bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody-Drug Conjugates for Breast Cancer
Authors: Marmé Frederik
Published: December 2021

Background: Despite the advances that have been made to improve conventional chemotherapies, their use is limited by a narrow therapeutic window based on off-target toxicities. Antibody-drug conjugates (ADCs) are composed of an antibody and a toxic payload covalently coupled by a chemical linker. They constitute an elegant means to tackle the limitations of conventional chemotherapeutics by selectively delivering a highly toxic payload directly to target cells and thereby increasing efficacy of the delivered cytotoxic but at the same time limiting systemic exposure and toxicities. As such, they appear inspired by Paul Ehrlich’s concept of a “magic bullet,” which he envisioned as drugs that go directly to their target to attack pathogens but remain harmless in healthy tissues. Summary: The concept of conjugating drugs to antibodies via chemical linkers is not new. As early as in the 1960s, researchers started to investigate such ADCs in animal models and first clinical trials based on mouse antibodies began in the 1980s. Although the concept appears relatively straightforward, ADCs are highly complex molecules, and it took several decades of research and development until the first ADC was approved by the FDA in 2000 and the second followed not until 11 years later. The development of an effective ADC is highly demanding, and each individual component of an ADC must be optimized: the target, the antibody, the linker, and its conjugation chemistry as well as the cytotoxic payload. Today, there are 9 approved ADCs overall and 3 for breast cancer. So, the pace of development seems to pick up with over 100 candidates in various stages of clinical development. Many ADCs of the newest generation are optimized to elicit a so-called bystander effect, to increase efficacy and tackle heterogeneous antigen expression. This approach requires a balancing of efficacy and systemic toxicity. Hence, ADCs based on their complex biology cause relevant toxicities, which are characteristic for each specific compound and may include hematologic toxicities, elevated transaminases, gastrointestinal events, and pneumonitis but also ocular toxicities as well as others many physicians may initially not be very familiar with. Management of the side effects will be key to the successful clinical use of these potent drugs. Key Messages: This review focusses on the clinical experience with ADCs approved in breast cancer as well as promising candidates in late-stage clinical development. We will discuss the mode of action, biology, and composition of ADCs and how each of these crucial components influences their properties and efficacy.
Abstract 10125: Continuous Heart Rate Dynamics Preceding In-Hospital Cardiac Arrest of Respiratory Etiology
Authors: Shan Rongzi , Hu Xiao , Boyle Noel G , Do Duc H
Published: December 2021

Introduction:
Respiratory failure is a common cause of pulseless electrical activity (PEA) arrest in hospitalized patients, but how pathophysiologic changes in these conditions affect heart rate (HR) pre-arrest is not well described. We describe HR dynamics prior to in-hospital cardiac arrest (IHCA) among PEA/asystole arrest patients with respiratory etiology.

Methods:
In this retrospective descriptive study, we evaluated 67 patients with ≥3 hours of continuous ECG data recorded immediately preceding PEA/asystole IHCA in a single institution from 2010-2014. We identified respiratory arrest cases (eg. pneumonia, aspiration, pulmonary embolism, acute respiratory distress syndrome) by chart review and evaluated ECG patterns up to 24 hours prior to arrest to identify patterns of HR increase, HR decrease, sinus arrest, and escape rhythms.

Results:
We identified 31/67 patients with respiratory etiology (age 59±17 years, 52% male, 83% return of spontaneous circulation, 41% survived to discharge); of these 23/31(74%) fit an a priori model of HR response (Figure). Twelve cases demonstrated clear onset of HR increase at a median of 44 (IQR 28-507) minutes prior to arrest, while the remaining 11 cases started the monitoring period in sinus tachycardia. The mean peak HR was 120±20 bpm. An abrupt onset of HR decrease occurred at a median of 3.4 (IQR 2.3-5.9) minutes prior to arrest. Sinus arrest occurred during the HR decrease phase in 18/23 cases; the first escape rhythm was atrial in 11 (61%), junctional in 2 (11%) and ventricular in 3 (17%) cases.

Conclusion:
The majority of IHCA due to respiratory etiology (74%) follow a typical model of HR increase due to physiologic compensation to hypoxia, followed by rapid HR decrease leading to PEA arrest, likely from the vagal effect of hypoxia and sinus node suppression from acidosis. Understanding HR trends can aid clinical management as well as development of artificial intelligence models for prediction of IHCA.
Abstract 10169: Changes in Cytokine Responses by Treatment with Tocilizumab After Out-of-Hospital Cardiac Arrest - A Sub Study of the IMICA Trial
Authors: Meyer Martin A , Bjerre Mette , Wiberg Sebastian , Grand Johannes , Meyer Anna Sina P , Obling Laust E , Kjaergaard Jesper , Hassager Christian
Published: December 2021

Background:
Out-of-hospital cardiac arrest (OHCA) patients are at high risk of morbidity and mortality attributable to the post-cardiac arrest syndrome, in which systemic inflammation is a major component. Cytokines are involved in many processes, including inflammation. In the IMICA trial, treatment with the interleukin 6 receptor (IL-6R) antagonist tocilizumab in resuscitated comatose OHCA patients reduced systemic inflammation as characterized by a greatly reduced CRP response and lower levels of leukocytes as compared to placebo. Markers of myocardial injury were also reduced by treatment.

Aim:
To investigate changes in cytokine levels induced by blocking the IL-6-mediated signaling with tocilizumab after OHCA by employing a broad cytokine panel.

