tbuckley/cabot-search huggingface dataset:
Abstract 11777: Global Radial Strain Predicts Cardiovascular Events in Patients With Myocarditis Related to the Use of Immune Checkpoint Inhibitors
Authors: Thiago Silva, Magid Awadalla, Malek Hassan, Amna Zafar, Zsofia Drobni, Carlos Gongora, Syed S Mahmood, Lili Zhang, Carol Chen, Stephane EDERHY, Ana Barac, Maeve Jones-O'Connor, Sean Murphy, Otavio R Coelho-filho, Muhammad Rizvi, GAGAN SAHNI, Tocchetti G Carlo Gabriele, Sarah Hartmann, Hannah Gilman, Eduardo Zatarain-Nicolás, Michael Mahmoudi, Dipti Gupta, Caroline Michel, Ana Gonzalez Mansilla, Antonio Calles, Marcella Cabral, Francisco Fernandez-Aviles, Juan Jose Gavira, Nahikari S Gonzalez, Manuel Y Garcia de Yebenes Castro, Jonathan Afilalo, Ryan Sullivan, Sarju Ganatra, Daniel Zlotoff, Eric Yang, Lucie Heinzerling, Franck Thuny, Leyre Zubiri, Kerry Reynolds, Alexander Lyon, Michael Fradley, Paaladinesh Thavendiranathan, Tomas Neilan
Journal: Circulation (2021)

Introduction: Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis. Hypothesis: We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications. Methods: Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of &gt;50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p&lt;0.01). This lower GRS value was noted in patients with both preserved EF (31.7±5.5 vs. 47.0±7.6, p&lt;0.001) and reduced EF (24.7±6.1 vs. 49.2±4.7, p&lt;0.005). In total, 28 events occurred during a median follow-up of 30 days. In survival analysis, a GRS &lt; the median (29.4%) was associated with an increased rate of events (HR: 3.92, 95% CI: 1.42-10.78, p=0.008) adjusted for age and LVEF. The association between GRS and events was also noted when the variable is treated as continuous adjusted for age and LVEF (HR: 1.07, 95% CI: 1.001-1.15 p=0.04). Conclusions: Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.
Abstract 11897: Prevalence of Abnormalities of Mineral Metabolism in Patients With Stable Coronary Artery Disease According to Renal Function
Authors: Hans P Gaebelt, Juan Martinez-milla, Ana M Pello, Marta Lopez-Castillo, Alvaro Acena, Carmen Cristobal, Tarin Nieves, Ana Huelmos, Maria L Gonzalez Casaus, Carlos Gutierrez Landaluce, oscar lorenzo, Ester Canovas, Andrea Kallmeyer, Joaquin Alonso, Jose tunon
Journal: Circulation (2021)

Background: Disturbances of mineral metabolism (MM) are present in pts. with stable coronary artery disease (SCAD) and average renal function. However, differences in these abnormalities in pts. with or without renal disease have not been reported previously. Purpose To describe the differences in MM markers (phosphate, calcidiol, parathormone [PTH], fibroblast growth factor23 [FGF23] and klotho) in patients with SCAD and estimated glomerular filtration rate (eGFR)&lt;60 ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60 ml/min/1.73 m2 (HGFR). Methods: We analyzed MM parameters in 964 patients with SCAD in five hospitals of Spain. Patients were divided in two subgroups: LGFR and HGFR. Total death was assessed during follow-up. eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Results: There were 790 pts. with HGFR and 174 with LGFR. Pts with LGFR were older and had more incidence of hypertension, diabetes, peripheral artery disease, history of cerebrovascular attack and prior coronary artery by-pass graft than those with HGFR. Left ventricular ejection fraction&lt;40%, and previous diagnoses of heart failure, and atrial fibrillation were also more common in LGFR pts. Phosphate, FGF23 and PTH plasma levels were higher in LFGR pts., while klotho levels were lower in this subgroup. Calcidiol plasma levels did not show significant differences between both subgroups. During follow-up (median 5.1 years), death by any cause was more frequent in patients with LGFR vs HGFR (17.2% vs 5.7%, respectively; p&lt;0.001). Conclusion: Pts. with SCAD and eGFR&lt;60 ml/min/1.73 m2 show lower klotho plasma levels, higher levels of phosphate, FGF23, and PTH, and increased mortality than those with eGFR≥60 ml/min/1.73 m2.
Higher frequency of comorbidities in fully vaccinated patients admitted to the ICU due to severe COVID-19: a prospective, multicentre, observational study
Authors: Anna Motos, Alexandre López-Gavín, Jordi Riera, Adrián Ceccato, Laia Fernández-Barat, Jesús F. Bermejo-Martin, Ricard Ferrer, David de Gonzalo-Calvo, Rosario Menéndez, Raquel Pérez-Arnal, Dario García-Gasulla, Alejandro Rodriguez, Oscar Peñuelas, José Ángel Lorente, Raquel Almansa, Albert Gabarrus, Judith Marin-Corral, Pilar Ricart, Ferran Roche-Campo, Susana Sancho Chinesta, Lorenzo Socias, Ferran Barbé, Antoni Torres
Journal: European Respiratory Journal (2021)

