Performative Manipulation of the Environment by Displaying Albert's Lyrebirds.

AbstractWhere dramatic sexual displays are involved in attracting a mate, individuals can enhance their performances by manipulating their physical environment. Typically, individuals alter their environment either in preparation for a performance by creating a "stage" or during the display itself by using discrete objects as "props." We examined an unusual case of performative manipulation of an entire stage by male Albert's lyrebirds (Menura alberti) during their complex song and dance displays. We found that males from throughout the species' range shake the entangled forest vegetation of their display platforms, creating a highly conspicuous and stereotypical movement external to their bodies. This "stage shaking" is performed in two different rhythms, with the second rhythm an isochronous beat that matches the beat of the coinciding vocalizations. Our results provide evidence that stage shaking is an integral, and thus likely functional, component of male Albert's lyrebird sexual displays and so highlight an intriguing but poorly understood facet of complex communication.

Early Fluid Is Less Fluid: Comparing Early Versus Late ICU Resuscitation in Severely Injured Trauma Patients.

OBJECTIVES: The temporal trends of crystalloid resuscitation in severely injured trauma patients after ICU admission are not well characterized. We hypothesized early crystalloid resuscitation was associated with less volume and better outcomes than delaying crystalloid. DESIGN: Retrospective, observational. SETTING: High-volume level 1 academic trauma center. PATIENTS: Adult trauma patients admitted to the ICU with emergency department serum lactate greater than or equal to 4 mmol/dL, elevated lactate (≥ 2 mmol/L) at ICU admission, and normal lactate by 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the 333 subjects, we analyzed patient and injury characteristics and the first 48 hours of ICU course. Receipt of greater than or equal to 500 mL/hr of crystalloid in the first 6 hours of ICU admission was used to distinguish early vs. late resuscitation. Outcomes included ICU length of stay (LOS), ventilator days, and acute kidney injury (AKI). Unadjusted and multivariable regression methods were used to compare early resuscitation vs. late resuscitation. Compared with the early resuscitation group, the late resuscitation group received more volume by 48 hours (5.5 vs. 4.1 L; p ≤ 0.001), had longer ICU LOS (9 vs. 5 d; p ≤ 0.001), more ventilator days (5 vs. 2 d; p ≤ 0.001), and higher occurrence rate of AKI (38% vs. 11%; p ≤ 0.001). On multivariable regression, late resuscitation remained associated with longer ICU LOS and ventilator days and higher odds of AKI. CONCLUSIONS: Delaying resuscitation is associated with both higher volumes of crystalloid by 48 hours and worse outcomes compared with early resuscitation. Judicious crystalloid given early in ICU admission could improve outcomes in the severely injured.

Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.

The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy).

Fever and infections in surgical intensive care: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.

The evaluation and workup of fever and the use of antibiotics to treat infections is part of daily practice in the surgical intensive care unit (ICU). Fever can be infectious or non-infectious; it is important to distinguish between the two entities wherever possible. The evidence is growing for shortening the duration of antibiotic treatment of common infections. The purpose of this clinical consensus document, created by the American Association for the Surgery of Trauma Critical Care Committee, is to synthesize the available evidence, and to provide practical recommendations. We discuss the evaluation of fever, the indications to obtain cultures including urine, blood, and respiratory specimens for diagnosis of infections, the use of procalcitonin, and the decision to initiate empiric antibiotics. We then describe the treatment of common infections, specifically ventilator-associated pneumonia, catheter-associated urinary infection, catheter-related bloodstream infection, bacteremia, surgical site infection, intra-abdominal infection, ventriculitis, and necrotizing soft tissue infection.

The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

The Sensitivity of Limited-Sequence MRI in Identifying Pediatric Cervical Spine Injury: A Western Pediatric Surgery Research Consortium Multicenter Retrospective Cohort Study.