Methods:
We randomized 80 patients to a single infusion of tocilizumab 8 mg/kg or placebo after admission. Blood samples were drawn at 0, 24, 48, and 72 hours. Cytokines were measured using a 17-plex cytokine assay: G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1β, TNF-α, IL- 1β, 2, 4-8, 10, 12, 13, and 17. Data were log2 transformed and analyzed by constrained linear mixed models.

Results:
Most cytokines had temporal changes after OHCA. However, only for IL- 5, 6 (Figure) and 17 were the treatment-by-time interactions significant, all p<0.05. Circulating IL-5 and in particular IL-6 was markedly increased by inhibition of the IL-6R with tocilizumab as compared to the placebo group. For IL-17 the changes were less pronounced and only differed between groups at 72 hours.

Conclusions:
Treatment with the IL-6R antagonist, tocilizumab, did not alter the cytokine responses in general, however, IL-5 and IL-6 were markedly increased. Experimental data suggests that IL-5 may play a role in cardiac recovery after ischemia. Blockage of the IL-6R greatly increased the IL-6 levels, and as the CRP response was greatly reduced by tocilizumab, a response strongly associated with IL-6, it can be demonstrated that the function of IL-6 was blunted.
Abstract 10327: Protected Mock Codes Using
In-situ
Simulation in Times of the COVID-19 Pandemic
Authors: Wan Lai Ping Atalanta
Published: December 2021

Introduction:
Our hospital faced an uphill battle with increasing clinical emergencies, a surge of patients, and compliance with the new regulations during the COVID-19 pandemic. Thereby, the code blue team developed a protected code blue protocol to minimize the infectious risk of the code team members and provide efficient management of emergencies during a lifesaving situation.

Objectives:
This project aimed to help the core team members to practice the new protected code blue protocol using in-situ simulation. The drills might improve the self-confidence of the code team members in performing their role, clear identification of themselves, effective communication skills, and teamwork.

Methods:
The mock code team developed different scenarios and ran the drills in 17 departments in different shifts within 8 weeks. A convenience sample of 269 staff participated in the drills. Participants included physicians, respiratory therapists, nurses, and other disciplinary staff. A debriefing was conducted to identify areas of improvement. Participants completed an evaluation form during the debriefing. The form included questions using a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree) to rate the variables. Descriptive statistics and the Pearson correlation coefficient were used to test the hypotheses.

Results:
Out of the 269 participants, 125 staff completed and returned the evaluation form. The mean overall rating of the protected mock codes was 4.184 at a scale from 1 (very poor) to 5 (excellent) with a standard deviation of .827. The Pearson correlation coefficient (
r
) between the overall rating of the training and the amount of self-confidence in performing their role was .697 (
p
=.000); clear identification of themselves was .329 (
p
= .000); effective communication skills was .500 (
p
= .000); and teamwork was .526 (
p
= .000).

Limitations:
The project was conducted in a teaching hospital. The results might not apply to different care delivery settings.

Conclusions:
The findings of this project demonstrated that in-situ simulation improved the self-confidence of the code team members, communication skills, and teamwork in performing the protected code blue protocol for a COVID-19 suspected or confirmed patient with cardiac arrest.
Abstract 10394: Long-Term Functional and Quality-of-Life Outcomes of Cardiac Arrest Survivors Stratified by Shock Provider: A 10 Year Retrospective Study
Authors: Haskins Brian A , Nehme Ziad , Andrew Emily , Bernard Stephen , Cameron Peter , Smith Karen L
Published: December 2021

Introduction:
To assess the long-term functional recovery and health related quality-of-life (HRQoL) outcomes for out-of-hospital cardiac arrest (OHCA) survivors stratified by shock provider.

Methods:
We included adult OHCA in initial shockable rhythms between 2010-2019. Those surviving to 12 months post arrest were invited to participate in telephone interviews to identify functional recovery and HRQoL outcomes, using the following assessment tools, Glasgow Outcome Scale-Extended (GOS-E), EuroQol-5D (EQ-5D), and 12-Item Short Form (SF-12).

Results:
Of the 1,581 patients surviving to 12 months, 1,325 (85.5%) responded to the interviews, of these, 227 (17.1%) and 144 (10.9%) were initially shocked by bystanders and first responders, respectively. A higher proportion of patients shocked by bystanders were located in public (p<0.001), received bystander CPR (p<0.001) and received initial defibrillation faster from time of collapse (P<0.001). Survivors receiving bystander defibrillation reported higher rates of living at home without care (p=0.004), upper good recovery (GOS-E) (p=0.008) and EQ-5D index score of 1 (perfect health) (p=0.023). After adjustment, bystander defibrillation was associated with a 64% increase in the odds of an EQ-5D current Visual Analogue Scale ≥ 80 (AOR 1.64, 95%CI: 1.17-2.31; p=0.004) and a 45% increase in the odds of a good functional recovery (GOS-E ≥ 7) (AOR 1.45, 95% CI: 1.02-2.06; p=0.037), than those initially shocked by paramedics. No improvement in adjusted outcomes were observed for survivors initially defibrillated by first responders.

