tbuckley/cabot-search huggingface dataset:
NCMP-11. SPINAL CORD INFARCT AFTER CAR-T TREATMENT
Authors: rusha Shah, Vyshak Venur, Tresa McGranahan
Journal: Neuro-Oncology (2021)

Abstract Cortical and subcortical neurotoxicity from CAR-T therapy is a well described complication in literature, with over 40% of patients experiencing at least one neurologic side effect. However, spinal cord toxicity from CAR-T therapy is less well described. To our knowledge, this is the first reported case of a spinal cord infarct following CAR-T therapy. A 44 year old male with primary refractory DLBCL without CNS involvement, which was refractory to R-CHOP, R-ICE, and hyperCVAD part B underwent CD-19 CAR-T treatment. The day after infusion he developed grade 1 cytokine release syndrome (CRS) with fever and up trending inflammatory markers. Infectious work up was negative and he was treated with tocilizumab and dexamethasone. His fever resolved and markers down trended. On day 5 post CAR-T, he became encephalopathic, developed severe back pain, and was unable to move his bilateral lower extremities. He was treated with 2nd and 3rd doses of tocilizumab, dexamethasone and was started on anakinra. Patient’s mental status cleared by day 7 and he was found to have a dermatome sensory level at T10 with flaccid bilateral lower extremity paralysis. MRI Brain was unremarkable, but a spinal MRI showed longitudinally extensive cord edema and diffusion restriction at T10. Due to an initial question of transverse myelitis, he was treated with a 3-day course of IV methylprednisolone, with no improvement in symptoms. CSF studies were unable to be obtained due to his thrombocytopenia. Repeat MRI obtained 10 days after initial imaging showed resolution of cord edema, but continued areas of FLAIR hyperintensity at T10 through the conus. Despite aggressive rehabilitation services, four months later, patient remained paralyzed in his lower extremities with an indwelling foley catheter. He remains in a complete remission.
제3차 대한간학회 춘계학술대회 초록집 : 간암세포에서 p53-유전자와 Retinoid 유도 아포토시스
Authors: 김대곤 ( Kim Dae Gon ), 이승옥 ( Lee Seung Og ), 김현철 ( Kim Hyeon Cheol ), 안득수 ( An Deug Su )
Journal: Clinical and Molecular Hepatology (1997)
Abstract 10291: Electrocardiographic Markers of Subclinical Myocardial Dysfunction in Patients with Severe Obesity and Normal Ejection Fraction. The FatWest Study
Authors: Lisa M Grymyr, Eva Gerdts, Saied Nadirpour, Peter Schuster, Bjørn G Nedrebø, Dana Cramariuc
Journal: Circulation (2021)

Introduction: Patients with severe obesity are predisposed to left ventricular (LV) myocardial dysfunction and increased myocardial oxygen (O 2 ) demand despite preserved ejection fraction (EF). Hypothesis: To test whether electrocardiography (ECG) may be used to identify patients with severe obesity that have myocardial dysfunction despite normal EF by echocardiography. Methods: In the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study, 116 severely obese patients (41±11 years, 75% women, body mass index [BMI] 41.7±4.6 kg/m 2 , 57% with hypertension, EF 61±5%) underwent 12-lead ECG and echocardiography before a Roux-en-Y gastric bypass surgery. Low LV mechanics was defined as global longitudinal strain (GLS) below the median, and high myocardial O 2 demand as LV mass-wall stress-heart rate product above the median value. ECG markers of atrial (P axis and duration) and ventricular (QRS axis and duration, T axis, QRS-T angle, time to intrinsicoid deflection (ID), and corrected QT (QTc)) de- and repolarization were analyzed. Results: Median GLS was -15.5%, and median myocardial O 2 demand 1.47 x106 g kdyne/cm 2 bpm. Patients with low GLS had longer QRS, time to ID and QTc duration, while those with high myocardial O 2 demand had increased P axis and duration (all p&lt;0.05). In multivariate regression analyses, longer QTc was associated with lower GLS (R 2 0.24) and increased P axis with higher myocardial O 2 demand (R 2 0.21) independent of age, gender, BMI and hypertension (all p&lt;0.05). A QTc &gt;435ms and P axis &gt;42° had 70% specificity in detecting low GLS and high myocardial O 2 demand (Figure). Conclusion: In severely obese patients, ECG measures of atrial activation and delayed ventricular repolarization were independently associated with low LV myocardial function and high myocardial O 2 demand. ECG screening before bariatric surgery may identify patients in whom advanced echocardiography is warranted.
Sirtuin 3 Inhibition Targets AML Stem Cells through Perturbation of Fatty Acid Oxidation
Authors: Cristiana O'Brien, Jacob Berman, Rachel Culp-Hill, Julie Reisz, Tianyi Ling, Vincent Rondeau, Meng Li, Min Yang, Jun Young Hong, Hening Lin, Ari Melnick, Andrea Arruda, Mark D. Minden, Angelo D'Alessandro, Courtney L Jones
Journal: Blood (2021)
Dissecting the Adaptive Response to Arginine Deprivation in Hodgkin Lymphoma
Authors: Fabrizio Puglisi, Antonella Padella, Nunziatina Laura Parrinello, Grazia Scandura, Daniela Cambria, Enrico La Spina, Alessandro Barbato, Cesarina Giallongo, Daniele Tibullo, Giuseppe A. Palumbo, Claudio Cerchione, Giovanni Martinelli, Giorgia Simonetti, Francesco Di Raimondo, Alessandra Romano
Journal: Blood (2021)
Abstract 10103: The Prognostic Impact of D-dimer on Long-Term Mortality in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention
Authors: Yuta Kurosawa, Takeshi Shimizu, Yuki Muto, Yusuke Kimishima, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2021)

