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TPS11578 Background: Conventional chondrosarcoma (cCS) accounts for ̃25% of primary bone cancers and is the second most common primary bone tumor after osteosarcoma. Surgical resection is the primary treatment for localized disease. No FDA approved therapy exists for advanced disease and chemotherapy has marginal efficacy with ORR < 12%. IDH1/2 mutation is seen in 50% of cases. Epigenetic dysregulation is central to oncogenesis in both IDH1/2 mutant and wild-type CS. Pre-clinical studies from our group show that combination treatment with HDAC and DNMT inhibitors is significantly more effective at suppressing the growth of CS models in vitro and in vivo compared to either therapy alone. The combination regimen mediates anti-tumor effects on CS by induction of apoptosis, induction of tumor suppressor genes (eg. E-cadherin), the induction of interferon responsive genes (eg. IRF7, OASL, ISG15, DDX58) and reversal of global hypomethylated state. Based on these findings we have designed a phase 2 clinical trial with an HDAC inhibitor (belinostat) and a DNMT inhibitor (guadecitabine) in patients with advanced cCS. Methods: NCI # 10330 is a single-arm, multi-center, Simon 2-stage, phase 2 clinical trial evaluating belinostat and guadecitabine in patients with advanced cCS. Eligible patients will have biopsy proven cCS which is measurable by RECIST v1.1 and amenable to biopsy, ECOG PS ≤ 2, any number of prior treatments (including none). Patients will receive guadecitabine 45 mg/m2 SC followed by belinostat 1000 mg/m2 IV once daily on days 1-5 of a 28-day cycle. A safety lead-in and continuous toxicity monitoring rule will be applied. The primary endpoint will be ORR. Since chemotherapy is associated with an ORR of 8-12% and targeted agents have shown an ORR of 0% in cCS, we will consider an ORR of 8% as inactive while an ORR of 28% will suggest promising activity. A Simon 2-stage design is employed. The design calls for 26 patients. If ≥ 2 responses are observed among 13 patients in stage I, the study will proceed to full accrual. If ≥ 5 responses are seen among 26 patients, the study treatment is considered promising. This design has 85% power with α of 0.054 to test for a response rate of 8% vs 28%. Secondary objectives include safety, tolerability and PFS. All patients will undergo pre-treatment and on-treatment tumor biopsies. Paired tissue will be used for correlative analysis including: 1) whole exome sequencing/RNAseq to evaluate changes in gene expression in response to treatment, 2) multiplex IHC to interrogate the effect of combination therapy on tumor immune microenvironment and 3) a global DNA methylation assay to better understand the changes in epigenetic landscape in response to treatment. This study is open throughout the ETCTN (NCT04340843). Six of the planned 26 patients in the safety lead-in have been enrolled without DLT. Further accrual is on hold pending completion of the safety lead-in. Clinical trial information: 04340843.

Background The role of race and ethnicity in the outcomes of cardiac arrest (CA) complicating acute myocardial infarction (AMI) is incompletely understood. Methods and Results This was a retrospective cohort study of adult admissions with AMI‐CA from the National Inpatient Sample (2012–2017). Self‐reported race/ethnicity was classified as White, Black, and others (Hispanic, Asian or Pacific Islander, Native American, Other). Outcomes of interest included in‐hospital mortality, coronary angiography, percutaneous coronary intervention, palliative care consultation, do‐not‐resuscitate status use, hospitalization costs, hospital length of stay, and discharge disposition. Of the 3.5 million admissions with AMI, CA was noted in 182 750 (5.2%), with White, Black, and other races/ethnicities constituting 74.8%, 10.7%, and 14.5%, respectively. Black patients admitted with AMI‐CA were more likely to be female, with more comorbidities, higher rates of non–ST‐segment–elevation myocardial infarction, and higher neurological and renal failure. Admissions of patients of Black and other races/ethnicities underwent coronary angiography (61.9% versus 70.2% versus 73.1%) and percutaneous coronary intervention (44.6% versus 53.0% versus 58.1%) less frequently compared to patients of white race ( p <0.001). Admissions of patients with AMI‐CA had significantly higher unadjusted mortality (47.4% and 47.4%) as compared with White patients admitted (40.9%). In adjusted analyses, Black race was associated with lower in‐hospital mortality (odds ratio [OR], 0.95; 95% CI, 0.91–0.99; P =0.007) whereas other races had higher in‐hospital mortality (OR, 1.11; 95% CI, 1.08–1.15; P <0.001) compared with White race. Admissions of Black patients with AMI‐CA had longer length of hospital stay, higher rates of palliative care consultation, less frequent do‐not‐resuscitate status use, and fewer discharges to home (all P <0.001). Conclusions Racial and ethnic minorities received less frequent guideline‐directed procedures and had higher in‐hospital mortality and worse outcomes in AMI‐CA.

