Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

Pulmonary Artery Pressures and Mortality During Venoarterial ECMO: An ELSO Registry Analysis.

BACKGROUND: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support. METHODS: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. RESULTS: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times (P<0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P=0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P=0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P<0.001). CONCLUSIONS: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered.

Resuscitative transesophageal echocardiography in emergency departments in the United States and Canada: A cross-sectional survey.

INTRODUCTION: Over the past two decades, transesophageal echocardiography (TEE) has been used with increasing frequency to evaluate critically ill patients outside of traditional settings. The purpose of this study was to characterize the number of programs, users, practice characteristics, training and competency requirements and barriers for the current use of resuscitative transesophageal echocardiography (TEE) in Emergency Departments (EDs) in the United States and Canada. METHODS: A closed internet-based, cross-sectional, point-prevalence survey was administered via email to 120 program directors of emergency ultrasound fellowships (EUSF) and 43 physicians from EDs without EUSF from the United States and Canada. RESULTS: Ninety-eight percent of surveyed participants responded. Twenty percent of respondents reported having active resuscitative TEE programs. The majority of participating hospitals (70%) were academic centers with residency programs. A total of 33 programs reported using resuscitative TEE in their ED and of those, 82% were programs with EUSF. Most programs performing TEE (79%) had less than five attending physicians performing TEE. Evaluation of patients during resuscitation from cardiac arrest (100%) and post-arrest care (76%) are the two most frequent indications for TEE in the ED. The most common core elements of resuscitative TEE protocols used are: assessment of left ventricular (LV) systolic function (97%), assessment of right ventricular (RV) function (88%), evaluation of pericardial effusion / tamponade (52%). All programs reported using formal didactics in their training programs, 94% reported using high-fidelity simulation, and 79% live scanning of patients. Financial concerns were the most common barrier use of TEE in the ED (58%), followed by maintenance of equipment (30%), and credentialing/privileges (30%). CONCLUSIONS: This study provides a snapshot of the practice of resuscitative TEE in EDs in the United States and Canada revealing the existence of 33 programs using this emerging modality in the care of critically ill patients.

The Latest in Resuscitation Research: Highlights From the 2022 American Heart Association's Resuscitation Science Symposium.

BACKGROUND: Every year the American Heart Association's Resuscitation Science Symposium (ReSS) brings together a community of international resuscitation science researchers focused on advancing cardiac arrest care. METHODS AND RESULTS: The American Heart Association's ReSS was held in Chicago, Illinois from November 4th to 6th, 2022. This annual narrative review summarizes ReSS programming, including awards, special sessions and scientific content organized by theme and plenary session. CONCLUSIONS: By exploring both the science of resuscitation and important related topics including survivorship, disparities, and community-focused programs, this meeting provided important resuscitation updates.

Extracorporeal membrane oxygenation for cardiac arrest: what, when, why, and how.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) facilitated resuscitation was first described in the 1960s, but only recently garnered increased attention with large observational studies and randomized trials evaluating its use. AREAS COVERED: In this comprehensive review of extracorporeal cardiopulmonary resuscitation (ECPR), we report the history of resuscitative ECMO, terminology, circuit configuration and cannulation considerations, complications, selection criteria, implementation and management, and important considerations for the provider. We review the relevant guidelines, different approaches to cannulation, postresuscitation management, and expected outcomes, including neurologic, cardiac, and hospital survival. Finally, we advocate for the participation in national/international Registries in order to facilitate continuous quality improvement and support scientific discovery in this evolving area. EXPERT OPINION: ECPR is the most disruptive technology in cardiac arrest resuscitation since high-quality CPR itself. ECPR has demonstrated that it can provide up to 30% increased odds of survival for refractory cardiac arrest, in tightly restricted systems and for select patients. It is also clear, though, from recent trials that ECPR will not confer this high survival when implemented in less tightly protocoled settings and within lower volume environments. Over the next 10 years, ECPR research will explore the optimal initiation thresholds, best practices for implementation, and postresuscitation care.

Virtual assessment of coronal balance prior to bone resection with the MAKO robotic-assisted system accurately predicts final balance in TKA.

Total knee arthroplasty (TKA) has traditionally relied on the surgeon's judgement and manual instruments to determine balance. The MAKO robotic system (Stryker Ltd, Kalamazoo, MI, USA) allows assessment of virtual compartmental gaps from CT-derived bone models intra-operatively as a predictor of soft tissue balance that will be achieved, prior to any bony resection. This study aims to assess the accuracy of this pre-resection balancing technique in determining the resultant final soft tissue balance of the TKA. A consecutive prospective cohort of 2027 Robotic-Assisted TKAs (RATKA) were performed between January'17 and March'22. Osteophytes were removed; initial virtual gaps on the virtual bone model were measured at 10° and 90° of flexion prior to bone resections. Optimization of the virtual component positions was then made and final pre-resection gaps were measured. The gaps were then re-assessed post-implantation and compared to the final pre-resection values. Virtual balancing in extension within 1 mm was achieved in 95% of cases. Of those, 98% maintained coronal balance within 1 mm after implantation, with 1.5% requiring a coronal plane soft tissue release. Inability to virtually balance a TKA within 2 mm prior to bone resection resulted in a soft tissue release in 44.4% of cases. The absolute values of the final gaps achieved were a mean of 1.3 mm greater than virtual gaps. The ability to balance a knee on the virtual bone model prior to bone resection, in conjunction with robotic-assisted execution of TKA, consistently achieves a balanced knee after component implantation.