Background: D-dimer is one of common measurable coagulation markers, that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. Here we investigated the association between D-dimer and long-term mortality in CAD patients. Methods and Results: Consecutive 1440 patients with CAD who underwent percutaneous coronary intervention and survived to discharge were enrolled. We divided these patients into three groups based on plasma D-dimer levels at admission: first (D-dimer &lt; 0.7 μg/ml, n = 455), second (0.7 ≤ D-dimer &lt; 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532) tertiles. We compared clinical characteristics among three groups, and prospectively followed all-cause, cardiac, non-cardiac and cancer mortalities. Clinical characteristics for three groups were as follows; mean age (first tertile, second tertile, third tertile; 61.3 ± 11.3, 69.0 ± 10.8, 72.4 ± 10.8 years, P &lt; 0.001), prevalence of chronic kidney disease (31.6%, 36.0%, 61.3%, P &lt; 0.001), anemia (25.1%, 39.7%, 64.5%, P &lt; 0.001), atrial fibrillation (10.8%, 14.1%, 19.7%, P &lt; 0.001), peripheral artery disease (4.8%, 12.4%, 18.8%, P &lt; 0.001) and heart failure (27.0%, 33.1%, 51.9%, P &lt; 0.001). In the Kaplan-Meier analysis (mean follow-up periods 1572 days), all-cause, cardiac, non-cardiac and cancer mortalities were significantly higher in third tertile than others (P &lt; 0.01, P &lt; 0.01, P &lt; 0.01 and P &lt; 0.01, respectively). In the multivariable Cox proportional hazard analyses after adjusting for confounding factors, the high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.62, P &lt; 0.01; HR 3.50, P &lt; 0.01; HR 3.69, P &lt; 0.01; and HR 3.17, P = 0.02). Conclusion: D-dimer is associated with long-term cause-specific mortality in CAD patients.
Abstract 12337: Gender Specific Phenomapping and Outcomes in Ischemic Cardiomyopathy
Authors: Chris Anthony, Nancy Obuchowski, Zoran B Popovic, Wai Hong W Tang, Brian P Griffin, Scott D Flamm, Deborah H Kwon
Journal: Circulation (2021)

Background: There is limited data on gender specific remodeling and its associated risk in patients with ischemic cardiomyopathy (ICM). We conducted gender based phenomapping analysis using Cardiac MRI (CMR) variables to identify novel sex-specific phenotypes in patients with ICM. We then assessed if these phenotypes were predictive of overall survival. Methods: Patients with ICM who underwent CMR between January 2002 and January 2017, were retrospectively evaluated . Cluster analysis was performed using nearest centroid sorting with nine variables: left ventricular end systolic volume index (LVESVi), mitral regurgitation severity on CMR (MR) , left atrial volume index (LAVi), right ventricular ejection fraction (RVEF), RV end diastolic volume index (RVEDVi) , LVEF, LV mass index (LVmassi), left atrial ejection fraction (LAEF), and myocardial scar burden (Scar). For each cluster size a Cox proportional hazards model was used to test if the phenotypes were predictive of survival. Results: Data was analyzed from 407 males and 119 females. The optimal number of clusters was four, based on the ability of the phenotypes to predict overall survival. Phenotype was a statistically significant predictor of overall survival in men (p=0.002) and women (p=0.016) after adjusting for age, body mass index, renal function, hypertension, diabetes, revascularization and mitral valve intervention. (Figure 1a) These distinct phenotypes predicted survival differently in men compared to women. Of interest, there were significant differences in the contribution of each CMR variable to predict the phenotype based on sex. (Figure 1b) In females, CMR MR and RVEF were stronger contributors to the phenotype. Conclusion: Significant differences in phenotypic signatures based on gender are present in patients with ICM. These distinct phenotypes predicted survival differently in men compared to women and emphasizes the importance of sex specific risk stratification in the ICM cohort.
Abstract 13706: Expanded Coverage for Cardiac Rehabilitation in Heart Failure Patients Accelerated Annual Rates of Use
Authors: Vinay Guduguntla, Hechuan Hou, Devraj Sukul, Steven J Keteyian, Keith D Aaronson, Mike P Thompson
Journal: Circulation (2021)