Conclusion:
Patients receiving bystander defibrillation reported better functional recovery and HRQol outcomes at 12 months compared to those defibrillated by first responders and paramedics.
Abstract 10476: Patient Characteristics and Survival Outcomes of Cardiac Arrest in the Cardiac Catheterization Laboratory: Insights from Get with the Guidelines-Resuscitation Registry
Authors: Elkaryoni Ahmed , Lopez John J , Chan Paul S
Published: December 2021

Background:
The characteristics and outcomes of in-hospital cardiac arrest (IHCA) in the cardiac catheterization laboratory (CCL) have not been well-described. We compared the characteristics and outcomes of patients with an IHCA in the CCL versus those in the operating room (OR) and the intensive care unit (ICU).

Methods:
Within the American Heart Association’s Get With the Guidelines-Resuscitation® registry, we identified patients 18 years of age or older with an IHCA in the CCL, OR, or ICU between 2000 and 2019. We compared rates of survival to discharge for patients in the CCL, OR, and ICU. Additionally, we examined predictors of survival to discharge for patients with IHCA in the CCL.

Results:
There were 6866, 5181, and 181,832 patients with an IHCA in the CCL, OR, and ICU, respectively. Patients with IHCAs in the CCL were more likely to have a shockable cardiac arrest rhythm as compared with those in the OR and ICU. Overall, 2614 (38.1%) patients with IHCA in the CCL survived to discharge, as compared with 30,833 (16.9%) from the ICU and 2096 (40.5%) from the OR. After adjustment for 27 patient and cardiac arrest factors, patients with IHCA in CCL were more likely to survive to discharge as compared with those with IHCA from the ICU (odds ratio, 1.37 [95% CI: 1.29-1.46], p<0.001). In contrast, they were less likely to survive to discharge as compared with those with IHCA in the OR (odds ratio, 0.81 [95% CI: 0.69-0.94], p=0.006). Predictors of survival to discharge in patients with IHCA in the CCL included white race, pulseless ventricular tachycardia/fibrillation, and IHCA during normal hours and on weekdays, while having myocardial infarction during this or prior hospitalization was associated with less survival to discharge. (Table).

Conclusion:
IHCA in the CCL is not uncommon and has a lower survival rate as compared with IHCA in other procedural areas such as the OR. The reasons for this difference deserve further study given that response to IHCAs in both settings should be similar.
Abstract 10559: Association of Intra-Arrest Transport versus Continued On-scene Resuscitation with Survival to Hospital Discharge Among Pediatric Patients with Out-of-Hospital Cardiac Arrest
Authors: Okubo Masashi , Komukai Sho , Izawa Junichi , Drennan Ian , Grunau Brian , Rea Thomas , CALLAWAY Clifton W
Published: December 2021

Introduction:
For pediatric patients with out-of-hospital cardiac arrest (OHCA) who do not achieve return of spontaneous circulation (ROSC), it remains unclear whether patients should be transported to a hospital with ongoing resuscitation or remain on-scene for further resuscitation. We therefore evaluated: (1) the association between intra-arrest transport, with reference to continued on-scene resuscitation, and survival to hospital discharge; and, (2) whether the association differs across the timing of intra-arrest transport.

Methods:
We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epidemiologic Registry. We included pediatrics (<18 years) with emergency medical services (EMS)-treated OHCA between 2005 and 2015. Our exposure of interest was intra-arrest transport, defined as transport to a hospital prior to ROSC. Patients who had intra-arrest transport at any minute after EMS arrival underwent risk-set matching with patients who had continued on-scene resuscitation within the same minute using time-dependent propensity score calculated from patient demographics, arrest characteristics, and EMS interventions. We repeated the main analysis with 5-minute strata by the time of matching.

Results:
Of 2,854 included patients, the median age was 1 year (IQR, 0-9), 59.3% were male, 9.8% were public location, 22.1% were bystander witnessed, 6.0% had initial shockable rhythms, and 66.3% underwent intra-arrest transport at a median of 15 minutes (IQR 9-22) after EMS arrival. In the propensity-matched cohort including 2,080 patients, 5.5 % (57/1040) in intra-arrest transport group and 5.9% (61/1040) in continued on-scene resuscitation group had survival to hospital discharge (risk ratio [RR]=0.94, 95% CI 0.65-1.37). We did not detect an association within the time-based strata: 0-5 minutes (RR=0.74, 95% CI 0.19-2.85), 5-10 minutes (RR=0.52, 95% CI 0.23-1.16), 10-15 minutes (RR=1.13, 95% CI 0.58-2.22), 15-20 minutes, (RR=1.70, 95% CI 0.78-3.71), or >20 minutes (RR=0.73, 95% CI 0.32-1.63) after EMS arrival.

Conclusions:
Among pediatric patients with OHCA, intra-arrest transport was not associated with survival to hospital discharge. The findings persisted across the timing of intra-arrest transport.
Abstract 10617: Antiarrhythmic Use and the Posterior Probability of Neurologically Intact Survival in a Reanalysis of the Amiodarone, Lidocaine or Placebo Study in Out-of-Hospital Cardiac Arrest
Authors: Brown Frederick J , Rigdon Steven E , Brown David L
Published: December 2021

Introduction:
There are no randomized controlled trials (RCT) demonstrating improvement in neurologically intact survival from antiarrhythmic therapy given during out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation/tachycardia (VF/VT). The Amiodarone, Lidocaine or Placebo Study in Out-of-Hospital Cardiac Arrest (ALPS) was an RCT of amiodarone, lidocaine or placebo whose primary end-point was survival to hospital discharge. We sought to estimate the posterior probability of the absolute risk difference of neurologically intact survival (modified Rankin Score ≤ 3) from antiarrhythmic use (amiodarone or lidocaine) compared to placebo and from the use amiodarone versus lidocaine.

