reed National Military Medical Center (WRNMMC) is a cognitive rehabilitation clinic that offers computer-based cognitive training programs as an adjunctive rehabilitation resource for a diverse patient population with cognitive complaints. METHODS Using a retrospective analysis of data from the BFC at WRNMMC, our study analyzed forty patients with primary brain tumors who had completed both symptom self-report questionnaires and cognitive assessments at the BFC. Self-report questionnaires included the neurobehavioral symptom inventory (NSI) and headache symptom inventory (HIT-6) while cognitive assessments were done using the Automated Neuropsychological Assessment Metrics (ANAM). Our study examined the relationship between subjective cognitive complaints, headache severity, neuropsychiatric symptoms and objective cognitive performance before and after initial CRT. The influence of high vs low grade tumors was also evaluated. RESULTS Our analysis demonstrated that increased number of affective symptoms, particularly self-reported irritability, were the strongest predictors of baseline, objective cognitive performance (r= -.377, p=0.008). Patient self-reported forgetfulness, but not overall subjective cognitive complaints, was also negatively correlated with objective cognitive performance (r= - 0.353, p= 0.020). A mean difference in objective cognitive performance between high grade and low grade tumors was also found (p=0.003). CONCLUSIONS Our results point to potential patient-level factors which could predict benefit from CRT including self-reported irritability, self-reported forgetfulness, and tumor grade. Further prospective studies will help to examine the true benefit of sustained CRT, and the subset of patients with CNS neoplasms most likely to benefit from this training.
PATH-14. ALPHA CARDIAC ACTIN EXPRESSION IS OBSERVED IN AGGRESSIVE GLIOMA SUBTYPES AND GLIOBLASTOMA STEM CELLS
Authors: Rahul Suresh, Sophie Fiola, Jamie Beaulieu, Roberto Diaz
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Alterations in actin subunit expression have previously been observed in multiple cancers. In glioblastoma (GBM), the expression of ACTC1 has been associated with a more invasive phenotype and with shorter survival. We sought to explore the diversity of actin subunit expression across glioma subtypes and patient derived glioblastoma stem cells (GSCs). METHODS Bioinformatic analysis of multiple glioma databases was performed to profile actin subunit (ACTA1, ACTA2, ACTC1, ACTG1, ACTG2, and ACTB) mRNA levels. Expression levels were also evaluated in normal brain in comparison to liver and heart tissue. Western blot was used to analyze protein expression in GSCs, surgical tissue and human fetal astrocytes. RESULTS The primary actin subunits expressed in normal brain are beta actin (ACTB) and gamma actin (ACTG1). RNA sequencing of tissue from multiple glioma subtypes or different brain regions reveals a global increase in ACTG1 and ACTB abundance in gliomas compared to normal brain. LGG-GCIMP high and LGG-co-deleted glioma subtypes have the lowest ACTC1 expression. LGG-GCIMP low (HR 9.75, P&amp;lt; 0.001), LGG-mesenchymal-like (HR11.1, P&amp;lt; 0.001), LGG-classic-like (HR10.96, P&amp;lt; 0.001) subtypes are associated with ACTC1 expression. ACTC1, ACTCB, and ACTG protein expression was observed in GSCs, freshly resected GBM tissue, and human fetal astrocytes. CONCLUSIONS Gliomas have a specific pattern of actin subunit expression that differs in actin subunit type and abundance when compared to normal adult brain. Expression of ACTC1 is found in aggressive glioma subtypes and is shared by GSCs and human fetal astrocytes. Investigation into the neurodevelopmental role of ACTC1 and its contribution to oncogenic transformation in GBM is warranted.
Abstract 12826: Genetic Variation in <i>SLC5A2</i> Mimicking SGLT2-Inhibition Lowers Risk of Cardiovascular Disease and All-Cause Mortality
Authors: Louise E Bechmann, Frida Emanuelsson, Borge G Nordestgaard, Marianne Benn
Journal: Circulation (2021)

Background: Treatment with sodium-glucose co-transporter 2 (SGLT2)-inhibitors reduces risk of hospitalization for heart failure and all-cause mortality, but the mechanisms are unclear. Hypothesis: We hypothesized that a functional genetic variant in SLC5A2 , encoding SGLT2, mimics pharmacological SGLT2-inhibition on risk of cardiovascular disease and all-cause mortality. Methods: 112,745 individuals from two similar studies of the Danish general population were included and genotyped for a common variant causing familial renal glucosuria, rs61742739 (c.1961A&gt;G; p.Asn654Ser) in SLC5A2 . This variant was examined for association with risk of heart failure (N=6,260), myocardial infarction (N=5,778), ischemic heart disease (N=12,504), and all-cause mortality (N=16,410) during a median of 42 years of follow-up, and for potential mediators of these associations related to glycemic control, body mass, blood pressure, circulating blood volume, and lipids. Results: The rs61742739 variant lowered risk of heart failure by 31%, myocardial infarction by 21%, ischemic heart disease by 16%, and all-cause mortality by 22%, and was associated with lower plasma glucose and lipoprotein(a). Lower plasma glucose mediated 4.2% (95%CI:1.3-10.2%; p=0.01) of the effect of genotype on risk of heart failure, 5.3% (1.5-21.2; p=0.02) on risk of myocardial infarction, 7.5% (2.2-25.1; p=0.01) on risk of ischemic heart disease, and 10.5% (3.0-26.8; p&lt;0.01) of the effect on risk of all-cause mortality. Similar estimates for lipoprotein(a) lacked statistical significance. Conclusion: A functional genetic variant in SLC5A2 , encoding SGLT2, is causally associated with a 31% lower risk of heart failure, a 21% lower risk of myocardial infarction, a 16% lower risk of ischemic heart disease, and a 22% lower risk of all-cause mortality. These effects were partly mediated through lower plasma glucose.