Introduction: Cardiac rehabilitation (CR) reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). In an effort to improve enrollment, Medicare expanded coverage for CR to include HFrEF patients in 2014, but the impact of this policy change is unknown. Methods: A 20% sample of Medicare inpatient, outpatient, and carrier claim files (2008 to 2017) were used to identify 849,054 patients with HFrEF, defined as having ≥ 2 outpatient claims or ≥ 1 inpatient hospitalization for chronic systolic heart failure during a calendar year. Patients who died within the calendar year of diagnosis were excluded. CR participation was identified using CPT and revenue center codes. We performed an interrupted time-series analysis to estimate annual rates of CR use over the ten year period, annual changes in CR use in the pre- (2008-2013) and post-policy (2014-2017), and the differences in annual trends pre- vs. post-policy. Results were risk adjusted by age, sex, race, dual eligibility, and Charlson comorbidities. Results: A total of 34,179 (4.0%) beneficiaries with HFrEF attended CR during the study period. Annual trends in CR enrollment are shown in Figure 1 . From 2008 to 2014, CR utilization increased from 3.30% to 4.30% at an annual absolute change of 0.15% per year (p&lt;0.001). After Medicare expanded coverage, rates of CR enrollment went from 4.30% in 2014 to 5.54% in 2017, at an annual absolute change of 0.31% (p&lt;0.001). Comparing trends in participation before and after the change in policy, the annual rate of change in CR enrollment was 0.16% higher on an absolute scale (p&lt;0.001). Conclusions: Although the absolute enrollment rate of patients with HFrEF in CR remains low, expanding coverage in 2014 was associated with a doubling in the annual rate of increase of CR use. Interventions beyond coverage changes, at the individual, provider, and system level, are needed to improve CR participation in HFrEF patients.
Abstract 10335: Increased Left Atrial Minimum Volume Index is Associated with Low Left Atrial Appendage Emptying Velocity
Authors: Kelly Jia, Ravi Shah, Robert Park, Nathaniel Mcconkey, Peter Malamas, Jovan Plamenac, Mario D Gonzalez, Gerald Naccarelli, Ankit Maheshwari
Journal: Circulation (2021)

Background: Increased left atrial minimum volume indexed by body surface area (LAVImin) is a risk factor for ischemic stroke. The mechanism underlying this association is not well defined. Hypothesis: We hypothesized that increased LAVImin is associated with low left atrial appendage emptying velocity (LAAV). Methods: We reviewed medical records of 167 patients who underwent transesophageal echocardiography (TEE) within twelve months of transthoracic echocardiography (TTE), which was obtained during sinus rhythm, in a tertiary care medical center from 2017 to 2020. We used the student’s T-test to compare the means of continuous variables. We used logistic regression analysis to estimate the odds ratio of LAVImin (per unit increase) for low LAAV (≤40 cm/s) adjusting for CHA 2 DS 2 VASc variables and heart rate during TEE. We also stratified our analysis by rhythm during TEE. Results: In our final cohort, patients with LAAV≤40 cm/s and LAAV&gt;40 cm/s had a mean (SD) LAVImin of 27.6 (16.6) ml/m 2 and 20.3 (12.0) ml/m 2 , respectively (P=0.003). In our subgroup of sinus rhythm TEEs, patients with LAAV≤40 cm/s and LAAV&gt;40 cm/s had a mean (SD) LAVImin of 22.5 (12.8) ml/m 2 and 20.0 (12.4) ml/m 2 , respectively (P=0.30). In our subgroup of atrial fibrillation TEEs, patients with LAAV≤40 cm/s and LAAV&gt;40 cm/s had a mean (SD) LAVImin of 39.0 (19.7) ml/m 2 and 23.7 (10.6) ml/m 2 , respectively (P=0.01). LAVImin was independently associated with low LAA emptying velocity. When stratified by rhythm during TEE, this association was only significant for patients in atrial fibrillation (OR 1.17 [1.06-1.39], p&lt;0.01), and not in sinus rhythm (OR 0.99 [0.96-1.03], p= 0.75). Conclusion: The association between increased LAVImin and low LAAV is dependent on heart rhythm.
Abstract 12588: Biomechanical Analysis of Neochordal Mitral Valve Repair Geometry to Quantitate the Impact of Diastolic Phase Inversion During Static Left Ventricular Pressurization
Authors: Matthew H Park, Mateo Marin-Cuartas, Yuanjia Zhu, Robert Wilkerson, Pearly Pandya, Annabel M Imbrie-moore, Michael Borger, Y J Woo
Journal: Circulation (2021)