Methods:
We performed a Bayesian reanalysis on the per-protocol population of the ALPS trial in order to calculate the posterior probability of neurologically intact survival. We derived prior probabilities from the Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation (ARREST) and Amiodarone Compared with Lidocaine for Shock-Resistant Ventricular Fibrillation (ALIVE) trials. We considered a clinically meaningful absolute difference to be ≥ 1%.

Results:
The posterior median probability of the absolute difference in neurologically intact survival between antiarrhythmic therapy and placebo was 2.2% (95% credible interval of -0.15% to 4.7%). There is a 96% chance that antiarrhythmic improves neurologic outcome and 86% chance of a clinically meaningful improvement. The posterior median probability of the absolute difference in neurologically intact survival between amiodarone and lidocaine was 1.5% (95% credible interval -1.6% to 4.5%).

Conclusion:
The results of this Bayesian analysis of the ALPS trial using likely optimistic prior probabilities derived from the ARREST trial may help inform clinicians of the value of antiarrhythmic therapy in OHCA.
Abstract 11036: Enhanced Oxygen Utilization Efficiency with Concomitant Activation of the AMPK-TBC1D1 Signaling Nexus in Cyclophilin-D Conditional Knock-Out Mice
Authors: Radhakrishnan Jeejabai , Baetiong Alvin , Gazmuri Raul J
Published: December 2021

We have previously reported in HEK 293T cells and in constitutive cyclophilin-D (Cyp-D) knock-out (KO) mice that Cyp-D ablation downregulates oxygen consumption (VO
2
) and triggers an adaptive response that manifests in higher exercise endurance with less VO
2
. This adaptive response involves a metabolic switch toward preferential utilization of glucose via the AMPK-TBC1D1 signaling nexus. We now investigated whether a similar response could be triggered in mice after acute ablation of Cyp-D using conditional KO (CKO) mice by subjecting them to treadmill exercise involving five running sessions. At their first treadmill running session, CKO mice and controls had comparable VO
2
(208.4±17.9 vs 209.1±16.8 ml/kg·min
-1
), VCO
2
(183.6±17.2 vs 184.8±16.9 ml/kg·min
-1
), and RER (0.88±0.043 vs 0.88±0.042). With subsequent sessions, CKO mice displayed more prominent reduction in VO
2
(genotype & session interaction p<0.001) with less prominent reduction in VCO
2
resulting in significantly increased RER (genotype & session interaction p=0.013). The increase in RER was consistent with preferential utilization of glucose as respiratory substrate (4.6±0.8 vs 4.0± 0.9 mg/min, p=0.003). CKO mice also performed a significantly higher treadmill work for given VO
2
expressed as a power/VO
2
ratio (7.4±0.2 x 10
-3
vs 6.7±0.2 10
-3
ratio, p=0.025). Analysis of CKO skeletal muscle tissue after completion of five treadmill running sessions showed enhanced AMPK activation (0.669±0.06 vs 0.409±0.11 pAMPK/β-tubulin ratio, p=0.005) and TBC1D1 inactivation (0.877±0.16 vs 0.565±0.09 pTBC1D1/β-tubulin ratio, p<0.05) accompanied by increased glucose transporter-4 levels consistent with activation of the AMPK-TBC1D1 signaling nexus enabling increased glucose utilization. Taken together, our study demonstrates that like constitutive Cyp-D ablation, acute Cyp-D ablation also induces a state of increased O
2
utilization efficiency, paving the way for exploring the use of a pharmacological approach to elicit the same response, which could be beneficial under O
2
limiting conditions.
Abstract 11053: The Association Between the Systemic Immune-Inflammation Index with the Duration of Cardiopulmonary Bypass in Cardiac Surgery: A Retrospective, Single-Center Study
Authors: Hu Yanan , Liu Yi , Liu Yongzhe , Chen Hui , Jiang Wei , Xu Longhe
Published: December 2021

Introduction:
Systemic inflammatory response evoked by cardiac surgery involving a cardio-pulmonary bypass (CPB) in combination of surgical trauma, ischemia/reperfusion injury, hypothermia, and endotoxin release contributed to the postoperative morbidity and mortality. This study aimed to explore the potential of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) as novel markers to evaluate and predict the adverse clinical outcomes after longer CPB time in cardiac surgery.

Methods:
Patients who underwent cardiac surgery with or without CPB were allocated into two groups, CPB group (n=11) and N-CPB group (n=21). The time course of NLR, PLR, SII, and C-reactive protein (CPR) were analyzed at preoperative day 1 and postoperative day 1, 3, and 7. The baseline and postoperative parameters, the ICU and hospital stay were recorded.

Results:
There were no differences of baseline parameters between groups. The level of NLR, PLR, SII, and CPR at postoperative day 1 was higher than that in the preoperative day 1 in both groups (p < 0.01). The level of NLR, SII and CPR at postoperative day 3 was higher than that in the preoperative day 1 in both groups (p < 0.05). The NLR and SII at postoperative day 3 were higher in CPB group than that in N-CPB group (p < 0.05). The ICU and hospital stay was longer in CPB group than N-CPB group (p < 0.05).

