tbuckley/cabot-search huggingface dataset:
Abstract 11327: Relationship of Neighborhood Socioeconomic Deprivation with Outcomes of a Comprehensive STEMI Protocol
Authors: Chetan Huded, Jarrod Dalton, Anirudh Kumar, Nikolas Krieger, Nicholas Kassis, Michael Phelan, Kathleen Kravitz, Grant W Reed, Amar Krishnaswamy, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2021)

Introduction: Social determinants of health have an established impact on cardiovascular outcomes. STEMI quality improvement programs have resulted in reductions in door to balloon time (D2BT) and improved STEMI outcomes nationally. We evaluated whether a comprehensive STEMI protocol (CSP) improves care and outcomes in patients with moderate and high socioeconomic deprivation. Methods: Patients with STEMI treated with PCI at a single tertiary care hospital before (1/1/11-7/14/14, n=674) and after (7/15/14-7/15/19, n=1087) implementation of a CSP were included. Patients were stratified into low ( &lt; 50 th percentile), medium (51-90 th percentile), and high (&gt;90 th percentile) deprivation groups based on census block group level area deprivation index. Outcomes were D2BT and mortality. Results: Neighborhood deprivation was 29.0% low (174 pre-CSP, 338 post-CSP), 40.8% moderate (268 pre, 450 post), and 30.2% high (232 pre, 299 post). Female sex (low 28.3%, moderate 31.9%, high 38.6%, p=0.001) and black race (2.5%, 20.7%, 61.8%, p&lt;0.001) were associated with higher levels of deprivation. Improvements in median D2BT were observed in all deprivation groups after CSP implementation (Figure). Risk-adjusted median D2BT among ER/hospital patients from higher neighborhood deprivation levels was significantly non-inferior (non-inferiority limit = 5m) to those from lower deprivation levels after CSP implementation. In-hospital mortality was similar before and after CSP implementation in the low deprivation group (4.6% vs. 3.6%, p=0.56), and decreased significantly in moderate/high deprivation groups (7.0% vs. 3.1%, p=0.001). Conclusions: A CSP was associated with improvements in D2BT across all deprivation groups and a substantial mortality reduction in moderate/high deprivation groups. Standardized quality improvement initiatives may mitigate social determinants of health in time-sensitive high acuity conditions such as STEMI.
Abstract 14342: Artificial Intelligence Dramatically Reduces Annual False Alerts From Insertable Cardiac Monitors
Authors: Kevin Ousdigian, Ya-Jian Cheng, Jodi L Koehler, Andrew Radtke, Sarah Rosemas, john rogers
Journal: Circulation (2021)

Introduction: Insertable Cardiac Monitors (ICMs) continuously monitor Atrial Fibrillation (AF) episodes and Pause episodes with high sensitivity, however their false detections create clinician review burden. Cloud-based Artificial Intelligence (AI) algorithms for ICM AF and Pause episodes were recently developed and independently validated but their combined impact in widespread use are unknown. Hypothesis: To determine the projected annual impact of AF and Pause AI on alerts in real-world patient population. Methods: Real-world data was obtained from de-identified LINQ II ICM patients with ≥3 months of follow-up. For practical purposes, the results were extrapolated to a 200 ICM clinic. The previously published AF and Pause AI performance results were projected onto the real-world data controlling for the patient’s reason for monitoring. The endpoints were daily relative true (sensitivity) and false (specificity) alerts since alerts are triggered based on all episodes in a day. Results: The dataset consisted of 2,510 ICMs inserted for Known AF (31%), AF Diagnosis (37%), Syncope (21%), and Other (11%) with a mean follow-up of 4 months. The projected annual volume of alerts was 3,965 AF and 740 Pause alerts for a 200 ICM clinic. AI resulted in minimal (0.6%) overall loss in AF and Pause annualized true alerts, with no loss in true Pause alerts and 0.7% for AF. AI reduced annualized false alerts by 83% including nearly all (97.4%) false Pause and 78% of AF (Figure). Conclusions: The AF and Pause AI dramatically reduced the annual data review burden by eliminating most false alerts while maintaining very high sensitivity to true alerts.