Introduction: Artificial neochord implantation is a common form of surgical mitral valve (MV) repair, and neochord length is commonly determined by static left ventricular (LV) pressurization in diastole. However, this causes a geometric phase inversion as the subvalvular apparatus will dilate when the LV would be contracting during systole in a beating heart. We hypothesize that static LV pressurization and the subsequent papillary muscle (PM) geometric shift affects the implanted neochord length, which may alter hemodynamic performance and chordal stresses. Methods: Porcine MV (n=6) were explanted and mounted in an ex vivo heart simulator and PM were affixed to image-guided robots that accurately simulate PM motion (Fig A, B). Baseline valve hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation (MR) (Fig C). Neochord implantation was performed in both systolic and diastolic stationary PM configurations. Data is presented as mean ± standard error, and statistics were performed using two-tailed Student’s T-Tests. Results: While both repairs adequately reduced MR, we found that the systolic vs diastolic configuration repair resulted in marginally reduced MR and neochord lengths, 2.25±1.384% and 2.19±0.4 mm or 16.0±3.2%, respectively ( p=0.011 , p=0.004 ). Moreover, peak primary and secondary chordal forces were reduced by 14.4±7.0% ( p=0.07 ) and 18.8±6.4% ( p=0.03 ), respectively. Conclusions: By leveraging advanced ex vivo technologies and biomechanics analyses, we were able to quantify the impact of diastolic phase inversion on neochordal MV repair geometry. Our findings suggest that this technique may slightly overestimate the neochordal length and that marginal additional shortening of neochordae may positively affect MV repair performance and durability by reducing load on surrounding native chordae.
CTIM-32. IMMUNE CHECKPOINT INHIBITOR NIVOLUMAB IN PEOPLE WITH RECURRENT SELECT RARE CNS CANCERS: RESULTS OF INTERIM ANALYSIS IN A HEAVILY PRETREATED COHORT
Authors: Marta Penas-Prado, Ying Yuan, Kathleen Wall, Elizabeth Vera, Ukeme Ikiddeh-Barnes, Katie Blackburn, Claudia Chambers, Nivi Ratnam, Stephen Frederico, Alvina Acquaye, Kenneth Aldape, Nicole Briceno, Anna Choi, Alexa Christ, Varna Jammula, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Lily Polskin, Valentina Pillai, Martha Quezado, Brett Theeler, Jing Wu, Terri Armstrong, Mark Gilbert
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Standard and experimental therapies for patients with rare CNS tumors are scarce. Nivolumab (PD-1 inhibitor) is approved for several non-CNS cancers. This ongoing Phase II trial (NCT03173950) will determine the efficacy of nivolumab in adults with recurrence/progression of one of 11 selected rare primary CNS tumors. Efficacy is measured by Disease Control Rate (DCR; confirmed CR/PR or durable SD for ≥ 6 months) in 2 cohorts: heavily and non-heavily pretreated patients (heavily pretreated: ≥ 3 prior therapies; non-heavily pretreated: ≤ 2). We report efficacy and safety results of a preplanned interim analysis in the heavily pretreated cohort. METHODS Eligibility includes recurrence/progression of an eligible tumor; age ≥ 18 years; tumor tissue available for histopathology, molecular and immune profiling; KPS ≥ 70; and no steroids at study entry. A total of 150 evaluable patients will be enrolled (75 to each cohort). Prior therapies include radiation and/or standard or investigational drugs. Nivolumab treatment is 240 mg IV every 2 weeks (4 doses); then 480 mg every 4 weeks (14 additional doses). Interim analysis was planned when sample size reached 32 in each cohort. RESULTS As of March 10, 2021, DCR exceeded the minimum required for interim analysis in the heavily pretreated cohort. Among 30 patients, 4 achieved SD &amp;gt; 6 months (medulloblastoma, anaplastic ependymoma, myxopapillary ependymoma, metastatic atypical meningioma). Safety profile (related AEs): grade 3 = 7; grade 4 = 1. Most frequent grade 3-5 AEs regardless of attribution: tumor progression (6); anemia, hydrocephalus, lymphopenia (3 each); cerebral edema, headache (2 each). CONCLUSION DCR exceeded the “go” boundary (i.e., &amp;gt; 2) in the heavily pretreated cohort. Nivolumab showed safety profile consistent with other studies. This cohort will continue to stage 2 and complete total accrual of 75 patients. The trial is currently being expanded to 10 additional sites across the BTTC/NCI-CONNECT consortium.
Abstract 13855: Invasive Versus Conservative Strategy For Stable Coronary Artery Disease In Patients With Heart Failure
Authors: Nitish K Sharma, Qiying Dai, Abhishek Bose, Ibragim Alseykal, neeta shah, Eddison Ramsaran
Journal: Circulation (2021)