Conclusions:
The longer duration of CPB time induced higher systemic inflammatory response characterized by higher level of NLR, PLR and SII. The SII predicted the poor outcome after longer CPB. The peak of systemic inflammatory response occurred on the third day after cardiac surgery.
Abstract 11156: Thoracic Bioimpedance Ventilation Waveforms: Increased Amplitude with Larger Tidal Volume and Female Sex
Authors: Shaver Sarah , Gonzalez Amanda , Chang Mary , manley james , ARAMENDI ELISABETE , Idris Ahamed
Published: December 2021

Introduction:
Effective ventilation during 30:2 CPR has been linked to improved outcomes, but definitive evidence is lacking. We developed a method to identify thoracic bioimpedance ventilation waveforms from defibrillator recordings.

Hypothesis:
Bioimpedance ventilation waveform amplitude is proportional to tidal volume. It is possible to identify a minimum amplitude for a valid ventilation waveform.

Methods:
To determine the relationship between tidal volume and bioimpedance waveform amplitude, we studied 26 healthy volunteers (12 males and 14 females). Volunteers breathed fixed positive pressure tidal volumes (250mL, 300 mL, 400 mL, 600 mL, and 800 mL) given by a Maquet SERVO-I ventilator (Getinge US Sales, Wayne, NJ, USA) through a mouthpiece while a Lifepak12 (Physio-Control, Redmond, WA) defibrillator recorded thoracic bioimpedance through electrode pads placed on the chest. We measured the impedance amplitudes of six breaths at each tidal volume and the weight and height of each volunteer. We set the minimum effective tidal volume at 250 mL.

Results:
For males and females, respectively, mean (±SD) was 180.1±8 cm vs. 164±3.5 cm, and mean weight was 85.6±9.6 kg vs. 58.3±8.6 kg. Median (IQR) bioimpedance amplitude for each tidal volume split by sex is shown in the Figure (Y-axis, 1 mm = 0.25 Ohm).

Conclusion:
Bioimpedance amplitude is proportional to tidal volume and also varies by height, weight, and sex. Sex may be a possible surrogate for height and weight. The minimum amplitude is 0.375 Ohm for a valid bioimpedance ventilation waveform.
Abstract 11243: Novel Peptide for Cardiopulmonary Resuscitation
Authors: Li Jing , Zhu Xiangdong , Oberdier Matt , Lee Chunpei , Granado Misha , Fink Sarah , Lin Shaoxia , Qin Kevin , JUSTICE CODY , Kim Hajwa , Damen Frederick , Cai Kejia , Doshi Pratik B , Wang Henry , Halperin Henry R , Vanden Hoek Terry L
Published: December 2021

Introduction:
While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling.

Hypothesis:
We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival.

Methods:
We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival.

Results:
In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p < 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p< 0.001).

Conclusions:
TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.
Abstract 11269: Recombinant Soluble Thrombomodulin in Prolonged Porcine Cardiac Arrest
Authors: Zhang Boya , McCracken Brendan , Leander Danielle , Colmenero Carmen , Greer Nicholas , Hsu Cindy H , Cranford James , Tiba Mohamad , Neumar Robert W , Greineder Colin
Published: December 2021

Introduction:
Sudden Cardiac Arrest (CA) affects more than 400,000 people per year in the United States. Although a third of these patients survive to hospital admission, another 60-70% go on to die due to failed recovery of vital organ function. Microvascular thrombosis has been suggested as a potential contributor to prolonged organ dysfunction, but no antithrombotic therapies have been shown to be beneficial and coagulofibrinolytic abnormalities in prolonged CA remain poorly understood.

Objectives:
To establish key biomarkers of porcine coagulation and fibrinolysis in the setting of prolonged CA and cardiopulmonary resuscitation (CPR) and test the ability of ART-123 (recombinant human thrombomodulin alpha) to reverse these abnormalities.

Methods:
15 pigs (n=5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR. Animals were randomized to receive saline or ART-123 (~1mg/kg) pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR).

Results:
Robust and ongoing activation of coagulation and fibrinolysis were detected throughout the resuscitation. After 50 minutes of CPR, plasma tests suggested consumptive coagulopathy, while whole blood testing (thromboelastography) indicated a persistent hypercoagulable state. ART-123 had a clear anticoagulant effect irrespective of timing (TAT complexes 381±25 vs. 238±18 vs. 226±12, p<0.01, and d-dimer 4.86±0.54 vs. 2.39±0.2 vs. 2.46±0.21 for vehicle, pre-arrest, post-arrest, p = 0.05). A pro-fibrinolytic effect was also observed, but only when the drug was given before no-flow, with a significant increase in levels of free endogenous tPA (1.2±0.12 vs. 3.29±0.29 vs. 1.72±0.3, p < 0.001) and corresponding suppression of free PAI-1 (0.59±0.15 vs. 0.14±0.01 vs. 0.41±0.09, p < 0.001).

Conclusion:
Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration.
Abstract 11324: Immediate Percutaneous Coronary Intervention in Patients with Refractory Out of Hospital Cardiac Arrest
Authors: Rob Daniel , Smalcova Jana , Kovarnik Tomas , Zemanek David , Kral Ales , Smid Ondrej , Kavalkova Petra , Huptych Michael , Komarek Arnost , Belohavek Jan
Published: December 2021

Background:
An increasing number of cardiac centres are using immediate percutaneous coronary intervention (PCI) and extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out of hospital cardiac arrest (r-OHCA). Published evidence regarding PCI in OHCA has been mainly reporting to patients with early return of spontaneous circulation and the influence of PCI and ECPR on survival in the population of patients with r-OHCA and acute coronary syndrome (ACS) remains unclear.

