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Article ; Online: Paleozoic diversification of terrestrial chitin-degrading bacterial lineages.

Gruen, Danielle S / Wolfe, Joanna M / Fournier, Gregory P

2019 Volume 19, Issue 1, Page(s) 34

Abstract: Background: Establishing the divergence times of groups of organisms is a major goal of evolutionary biology. This is especially challenging for microbial lineages due to the near-absence of preserved physical evidence (diagnostic body fossils or ... ...

Abstract	Background: Establishing the divergence times of groups of organisms is a major goal of evolutionary biology. This is especially challenging for microbial lineages due to the near-absence of preserved physical evidence (diagnostic body fossils or geochemical biomarkers). Horizontal gene transfer (HGT) can serve as a temporal scaffold between microbial groups and other fossil-calibrated clades, potentially improving these estimates. Specifically, HGT to or from organisms with fossil-calibrated age estimates can propagate these constraints to additional groups that lack fossils. While HGT is common between lineages, only a small subset of HGT events are potentially informative for dating microbial groups. Results: Constrained by published fossil-calibrated studies of fungal evolution, molecular clock analyses show that multiple clades of Bacteria likely acquired chitinase homologs via HGT during the very late Neoproterozoic into the early Paleozoic. These results also show that, following these HGT events, recipient terrestrial bacterial clades likely diversified ~ 300-500 million years ago, consistent with established timescales of arthropod and plant terrestrialization. Conclusions: We conclude that these age estimates are broadly consistent with the dispersal of chitinase genes throughout the microbial world in direct response to the evolution and ecological expansion of detrital-chitin producing groups. The convergence of multiple lines of evidence demonstrates the utility of HGT-based dating methods in microbial evolution. The pattern of inheritance of chitinase genes in multiple terrestrial bacterial lineages via HGT processes suggests that these genes, and possibly other genes encoding substrate-specific enzymes, can serve as a "standard candle" for dating microbial lineages across the Tree of Life.
MeSH term(s)	Animals ; Bacteria/classification ; Base Sequence ; Bayes Theorem ; Calibration ; Chitin/metabolism ; Chitinases/genetics ; Fossils ; Fungi/classification ; Models, Biological ; Paleontology ; Phylogeny ; Time Factors
Chemical Substances	Chitin (1398-61-4) ; Chitinases (EC 3.2.1.14)
Language	English
Publishing date	2019-01-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2041493-6
ISSN	1471-2148 ; 1471-2148
ISSN (online)	1471-2148
ISSN	1471-2148
DOI	10.1186/s12862-019-1357-8
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Article ; Online: Association between trauma triage and time-to-vaso-occlusive events in patients with sickle cell disease after traumatic injury: a retrospective study.

Parchuri, Ektha / Pacella-LaBarbara, Maria / O'Brien, Julia / Gruen, Danielle S / Guyette, Frances / Brown, Joshua B / De Castro, Laura / Jonassaint, Charles R

Trauma surgery & acute care open

2023 Volume 8, Issue 1, Page(s) e001200

Abstract: Introduction: Sickle cell disease (SCD) is associated with vaso-occlusive events (VOEs) that can lead to disease complications, including early mortality. Given that similar inflammatory responses characterize VOE and traumatic injury, injured patients ... ...

Abstract	Introduction: Sickle cell disease (SCD) is associated with vaso-occlusive events (VOEs) that can lead to disease complications, including early mortality. Given that similar inflammatory responses characterize VOE and traumatic injury, injured patients with SCD may be vulnerable to acute complications. This study is the first to examine whether traumatic injury is associated with increased severity of future VOEs. Methods: This cohort study was conducted using electronic health record data from an SCD clinic in Western Pennsylvania; 356 patients with SCD from January 2000 to July 2021 were identified via retrospective chart review. 55 patients were eligible based on continuous medical record data spanning 1 year preinjury and postinjury. Patients were sorted into three treatment groups based on injury management: (1) Neither triage to trauma team activation (TTA) nor inpatient admission ( Results: Early Discharge Conclusion: Despite minimal changes in long-term VOE outcomes after injury, traumatic injuries may accelerate the time-to-VOE among the Level of evidence: Level IV: retrospective case-control study with three negative criteria.
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article
ISSN	2397-5776
ISSN (online)	2397-5776
DOI	10.1136/tsaco-2023-001200
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Article ; Online: Prehospital Lactate is Associated with the Need for Blood in Trauma.