INTRODUCTION: Clinical clearance of a child's cervical spine after trauma is often challenging due to impaired mental status or an unreliable neurologic examination. Magnetic resonance imaging (MRI) is the gold standard for excluding ligamentous injury in children but is constrained by long image acquisition times and frequent need for anesthesia. Limited-sequence MRI (LSMRI) is used in evaluating the evolution of traumatic brain injury and may also be useful for cervical spine clearance while potentially avoiding the need for anesthesia. The purpose of this study was to assess the sensitivity and negative predictive value of LSMRI as compared to gold standard full-sequence MRI as a screening tool to rule out clinically significant ligamentous cervical spine injury. METHODS: We conducted a ten-center, five-year retrospective cohort study (2017-2021) of all children (0-18y) with a cervical spine MRI after blunt trauma. MRI images were re-reviewed by a study pediatric radiologist at each site to determine if the presence of an injury could be identified on limited sequences alone. Unstable cervical spine injury was determined by study neurosurgeon review at each site. RESULTS: We identified 2,663 children less than 18 years of age who underwent an MRI of the cervical spine with 1,008 injuries detected on full-sequence studies. The sensitivity and negative predictive value of LSMRI were both >99% for detecting any injury and 100% for detecting any unstable injury. Young children (age < 5 years) were more likely to be electively intubated or sedated for cervical spine MRI. CONCLUSION: LSMRI is reliably detects clinically significant ligamentous injury in children after blunt trauma. To decrease anesthesia use and minimize MRI time, trauma centers should develop LSMRI screening protocols for children without a reliable neurologic exam. LEVEL OF EVIDENCE: 2 (Diagnostic Tests or Criteria).

Assessment of PTSD and Trauma Symptoms With the MMPI-3 in College Students: Validity and Incremental Utility of the Anxiety Related Experiences (ARX) Scale.

Post Traumatic Stress Disorder (PTSD) is heterogeneous in nature, which complicates diagnostic efforts and makes accurate assessment tools critical. The MMPI family of instruments are widely used broadband measures of psychopathology, including trauma symptomology. The MMPI-3's Anxiety Related Experiences scale (ARX) is an expansion of the MMPI-2-RF Anxiety (AXY) scale which has historically represented the MMPI family's best measure of trauma symptoms. This study expands research on ARX in 2 samples of college students (n = 332 [PCL-5 Criterion] & n = 58 [CAPS-5 Criterion]) by examining ARX's incremental, criterion, and classification validity. ARX incrementally predicted PCL-5 total and cluster scores beyond that accounted for by AXY (R2Δ = .01-.09). ARX accounted for the most unique variance, beyond RCd and RC7, in CAPS-5 interview ratings of intrusion symptoms (R2Δ = .16). ARX was strongly related to trauma symptomology broadly (r = .42-.58) and demonstrated strong screening ability at T65 (sensitivity = .37-.40; specificity = .91-.92) and stronger diagnostic screening at T75 (sensitivity = .31; specificity = .93). We discuss clinical considerations when using ARX for assessing PTSD.

A core outcome set for acute necrotizing pancreatitis: An Eastern Association for the Surgery of Trauma modified Delphi method consensus study.

BACKGROUND: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias. METHODS: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study. RESULTS: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors. CONCLUSION: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Whole genome sequencing reveals stepping-stone dispersal buffered against founder effects in a range expanding seabird.

Many species are shifting their ranges in response to climate-driven environmental changes, particularly in high-latitude regions. However, the patterns of dispersal and colonization during range shifting events are not always clear. Understanding how populations are connected through space and time can reveal how species navigate a changing environment. Here, we present a fine-scale population genomics study of gentoo penguins (Pygoscelis papua), a presumed site-faithful colonial nesting species that has increased in population size and expanded its range south along the Western Antarctic Peninsula. Using whole genome sequencing, we analysed 129 gentoo penguin individuals across 12 colonies located at or near the southern range edge. Through a detailed examination of fine-scale population structure, admixture, and population divergence, we inferred that gentoo penguins historically dispersed rapidly in a stepping-stone pattern from the South Shetland Islands leading to the colonization of Anvers Island, and then the adjacent mainland Western Antarctica Peninsula. Recent southward expansion along the Western Antarctic Peninsula also followed a stepping-stone dispersal pattern coupled with limited post-divergence gene flow from colonies on Anvers Island. Genetic diversity appeared to be maintained across colonies during the historical dispersal process, and range-edge populations are still growing. This suggests large numbers of migrants may provide a buffer against founder effects at the beginning of colonization events to maintain genetic diversity similar to that of the source populations before migration ceases post-divergence. These results coupled with a continued increase in effective population size since approximately 500-800 years ago distinguish gentoo penguins as a robust species that is highly adaptable and resilient to changing climate.