Methods:
In this post hoc analysis of the randomized r-OHCA trial, all patients with ACS as a cause of r-OHCA were included. The effect of successful PCI and ECPR on 180-days survival was examined using Kaplan-Meier estimates and multivariable Cox regression.

Results:
In total, 256 patients were evaluated in Prague OHCA study and 127 (49.6 %) had ACS as the cause of r-OHCA constituting current study population. The mean age was 58 years (46.3-64) and duration of resuscitation was 52.5 minutes (36.5-68). ECPR was used in 51 (40.2 %) of patients. Immediate PCI was performed in 86 (67.7%) patients and TIMI flow 2 or 3 was achieved in 75 (87.2%) patients. The overall 180-days survival of patients with successful PCI was 40 % compared to 7.7 % with no or failed immediate PCI (log-rank p < 0.001). After adjustment for confounders, successful PCI was associated with a lower risk of death (HR 0.47, CI 0.24-0.93, p = 0.031). Likewise, ECPR was associated with a lower risk of death (HR 0.11, CI 0.05-0.24, p< 0.001).

Conclusion:
In this post hoc analysis of the randomized r-OHCA trial, successful immediate PCI as well as ECPR were associated with improved 180-days survival in patients with r-OHCA due to ACS.
Abstract 11372: A Risk-Adjustment Model for Patients Presenting to Hospitals with Out-of-Hospital Cardiac Arrest and ST-Elevation Myocardial Infarction
Authors: Tran Andy T , Hart Anthony , Spertus John , Jones Philip , McNally Bryan , Malik Ali O , Chan Paul S
Published: December 2021

Background:
Given the diversity of patients resuscitated from out-of-hospital cardiac arrest (OHCA) complicated by STEMI, adequate risk adjustment is needed to account for potential differences in case-mix to reflect the quality of percutaneous coronary intervention.

Objectives:
We sought to build a risk-adjustment model of in-hospital mortality outcomes for patients with OHCA and STEMI requiring emergent angiography.

Methods:
Within the Cardiac Arrest Registry to Enhance Survival, we included adult patients with OHCA and STEMI who underwent angiography within 2 hours from January 2013 to December 2019. Using pre-hospital patient and arrest characteristics, multivariable logistic regression models were developed for in-hospital mortality. We then described model calibration, discrimination, and variability in patients’ unadjusted and adjusted mortality rates.

Results:
Of 2,999 hospitalized patients with OHCA and STEMI who underwent emergent angiography (mean age 61.2 ±12.0, 23.1% female, 64.6% white), 996 (33.2%) died. The final risk-adjustment model for mortality included higher age, unwitnessed arrest, non-shockable rhythms, not having sustained return of spontaneous circulation upon hospital arrival, and higher total resuscitation time on scene (
C
-statistic, 0.804 with excellent calibration). The risk-adjusted proportion of patients died varied substantially and ranged from 7.8% at the 10
th
percentile to 74.5% at the 90
th
percentile (Figure).

Conclusions:
Through leveraging data from a large, multi-site registry of OHCA patients, we identified several key factors for better risk-adjustment for mortality-based quality measures. We found that STEMI patients with OHCA have highly variable mortality risk and should not be considered as a single category in public reporting. These findings can lay the foundation to build quality measures to further optimize care for the patient with OHCA and STEMI.
Abstract 11394: Comparison Between Advanced Cardiovascular Life Support Course and a New Emergency Cardiovascular Care Course for Developing Countries
Authors: Furtado Fabricio , Canesin Manoel , Gonçalves Rodrigo , Almeida Dirceu , Gonçalves Iran , Timerman Sergio
Published: December 2021

Introduction:
Training and cardiovascular emergency care (CEC) is different in developing countries from developed countries. Emergency medicine specialty in developing countries is not established without a large number of specialists and the Advanced Cardiovascular Life Support course (ACLS) is a very common course.

Objective:
To compare the ACLS with the Advanced Cardiovascular Emergency Training course (TECA) developed in Brazil according to the needs of local doctors. Both courses with 16 hours of training but the TECA adding more skills training time in Arrhythmia, Stroke, Acute Coronary Care (ACC) and Acute Heart Failure (AHF) in addition to the traditional training in cardiac arrest management (CAM).

Methods:
The study included the participation of 119 senior medical students divided into 2 groups: 56 students submitted to TECA training and 63 students submitted to the ACLS course. Both groups performed a mannequin simulated CAM skills evaluation care before and after participating in each course and a multiple-choice test after training. Performance in simulated scenario was compared through structured assessment score, time to onset of chest compression and time to perform defibrillation after collapse, as well as the number of correct answers in the multiple-choice assessment.

Results:
TECA group presented statistical higher grade than the ACLS group in the evaluation of the simulated case attendance (10,0 points (9,00-10,00) vs 9,0 (8,00-10,00) points; p<0,001). There was no statistical difference between the groups in time to onset of chest compression (19,0 sec (16,25-23,00) vs 19,5 (15,75-25,25) sec; p = 0,500) and time to defibrillation (48,0 (39,00-53,00) sec vs 48,0 (39,00-55,00) sec; p = 0,740). TECA students had a better performance in questions related to AHF treatment (4,0 (3,00-4,00) vs 3,0 (2,00-3,00); p < 0,001). There was no significant difference in the number of correct answers on arrhythmia, CAM, ACC and stroke.

