tbuckley/cabot-search huggingface dataset:
Abstract 6918: Cardiovascular Magnetic Resonance Imaging Features and Prognostic Value in Immune Checkpoint Inhibitor-Induced Myocarditis
Authors: Farah Cadour, Jennifer Cautela, Stanislas Rapacchi, Arthur Varoquax, Paul Habert, Francois Arnaud, Alexis Jacquier, Alexandra Meilhac, Franck Paganelli, Natalie Lalevee, Ugo Scemama, Franck Thuny
Journal: Circulation (2021)

Introduction: Immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) is an emerging and severe complication of cancer treatment, for which diagnosis and risk stratification are challenging. Very few data exist on CMR findings and predictive value in ICI-M. Hypothesis: We hypothesized that ICI-M would have specific CMR features, and we sought to explore the prognostic value of CMR. Methods: In this case-control multicenter study, the clinical, biological, and CMR findings (including late gadolinium enhancement [LGE], T1/T2 mapping, and extracellular volume fraction [ECV] values) of adults with ICI-M (n=33) were compared with those of two other groups, including cancer patients without myocarditis scheduled to receive ICIs (w/o-M, n=21), and patients with non-ICI-induced myocarditis (NI-M, n=85). As secondary objective, we explored the potential value of LGE and T1/T2/ECV for predicting major adverse cardiovascular events (MACE) in ICI-M patients. Results: Compared with w/o-M, the global native T1, ECV, and T2 z-scores were significantly higher in ICI-M ( P &lt;0.001 for T1, P =0.03 for ECV, and P =0.004 for T2). LGE was more frequently observed in ICI-M than in w/o-M (82% vs. 9%, P &lt;0.001). The sensitivity of the main 2018-Lake Louise criteria was only 61% and the specificity was 100% in the diagnosis of ICI-M. No significant difference was found between ICI-M and NI-M in terms of the global native T1, ECV, and T2 z-scores. LGE was less frequent in ICI-M (82% vs. 100%, P &lt;0.001) but was more likely to involve the midwall layer ( P &lt;0.001) and septal segments ( P &lt;0.001) than in NI-M. For ICI-M patients, septal LGE was the only CMR predictor of MACE even after adjustment for age, sex, risk factors, left ventricular ejection fraction&lt;50%, and magnitude of increase in peak troponin I or T (adjusted hazard ratio, 3.57; 95% CI, 1.26-10.18; P =0.02). Conclusions: ICI-M demonstrates specific features on CMR, and septal LGE may be a predictor of poor prognosis.
PATH-23. OLIGOSARCOMA, IDH-MUTANT IS A DISTINCT AGGRESSIVE TYPE
Authors: Abigail K Suwala, Marius Felix, Dennis Friedel, Damian Stichel, Daniel Schrimpf, Ekkehard Hewer, Leonille Schweizer, Hildegard Dohmen, Ute Pohl, Daniel Erny, Christian Koelsche, Clinton Turner, Koray Özduman, Marco Prinz, Till Acker, Christel Herold-Mende, Wolfgang Wick, David Capper, Pieter Wesseling, Felix Sahm, Andreas von Deimling, Christian Hartmann, David Reuss
Journal: Neuro-Oncology (2021)

Abstract Oligodendrogliomas are defined by IDH-mutations and the co-deletion of chromosomal arms 1p and 19q. In the past, case reports and small series described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a group of 23 IDH-mutant oligosarcomas that form a distinct methylation group. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 11 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Tumor cells were embedded in a reticulin fibers network in all oligosarcomas, frequently showing p53 accumulation, positivity for SMA, and regain of H3K27me3 as compared to primary lesions. In 5 oligosarcomas no 1p/19q co-deletion was detectable, even though it was present in the primary lesions. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional grade 3 oligodendrogliomas with consistent evidence for smooth muscle differentiation. Expression of several tumor suppressors including NF1 and STAG2 was lost whereas oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in TP53 and NF1 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as for grade 3 oligodendrogliomas but comparable to grade 4 IDH-mutant astrocytomas. These results establish oligosarcoma as a distinct type of IDH-mutant glioma differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. Diagnosis can be based on the characteristic DNA methylation profile or the combined evidence of sarcomatous histology, IDH-mutation and TERT promoter mutation with or without 1p/19q co-deletion.