Massive transfusion protocol reactivation as a novel marker of physician team under-triage after injury.

BACKGROUND: Large trauma centers have protocols for the assessment of injury and triaging of care with attempts to over-triage to ensure adequate care for all patients. We noted that a significant number of patients undergo a second massive transfusion protocol (MTP) activation in the first 24 h of care and conducted a retrospective cohort study of patients involved over a 3-year period. METHODS: Transfusion service records of MTP activations 2019-2021 were linked to Trauma Registry records and divided into cohorts receiving a single versus a reactivation of the MTP. Time of activation and amounts of blood products issued were linked to demographic, injury severity, and outcome data. Categorical and continuous data were compared between cohorts with chi-squared, Fisher's, and Wilcoxan tests as appropriate, and multivariable regression models were used to seek interactions (p < .05). RESULTS: MTP activation was recorded for 1884 acute trauma patients over our 3-year study period, 142 of whom (7.5%) had reactivation. Factors associated with reactivation included older age (46 vs. 40 years), higher injury severity score (ISS, 27 vs. 22), leg injuries, and presentation during morning shift change (5-7 a.m., 3.3% vs. 7.7%). Patients undergoing MTP reactivation used more RBCs (5 U vs. 2 U) and had more ICU days (3 vs. 2). CONCLUSIONS: Older patients and those presenting during shift change are at risk for failure to recognize their complex injury patterns and under-triage for trauma care. The fidelity and granularity of transfusion service records can provide unique opportunities for quality assessment and improvement in trauma care.

Predicting high-intensity resuscitation needs in injured patients in the post-hemostasis phase of care following intervention.

BACKGROUND: Best resuscitation practices in the posthemostasis phase of care are poorly defined; this phase of care is characterized by a range of physiologic derangements and multiple therapeutic modalities used to address them. Using a cohort of injured patients who required an immediate intervention in the operating room or angiography suite following arrival to the emergency department, we sought to define high-intensity resuscitation (HIR) in this posthemostasis phase of care; we hypothesized that those who would require HIR could be identified, using only data available at intensive care unit (ICU) admission. METHODS: Clinical data were extracted for consecutive injured patients (2016-2019) admitted to the ICU following an immediate procedure in the operating room or angiography suite. High-intensity resuscitation thresholds were defined as the top decile of blood product (≥3 units) and/or crystalloid (≥4 L) use in the initial 12 hours of ICU care and/or vasoactive medication use between ICU hours 2 and 12. The primary outcome, HIR, was a composite of any of these modalities. Predictive modeling of HIR was performed using logistic regression with predictor variables selected using Least Absolute Shrinkage and Selection Operator (LASSO) estimation. Model was trained using 70% of the cohort and tested on the remaining 30%; model predictive ability was evaluated using area under receiver operator curves. RESULTS: Six hundred five patients were included. Patients were 79% male, young (median age, 39 years), severely injured (median Injury Severity Score, 26), and an approximately 3:2 ratio of blunt to penetrating mechanisms of injury. A total of 215 (36%) required HIR. Predictors selected by LASSO included: shock index, lactate, base deficit, hematocrit, and INR. The area under receiver operator curve for the LASSO-derived HIR prediction model was 0.82. CONCLUSION: Intensive care unit admission data can identify subsequent HIR in the posthemostasis phase of care. Use of this model may facilitate triage, nursing ratio determination, and resource allocation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Cervical Collar-Associated Pressure Injury in Pediatric Trauma Patients: A Western Pediatric Surgery Research Consortium Study.