<b>Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population.</b>https://bit.ly/3Fw6vCP
Abstract 11576: Demand Ischemia in Patients with Diabetic Ketoacidosis : A Retrospective Analysis
Authors: Saad M Amin, Harsh Mehta, Dr. Shyam Shah
Journal: Circulation (2021)

Introduction: Demand ischemia (DI) or type 2 myocardial infarction refers to a mismatch between supply and demand of oxygen to myocardium leading to ischemia. Volume depletion is a cardinal feature of Diabetic Ketoacidosis (DKA) that can lead to decrease flow to myocardium. The purpose of this study is to document the incidence of demand ischemia in patients admitted with DKA. Methods: Using the Nationwide Inpatient Sample (NIS) for 2018, we performed a retrospective analysis of adults older than 18 years who were admitted to the hospital with a diagnosis of DKA. They were further divided in 2 groups. One group developed demand ischemia and the other group did not. Patients who suffered acute myocardial infarction were excluded from the study. Results: We had a total population of 202,505 that were admitted with the diagnosis of DKA, out of which 1685 (0.83%) patients suffered from demand ischemia. Comorbidities like prior diagnosis of DM, dyslipidemia, obesity, CKD, atrial fibrillation, chronic lung and liver disease were more prevalent in patients within the DI group (table 1). Complications like Acute kidney Injury (77.45% vs 39.77% p0.0001), Acute Respiratory Failure (15.43% vs 2.86% &lt;0.0001), Ventricular arrhythmias (2.37% vs 0.43%) and Sudden cardiac arrest (1.48% vs 0.25% p&lt;0.0001) occurred more frequently in DI subpopulation. Patients with DI underwent more procedures like angiography (12.46% vs 0.47% p&lt;0.0001) and angioplasty (0.89% vs 0.08% p&lt;0.0001). Overall, patients with DI had higher inpatient mortality (1.78% vs 0.42% p&lt;0.0001) and longer length of stay (table 1). Conclusions: With wider availability of high sensitivity Troponin early recognition of myocardial ischemia has become possible. Demand Ischemia in DKA patients carried a higher burden of comorbidities, had more complications, underwent a higher number of procedures and had significantly higher number of deaths. Closer monitoring and precise management are prudent to avoid poor outcomes.
Abstract 12681: Implication of Aurora Kinase B in Pulmonary Arterial Hypertension
Authors: Melanie Sauvaget, Sarah-eve Lemay, Sandra Breuils Bonnet, Mark Orcholski, Ghada Mkannez, Kana Schimauchi, Roxane Paulin, François Potus, Olivier BOUCHERAT, Sebastien Bonnet
Journal: Circulation (2021)