Abstract 14116: Exercise and Specialized Proresolving Lipid Mediators Stimulate Mitochondrial Metabolism in Macrophages
Authors: Ernesto H Pena Calderin, Bradford G Hill, Jason Hellmann
Journal: Circulation (2021)

Exercise may prevent the development and progression of chronic inflammatory diseases through alterations in immune cell function. We find that macrophages isolated from mice subjected to 4 weeks of voluntary wheel exercise display enhanced basal and maximal mitochondrial respiration. We have previously shown that exercise also increases the production of specialized proresolving mediators (SPMs), macrophage phagocytosis, and resolution of acute inflammation; however, whether exercise-induced SPM formation directly alters macrophage metabolism remains unknown. SPMs stimulate resolution through actions on specific G-protein coupled receptors (GPCRs) in macrophages ( e.g. , RvD1=&gt; Fpr2). Therefore, we treated macrophages for 1 h with SPMs that act through distinct GPCRs ( e.g. , RvD1, RvD2, RvE1, and MaR1) and found enhanced basal (vehicle vs 1nM SPM; 6.11±0.1 vs RvD1 7.76±0.6 vs RvD2 9.48±0.9 vs RvE1 7.20±0.5 vs MaR1 8.73±0.9 pmol/min/μg protein; P&lt;0.05; n =3), maximal (vehicle vs 0.1nM SPM; 9.06±1.1 vs RvD1 14.37±1.1 vs RvD2 16.54±2.7 vs RvE1 12.32±1.5 vs MaR1 13.28±1.3 pmol/min/μg protein; P&lt;0.05; n =3), and ATP-linked respiration (vehicle vs 1nM SPM; 2.83±0.2 vs RvD1 4.50±0.3 vs RvD2 4.39±0.2 vs RvE1 4.71±0.3 vs MaR1 4.20±0.2 pmol/min/μg protein; P&lt;0.05; n =3). Stimulation of mitochondrial metabolism with RvD1 was receptor mediated as Fpr2 -deficient macrophages displayed no significant changes in mitochondrial respiration following treatment (vehicle vs 1nM RvD1; basal 6.74±0.6 vs 6.52±0.2; maximal 11.54±1.2 vs 13.26±1.0; ATP-linked 5.84±0.8 vs 5.33±0.2 pmol/min/μg protein). Collectively, these data suggest that exercise-induced production of SPMs stimulates mitochondrial metabolism in macrophages, which could underlie their common proresolving properties and the exercise-induced amelioration of chronic inflammatory diseases.