Abstract 13858: Improving the Compliance With the Use of ST Elevation Myocardial Infarction Cardiogenic Shock Protocol in an Urban Inner City Teaching Hospital- A Quality Initiative
Authors: Shreya V Ghetiya, Bashar Al-Turk, Pujan Patel, Gladys R Velarde, Andres Pineda
Journal: Circulation (2021)

Background: 5-10% of STEMI are complicated by Cardiogenic shock (CGS). From multiple shock initiative across the country, the survival is shown to improve from 50% to 70-80%.Problem: 1) To evaluate the outcomes and identify gaps in treatment of STEMI complicated with CGS at our institution between Jan, 2018 to Dec, 2019. Based on this, a STEMI shock protocol was implemented at our institution. 2) After its implementation on 7/1/2020, the compliance with its use was measured and the goal is to increase from 30% (July - Dec) to 70% by the end of June 2021. Method: 178 cases with STEMI between 1/1/2018 to 12/31/2019 were reviewed.Patients were classified into: Identified CGS (A), Unidentified CGS (B, those that met criteria), Non-CGS (C, no criteria for CGS). Basic demographics, in-hospital mortality, 30-day mortality, length-of-stay (LOS), incidence of acute kidney injury (AKI) &amp; acute liver injury (ALI) were measured. Results: In group A: average LOS was 16 d, mean LVEDP was 25 mmHg and in-hospital mortality/30-day mortality was 56.2% (9 pts)/62.5% (10 pts). 100% (16) had AKI, 25% (4) required new hemodialysis during that admission, 93.8% (15) had ALI and 100% (16) required vasopressors/inotropes.In group B: average LOS was 6 d, mean LVEDP was 24.5 mmHg and in-hospital mortality/30-day mortality was 0%/8.7% (2 pts).In group C: average LOS was 4 d, mean LVEDP was 20.6 mmHg and in-hospital/30-day mortality was 0%. After its implementation, the compliance rate was measured. It was estimated about 30%. A survey of 14 questions was sent out to all the involved providers. A Pareto chart was created and based on it, we provided more educational trainings, feedback programs and implemented order sets in the electronic medical record system. We will continue to measure improvement in the compliance over next PDSA cycles. This will ultimately help us evaluate any improvement in the outcomes in STEMI-CGS patients. Conclusions: This is a unique quality improvement project which will help improve patient outcomes in STEMI CGS patients. This is an attempt to standardize the care in our institution with a goal to early identify them and initiate measures derived from evidence-based practice.
IMMU-05. CCR2+ MYELOID-DERIVED SUPPRESSOR CELLS FROM MURINE GLIOMAS ARE SOURCED FROM THE BONE MARROW, SUPPRESS T CELL ACTIVATION, AND MIGRATE TO CCL2
Authors: Gregory Takacs, Christian Kreiger, Defang Luo, Joseph Flores-Toro, Loic Deleyrolle, Maryam Rahman, Duane Mitchell, Jeffrey Harrison
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Mounting evidence suggests infiltrating immune-suppressive cells contribute to immune checkpoint inhibitor resistance and poor survival in Glioblastoma (GBM) patients. We have previously shown glioma-associated monocytic-myeloid derived suppressor cells (M-MDSCs) express chemokine receptors CCR2 and CX3CR1. Genetic and pharmacologic targeting of CCR2 promoted sequestration of M-MDSCs in the bone marrow and, in combination with PD-1 blockade, slowed progression of KR158 and 005GSC murine gliomas. This combination treatment also enhanced infiltration of IFNg-producing T cells that were less exhausted. Although CCR2+/CX3CR1+ cells display surface markers indicative of bone marrow-derived M-MDSCs, additional studies are needed to formally establish the source of these cells and to determine if they exhibit an immune-suppressive phenotype as well as migrate to the CCR2 ligands, CCL2 and/or CCL7. OBJECTIVE Evaluate the source, migration, and immune suppressive function of CCR2+/CX3CR1+ myeloid cells from glioma bearing mice. METHODS To identify the source of CCR2+/CX3CR1+ myeloid cells, chimeric wild type mice harboring bone marrow cells from transgenic CCR2WT/RFP/CX3CR1WT/GFP mice were generated. CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from either wild-type or CCR2WT/RFP/CX3CR1WT/GFP naïve and glioma-bearing mice in order to evaluate their immune suppressive phenotype and ability to migrate to CCL2 and CCL7. RESULTS CCR2+/CX3CR1+ cells are present in glioma isolates from chimeric mice, indicative of a bone marrow-derived cell population, and are detectable within the tumor microenvironment as early as 3 days post orthotopic implantation of KR158 cells; these cells accumulate as tumors increase in size (r=0.7605, p=0.007). CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor bearing mice suppress CD8+ T cell production of IFNg and migrate to CCL2 more efficiently than CCL7. CONCLUSION CCR2+/CX3CR1+ cells from glioma bearing mice are derived from the bone marrow and represent an immune suppressive population that migrates to CCL2.