Objective: Pulmonary arterial hypertension (PAH) is a vascular disease characterized by a progressive remodelling of pulmonary arteries (PAs). This leads to an elevation in PA pressure and resistance, leading to right heart failure and death. Nowadays, it is recognized that PA smooth muscle cells (PASMCs) are key actors in the histopathological changes in PAH. As seen in cancer cells, PASMCs exhibit a pro-proliferative and anti-apoptotic cancer-like phenotype, sustained by an important metabolic switch known as Warburg effect. Aurora kinase B (AURKB) is strongly involved in cell proliferation, apoptosis and metabolism by controlling cell cycle activation and mitochondrial functions. Previous research has shown that AURKB is overexpressed in various human cancers and its inhibition repressed tumor progression both in vivo and in vitro, suggesting that it could be a novel therapeutic target in PAH. We thus hypothesized that AURKB is upregulated in PAH and contributes to PAH-PASMCs proliferation and resistance to apoptosis, inhibition of which may reverse PA remodeling. Methods/Results: Using Western blot (WB), we demonstrated a FOXM1-dependent upregulation of AURKB in PASMCs isolated from PAH patients compared to controls (p&lt;0.05 ; n=8-14). Similar results were found in the monocrotaline (MCT) and sugen-hypoxia (Su/Hx) rat models (p&lt;0.05 ; n=11-22). In vitro, we found that pharmacological inhibition of AURKB significantly decreases PAH-PASMC proliferation (EdU incorporation, Ki67 labeling) as well as resistance to apoptosis (Annexin V assay) (p&lt;0.05 ; n=6). We also demonstrated that inhibition of AURKB decreases pro-survival factors such as Survivin and PLK1 and increases apoptosis and cell cycle arrest factors including P21, P27, and P53 (WB; p&lt;0.05 ; n=6). As expected, inhibition of AURKB in PAH-PASMCs was associated with a dose-dependent decrease of phosphohistone H3 expression, a well-known target of AURKB (p&lt;0.05 ; n=6). The therapeutic potential of Barasertib, a clinically available and specific AURKB inhibitor, is currently investigated in both MCT and Su/Hx models. Conclusion: Our preliminary data suggests the contribution of AURKB in PA remodeling and the great potential of using AURKB inhibitors to reverse PAH development.
EXTH-34. ION CHANNELS AS A THERAPEUTIC TARGET IN PAEDIATRIC HIGH-GRADE GLIOMAS
Authors: Michaela Griffin, Stuart Smith, Raheela Khan, Surajit Basu, Joshua Branter
Journal: Neuro-Oncology (2021)

Abstract Pediatric Glioblastoma Multiforme (GBM) is a leading cause of CNS cancer-related death in children. The scarcity of treatments for GBM has opened the field to new pathways in adults, such as tumour treating fields(TTF). Studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence suggests that ion channels not only regulate electrical signalling of excitable cells, but are also crucial in the development/progression of brain tumours. Ion channels are essential in cell-cycle control, invasion and migration of cancer cells, therefore presenting as valuable therapeutic targets. Candidate ion channel genes(ICG) associated with high-grade glioma (HGG) were identified via analysis of inhouse and publicly available data sets. Expression patterns of selected ICGs were assessed along with clinician correlations.. Protein and RNA expression of target ICGs was assessed in pGBM cell lines/ TMAs. Finally, the Human ClariomTMS array was used for whole transcriptome gene expression analysis of paediatric GBM cell lines treated with tumour treating fields or low frequency electrical fields via deep brain stimulating electrodes. Paediatric brain tumour cells were exposed to genetic and pharmacological manipulation of CLIC1 and CLIC4 ion channels individually or in combination. We have shown that HGG exhibit increased expression of CLIC4 and CLIC1 at protein and RNA levels in both publically available data sets and inhouse cell lines / TMAs. Clinical correlation determined that high CLIC4 and CLIC1 expression was associated with poor overall survival. Further to this, DNA array analysis revealed a downregulation of CLIC1 and CLIC4 ion channels genes in KNS42 cells when treated with electrotherapy compared to untreated cells. Inhibition of CLIC1 and CLIC4 reduces Cl- flux across cell membranes and reduces cell proliferation. These data provide rationale that manipulation of ICGs will reduce the capacity of childhood brain tumours to proliferate and invade.
Abstract 14021: Brief Composite Mobility Index Predicts Post-Stroke Fallers After Hospital Discharge
Authors: Prudence Plummer, Jody Feld, Vicki Mercer, Pengsheng Ni
Journal: Circulation (2021)