Abstract 9701: Hemodynamic Parameters Deteriorate Over Time, and Relate to Adverse Clinical Outcomes, in Children and Adults with Fontan Circulation
Authors: Ryan Halickman, Alexandra Erdmann, Sara Trucco, Jacqueline Kreutzer, Michael D Seckeler, Tarek Alsaied, Bryan H Goldstein
Journal: Circulation (2021)

Introduction: In patients with univentricular heart disease, Fontan palliation allows for improved survival. However, Fontan circulatory function deteriorates over time, marked by the onset of functional limitations, morbidities, and mortality. Invasive surveillance offers insights into hemodynamic conditions and may facilitate identification of at-risk patients. Objective: To characterize longitudinal changes in invasive Fontan hemodynamics and evaluate for associations with adverse clinical outcomes. Methods: Single-center retrospective study of serial invasive hemodynamics (≥2 catheterizations) in Fontan patients from 2006-2020. The first and last procedures per patient were analyzed for Fontan pressure, ventricular end diastolic pressure (EDP), cardiac output (CO), systemic (SVR), pulmonary (PVR) and total vascular resistance (TVR). The composite clinical endpoint included death, heart transplant or listing, Fontan takedown, protein losing enteropathy, plastic bronchitis, admission for arrhythmia or congestive heart failure and Fontan revision. Results: Serial hemodynamic evaluations were analyzed in 71 Fontan patients, with first catheterization occurring at median age of 7.1 years (IQR 4.1, 14) and 8.4 years (4.7, 12.3) between assessments. The most common diagnosis was hypoplastic left heart syndrome (45%). Fontan pressure, CO and PVR did not significantly change between assessments, whereas EDP increased by 1.9±3.6 mmHg ( p &lt;0.001). The annualized rate of change in EDP was 0.2±0.14 mmHg/year. SVR (2.0±7.5 U x m 2 , p =0.012) and TVR (2.16 ±7.8 U x m 2 , p =0.031) also increased significantly between assessments. The clinical endpoint was met in 43 (61%) patients and was associated with a greater change in transpulmonary gradient (0.13±1.9 vs -0.87±2.0 mmHg, p =0.046) and Fontan pressure (1.1±5.4 vs -0.7±2.7 mmHg, p =0.066) but not EDP, CO, SVR, PVR or TVR. Conclusion: Over a relatively brief time period, this single-center cohort of Fontan patients demonstrated clinically significant longitudinal increases in EDP, SVR and TVR. Adverse clinical outcomes were common and associated with greater hemodynamic deterioration between assessments. Serial interrogation of Fontan hemodynamics is likely to prove clinically useful.
A Tale of Two Centers: Access to Private Care Improves Outcomes in Allogeneic Transplant Recipients
Authors: Xitlaly Judith Gonzalez Leal, Elías Eugenio González López, Felipe Soto-Lanza, Gerardo A De la Rosa-Flores, Perla R. R. Colunga-Pedraza, Anna Cecilia Rodríguez-Zuñiga, Cesar Homero Gutierrez-Aguirre, Olga Graciela Cantu Rodriguez, Luz del Carmen Tarin Arzaga, David Gomez-Almaguer, Andres Gomez-De Leon
Journal: Blood (2021)
Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination
Authors: Juliana Gonçalves, A. Margarida Juliano, Nádia Charepe, Marta Alenquer, Diogo Athayde, Filipe Ferreira, Margarida Archer, Maria João Amorim, Fátima Serrano, Helena Soares
Journal: Cell Reports Medicine (2021)
NIMG-68. SARCOPENIA AS MEASURED BY TEMPORALIS MUSCLE WIDTH IS A PREDICTOR OF SURVIVAL IN PRIMARY CNS LYMPHOMA
Authors: Alipi Bonm, Anthony Menghini, Jerome Graber
Journal: Neuro-Oncology (2021)

Abstract Sarcopenia refers to a loss of skeletal muscle mass, which has been associated with increased risk of injury and decreased ability to perform activities of daily living. In multiple cancers including systemic lymphomas, sarcopenia has been strongly associated with survival and may be an important way to risk stratify patients in clinical trials as well as routine practice. Temporalis muscle width has been reported as an indicator of sarcopenia and independent predictor of outcomes in multiple settings including glioblastoma, brain metastases and subarachnoid hemorrhage. We evaluated temporalis width in primary CNS lymphoma (PCNSL) patients at presentation and outcomes. Using an institutional database of immunocompetent PCNSL patients treated at the University of Washington, two independent readers reviewed the initial MRIs for 104 patients who presented from 2011-2021 and measured the width of the temporalis muscle on axial T1 images. Median duration of follow up was 42.2 months (range 0.59-125.9 months). Median age at diagnosis was 65 (range 19-90 years), and patients were 42.8% male, 57.2% female. Interrater variability was acceptable with an average intraclass correlation coefficient of 0.934. Temporalis measurements were normally distributed, with mean 0.79 cm and standard deviation 0.18 cm. We divided patients into two groups, those with temporalis width less than or greater than 1 standard deviation below the mean (absolute value 0.60 cm). Temporalis width was strongly associated with survival among all patients (χ2=15.5, p&amp;lt; 0.001) as well as patients 65 years or older (χ2=4.5, p=0.03). We conclude that sarcopenia as measured by temporalis muscle thickness is associated with survival in PCNSL and may be an important variable to consider in clinical trials and routine practice.