BACKGROUND: Healthcare-associated pressure injuries (HAPI) are known to be associated with medical devices and are preventable. Cervical spine immobilization is commonly utilized in injured children prior to clinical clearance or for treatment of an unstable cervical spinal injury. The frequency of HAPI has been quantified in adults with cervical spine immobilization but has not been well-described in children. The aim of this study was to describe characteristics of children who developed HAPI associated with cervical immobilization. METHODS: We analyzed a retrospective cohort of children (0-18 years) who developed a stage two or greater cervical HAPI. This cohort was drawn from an overall sample of 49,218 registry patients treated over a five-year period (2017-2021) at ten pediatric trauma centers. Patient demographics, injury characteristics, and cervical immobilization were tabulated to describe the population. RESULTS: The cohort included 32 children with stage two or greater cervical HAPI. The median age was 5 years (IQR 2-13) and 78% (n = 25) were admitted to the intensive care unit. The median (IQR) time to diagnosis of HAPI was 11 (7-21) days post-injury. The majority of cervical HAPI (78%, 25/32) occurred in children requiring immobilization for cervical injuries, with only four children developing HAPI after wearing a prophylactic cervical collar in the absence of a cervical spine injury. CONCLUSION: Advanced-stage HAPI associated with cervical collar use in pediatric trauma patients is rare and usually occurs in patients with cervical spine injuries requiring immobilization for treatment. More expedient cervical spine clearance with MRI is unlikely to substantially reduce cervical HAPI in injured children. LEVEL OF EVIDENCE: Level III (Epidemiologic and Prognostic).

Characteristics of victims of trauma requiring invasive mechanical ventilation with a short stay in critical care.

BACKGROUND: Many patients who are admitted to the intensive care unit (ICU) have needs which rapidly resolve and are discharged alive within 24 h. We sought to characterize the outcomes of critically ill trauma victims at our institution with a short stay in the ICU. METHODS: We conducted a retrospective cohort study of all critically ill adult trauma victims presenting to our ED between January 1st, 2011 and December 31st, 2019. We included patients who were endotracheally intubated in either the prehospital setting or the ED and were admitted either to the operating room (OR), angiography suite, or ICU. Our primary outcome was the proportion of patients who were discharged alive from the ICU within 24 h. RESULTS: We included 3869 patients meeting the criteria above who were alive at 24 h. This population was 78% male with a median age of 40 and 76% of patients suffered from blunt trauma. The median injury severity score (ISS) of the group was 21 [inter-quartile range (IQR) 11-30]. In-hospital mortality amongst the group was 12%. 17% of the group were discharged alive from the ICU within 24 h. Thirty-four percent of the group had an ISS ≤ 15. Of the group which left the ICU alive within 24 h, six patients (0.9%) died in the hospital, 2 % of patients were re-admitted to an ICU, and 0.6% of patients required re-intubation. CONCLUSIONS: We found that 17% of patients who were intubated in the prehospital setting or emergency department and subsequently hospitalized were discharged alive from the ICU within 24 h.

Early Fluid is Less Fluid: Comparing Early Versus Late Resuscitation in Severely Injured Trauma Patients.

Background: We aimed to characterize the temporal trends of crystalloid resuscitation in severely injured trauma patients after intensive care unit (ICU) admission. Using 500 mL/hr of crystalloid in the first 6 hours of ICU admission to distinguish early versus late resuscitation, we hypothesized early resuscitation was associated with less volume by 48 hours and better outcomes compared with late resuscitation. Methods: We performed a retrospective review of the trauma registry of a high-volume level 1 academic trauma center to examine adult trauma patients admitted to the ICU (2016-2019) with: with initial serum lactate ≥ 4 mmol/dL, elevated lactate (≥ 2 mmol/L) at ICU admission, and lactate normalization within 48 hours. We analyzed patient and injury characteristics, and the first 48 hours of ICU course. The primary outcome was ICU length of stay (LOS); secondary outcomes included ventilator days, acute kidney injury (AKI), and in-hospital death. We compared subjects who received early resuscitation to those received late resuscitation using unadjusted methods and multivariable regression models. Results: We analyzed 333 subjects. The late resuscitation group received less volume over the first 24 hours, but surpassed the early group by 48 hours (5.5 vs 4.1L, p ≤ 0.001). The late group had longer ICU LOS (9 vs 5 days, p ≤ 0.001) and ventilator days (5 vs 2 days, p ≤ 0.001), and higher incidence of AKI (38% vs 11%, p ≤ 0.001). On multivariable regression, late resuscitation remained associated with longer ICU LOS and ventilator days, and higher odds of AKI after adjusting for important confounders. Conclusions: After hemostasis, crystalloid can play an important role in restoration of organ perfusion. Delaying resuscitation is associated with both receipt of higher volumes of crystalloid by 48 hours and worse outcomes compared to early resuscitation. Judicious crystalloid given early in ICU admission could improve outcomes in the severely injured.