Introduction: Community-dwelling, ambulatory stroke survivors fall at very high rates in the first 3-6 months. Current inpatient clinical assessments for fall risk have inadequate predictive accuracy. We found that a pre-discharge obstacle-crossing test has excellent specificity (87%) but lacks acceptable sensitivity (67%) for identifying would-be fallers and non-fallers post discharge. Hypothesis: We assessed the hypothesis that combining the obstacle-crossing test with other highly discriminatory mobility factors would compensate for the obstacle-test’s fair sensitivity and yield an instrument with superior prediction accuracy. Methods: 45 ambulatory stroke survivors (60±11 years old, 15±11 days post stroke) being discharged home completed a battery of mobility and dynamic balance performance-based and self-reported measures 1-3 days prior to discharge. After discharge, participants were prospectively followed for 3 months and classified as fallers (≥1 fall) or non-fallers at 3 months. Four pre-discharge measures with the largest effect sizes for differentiating fallers and non-fallers (obstacle-crossing test, Walk-12, 5-meter gait speed, and paretic-limb Step Test score) were combined into a composite index. Results: The composite index significantly differentiated those who subsequently fell (11.1±4.5 points) from non-fallers (4.8±4.1 points, d =1.46, p&lt;0.001). A person with an index discharge score of 11 was 6 times more likely to fall in the first 3-months post discharge than a person with a score of 5. The goodness of fit of the regression model with the composite index was significantly better than the model with only the obstacle-crossing test, χ 2 (1) = 6.036, p=0.014. Furthermore, whereas the obstacle-crossing test had acceptable discrimination (AUC 0.75, 95% CI 0.60-0.90), the composite index had excellent discrimination ability (AUC 0.85, 95% CI 0.74-0.96). Conclusion: Strategic aggregation of performance-based and self-reported mobility measures, including a novel and demanding obstacle-crossing test, can predict post-discharge fallers with excellent accuracy. This brief tool is highly pragmatic for inpatient use and may facilitate identification of high-risk stroke survivors before the first fall.
Abstract 11645: Use of an Electronic Health Record to Identify Implantable Cardiac Rhythm Device Lead Failure
Authors: Jonathan Brock, Richa Bundy, Gary Rosenthal, Larisa Rodgers, Prashant Bhave
Journal: Circulation (2021)

Introduction: Electronic health records (EHR) offer the potential to facilitate research examining the real-world effectiveness and safety of medical interventions. However, few studies have used EHR data to evaluate medical devices. This study sought to devise a method using current procedural terminology (CPT) and international classification of disease (ICD) codes captured in EHR data to identify patients with implantable cardiac rhythm device lead failures. Hypothesis: CPT and ICD diagnosis codes within an EHR can be used to correctly identify implantable cardiac rhythm device lead failures. Methods: Study data were extracted from the EHR of a large North Carolina health system. Patients who had implantable cardiac rhythm devices implanted during January 2013 to December 2018 were identified using predetermined CPT codes. Patients were followed longitudinally to identify those undergoing subsequent lead insertions or removals through December 2019. Medical records were reviewed to determine reasons for the re-insertion or removal and identify true lead failures. Random forest modeling was used to develop an algorithm for predicting true lead failure using CPT and ICD codes for mechanical breakdown or cardiac device complication. Patients with potential lead failure were split into two cohorts: 60% for model training and 40% for testing. Results: A total of 4,148 encounters with billed CPT codes for implantable cardiac rhythm devices were initially identified. After applying study exclusion criteria, 2,390 patients met study inclusion criteria. Of those, 175 patients had a subsequent insertion indicating a potential lead failure. A total of 31 patients were found to have true lead failures. A random forest algorithm predicted true lead failures with good discrimination, achieving an AUROC (area under receiver operating curve) of 0.908. The model accurately detected 66% of true lead failure cases in the testing dataset. Conclusions: Applying a specific combination of CPT and diagnosis codes to a cohort of patients undergoing subsequent implantable cardiac rhythm device procedures following an index insertion can correctly identify patients with lead failure with strong accuracy and moderate sensitivity.
Abstract 13449: Myocardial Infarction With Non-Obstructive vs Obstructive Coronary Arteries Among Patients With Acute Coronary Syndrome at a Large Safety-Net Hospital
Authors: Shruti Singh, Rina Mauricio, Sandeep R Das
Journal: Circulation (2021)