NIMG-52. RADIOGENOMICS SIGNATURES IN KEY DRIVER GENES IN GLIOBLASTOMA EVALUATED WITH AND WITHOUT THE PRESENCE OF CO-OCCURRING MUTATIONS
Authors: Anahita Fathi Kazerooni, Hamed Akbari, Spyridon Bakas, Erik Toorens, Chiharu Sako, Elizabeth Mamourian, Vikas Bommineni, Nina Thakur, Costas Koumenis, Stephen J Bagley, Robert A Lustig, Donald M O’Rourke, Tapan Ganguly, MacLean Nasrallah, Christos Davatzikos
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Glioblastomas display significant heterogeneity on the molecular level, typically harboring several co-occurring mutations, which likely contributes to failure of molecularly targeted therapeutic approaches. Radiogenomics has emerged as a promising tool for in vivo characterization of this heterogeneity. We derive radiogenomic signatures of four mutations via machine learning (ML) analysis of multiparametric MRI (mpMRI) and evaluate them in the presence and absence of other co-occurring mutations. METHODS We identified a retrospective cohort of 359 IDH-wildtype glioblastoma patients, with available pre-operative mpMRI (T1, T1Gd, T2, T2-FLAIR) scans and targeted next generation sequencing (NGS) data. Radiomic features, including morphologic, histogram, texture, and Gabor wavelet descriptors, were extracted from the mpMRI. Multivariate predictive models were trained using cross-validated SVM with LASSO feature selection to predict mutation status in key driver genes, EGFR, PTEN, TP53, and NF1. ML models and spatial population atlases of genetic mutations were generated for stratification of the tumors (1) with co-occurring mutations versus wildtypes, (2) with exclusive mutations in each driver gene versus the tumors without any mutations in the pathways associated with these genes. RESULTS ML models yielded AUCs of 0.75 (95%CI:0.62-0.88) / 0.87 (95%CI:0.70-1) for co-occurring / exclusive EGFR mutations, 0.69 (95%CI:0.58-0.80) / 0.80 (95%CI:0.61-0.99) for co-occurring / exclusive PTEN mutations, and 0.77 (95%CI:0.65-0.88) / 0.86 (95%CI:0.69-1) for co-occurring / exclusive TP53 cases. Spatial atlases revealed a predisposition of left temporal lobe for NF1 and right frontotemporal region for TP53 in mutually exclusive tumors, which was not observed in the co-occurring mutation atlases. CONCLUSION Our results suggest the presence of distinct radiogenomic signatures of several glioblastoma mutations, which become even more pronounced when respective mutations do not co-occur with other mutations. These in vivo signatures can contribute to pre-operative stratification of patients for molecular targeted therapies, and potentially longitudinal monitoring of mutational changes during treatment.