Pulmonary Artery Pressures and Mortality during VA ECMO: An ELSO Registry Analysis.

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (VA ECMO). While these factors are intertwined with right ventricular (RV) function, the independent relationship between RV function and survival during VA ECMO is unknown. Objectives: To identify the relationship between RV function with mortality and duration of ECMO support. Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization (ELSO) Registry between 2010 and 2022 were queried. RV function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for Society for Cardiovascular Angiography and Interventions (SCAI) stage, age, gender, and concurrent clinical data (i.e., pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. Results: A total of 4,442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; non-survivors were more likely to be older, have a worse SCAI stage, and have longer pre-ECMO endotracheal intubation times (P < 0.05 for all) than survivors. Improving PAPP from pre-ECMO to on-ECMO time (Δ PAPP) was associated with reduced mortality per 10 mm Hg increase (OR: 0.91 [95% CI: 0.86-0.96]; P=0.002). Increasing on-ECMO PAPP was associated with longer time on ECMO per 10 mm Hg (Beta: 15 [95% CI: 7.7-21]; P<0.001). Conclusions: Early improvements in RV function from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of Δ PAPP into risk prediction models should be considered.

Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

Jupiter's Low-Altitude Auroral Zones: Fields, Particles, Plasma Waves, and Density Depletions.

The Juno spacecraft's polar orbits have enabled direct sampling of Jupiter's low-altitude auroral field lines. While various data sets have identified unique features over Jupiter's main aurora, they are yet to be analyzed altogether to determine how they can be reconciled and fit into the bigger picture of Jupiter's auroral generation mechanisms. Jupiter's main aurora has been classified into distinct "zones", based on repeatable signatures found in energetic electron and proton spectra. We combine fields, particles, and plasma wave data sets to analyze Zone-I and Zone-II, which are suggested to carry upward and downward field-aligned currents, respectively. We find Zone-I to have well-defined boundaries across all data sets. H+ and/or H3 + cyclotron waves are commonly observed in Zone-I in the presence of energetic upward H+ beams and downward energetic electron beams. Zone-II, on the other hand, does not have a clear poleward boundary with the polar cap, and its signatures are more sporadic. Large-amplitude solitary waves, which are reminiscent of those ubiquitous in Earth's downward current region, are a key feature of Zone-II. Alfvénic fluctuations are most prominent in the diffuse aurora and are repeatedly found to diminish in Zone-I and Zone-II, likely due to dissipation, at higher altitudes, to energize auroral electrons. Finally, we identify significant electron density depletions, by up to 2 orders of magnitude, in Zone-I, and discuss their important implications for the development of parallel potentials, Alfvénic dissipation, and radio wave generation.

Closed Fluxtubes and Dispersive Proton Conics at Jupiter's Polar Cap.

Two distinct proton populations are observed over Jupiter's southern polar cap: a ∼1 keV core population and ∼1-300 keV dispersive conic population at 6-7 RJ planetocentric distance. We find the 1 keV core protons are likely the seed population for the higher-energy dispersive conics, which are accelerated from a distance of ∼3-5 RJ. Transient wave-particle heating in a "pressure-cooker" process is likely responsible for this proton acceleration. The plasma characteristics and composition during this period show Jupiter's polar-most field lines can be topologically closed, with conjugate magnetic footpoints connected to both hemispheres. Finally, these observations demonstrate energetic protons can be accelerated into Jupiter's magnetotail via wave-particle coupling.

Real-time acoustic observations in the Canadian Arctic Archipelago.

The main sources of noise in the Arctic Ocean are naturally occurring, rather than related to human activities. Sustained acoustic monitoring at high latitudes provides quantitative measures of changes in the sound field attributable to evolving human activity or shifting environmental conditions. A 12-month ambient sound time series (September 2018 to August 2019) recorded and transmitted from a real-time monitoring station near Gascoyne Inlet, Nunavut is presented. During this time, sound levels in the band 16-6400 Hz ranged between 10 and 135 dB re 1 µPa2/Hz. The average monthly sound levels follow seasonal ice variations with a dependence on the timing of ice melt and freeze-up and with higher frequencies varying more strongly than the lower frequencies. Ambient sound levels are higher in the summer during open water and quietest in the winter during periods of pack ice and shore fast ice. An autocorrelation of monthly noise levels over the ice freeze-up and complete cover periods reveal a ∼24 h periodic trend in noise power at high frequencies (>1000 Hz) caused by tidally driven surface currents in combination with increased ice block collisions or increased stress in the shore fast sea ice.