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000–2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age‐, sex‐, and race‐stratified trends in CABG use; in‐hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98–0.98]; P <0.001), in ST‐segment–elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95–0.95]; P <0.001) and non–ST‐segment–elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99–0.99]; P <0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non–ST‐segment–elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In‐hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88–0.89 [ P <0.001]) in the overall cohort, with similar temporal trends in patients with ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST‐segment–elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in‐hospital mortality consistently decreased in this population.

AbstractBackgroundThere is a paucity of literature on safety and efficacy of various transseptal puncture (TSP) needles.ObjectivesTo assess the reported mechanisms of failure, complications, and outcomes among the most frequently used transseptal needles in the United States.MethodsWe queried the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database between January 2011 and January 2021 for reports on the most commonly used transseptal needles: NRG (Baylis Medical, Montreal, Canada), and BRK (St. Jude, Saint Paul, MN)]. The primary outcome was the mechanism of failure. Secondary outcomes included clinical consequences of device failure.ResultsThe final analysis included 306 reports of failure/complication with TSP needles (NRG n = 70, BRK n = 236). The most commonly reported mode of failure was detachment of the needle component (i.e., clip, hub, stopcock, shaft, spring, or needle tip) (14.7% overall; 17.8% BRK; and 4.3% NRG). Among these reports, cardiac perforation was the most common complication (69.9% overall; 69.1% for BRK; and 72.9% for NRG). Pericardiocentesis was the second most commonly reported complication (45.1% overall; 48.3% for BRK; and 34.3% for NRG). The procedure was successfully completed in 33.3% of all cases (36.4% for BRK and 22.9% for NRG), while surgical conversion was needed in (13.4% overall; 14% for BRK and 11.4% for NRG) of the reports. Death occurred in 3.9% of all cases overall (3.4% for BRK and 5.7% for NRG).ConclusionsNeedle detachment was the most common mode of failure, and cardiac perforation was the most common complication reported with TSP needles. Future efforts should focus on innovative TSP needle design, best practice guidelines, including role of imaging guidance, and increased TSP training.

Background: Ranolazine has the potential to prevent atrial fibrillation (AF) and plays a role in rhythm control strategy for atrial fibrillation in various clinical settings. However, data on the use of ranolazine in patients with left ventricular (LV) systolic dysfunction are limited. The aims of this meta-analysis of randomized clinical trials are to investigate the efficacy and safety of ranolazine in AF patients with LV systolic dysfunction. PubMed and the Cochrane Database of Systematic Reviews were searched until July 2020. The efficacy outcomes included the incidence of new-onset AF, the rate of sinus rhythm restoration, and the time until sinus rhythm restoration. Safety endpoints were at death, and any adverse events were reported in the enrolled studies. We initially identified 204 studies and finally retrieved 5 RCTs. Three studies were analyzed in the meta-analysis. Among AF patients with LV systolic dysfunction, our meta-analysis showed that the combination of ranolazine to amiodarone significantly increased the sinus rhythm restoration rate compared to amiodarone alone (risk ratio (RR) 2.87, 95% confidence interval (CI) 2.48–3.32). Moreover, the time to sinus rhythm restoration was 2.46 h shorter in the ranolazine added to amiodarone group (95% CI: 2.27–2.64). No significant adverse events and proarrhythmias in the ranolazine group were identified. In conclusion, in AF patients with LV systolic dysfunction, ranolazine as an add-on therapy to amiodarone potentiates and accelerates the conversion of AF to sinus rhythm. Moreover, ranolazine shows good safety profiles. Further studies to investigate the effectiveness of ranolazine in the prevention of new-onset AF among patients with LV systolic dysfunction are needed.