Abstract 13707: Body Mass Index and Mortality in Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Mohamad B Taha, Isaac Acquah, Javier Valero Elizondo, Tamer Yahya, Kobina Hagan, Zulqarnain Javed, Shiwani Mahajan, Priyanka Satish, Jamal S Rana, Kershaw Patel, Miguel Cainzos Achirica, Khurram Nasir
Journal: Circulation (2021)

Introduction: The association between body mass index (BMI) and mortality risk has been previously shown to follow a J- shaped pattern, with a greater mortality risk at the lowest and highest BMI levels. However, this association has not been fully evaluated in a population with atherosclerotic cardiovascular disease (ASCVD). We examined the BMI-mortality associations in the general population, and in a population with ASCVD. Methods: We used data from 2006-2014 National Death Index-linked National Health Interview Survey, a US nationally representative survey, for adults ≥ 18 years. Participants were classified based on self-reported ASCVD. BMI was calculated based on self-reported height and weight and was classified as normal/overweight (BMI 18.5-29.9 kg/m 2 ), obesity class 1 (30-34.9 kg/m 2 ), class 2 (35-39.9 kg/m 2 ), and class 3 (≥40 kg/m 2 ); participants who were underweight (&lt;18.5 kg/m 2 ) were excluded. Multivariable cox proportional hazards models were used to examine the risk of all-cause, cardiovascular, and non-cardiovascular mortality. Results: A total of 252,9568 adults, including a weighted 8.1% (or 18.6 million annually) with ASCVD, were included in the analysis. During a median follow-up of 4.5 (IQR: 2.5-6.8) years, (1179 million person-years), mortality rates, both cardiovascular and non-cardiovascular, were higher in the ASCVD group compared to the general population ( Fig: panel A ). In the general population, those with obesity class 3 had a higher risk of cardiovascular and non-cardiovascular mortality compared to individuals with normal/overweight, whereas individuals with obesity class 1 had a lower non-cardiovascular mortality risk. An overall similar pattern of association was observed in the ASCVD population in non-cardiovascular, but not cardiovascular, mortality ( Fig: panel B ). Conclusion: Greater BMI categories were associated with higher non-cardiovascular, but not cardiovascular, mortality in the ASCVD population.
Abstract 11664: Contractile Reserve is Impaired in Patients After Fontan Operation and Predicts Exercise Performance on Exercise Stress Echocardiography
Authors: Shivani M Bhatt, Jennifer Faerber, Yan Wang, Grace DeCost, Anh Duc Mai, Michael W McBride, Stephen Paridon, David Goldberg, Laura M Mercer-rosa
Journal: Circulation (2021)

Introduction: Exercise capacity is diminished in Fontan patients. There is limited understanding of their contractile reserve, or ventricular response to exercise. We sought to evaluate contractile reserve in Fontan patients and its association with exercise performance using exercise stress echocardiography. Methods: Single center prospective study of Fontan patients (n=56) and healthy controls (n=11) presenting for cardiopulmonary exercise test and rest/peak exercise research echocardiograms. Contractile reserve was defined as the change in the systemic ventricle’s global longitudinal strain (GLS), free wall strain (FWS) and global circumferential strain (GCS) (and strain rates) from rest to peak exercise. Fontan fenestration mean gradient was obtained by Doppler interrogation. Exercise outcomes included percent predicted maximum oxygen consumption (%mVO2), maximum work and oxygen pulse. Results: Fontan patients were 14.5 ± 4.4 years old at testing and (58%) males. There was a fenestration in 33 patients. Exercise parameters in Fontan patients were abnormal with reduced %mVO2 of 75.5 ± 21.5%. Most strain parameters were lower in Fontan patients than controls at rest and peak exercise. There was a significant increase in fenestration gradient from rest to peak exercise. GLS, GCS strain and GLS, GCS and FWS rates increased significantly from rest to peak exercise in both groups, but the magnitude of increase was significantly less in Fontan patients compared to controls, indicating reduced contractile reserve. An increase in FWS rate at peak exercise was independently associated with better %mVO2 and oxygen pulse in Fontan patients. Conclusions: Fontan patients have abnormal response to exercise with reduced contractile reserve compared to controls. Greater contractile reserve is associated with better exercise performance in these patients. Therapies aimed at increasing contractile reserve after the Fontan may improve exercise performance.
Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States
Authors: Kristin M. Zimmerman Savill, Ajeet Gajra, Kwanza Price, Jonathan K. Kish, Cherrishe Brown-Bickerstaff, Angelica Falkenstein, Talia Miller, JaLyna Laney, Sudipto Mukherjee
Journal: Blood (2021)
Abstract 13597: Poorer Outcomes Associated With More Invasive Lead Management Strategies for Abbott Riata® Leads in a Large, Multi-Center Retrospective Study
Authors: Philip Mar, Hiren Patel, Piotr Horbal, Christina Tsai, Deepak Bhakta, Rajesh Kabra, Sarah Longserre, Ahmed Hussein, Brian Olshansky, Sierra Dickey, Dhanunjaya R Lakkireddy, Rakesh Gopinathannair
Journal: Circulation (2021)

Introduction: Abbott Riata® (AR) leads are prone to conductor externalization but have similar annual failure rates compared to industry benchmarks. A recent multi-center study showed that lead extraction (LE), lead abandonment (LA), and generator change only (GC) have similar long-term outcomes for the recalled Sprint Fidelis® and AR leads when analyzed collectively. However, a study evaluating only AR lead management with these strategies has not been done. We sought to evaluate if outcomes are worse with more invasive strategies (LE and LA) vs. GC when managing AR leads. Hypothesis: To compare outcomes after LE, LA, and GC strategies for AR leads. Methods: This is a 5-center, retrospective study evaluating LE, LA and GC strategies for AR. The incidence of peri-procedural complications, 60-day extended or repeat hospitalization [ERHOSP], death within 60 days, subsequent lead malfunctions, and long-term mortality were compared amongst LE, LA, and GC strategies. Results: 165 patients (65± 13 years, 68% male) were followed for a mean 33 ± 30 months following intervention. Outcomes are listed on Table 1. Total AR lead dwell time follow-up was 16633 months. A total of 3 AR lead malfunctions were noted during long-term follow-up. Inappropriate shocks were similar between LE 7.7% (1/13), LA 6.3% (1/16) and GC 11.0% (15/136); P=0.74. Conclusions: More invasive lead management (LE and LA) resulted in increased death within 60 days and ERHOSP after adjusting for long-term lead malfunction with GC. Long-term mortality was also more favorable in the GC group. AR leads should only be extracted or revised if they demonstrate evidence of lead malfunction when the device reaches end of life.
Neutrophils prevent rectal bleeding in ulcerative colitis by peptidyl-arginine deiminase-4-dependent immunothrombosis
Authors: Moritz Leppkes, Aylin Lindemann, Stefanie Gößwein, Susanne Paulus, Dominik Roth, Anne Hartung, Eva Liebing, Sebastian Zundler, Miguel Gonzalez-Acera, Jay V Patankar, Fabrizio Mascia, Kristina Scheibe, Markus Hoffmann, Stefan Uderhardt, Christine Schauer, Sebastian Foersch, Clemens Neufert, Michael Vieth, Georg Schett, Raja Atreya, Anja A Kühl, Andre Bleich, Christoph Becker, Martin Herrmann, Markus F Neurath
Journal: Gut (2021)

Bleeding ulcers and erosions are hallmarks of active ulcerative colitis (UC). However, the mechanisms controlling bleeding and mucosal haemostasis remain elusive.We used high-resolution endoscopy and colon tissue samples of active UC (n = 36) as well as experimental models of physical and chemical mucosal damage in mice deficient for peptidyl-arginine deiminase-4 (PAD4), gnotobiotic mice and controls. We employed endoscopy, histochemistry, live-cell microscopy and flow cytometry to study eroded mucosal surfaces during mucosal haemostasis.Erosions and ulcerations in UC were covered by fresh blood, haematin or fibrin visible by endoscopy. Fibrin layers rather than fresh blood or haematin on erosions were inversely correlated with rectal bleeding in UC. Fibrin layers contained ample amounts of neutrophils coaggregated with neutrophil extracellular traps (NETs) with detectable activity of PAD. Transcriptome analyses showed significantly elevated PAD4 expression in active UC. In experimentally inflicted wounds, we found that neutrophils underwent NET formation in a PAD4-dependent manner hours after formation of primary blood clots, and remodelled clots to immunothrombi containing citrullinated histones, even in the absence of microbiota. PAD4-deficient mice experienced an exacerbated course of dextrane sodium sulfate-induced colitis with markedly increased rectal bleeding (96 % vs 10 %) as compared with controls. PAD4-deficient mice failed to remodel blood clots on mucosal wounds eliciting impaired healing. Thus, NET-associated immunothrombi are protective in acute colitis, while insufficient immunothrombosis is associated with rectal bleeding.Our findings uncover that neutrophils induce secondary immunothrombosis by PAD4-dependent mechanisms. Insufficient immunothrombosis may favour rectal bleeding in UC.
