TCT-66 Door to Impella Placement in Acute Coronary Syndrome Complicated by Cardiogenic Shock: An Updated Meta-analysis

Background: The impact of time to hemodynamic support in acute myocardial infarction complicated by cardiogenic shock (AMICS) has yet to be defined. The aim of this meta-analysis was to evaluate the impact of timing of mechanical circulatory support (MCS) with Impella. Methods: a systematic literature review and meta-analysis was conducted using PubMed and Cochrane databases. All studies reporting short-term mortality rates and timing of Impella insertion, pre vs during/post PCI, were included. Primary end point was short-term mortality (≤30 days), while secondary end pointswere midterm mortality, device-related bleeding and limb ischemia. Results: Of 1,289 studies identified, 13 studies (6,810 patients; 2,970 patients identified as receiving Impella before PCI and 3,840 patients receiving Impella during/after PCI) were included in this analysis. Median age was 63.8 years (IQR 63-65.7 years), 76% of patients were male, and a high prevalence of cardiovascular risk factors was noted across the entire population. Short-term mortality was significantly reduced in those receiving pre-PCI Impella support, 37.2% vs 53.6% (RR 0.7; CI 0.56-0.88). Midterm mortality was also lower in the pre-PCI group, 47.9% vs 73% (RR 0.81; CI 0.68-0.97). The rates of device-related bleeding (RR 1.05; CI 0.47-2.33) and limb ischemia (RR 1.6; CI 0.63-2.15) were similar between the two groups. Conclusion: This analysis suggests that MCS placement with Impella prior to PCI in AMICS may have a positive impact on short- and midterm mortality compared with post-PCI placement, with similar outcome in terms of safety. Categories: CORONARY: Hemodynamic Support and Cardiogenic Shoc

Timing of impella placement in PCI for acute myocardial infarction complicated by cardiogenic shock: An updated meta-analysis

INTRODUCTION: The timing of hemodynamic support in acute myocardial infarction complicated by cardiogenic shock (AMICS) has yet to be defined. The aim of this meta-analysis was to evaluate the impact of timing of Impella initiation on early and midterm mortality. METHODS: A systematic literature review and meta-analysis was conducted using PubMed and Cochrane databases. All studies reporting short-term mortality rates and timing of Impella placement in AMICS were included. Meta-regression analysis and sensitivity analysis were performed on the primary endpoint, short-term mortality (≤30 days), and secondary endpoints (midterm mortality, device-related bleeding, and limb ischemia). RESULTS: Of 1289 studies identified, 13 studies (6810 patients; 2970 patients identified as receiving Impella pre-PCI and 3840 patients receiving Impella during/post-PCI) were included in this analysis. Median age was 63.8 years (IQR 63-65.7); 76% of patients were male, and a high prevalence of cardiovascular risk factors was noted across the entire population. Short-term mortality was significantly reduced in those receiving pre-PCI vs. during/post-PCI Impella support (37.2% vs 53.6%, RR 0.7; CI 0.56-0.88). Midterm mortality was also lower in the pre-PCI Impella group (47.9% vs 73%, RR 0.81; CI 0.68-0.97). The rate of device-related bleeding (RR 1.05; CI 0.47-2.33) and limb ischemia (RR 1.6; CI 0.63-2.15) were similar between the two groups. CONCLUSION: This analysis suggests that Impella placement prior to PCI in AMICS may have a positive impact on short- and midterm mortality compared with post-PCI, with similar safety outcomes. Due to the observational nature of the included studies, further studies are needed to confirm this hypothesis (CRD42022300372)

CRT-700.05 Impella Utilization in High-Risk Percutaneous Coronary Intervention Mitigates the Risks of Procedural and Clinical Adverse Events Independent of Left Ventricular Ejection Fraction: The Protect III Study

Background: Left ventricular (LV) dysfunction is associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). However, the impact of LV ejection fraction (LVEF) on the outcomes of Impella-supported high-risk PCI (HRPCI) is unknown. Methods: Patients enrolled in the prospective, multicenter, and observational PROTECT III study from March 2017 to March 2020 who underwent Impella-supported HRPCI at the operator’s discretion (non-cardiogenic shock). Patients were divided into three tertiles (T) based on baseline LVEF: T1 (the lowest), T2, and T3 (the highest). The primary outcome is the rate of 90-day major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeated revascularization as adjudicated by an independent CEC. Results: Of 1237 patients, 940 with available baseline LVEF were analyzed. T1 included 353 patients (mean LVEF 19.6±4.7), T2 included 274 patients (mean LVEF 32.2±3.5), and T3 included 313 patients (mean LVEF 52.6±9.2). Patients in the higher tertiles were older, more likely to be females, presented more with acute coronary syndrome, and had more frequent left main disease. Also, severely calcified lesions and atherectomy utilization were more frequent in the higher tertiles. The rates of 90-day MACCE were comparable across all tertiles. Furthermore, PCI-related complications and 1-year mortality were also comparable (Table). After multivariable adjustment, 90-day MACCE was not significantly different between the LVEF tertiles (p=0.32). Conclusion: In patients with HRPCI supported by Impella, the rates of in-hospital adverse events, PCI-related complications, 90-day MACCE, and 1-year mortality were comparable among the different LVEF tertiles

TCT-545 Angiographic Features, Lesion, and Procedural Characteristics in Patients With Chronic Kidney Disease Undergoing Protected High-Risk Percutaneous Coronary Intervention