Abstract Aims This study aims to evaluate the impact of the combination of cardiogenic shock (CS) and cardiac arrest (CA) complicating non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results Adult (&gt;18 years) NSTEMI admissions using the National Inpatient Sample database (2000 to 2017) were stratified by the presence of CA and/or CS. Outcomes of interest included in-hospital mortality, early coronary angiography, hospitalization costs, and length of stay. Of the 7 302 447 hospitalizations due to NSTEMI, 147 795 (2.0%) had CS only, 155 522 (2.1%) had CA only, and 41 360 (0.6%) had both CS and CA. Compared with 2000, the adjusted odds ratios (ORs) and 95% confidence interval (CIs) for CS, CA, and both CS and CA in 2017 were 3.75 (3.58–3.92), 1.46 (1.42–1.50), and 4.52 (4.16–4.87), respectively (all P &lt; 0.001). The CS + CA (61.2%) cohort had higher multiorgan failure than CS (42.3%) and CA only (32.0%) cohorts, P &lt; 0.001. The CA only cohort had lower rates of overall (52% vs. 59–60%) and early (17% vs. 18–27%) angiography compared with the other groups (all P &lt; 0.001). CS + CA admissions had higher in-hospital mortality compared with those with CS alone (aOR 4.12 [95% CI 4.00–4.24]), CA alone (aOR 1.69 [95% CI 1.65–1.74]), or without CS/CA (aOR 22.66 [95% CI 22.06–23.27]). The presence of CS, either alone or with CA, was associated with higher hospitalization costs and longer hospital length of stay. Conclusions The combination of CS and CA is associated with higher rates of acute non-cardiac organ failure and in-hospital mortality in NSTEMI admissions as compared with those with either CS or CA alone.

AbstractAims and ObjectivesTo determine the level of convergent validity of the ‘6‐Clicks’ Basic Mobility and Daily Activity with the Bedside Mobility Assessment Tool (BMAT) in patients admitted to a tertiary care academic hospital.BackgroundAccurately measuring a patient's ability to mobilise during hospitalisation is necessary but can be challenging. Two instruments, the Activity Measure for Post‐Acute Care short‐form ‘6‐Clicks’ and the BMAT, are commonly used to determine patients’ mobility levels; however, these instruments have not been psychometrically evaluated together. Understanding the characteristics between these tools can support the process of shared decision making amongst healthcare providers.DesignRetrospective Cohort adhering to the STROBE statement.MethodsUsing 13,498 individual patient admissions from an electronic health record, the BMAT score measured closest in time to the ‘6‐Clicks’ Basic Mobility and Daily Activity evaluation was collected. Spearman rank correlations with 95% confidence intervals (CIs) were calculated to determine the level of convergent validity between the ‘6‐Clicks’ Basic Mobility and Daily Activity with the BMAT. Pairwise correlations were also calculated and stratified by admitting medical service.ResultsAll correlations for the ‘6‐Clicks’ Basic Mobility or Daily Activity summative scores and the BMAT mobility levels were statistically significant and moderately correlated. The weakest correlations were seen within the Orthopaedic admitting service group. Most correlations stratified by admitting service [CVD/Pulmonary, Medicine/Hospitalist, Other Surgery and Solid Organ Transplant] were moderate. The strongest correlations were seen within the Neuro/Stroke admitting service.ConclusionModerate levels of convergent validity exist between the ‘6‐Clicks’ and the BMAT in this sample. These findings demonstrate that the construct of patient mobility is not being assessed similarly between the two instruments.Relevance to Clinical PracticeThese findings suggest the continued use of both instruments to allow interdisciplinary assessment of patient mobility status during a hospital stay.

Racial disparities in utilization and outcomes of mechanical circulatory support (MCS) in patients with acute myocardial infarction-cardiogenic shock (AMI-CS) are infrequently studied. This study sought to evaluate racial disparities in the outcomes of MCS in AMI-CS. The National Inpatient Sample (2012–2017) was used to identify adult AMI-CS admissions receiving MCS support. MCS devices were classified as intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD) or extracorporeal membrane oxygenation (ECMO). Self-reported race was classified as white, black and others. Outcomes included in-hospital mortality, hospital length of stay and discharge disposition. During this period, 90,071 admissions were included with white, black and other races constituting 73.6%, 8.3% and 18.1%, respectively. Compared to white and other races, black race admissions were on average younger, female, with greater comorbidities, and non-cardiac organ failure (all p < 0.001). Compared to the white race (31.3%), in-hospital mortality was comparable in black (31.4%; adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.93–1.05); p = 0.60) and other (30.2%; aOR 0.96 (95% CI 0.92–1.01); p = 0.10). Higher in-hospital mortality was noted in non-white races with concomitant cardiac arrest, and those receiving ECMO support. Black admissions had longer lengths of hospital stay (12.1 ± 14.2, 10.3 ± 11.2, 10.9 ± 1.2 days) and transferred less often (12.6%, 14.2%, 13.9%) compared to white and other races (both p < 0.001). In conclusion, this study of AMI-CS admissions receiving MCS devices did not identify racial disparities in in-hospital mortality. Black admissions had longer hospital stay and were transferred less often. Further evaluation with granular data including angiographic and hemodynamic parameters is essential to rule out racial differences.