Defining the Optimal Antibiotic Duration in Necrotizing Skin and Soft Tissue Infections: Clinical Experience from a Quaternary Referral Center.

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

A Description of Mechanically Ventilated Patients Admitted From the Emergency Department With a Short Critical Care Stay.

BACKGROUND: Patients admitted to an intensive care unit (ICU) requiring invasive mechanical ventilation who are discharged alive from the ICU within 24 h are poorly characterized in the literature. OBJECTIVE: Our aim was to characterize a cohort of intubated emergency department (ED) patients who are extubated and discharged from the ICU within 24 h. METHODS: We conducted a retrospective, observational cohort study at a single level I trauma center from January 2017 to December 2019. We included adults who were admitted to an ICU from the ED requiring invasive mechanical ventilation. Our primary outcome was the proportion of patients who were discharged from the ICU alive within 24 h. RESULTS: Of 13,374 ED patients admitted to an ICU during the study period, 2871 patients were intubated and ventilated in the prehospital or ED settings. Of these, 14% were discharged alive from the ICU within 24 h of admission. Only 21% of these patients were intubated in the ED. We identified the following two distinct subpopulations comprising 62% of this short-stay group: patients with a primary discharge diagnosis of intoxication (47%) and minimally injured trauma patients (53%), with 4% of patients in both subgroups. CONCLUSIONS: A total of 14% of patients receiving intubation with mechanical ventilation in the prehospital environment or in the ED were discharged alive from the ICU within 24 h. We identified two distinct subgroups of patients with a short stay in intensive care who may be candidates for ED extubation, including patients with intoxication and minimally injured trauma patients.

Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies.

Importance: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies. Objective: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies. Design, Setting, and Participants: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022. Exposures: TEs identified by K-means clustering of plasma biomarkers collected at hospital arrival. Main Outcomes and Measures: An association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS. Results: A total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001). Conclusions and Relevance: Results of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes.

Long-term health-related quality of life and independence among older survivors of serious injury.

BACKGROUND: Little is known about the recovery experiences of older trauma intensive care unit (TICU) survivors and the relationship between geriatric trauma care and long-term functional ability and health-related quality of life (HRQOL). METHODS: We conducted a prospective cohort study of 218 patients (age, ≥65 years) admitted to a Level 1 regional trauma center TICU before versus after implementation of a geriatric care bundle with protocolized geriatrics consultations (Geri-T). Survivors or their proxies were interviewed approximately 1 year after hospitalization. Outcomes included the Katz Index of Independence in Activities of Daily Living (ADLs), Lawton Instrumental Activities of Daily Living (IADLs), and EQ-5D-5L HRQOL survey. Two investigator-developed questions regarding recovery experiences were included. Differences in outcomes among survivors admitted before versus after Geri-T were analyzed using multivariable linear regression. Responses to questions about recovery experiences were qualitatively assessed using content analysis. RESULTS: We reached 67% (146/218) of hospital survivors or their proxies across both groups; 126 patients were still alive and completed the survey. Mean age was 76 (SD, 8), 36% were female, and 90% were independent with ADLs preinjury. At follow-up, independence with ADLs was 76% and IADLs was 63%. The mean EQ-5D-5L index score was 0.78 (SD, 0.18). Most patients (65%) reported having not returned to preinjury functional status. Neither functional ability or HRQOL differed significantly among patients admitted before versus after Geri-T. Content analysis of open-ended questions revealed themes of activity limitations, persistent pain, and cognitive dysfunction. CONCLUSION: Nearly one-fifth of TICU survivors experienced loss of ADL function 1 year after injury, and most reported having not returned to preinjury functional status. Nonetheless, patient-reported HRQOL was comparable to age-adjusted norms. Geri-T was not associated with differences in HRQOL or functional ability. Survivors reported persistent difficulty with activities beyond those of daily living, pain, and cognition. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level III.