Conclusions:
TECA course provided greater adherence to CAM care protocol, without prejudice to the time to start chest compression or time to defibrillation. In addition, it added training in AHF management, suggesting to be a good option for cardiac emergency care training in developing countries.
Abstract 11503: Mindfulness is Inversely Associated with Psychological Symptoms in Long-Term Cardiac Arrest Survivors
Authors: Presciutti Alex , Greenberg Jonathan , Lester Ethan , Newman Mary M , Elmer Jonathan , Shaffer Jonathan , Vranceanu Ana-maria , Perman Sarah M
Published: December 2021

Introduction:
We sought to identify correlates with psychological symptoms in long-term cardiac arrest (CA) survivors. Mindfulness, or nonjudgmental awareness of the present moment, is a modifiable protective factor against psychological symptoms in various clinical populations and could be a potential treatment target for CA survivors.

Methods:
We conducted a longitudinal survey study between 10-11/2019 (baseline) and 10-11/2020 (1-year follow-up) with long-term CA survivor members of the Sudden Cardiac Arrest Foundation. We collected demographic and CA characteristics at baseline. At both timepoints, we assessed posttraumatic stress symptoms (PTS) through the PTSD Checklist-5 (PCL-5) and depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4). At follow-up, we assessed mindfulness through the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). We used adjusted linear regression to predict 1-year PCL-5 and PHQ-4 scores, with particular consideration of the CAMS-R as a cross-sectional correlate of outcome.

Results:
We included 129 CA survivors (mean age: 52 years, 52% male, 98% white). At 1-year follow-up, in adjusted models, CAMS-R (β: -0.35, p <0.001) and baseline PCL-5 scores (β: 0.56, p <0.001) were associated with 1-year PCL-5 scores. CAMS-R (β: -0.34, p <0.001) and baseline PHQ-4 scores were associated with 1-year PHQ-4 scores (β: 0.37, p<0.001).

Conclusion:
Mindfulness was inversely associated with psychological symptoms in long-term CA survivors. Future studies should examine the longitudinal relationship of mindfulness and psychological symptoms after CA.
Abstract 11710: Poloxamer 188 Protects Coronary Artery Endothelial Cells After Extended Hypoxia and Reoxygenation in an in vitro Model of Simulated Ischemia/Reperfusion Injury
Authors: li zhu , Hampton Matthew J , Barajas Matthew B , Riess Matthias L
Published: December 2021

Reperfusion restores blood flow after myocardial ischemia but can cause additional cellular injury by the sudden reintroduction of oxygen and nutrients. There is still no effective remedy for myocardial ischemia/reperfusion (IR) injury. Our previous study using cardiomyocytes (CMs) found that, after 3 hrs hypoxia followed by 2 hrs reoxygenation, viability decreased, and release of lactate dehydrogenase (LDH), calcium influx, membrane leakage (insertion of fluorescent probe FM1-43) significantly increased, indicating that cell membrane function was negatively affected. This was attenuated by the triblock copolymer Poloxamer (P)188. Here, we first hypothesized that endothelial cells are also susceptible to simulated IR injury, albeit requiring longer hypoxia times. We further hypothesized that P188 can also attenuate simulated IR injury in endothelial cells when given upon reoxygenation. Mouse coronary artery endothelial cells (MCAECs) were exposed to different durations of hypoxia (2, 3, 12 and 24 hrs) in serum- and glucose-free media +/- reoxygenation for 2 hrs in regular media. P188 was administered upon reoxygenation at 0, 100, 300 or 1,000 μM in experiments of 24 hrs hypoxia / 2 hrs reoxygenation. LDH release was measured and compared to appropriately timed normoxic control experiments. Reoxygenation and hypoxia times significantly longer than 3 hrs were required to elicit sufficient injury (panel A). When P188 was given upon reoxygenation after 24 hrs hypoxia, it dose-dependently attenuated LDH release (panel B). These findings contrast to the higher susceptibility of CMs to IR injury that only allowed shorter hypoxia durations. They also confirm a protective effect of P188 on the endothelium, not just on CMs. These findings have important implications for co-culture models with MCAECs and CMs to elucidate the interplay of both cell types on each other when studying mechanisms of cardioprotective strategies and compounds like P188.
Abstract 11781: Association of Rapid Response Teams With Hospital Mortality in Medicare Patients
Authors: Girotra Saket , Jones Philip , Peberdy Mary A , Vaughan Sarrazin Mary S , Chan Paul S
Published: December 2021

Background:
Rapid response teams (RRT) have been promoted as a strategy to reduce unexpected hospital deaths, as they are designed to evaluate and treat patients experiencing sudden decline. However, evidence to support their effectiveness in reducing in-hospital mortality remains uncertain.

Methods:
Using data from 56 hospitals participating in Get With The Guidelines Resuscitation linked to Medicare, we calculated annual rates of case-mix adjusted mortality for each hospital during 2000-2014. We constructed a hierarchical interrupted time series model to determine whether implementation of a RRT was associated with a reduction in mortality that was larger than expected based on pre-implementation trends alone.