Background: Patients with chronic kidney disease (CKD) are at risk for accelerated atherosclerosis. There is a paucity of data regarding coronary lesion characteristics and procedural details of CKD patients, especially those on dialysis, undergoing high-risk percutaneous coronary intervention (HRPCI) with left ventricular support. Methods: We analyzed patients from the PROTECT III study who underwent Impella-supported HRPCI, stratified into 3 groups according to kidney function status based on history: 1) normal kidney function; 2) CKD not on dialysis; and 3) CKD on dialysis. Baseline characteristics, angiographic features, and procedural details were assessed. Results: The study population included 3,702 treated lesions in 1,223 patients with a mean age of 71 ± 11 years; 73% (893) were male, 68% (834) had normal kidney function (serum creatinine = 1 mg/dL [IQR: 0.9-1.2]), 23% (278) had CKD not on dialysis (serum creatinine = 1.6 mg/dL [IQR: 1.3-1.9]), and 9% (111) were on dialysis. Patients on dialysis were significantly younger and had more comorbidities, as well as a greater incidence of acute myocardial infarction as an indication for HRPCI compared with the other 2 groups (45.0 [dialysis] vs 30.1 [CKD not on dialysis] vs 36.0 [normal kidney function]; P = 0.03). There was no difference between groups in prevalence of 3-vessel disease (P = 0.63). Patients on dialysis had greater prevalence of severely calcified lesions and higher use of rotational and orbital atherectomy with greater number of passes (Table 1). Despite this, no significant differences were observed in post-PCI Thrombolysis In Myocardial Infarction flow, incidence of no-reflow, or dissection/perforation. Conclusion: In contrast to patients with normal kidney function, patients with CKD with or without dialysis treated with Impella had more comorbidities, higher prevalence of severely calcified lesions, and greater use of atherectomy with more passes. Despite the complexity of PCI, no significant differences in complications were observed. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

TCT-99 Short- and Long-Term Outcomes of Patients With Chronic Kidney Disease Undergoing Protected High-Risk Percutaneous Coronary Intervention

Background: Patients with chronic kidney disease (CKD) and concomitant multivessel coronary artery disease (CAD) with or without left ventricular dysfunction often have high surgical risk and are declined for coronary artery bypass grafting. There is little data regarding clinical outcomes in these patients undergoing high-risk PCI (HRPCI) using Impella. Methods: We analyzed patients from the PROTECT III Study who underwent Impella-supported HRPCI and stratified them into 3 groups by kidney function status based on history: 1) normal kidney function, 2) CKD without dialysis, and 3) CKD with dialysis. We compared the composite incidence of major adverse cardiac and cerebrovascular events (MACCE) rate, defined as all-cause death, myocardial infarction (MI), stroke/transient ischemic attack (TIA), and repeat revascularization at 30 and 90 days. Results: We included 1,223 patients, aged 71 ± 11 years; 73% (893) were men, 68% (834) had normal kidney function (serum creatinine [Cr] 1.1 mg/dL, IQR 0.9-1.2), 23% (278) had CKD without dialysis (Cr 1.7 mg/dL, IQR 1.3-1.9), and 9% (111) were on dialysis. Patients on dialysis were younger with more comorbidities such as diabetes, heart failure, anemia, PVD and prior stroke. HRPCI status (urgent or elective), proportion of acute MI, and mean SYNTAX scores were similar. No significant differences in MACCE were shown between groups at 30 days or 90 days (Table). Patients with normal kidney function had comparable risks of 30-day and 90-day MACCE compared with CKD patients without dialysis with Cox proportional hazards analysis, and lower risk of 90-day MACCE compared to CKD patients with dialysis. Notably, CKD patients with or without dialysis also had similar 90-day MACCE risk (Table). Conclusion: Patients with CKD and dialysis undergoing HRPCI exhibit higher risk for 90-day MACCE compared to patients with normal kidney function. CKD patients without dialysis also had higher risk of MI at 90 days. Further research is needed. Categories: CORONARY: Complex and Higher Risk Procedures for Indicated Patients (CHIP

Methane Clumped Isotopes: Progress and Potential for a New Isotopic Tracer

The isotopic composition of methane is of longstanding geochemical interest, with important implications for understanding petroleum systems, atmospheric greenhouse gas concentrations, the global carbon cycle, and life in extreme environments. Recent analytical developments focusing on multiply substituted isotopologues (‘clumped isotopes’) are opening a valuable new window into methane geochemistry. When methane forms in internal isotopic equilibrium, clumped isotopes can provide a direct record of formation temperature, making this property particularly valuable for identifying different methane origins. However, it has also become clear that in certain settings methane clumped isotope measurements record kinetic rather than equilibrium isotope effects. Here we present a substantially expanded dataset of methane clumped isotope analyses, and provide a synthesis of the current interpretive framework for this parameter. In general, clumped isotope measurements indicate plausible formation temperatures for abiotic, thermogenic, and microbial methane in many geological environments, which is encouraging for the further development of this measurement as a geothermometer, and as a tracer for the source of natural gas reservoirs and emissions. We also highlight, however, instances where clumped isotope derived temperatures are higher than expected, and discuss possible factors that could distort equilibrium formation temperature signals. In microbial methane from freshwater ecosystems, in particular, clumped isotope values appear to be controlled by kinetic effects, and may ultimately be useful to study methanogen metabolism

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The effect of pressure on the autoignition of octahydro -1,3,5,7,- Tetranitro, -1,3,5,7,-Tetrazine (HMX)

The autoignition of HMX under various conditions of initial pressure yields a family of curves similar to those encountered in rate of burning studies of propellents. From this a hypothesis that the two phenomena are coupled is developed. A description of current theories of thermal decomposition of explosives, autoignition techniques, and the polymorphs of HMX is presented. A new machine for sealing standard Pyrex melting point tubes under various conditions of initial pressure is described.http://www.archive.org/details/effectofpressure00trueLieutentant, United States Nav

NA

http://archive.org/details/analysisofnation00trueNAN