Abstract 10281: Predictors of Gastrointestinal Bleeding in Patients Undergoing Percutaneous Mitral Valve Repair- A Us National Inpatient Database Analysis
Authors: Salman Zahid, Fnu Salman, Madeeha Shafaqat, Abid Nawaz Khan Adil, Abdul Baqi, Waqas Ullah, Hamza Muhammadzai, Mian Tanveer Ud Din, Muhammad Atif Khan, AAMER UBAID, Muhammmad Khan, Muhammad U Khan
Journal: Circulation (2021)

Introduction: Data on outcomes and predictors of gastrointestinal (GI) bleeding in patients undergoing percutaneous mitral valve repair (PMVR) remains limited. Hypothesis: GI bleed is associated with worse outcomes in patients undergoing PMVR Methods: We utilized the national inpatient sample data from the year 2015 to 2018 to evaluate outcomes and predictors of GI bleed in patients undergoing PMVR. Results: A total of 21,505 weighted hospitalizations were included in the analysis. Of the patients who underwent PMVR, 285 (1.3%) developed GI bleed whereas 21220 (98.7%) did not have in-hospital GI bleed event. The mean age of patient with and without GI bleed was 77 and 76 years respectively (P&lt;0.01). A logistic regression model was developed for adjusted comparison based on age, gender and baseline comorbidities. On adjusted comparison history of MI (OR 1.56, 95% CI 1.17-2.08), congestive heart failure (OR 1.79, 95% CI 1.18-2.73), African American race (OR 1.75, 95% CI 1.16-2.66) and history of weight loss (OR 2.71, 95% CI 1.97-3.74) were associated with significantly increased risk of gastrointestinal bleeding. Patients who developed GI bleed had significantly higher in-hospital mortality (8.8%) compared to non-GI bleeders (2.1%). Length of stay (16 vs. 4 days) and cost of hospitalization ($ 66118 vs. $49167) was significantly higher for GI bleeders undergong PMVR. Conclusions: In conclusion we report that GI bleed is associated with higher in-hospital mortality and resource utilization in patients undergoing PMVR.
Abstract 14067: A Novel Tool for Highly Reliable and Accurate Prediction of Multiple Complications in Patients Undergoing Percutaneous Coronary Intervention
Authors: David Hamilton, Milan Seth, Devraj Sukul, Hitinder S Gurm
Journal: Circulation (2021)

Introduction: Precise risk-prediction of post-procedural adverse events and outcomes after percutaneous coronary intervention (PCI) is critical to weighing treatment options and shared decision-making. Post-PCI complications are becoming less coming with quality improvement initiatives, however, there remains a significant risk for acute kidney injury (AKI), bleeding, and death. We hypothesized that with the use of random forest algorithms, we would be able to create accurate models to predict post-PCI complications. Methods: Our study cohort included 71,963 PCI procedures from the BMC2 registry performed at 48 hospitals in Michigan between 4/1/2018 and 9/30/2020. Random forest models were created using 74 pre-procedural clinical and laboratory variables to estimate the risk of each in-hospital outcome including mortality, AKI, major bleeding, and the need for a blood transfusion. A reduced model was created with the 20 most influential variables. The entire cohort was randomly separated into two groups for training (n=35,981) and validation (n=35,982). Model performance was evaluated in an independent validation data set using area under the receiver-operating characteristic curve (AUC). Results: The overall mortality was 1.76% (n = 1,264), there were 1,743 (2,42%) AKI events, 665 (0.92%) major bleeds, and 1,745 (2.42%) transfusions. The reduced models demonstrated excellent discrimination for all measured outcomes (Fig. 1) including mortality (AUC: 0.936 [95%CI 0.931-0.941]), AKI (AUC: 0.857 [95%CI 0.848-0.865]), major bleeding (AUC: 0.859 [95%CI 0.846-0.872]), and need for transfusion (AUC: 0.881 [95%CI 0.874-0.888]). Conclusions: The risk of post-PCI complications including mortality, AKI, major bleeding, and need for transfusion can be accurately calculated using a random forest algorithm of common pre-procedural factors to help better inform clinicians of a patient’s risk for better treatment selection and shared decision-making.