Abstract 13953: A Quality Improvement Initiative Increasing Early Discharges for Cardiovascular Surgery and Cardiology Patients on the Acute Care Cardiology Unit Was Associated With Reduced Hospital Length of Stay
Authors: Jessica H Colyer, Lisa Ring, Sarah Gallagher, Mary Mullenholz, Jan Robison, Kathleen M Rigney-Radford, Ashraf S Harahsheh
Journal: Circulation (2021)

Introduction: The discharge process in the acute care setting is a complex process composed of many parallel and sequential steps. Safe and timely discharges improve patient throughput. Early discharges off-load full ICUs and improve transitions to the outpatient setting. Review of our data demonstrated the majority of discharges occurred later in the day. We set out to improve our discharge times for cardiology and cardiovascular surgery (CVS) patients on our 26-bed inpatient acute care cardiology unit (ACCU) Hypothesis: Smart Aim: Increase the number of discharges between 6 am and 12 pm for cardiology and CVS patients on ACCU from 5 to 10 patients per month over 12 months and to sustain. Methods: We performed a Failure Mode Analysis to highlight the steps of the discharge process and identify opportunities for improvement. Our key drivers centered around education, documentation, and planning. Our interventions included: education of front-line staff, communication of discharge expectations, daily quality board rounds, hospital-wide collaboration emphasizing conditional discharges, and hospital IT improvements. Statistical process control charts were utilized to analyze the data. Results: The number of discharges between 6am and 12 pm more than doubled from a baseline of 5 (8%) to 12 (18%) patients per month with a centerline shift. As part of our process measures, appropriate conditional discharge usage linked to earlier discharges. Upgrades to our EMR discharge system further increased our timely discharges. Our efforts resulted in 22% reduction of hospital length of stay from 11.1 to 8.7 days without an increase in readmission rates suggesting that improved efficiency did not impact care quality. Conclusions: We successfully show how multidisciplinary collaboration and systems-based improvement can increase the number of safe, early discharges.
IMMU-26. SAFETY AND EFFICACY OF PVSRIPO IN RECURRENT GLIOBLASTOMA: LONG-TERM FOLLOW-UP AND INITIAL MULTICENTER RESULTS
Authors: Annick Desjardins, Matthias Gromeier, Henry Friedman, Daniel Landi, Allan Friedman, David M Ashley, William Curry, Nicholas Butowski, Andrew Sloan, Patrick Wen, Robert Cavaliere, Elizabeth Gerstner, Mitchel Berger, Robin Buerki, E Antonio Chiocca, Eric Sauvageau, Andrea Kelly, W Garrett Nichols, Lori Mixson, Adam Dickinson, Kristin Orr, Chris Learn, Darell Bigner
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Recurrent glioblastoma (rGBM) is rapidly fatal (median overall survival [mOS] of ~9 months; OS at 12 months [OS12] &amp;lt; 35%) with approved therapies (lomustine±bevacizumab). PVSRIPO is an intratumoral immunotherapy targeting CD155 on antigen-presenting and malignant cells of solid tumors. Preclinically, PVSRIPO delivers a systemic, tumor antigen-specific, polyfunctional T-cell mediated anti-tumor response. Interim, single-center, phase (Ph) 1 results showed greater long-term survival with PVSRIPO vs. criteria-matched external control rGBM patients (Desjardins 2018). Updates to Ph1 safety (at the Ph2 dose) and efficacy and interim multicenter (Ph2) results are presented. METHODS Adults with histologically-confirmed rGBM, Karnofsky performance status ≥ 70, and an active, supratentorial, contrast-enhancing lesion (1-5.5cm) received PVSRIPO (5x107 TCID50) intratumorally via convection-enhanced delivery on Day 1, with a planned follow-up of 24 months. Safety (treatment-emergent adverse events [TEAEs]), efficacy (reported as OS12, OS24, mOS), and blood/tissue were assessed. RESULTS 149 patients (&amp;gt;90% with 1-2 prior progressions, including failure of SOC and patients with prior bevacizumab failure) received the Ph2 dose of PVSRIPO (n=30 received other doses in Ph1 with safety summarized previously). Follow-up durations for surviving patients were 51-74 months (Ph1) and 10-44 months (Ph2). No dose-limiting toxicities occurred; up to 97% of patients experienced mostly grade 1-2 related TEAEs; ≤ 23% patients experienced grade ≥ 3 related events. Neurologic symptoms related to peritumoral edema were most common ( &amp;gt; 90% patients) and were effectively managed with low-dose bevacizumab/corticosteroids. Survival estimates were: OS12: 54%, 50%; OS24: 18%, 17%; mOS: 12.3 (95% CI 10,15.3), 12 (10.6,13.7) months, for the Ph1 and Ph2 trials, respectively. Baseline correlates of longer survival included smaller lesions and methylated MGMT-promoter status. CONCLUSIONS The multicenter/Ph2 study replicated the single-center/Ph1 results. Relative to published data with approved therapies, PVSRIPO was associated with greater long-term survival and mOS in patients with rGBM and was generally well-tolerated.