Results:
Over the study period, the median annual number of Medicare admissions across study hospitals was 5214 (range: 408-18,398). The median duration of the pre-implementation period was 7.6 years comprising ~2.5 million admissions, and the median duration of the post-implementation period was 7.2 years comprising ~2.6 million admissions. Before implementation of RRTs, hospital mortality was already decreasing by 2.7% annually (Figure). Implementation of RRTs was not associated with change in mortality in the initial year of implementation (RR for model intercept: 0.98; 95% CI 0.94-1.02;
P=
0.30) or in the mortality trend over time (RR for model slope: 1.01 per-year; 95% CI 0.99-1.02;
P
=0.30). Within individual hospitals, a RRT was associated with a significantly lower than expected mortality at 4 (7.1%) of hospitals, and significantly higher than expected mortality at 2 (3.6%), when compared to pre-implementation trends.

Conclusion:
Among a diverse sample of U.S. hospitals, we found that the implementation of a RRT was not associated with a significant reduction in hospital mortality. Given their prevalence in most U.S. hospitals, further studies are needed to understand best practices in composition, design, and implementation of RRTs.
Abstract 11809: Trans-Endothelial Electrical Resistance to Assess Cell Layer Integrity in Coronary Artery Endothelial Cells After Hypoxia/Reoxygenation Injury
Authors: Hampton Matthew J , Maknojia Insha H , li zhu , Barajas Matthew B , Riess Matthias L
Published: December 2021

Introduction:
Cardiovascular disease remains one of the leading causes of complications and death worldwide. Therefore, accurate and reliable methods of mimicking ischemia/reperfusion (IR) injury in cardiac cells
in vivo
are crucial when testing drugs/substances for prevention and treatment. Coronary artery endothelial cells play a critical role in not only supplying blood to myocardial cells but protecting them from insult as well. However, the endothelial layer can be compromised by ischemic injury, heightening damage to the heart during reperfusion.

Hypothesis:
Varied ischemic insult of mouse coronary artery endothelial cells (MCAECs) affects cell layer integrity as measured by Trans-Endothelial Electrical Resistance (TEER).

Methods:
MCAECs were cultured on Grenier Bio-One ThinCert™-cell culture inserts for 72 hrs to allow for adequate confluency. Cells were then subjected to either continued normoxic conditions or hypoxia for 3, 6, 12, or 24 hrs, with a 2-hr reperfusion period immediately following. TEER was used to measure the integrity of the endothelial cell layer on the insert.

Results:
Our data showed a significant decrease in TEER between control and hypoxic groups after 6 hrs (p = 0.0400), 12 hrs (p = 0.0179) and 24 hrs (p = 0.0103), but not after 3 hrs (p = 0.4453) of hypoxia.

Conclusion:
This indicates that titrating the hypoxia time to a sufficient duration is necessary to achieve an adequate H/R injury which can then be used for potential cardioprotective agents and/or strategies to be tested. Furthermore, TEER is a reliable and reproducible method to assess the role of endothelial cell membrane integrity in cardioprotection.
Abstract 11939: Can Live Video Streaming From Bystander's Smartphone Improve the Quality of Chest Compressions in Real Out-of-Hospital Cardiac Arrest?
Authors: Linderoth Gitte , Rosenkrantz Oscar , Lippert Freddy , Oestergaard Doris , Ersbøll Annette K , Meyhoff Christian S , Folke Fredrik , Christensen Helle C
Published: December 2021

Introduction:
Good quality of cardiopulmonary resuscitation (CPR) provided by bystanders is important for the outcome in out-of-hospital cardiac arrest (OHCA). A live video stream from the bystander’s smartphone to the medical dispatcher might improve the quality of chest compressions performed during CPR.

Methods:
At the Copenhagen Emergency Medical Services in Denmark, the medical dispatcher can add a live video to the emergency call. In case of OHCA, the medical dispatcher guides bystanders in dispatcher-assisted CPR (DA-CPR). After initiating chest compressions, the medical dispatcher can add live video streaming. A cohort study was conducted with an evaluation of performed chest compressions from the video footage before and after the dispatcher used the video to instruct CPR (video-instructed DA-CPR). Correct chest compressions were defined according to European Resuscitation Council Guidelines.

Results:
CPR was provided with a live video stream in 52 OHCA calls, in which 90 bystanders performed chest compressions. Thirty OHCA occurred at a public location, and more than four bystanders were present in 32 (62%) cases. In 26 cases, chest compressions were performed by more than one bystander. Eight (9%) bystanders performed correct chest compressions before video-instructed DA-CPR. For the bystanders first initiating insufficient CPR improvements were observed for: hand placement 58% (n=17/29), compressions rate 73% (n=17/21), and compressions depth 62% (n=19/31) following video-instructed DA-CPR. For the second bystander providing CPR (n=26) improvements were still observed for: hand placement 57% (n=4/7), compressions rate 73% (N=8/11), and compressions depth 53% (n=11/21) following video-instructed DA-CPR. For the third and fourth bystander (n=10), providing CPR improvements were seen for: hand placement 100% (n=2/2), compressions rate 50 % (n=2/4), and compressions depth 60% (n=3/5). Eighteen bystanders had a chest compressions performance measurement that could not be observed.

Conclusions:
A live video from the bystander`s smartphone to the medical dispatcher could improve the quality of chest compressions in CPR, and guidance seems important not just for the first bystander but for all bystanders performing CPR.