Abstract 13859: Efficacy and Safety of Ticagrelor Monotherapy versus Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Drug Eluting Stent in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Billy Joseph B David, Ferdinand R Gerodias, Althea Tanedo, John Derrik Tee
Journal: Circulation (2021)

Introduction: Dual AntiplateletTherapy(DAPT) with aspirinanda P2Y12inhibitoris the currentstandardofcareforthe preventionofthromboticeventsinpatientsundergoingpercutaneouscoronaryintervention(PCI). Type2Diabetes Mellitus (DM) patientsare a subgroupofpopulationwith higher risk ofbleedinganddevelopmentofthromboticeventsafter PCI. There is currentlylimited data onthe efficacy andsafety ofTicagrelormonotherapyinterms of bleeding and thrombotic event risk aftera short-course DAPT among DM patients undergoing PCI. Methods: A comprehensiveandrelevantsearch ofrandomizedcontrolledtrials (RCT) was conducted.Outcomemeasures formajorbleeding,myocardialinfarctionandall-cause mortalitywere extracted andanalyzedusingarandom effects model via Review Manager V5.3. Results: A totalofthree RCTs, with 7482subjects were analyzed.There were nosignificantdifferencesinmajorbleeding(p=0.26)andmyocardialinfarction(p=0.66)eventsbetweenthe TicagrelorandDAPT groups.However,there was a higher rate ofall-cause mortalityinthe DAPT group,which was statistically significant(RR 0.76[95%CI:0.59-0.98], p=0.03). Figure 1 Forestplotcomparison: Ticagrelor Monotherapyversus DAPT onBleedingRisk usingthe BleedingAcademic Research Consortium (BARC) 3 to 5 Figure 2 Forest plot comparison: Ticagrelor Monotherapyversus DAPT onAll Cause Mortality Figure 3 Forest plot comparison:Ticagrelor Monotherapyversus DAPT on Myocardial Infarction Conclusion: TicagrelormonotherapyandDAPT have similar rates ofmajorbleedingandmyocardialinfarctionamongDM patientsundergoingPCI with DES after initialshort-courseDAPT. However, DAPT strategy had a higherincidenceofall-cause mortality, which suggests that Ticagrelormonotherapymay be a preferableantiplateletstrategyin DM patients undergoing PCI.
