Traumatic and hemorrhagic complications after extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging invasive rescue therapy for treatment of refractory out-of-hospital cardiac arrests (OHCA). We aim to describe the incidence of traumatic and hemorrhagic complications among patients undergoing ECPR for OHCA and examine the association between CPR duration and ECPR-related injuries or bleeding. METHODS: We examined prospectively collected data from the Extracorporeal Resuscitation Outcomes Database (EROD), which includes ECPR-treated OHCAs from participating hospitals (October 2014 to August 2019). The primary outcome was traumatic or hemorrhagic complications, defined any of the following: pneumothorax, pulmonary hemorrhage, major bleeding, cannula site bleeding, gastrointestinal bleeding, thoracotomy, cardiac tamponade, aortic dissection, or vascular injury during hospitalization. The primary exposure was the cardiac arrest to ECPR initiation interval (CA-ECPR interval), measured as the time from arrest to initiation of ECPR. Descriptive statistics were used to compare demographic, cardiac arrest, and ECPR characteristics among patients with and without CPR-related traumatic or bleeding complications. Multivariable logistic regression was used to examine the association between CA-ECPR interval and traumatic or bleeding complications. RESULTS: A total of 68 patients from 4 hospitals receiving ECPR for OHCA were entered into EROD and met inclusion criteria. Median age was 51 (interquartile range 38-58), 81% were male, 40% had body mass index > 30, and 70% had pre-existing medical comorbidities. A total of 65% had an initial shockable cardiac rhythm, mechanical CPR was utilized in at least 29% of patients, and 27% were discharged alive. The median time from arrest to ECPR initiation was 73 min (IQR 60-104). A total of 37% experienced a traumatic or bleeding complication, with major bleeding (32%), vascular injury (18%), and cannula site bleeding (15%) being the most common. Compared to patients with shorter CPR times, patients with a longer CA-ECPR interval had 18% (95% confidence interval - 2-42%) higher odds of suffering a mechanical or bleeding complication, but this did not reach statistical significance (p = 0.08). CONCLUSIONS: Traumatic injuries and bleeding complications are common among patients undergoing ECPR. Further study is needed to investigate the relation between arrest duration and complications. Clinicians performing ECPR should anticipate and assess for injuries and bleeding in this high-risk population.

The utility of the triage electrocardiogram for the detection of ST-segment elevation myocardial infarction.

INTRODUCTION: Current AHA/ACC guidelines on the management of ST-elevation myocardial infarction (STEMI) suggest that an ECG is indicated within 10minutes of arrival for patients arriving to the Emergency Department (ED) with symptoms concerning for STEMI. In response, there has been a creep towards performing ECGs more frequently in triage. The objectives of this study were to quantify the number of triage ECGs performed at our institution, assess the proportion of ECGs performed within current hospital guidelines, and evaluate the rate of STEMI detection in triage ECGs. METHODS: A retrospective chart review of all emergency department patients presenting over a period of 8days who had a triage ECG performed. Cases of bradycardia or tachycardia were excluded. Data collection included patient demographics, presenting complaint, cardiac risk factors, troponin values, and final diagnosis. Summary statistics are reported in a descriptive manner. RESULTS: During the study period, 538 patients had a triage ECG for possible STEMI with no STEMI identified and 16 NSTEMI diagnoses (confirmed as positive troponins following ED assessment). Sixty-three (11.7%) patients did not meet internal criteria for a triage ECG. A NSTEMI ED diagnosis was identified in 3% of patients who met internal triage ECG criteria and 1.6% who did not meet criteria (p=0.29). A cost analysis was performed using an average of 50 STEMI cases diagnosed in our ED per given year. Current institutional ECG billing rates for ECGs performed and interpreted is $125 per ECG, providing an estimated triage ECG charge to detect one STEMI at $54,295. DISCUSSION: This retrospective study of 538 triage ECG's performed over an 8day period identified no STEMIs and 16 NSTEMIs. A very large number of ECGs were done at triage overall and included patients who do not meet our own hospital criteria. Given the extremely low yield and high associated charges, current guidelines for triage ECG for identifying a possible STEMI should be reviewed.

Widespread transient Hoogsteen base pairs in canonical duplex DNA with variable energetics.

Hoogsteen (HG) base pairing involves a 180° rotation of the purine base relative to Watson-Crick (WC) base pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction and replication. Here, using nuclear magnetic resonance R1ρ relaxation dispersion, we show that transient HG base pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in HG base pair energetic stabilities that are comparable with variations in WC base pair stability, with HG base pairs being more abundant for energetically less favourable WC base pairs. Our results suggest that the variations in HG stabilities and rates of formation are dominated by variations in WC base pair stability, suggesting a late transition state for the WC-to-HG conformational switch. The occurrence of sequence and position-dependent HG base pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions.

A historical account of Hoogsteen base-pairs in duplex DNA.

In 1957, a unique pattern of hydrogen bonding between N3 and O4 on uracil and N7 and N6 on adenine was proposed to explain how poly(rU) strands can associate with poly(rA)-poly(rU) duplexes to form triplexes. Two years later, Karst Hoogsteen visualized such a noncanonical A-T base-pair through X-ray analysis of co-crystals containing 9-methyladenine and 1-methylthymine. Subsequent X-ray analyses of guanine and cytosine derivatives yielded the expected Watson-Crick base-pairing, but those of adenine and thymine (or uridine) did not yield Watson-Crick base-pairs, instead favoring "Hoogsteen" base-pairing. More than two decades ensued without experimental "proof" for A-T Watson-Crick base-pairs, while Hoogsteen base-pairs continued to surface in AT-rich sequences, closing base-pairs of apical loops, in structures of DNA bound to antibiotics and proteins, damaged and chemically modified DNA, and in polymerases that replicate DNA via Hoogsteen pairing. Recently, NMR studies have shown that base-pairs in duplex DNA exist as a dynamic equilibrium between Watson-Crick and Hoogsteen forms. There is now little doubt that Hoogsteen base-pairs exist in significant abundance in genomic DNA, where they can expand the structural and functional versatility of duplex DNA beyond that which can be achieved based only on Watson-Crick base-pairing. Here, we provide a historical account of the discovery and characterization of Hoogsteen base-pairs, hoping that this will inform future studies exploring the occurrence and functional importance of these alternative base-pairs.