Introduction: Patients with stable ischemic heart disease (SIHD) and intermediate to high-risk stress tests with underlying heart failure (HF) are at increased risk for cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina and HF. In this patient population, the decision to pursue an early invasive strategy versus continuing medical management remains unclear. To evaluate this conundrum further, we performed a retrospective analysis. Method: We followed 308 SIHD patients with both reduced and preserved ejection fraction HF for a period of at least 16 months. All patients were classified as intermediate to high-risk based on their nuclear stress test results. They were further divided based on whether they underwent an initial invasive strategy versus medical management. A multivariable Cox regression analysis was performed to compare the primary outcome of all-cause mortality and cardiac mortality between the two groups. Results: Patients undergoing an initial invasive strategy were younger (70.64 ± 10.94 vs. 73.7 ± 12.04 years, P = 0.021), with a positive family history (24.4% vs 13.3%, p=0.023) and more likely to have high-risk nuclear stress tests (53.3% vs. 35.9%, p = 0.004) and prior percutaneous coronary intervention (35.0% vs. 23.4%, p =0.04) compared to the medical therapy group. Peripheral Vascular Disease (PVD) was more common in medical treatment group (35.2% vs.17.8%, p=0.001). During follow-up, all-cause death was 19.4% (n=35) vs. 33.6% (n=43), and cardiac death was 3.3% (n=6) vs.15.6% (n=20) in the invasive and medical therapy groups respectively. There was no difference in the all-cause mortality between the two groups, but cardiac mortality was noted to be lower in the invasive strategy group (Figure 1 &amp; 2). Conclusions: In our patient population with SIHD and HF, pursuing an early invasive strategy provided cardiac mortality benefit when compared to conservative medical therapy.
Abstract 9711: Unexplained Dyspnea on Exertion: The Difference the Right Test Can Make
Authors: Vishal N Rao, Michael A BLAZING, Neha J Pagidipati, Marat Fudim
Journal: Circulation (2021)

A 66-year-old male with past history of coronary atherosclerosis by angiography was referred for chronic dyspnea. He is a pastor and had noted dyspnea with prolonged standing or walking that resolved with sitting. Serial orthostatic vitals and natriuretic peptides were normal. Subsequent diagnostics included normal pulmonary function and ventilation-perfusion tests, and echocardiography with normal biventricular function, sizes, and estimated pressures. Given ongoing dyspnea, he underwent supine invasive cardiopulmonary exercise testing (iCPET). Resting invasive pressures and cardiac output were normal. At peak exercise, exertional dyspnea was absent but pressures increased to mean PAP 40 and PCWP 28 with preserved cardiac output and 77% predicted maximal aerobic capacity (pVO2). He was diagnosed with exercise induced heart failure with preserved ejection fraction and started on furosemide and spironolactone. On follow-up, he reported worsened dyspnea on therapy, most notably when upright. Stress cardiac MRI showed no scar. Given the positional nature of his symptoms, an iCPET was repeated in the upright position. His diuretics were stopped. Resting supine measurements were similar to the prior iCPET. Upright resting to peak exercise pressures changed minimally ( Figure ). His profound dyspnea recurred at peak exertion as MAP dropped unexpectedly with paradoxical bradycardia (Bezold-Jarisch reflex) and 62% pVO2. His diagnosis was reclassified as cardiac preload failure. He was advised to increase fluid and salt intake alongside use of leg stockings which remarkably improved his upright and exercise dyspnea symptoms at follow-up. This case highlights an advantage of upright iCPET over supine diagnostics in the comprehensive evaluation of unexplained dyspnea. Cardiac preload failure is the failure to augment preload with exercise and is a common but under-recognized cause of dyspnea often undiagnosed during supine resting and exercise testing.