Abstract 12554: A Quality Improvement Program to Promote Assessment of Social Determinants of Health among Patients in an Urban Community Clinic
Authors: Laura Lee L Hall, PAULA POLLARD-THOMAS, Henry Nuss, Heartley Egwuogu, Keith Ferdinand, Kristen Hobbs, Melvin Echols
Journal: Circulation (2021)

Introduction: Social determinants of health (SDoH) have been linked to poorer health outcomes and health disparities among patients (pts) with heart failure (HF). Attainment rates of selected SDoH indicators vary depending on the pt care environment. We sought to assess whether there are challenges in collecting SDoH indicators in an urban community clinic through a Plan-Do-Study-Act (PDSA) method of quality improvement (QI) using a physician-medical assistant team (PMAT). Methods: Using PDSA QI methodology, a trained PMAT tested use of an EHR-based survey to measure and record selected SDoH at each pt-visit over a span of four weeks. The survey includes questions about financial resource strain, housing stability, transportation needs, food insecurity and alcohol use. The target for improvement was input of SDoH indicators for 90% of consecutive patient visits. Successful completion of the survey required recording of responses for all SDoH measures. Results: Prior to the PDSA, SDoH indicators were collected in 51% of the pts seen between Jan 2019 and Dec 2020. Between April 26 and May 21, 2021, 114 pts were seen by the PMAT, with the SDoH indicators recorded in 88% of the pt-visits (n=101). Weekly rates ranged from 76.9%-100% (Week 1, 30/30 pts (100%); Week 2, 24/29 pts (82.7%); Week 3, 27/29 pts (93.1%); and Week 4, 20/26 pts (76.9%). Conclusion: The PMAT successfully increased measurement and recording of SDoH factors, although the target goal for improvement was not completely met 2 of the 4 weeks. Personnel substitutions and variable approaches to accessing the survey tool in the EHR resulted in smaller rates of improvement. Nonetheless the PDSA demonstrated the feasibility of increasing SDoH measurement. Expansion of the QI program will focus on clinic-wide staff training, standardization of SDoH assessment tool access in the EHR, and linking patients to resources with demonstrated social and economic needs identified by the SDoH survey tool.
Abstract 12602: Local NET Burden is Associated With Biomarkers of Thrombosis and Cardiac Damage in Left Atrial Cardiopathy
Authors: Kimberly Martinod, Annika Claessen, Caroline P Martens, Krystin Krauel, Leydi Carolina Pereira Velàsquez, Thilo Witsch
Journal: Circulation (2021)

Atrial cardiopathy results in disturbed blood flow, providing an ideal thrombogenic environment. Neutrophils promote large vessel occlusions and microthrombosis via release of neutrophil extracellular traps (NETs) and thus lie at the interface of (sterile) inflammation, thrombosis, and fibrosis. We profiled NETs, cytokines, thrombotic factors, and cardiac damage markers in left atrial (LA) cardiopathies together with LA structural analysis. A total of 71 patients (median age 66, 46.5% male) undergoing catheterization procedures with atrial transseptal access at the Freiburg Heart Center were enrolled in this prospective study. Paired samples were collected from peripheral blood draws or from within the left atrium (LA). NET biomarkers, sP-selectin, PAD4, proinflammatory cytokines, thrombotic factors (D-dimers, VWF, ADAMTS13), and cardiac damage markers (TropT, proBNP, ICTP) were measured in plasma or serum as appropriate. Echocardiography was performed to assess LA structure and left ventricular function. Data were analyzed by the type of procedure (MitraClip (MC), left atrial appendage closure (LAAC), pulmonary vein ablation (PVA), or patent foramen ovale closure (PFOC), and by atrial fibrillation (Afib) status at time of procedure. NETs, but not other markers, were elevated in local LA samples as compared to peripheral blood. Conversely, most thrombotic, inflammatory, and cardiac damage markers, but not NETs, were elevated in MC or LAAC as compared to PFOC or PVA patients. Across all patients, NET biomarkers positively correlated with IL-6/TNF-α, VWF, and cardiac damage biomarkers. PAD4/NETs negatively correlated with ADAMTS13 activity, indicating that citrullination may contribute to the prothrombotic phenotype of these patients. Afib was not key to these observations. NETs are locally elevated within the left atrium, with elevation of thrombosis markers including VWF in patients with a diseased left atrium. These elevations partly correlate with structural changes of the left atrium and, therefore, may point toward a disturbed local blood flow. This may provide insight on mechanisms that drive detrimental left atrial remodeling as well as clues regarding thromboembolic risks that are rooted in LA changes rather than Afib.