Similarities in extracorporeal membrane oxygenation management across intensive care unit types in the United States: An analysis of the Extracorporeal Life Support Organization Registry.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) use in the United States occurs often in cardiothoracic ICUs (CTICU). It is unknown how it varies across ICU types. METHODS: We identified 10 893 ECMO runs from the Extracorporeal Life Support Organization (ELSO) Registry across 2018 and 2019. Primary outcome was ECMO case volume by ICU type (CTICU vs. non-CTICU). Adjusting for pre-ECMO characteristics and case mix, secondary outcomes were on-ECMO physiologic variables by ICU location stratified by support type. RESULTS: CTICU ECMO occurred in 65.1% and 55.1% (2018 and 2019) of total runs. A minority of total runs related to cardiac surgery procedures (CTICU: 21.7% [2018], 18% [2019]; non-CTICU: 11.2% [2018], 13% [2019]). After multivariate adjustment, non-CTICU ECMO for cardiac support associated with lower 4- and 24-h circuit flow (3.9 liters per minute [LPM] vs. 4.1 LPM, p < 0.0001; 4.1 LPM vs. 4.3 LPM, p < 0.0001); for respiratory support, lower on-ECMO mean fraction of inspired oxygen ([Fi O2 ], 67% vs. 69%, p = 0.02) and lower respiratory rate (14 vs. 15, p < 0.0001); and, for extracorporeal cardiopulmonary resuscitation (ECPR), lower ECMO flow rates at 24 h (3.5 LPM vs. 3.7 LPM, p = 0.01). CONCLUSIONS: ECMO mostly remains in CTICUs though a minority is associated with cardiac surgery. Statistically significant but clinically minor differences in on-ECMO metrics were observed across ICU types.

Juno's Close Encounter With Ganymede-An Overview.

The Juno spacecraft has been in orbit around Jupiter since 2016. Two flybys of Ganymede were executed in 2021, opportunities realized by evolution of Juno's polar orbit over the intervening 5 years. The geometry of the close flyby just prior to the 34th perijove pass by Jupiter brought the spacecraft inside Ganymede's unique magnetosphere. Juno's payload, designed to study Jupiter's magnetosphere, had ample dynamic range to study Ganymede's magnetosphere. The Juno radio system was used both for gravity measurements and for study of Ganymede's ionosphere. Remote sensing of Ganymede returned new results on geology, surface composition, and thermal properties of the surface and subsurface.

Juno Plasma Wave Observations at Ganymede.

The Juno Waves instrument measured plasma waves associated with Ganymede's magnetosphere during its flyby on 7 June, day 158, 2021. Three distinct regions were identified including a wake, and nightside and dayside regions in the magnetosphere distinguished by their electron densities and associated variability. The magnetosphere includes electron cyclotron harmonic emissions including a band at the upper hybrid frequency, as well as whistler-mode chorus and hiss. These waves likely interact with energetic electrons in Ganymede's magnetosphere by pitch angle scattering and/or accelerating the electrons. The wake is accentuated by low-frequency turbulence and electrostatic solitary waves. Radio emissions observed before and after the flyby likely have their source in Ganymede's magnetosphere.

Magnetosphere-Ionosphere-Thermosphere Coupling Study at Jupiter Based on Juno's First 30 Orbits and Modeling Tools.

The dynamics of the Jovian magnetosphere is controlled by the interplay of the planet's fast rotation, its solar-wind interaction and its main plasma source at the Io torus, mediated by coupling processes involving its magnetosphere, ionosphere, and thermosphere. At the ionospheric level, these processes can be characterized by a set of parameters including conductances, field-aligned currents, horizontal currents, electric fields, transport of charged particles along field lines including the fluxes of electrons precipitating into the upper atmosphere which trigger auroral emissions, and the particle and Joule heating power dissipation rates into the upper atmosphere. Determination of these key parameters makes it possible to estimate the net transfer of momentum and energy between Jovian upper atmosphere and equatorial magnetosphere. A method based on a combined use of Juno multi-instrument data and three modeling tools was developed by Wang et al. (2021, https://doi.org/10.1029/2021ja029469) and applied to an analysis of the first nine orbits to retrieve these parameters along Juno's magnetic footprint. We extend this method to the first 30 Juno science orbits and to both hemispheres. Our results reveal a large variability of these parameters from orbit to orbit and between the two hemispheres. They also show dominant trends. Southern current systems are consistent with the generation of a region of sub-corotating ionospheric plasma flows, while both super-corotating and sub-corotating plasma flows are found in the north. These results are discussed in light of the previous space and ground-based observations and currently available models of plasma convection and current systems, and their implications are assessed.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN: Retrospective review and analysis. SETTING: Stanford University Hospital, a 605-bed tertiary care center. PATIENTS: Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.