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been increasingly recognized. The differences between MINOCA and obstructive coronary artery disease (OCAD) patients have not been studied in lower socioeconomic status populations. Methods: The records of all patients undergoing angiography for ACS at a large Dallas County safety-net hospital from January 2018 to January 2020 were reviewed and categorized as MINOCA or OCAD. Results: During the study period, 592 cases of acute coronary syndrome (ACS) were identified; 10.8% (n=64) were MINOCA. OCAD patients had higher peak pre-angiography troponin compared with MINOCA patients (2498 vs 335 ng/L, p&lt;0.001). MINOCA patients were younger compared with OCAD patients (56 vs 60 y, p=0.01), while MINOCA men were younger than MINOCA women (53 vs 61 y, p=0.009). A higher proportion of MINOCA patients were Black, compared with OCAD (Figure 1). MINOCA patients had a lower prevalence of dyslipidemia and diabetes mellitus but there were no differences in the prevalence of smoking, hypertension, family history of premature CAD, current dialysis or heart failure between the groups. There were no differences in statin, aspirin, beta blocker or calcium channel blocker prescription at presentation between MINOCA and OCAD patients, regardless of sex. The majority of MINOCA patients (75%) did not have a definitive etiology of their ACS event by discharge. Conclusions: In this analysis of ACS patients presenting to a large safety-net hospital, MINOCA was common and MINOCA patients had many traditional risk factors. Men presented with MINOCA more commonly than has been seen in other studies. More Black patients presenting with ACS had MINOCA vs OCAD, likely reflecting the higher rates of left ventricular hypertrophy and diabetes in these patients. Lack of a definitive diagnosis for most MINOCA patients may reflect unfamiliarity with the diagnostic workup of MINOCA patients.
Abstract 9027: Predictors of Willingness to Change Dietary Patterns in Patients With Atrial Fibrillation
Authors: Jarred Strickling, Erica Mark, Sarah Swinehart, Joe Puthumana, Nishaki Mehta
Journal: Circulation (2021)

Introduction: There has been a significant body of international literature supporting the favorable role of diet and lifestyle interventions in improving outcomes in patients with atrial fibrillation (AF). US-based dietary studies are limited. We aimed to study the predictors for patients willing to consider diet changes so target populations can receive increased attention in regards to dietary education. Methods: We conducted a pilot telephone survey to discuss willingness to participate in guided dietary intervention in patients with AF at a tertiary care center. If the patients were willing to participate, the process would entail diet counseling via bi-weekly phone calls and monthly surveys to assess dietary compliance. There was no financial incentive offered for their participation. Chart review was done to collect patient characteristics. Zip code was used as a surrogate to determine income level based on census data. Results: We attempted to contact 409 patients of whom we were able to reach 162 (39%) patients. 59 patients (36%) were willing to consider diet modification (Group A) while the remainder patients declined (Group B). The average age for both groups was similar (69±8 and 68±9 years respectively). There were 38% and 47% women in groups A and B respectively (p=0.4) There was no difference in the BMI, type of atrial fibrillation, EF, history of hypertension, diabetes, CAD, CKD, anxiety or depression medication use. Social determinants such as marital status, insurance status was similar in both groups. The median income was $57,500 in the study population. The ratio of patients with income over this level was identical in Groups A and B (46 and 52% respectively, p =0.5)There were significantly higher proportion of Caucasian patients in Group A compared to Group B (p=0.02). Patients in Group A were on a lower number of medications compared to Group B (7.3±4 vs 9±4 respectively, p =0.03). Conclusions: Patient willingness is generally the first factor for successful implementation of lifestyle modifications. Determining the factors which drive this willingness or pose as barriers to lifestyle modification can assist in formulation of targeted intervention strategies.