High-Dose Intravenous Acyclovir Is Safe and Effective in the Treatment of EBV Reactivation Post Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yu Wang, Xuemei Ye, Hong Zheng, Yan Mao, Xuemei Wang, Feifei Che, Chunsen Wang, Xi Yang, Xiaobing Huang
Journal: Blood (2021)
Abstract 12903: Frailty Did Not Diminish the Prognostic Advantage of Guideline-Directed Medical Therapy in Elderly Patients With Heart Failure (Multicentral Cohort Study)
Authors: Takuro Abe, Kentaro Jujo, Katsumi Saito, Saito Kazuya, Hiroshi Saito, Iwata Kentaro, Masaaki Konishi, Takeshi Kitai, Takatoshi Kasai, Hiroshi Wada, Shinichi Momomura, Nobuyuki Kagiyama, Kentaro Kamiya, Yamashita Masashi, Nobuaki Hamazaki, Nozaki Kohei, Emi Maekawa, Junya Ako, Yuya Matsue
Journal: Circulation (2021)

Introduction: Numerous previous trials revealed that the effectiveness of guideline-directed medical therapy (GDMT) including beta-blockers (BB) and renin-angiotensin system inhibitors (RASi) in patients with heart failure (HF) with reduced/mildly reduced ejection fraction (HFr/mrEF). Although frailty is world-wide concern in HF patients, the impact of physical frailty on the prognostic effect of GDMT in geriatric patients with HFr/mrEF remains unclear. Hypothesis: The prognostic impact of GDMT in HF patients depends on whether they exhibit physical frailty or not. Methods: From the combined HF database of FRAGILE-HF and Kitasato cohort, 1,054 hospitalized HFr/mrEF patients &gt; 65 year-old were analyzed. Of them, 715 patients (32%) were on the full GDMT (both BB and RASi) at discharge, and 604 patients (57%) were diagnosed as physically frail. The primary endpoint was death from any cause. Results: In the whole population, patients on GDMT at discharge showed a significantly lower 1-year mortality than those without GDMT in Kaplan-Meier analysis (Log-rank, p=0.0014). In multivariable Cox regression analysis including GWTG-HF risk score, log-transformed BNP, left ventricular ejection fraction, anemia and NYHA class, the superiority of GDMT was confirmed (HR 0.53, 95%CI: 0.36-0.78). The rate of risk reduction for 1-year mortality by receiving GDMT was comparable between patients with and without physical frailty after adjusting covariates (HR: 0.57 and 0.59, respectively). Additionally, the prognostic advantages of GDMT were not significantly interacted by the presence or absence of physical frailty (P for interaction=0.77). Conclusions: GDMT was associated with the improved prognosis in geriatric hospitalized HFr/mrEF patients regardless of the frailty. We should not hesitate the administration of GDMT in elderly patients even if they are physically frail.