Zadorozny, Eva V / Weigel, Tyler / Stone, Andre / Gruen, Danielle S / Galvagno, Samuel M / Yazer, Mark H / Brown, Joshua B / Guyette, Francis X

Prehospital emergency care

2021 Volume 26, Issue 4, Page(s) 590–599

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Emergency Medical Services ; Emergency Service, Hospital ; Humans ; Injury Severity Score ; Lactic Acid ; Retrospective Studies ; Trauma Centers ; Vital Signs ; Wounds and Injuries/therapy
Chemical Substances	Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2021-11-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1461751-1
ISSN	1545-0066 ; 1090-3127
ISSN (online)	1545-0066
ISSN	1090-3127
DOI	10.1080/10903127.2021.1983096
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Article ; Online: Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Donohue, Jack K / Gruen, Danielle S / Iyanna, Nidhi / Lorence, John M / Brown, Joshua B / Guyette, Francis X / Daley, Brian J / Eastridge, Brian J / Miller, Richard S / Nirula, Raminder / Harbrecht, Brian G / Claridge, Jeffrey A / Phelan, Herb A / Vercruysse, Gary A / O'Keeffe, Terence / Joseph, Bellal / Neal, Matthew D / Billiar, Timothy R / Sperry, Jason L

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2747

Abstract: Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to ... ...

Abstract	Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.
MeSH term(s)	Humans ; Wounds, Penetrating/complications ; Wounds, Nonpenetrating/complications ; Proportional Hazards Models ; Emergency Medical Services ; Endothelial Cells ; Retrospective Studies
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-53398-1
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Article ; Online: Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.

Gruen, Danielle S / Brown, Joshua B / Guyette, Francis X / Johansson, Pär I / Stensballe, Jakob / Li, Shimena R / Leeper, Christine M / Eastridge, Brian J / Nirula, Raminder / Vercruysse, Gary A / O'Keeffe, Terence / Joseph, Bellal / Neal, Matthew D / Sperry, Jason L

The journal of trauma and acute care surgery

2023 Volume 95, Issue 5, Page(s) 642–648

Abstract: Background: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA ... ...

Abstract	Background: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. Methods: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. Results: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). Conclusion: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. Level of evidence: Therapeutic/Care Management; Level III.
MeSH term(s)	Humans ; Tranexamic Acid/therapeutic use ; Antifibrinolytic Agents/therapeutic use ; Syndecan-1 ; Prospective Studies ; Emergency Medical Services
Chemical Substances	Tranexamic Acid (6T84R30KC1) ; Antifibrinolytic Agents ; Syndecan-1
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000003955
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Article ; Online: Protective/reparative cytokines are suppressed at high injury severity in human trauma.

Cai, Jinman / McKinley, Todd / Billiar, Isabel / Zenati, Mazen S / Gaski, Greg / Vodovotz, Yoram / Gruen, Danielle S / Billiar, Timothy R / Namas, Rami A

Trauma surgery & acute care open

2021 Volume 6, Issue 1, Page(s) e000619

Abstract: Background: Trauma elicits a complex inflammatory response that, among multiple presenting factors, is greatly impacted by the magnitude of injury severity. Herein, we compared the changes in circulating levels of mediators with known proinflammatory ... ...

Abstract	Background: Trauma elicits a complex inflammatory response that, among multiple presenting factors, is greatly impacted by the magnitude of injury severity. Herein, we compared the changes in circulating levels of mediators with known proinflammatory roles to those with known protective/reparative actions as a function of injury severity in injured humans. Methods: Clinical and biobank data were obtained from 472 (trauma database-1 (TD-1), University of Pittsburgh) and 89 (trauma database-2 (TD-2), Indiana University) trauma patients admitted to the intensive care unit (ICU) and who survived to discharge. Injury severity was estimated based on the Injury Severity Score (ISS), and this was used as both a continuous variable and for the purpose of grouping patients into severity-based cohorts. Samples within the first 24 hours were obtained from all patients and then daily up to day 7 postinjury in TD-1. Sixteen cytokines were assayed using Luminex and were analyzed using two-way analysis of variance (p<0.05). Results: Patients with higher ISSs had longer ICU and hospital stays, days on mechanical ventilation and higher rates of nosocomial infection when compared with the mild and moderate groups. Time course analysis and correlations with ISS showed that 11 inflammatory mediators correlated positively with injury severity, consistent with previous reports. However, five mediators (interleukin (IL)-9, IL-21, IL-22, IL-23 and IL-17E/25) were suppressed in patients with high ISS and inversely correlated with ISS. Discussion: These findings suggest that severe injury is associated with a suppression of a subset of cytokines known to be involved in tissue protection and regeneration (IL-9, IL-22 and IL-17E/25) and lymphocyte differentiation (IL-21 and IL-23), which in turn correlates with adverse clinical outcomes. Thus, patterns of proinflammatory versus protective/reparative mediators diverge with increasing ISS.
Language	English
Publishing date	2021-03-02
Publishing country	England
Document type	Journal Article
ISSN	2397-5776
ISSN (online)	2397-5776
DOI	10.1136/tsaco-2020-000619
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Article ; Online: High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

Wu, Junru / Moheimani, Hamed / Li, Shimena / Kar, Upendra K / Bonaroti, Jillian / Miller, Richard S / Daley, Brian J / Harbrecht, Brian G / Claridge, Jeffrey A / Gruen, Danielle S / Phelan, Herbert A / Guyette, Francis X / Neal, Matthew D / Das, Jishnu / Sperry, Jason L / Billiar, Timothy R

Annals of surgery

2022 Volume 276, Issue 4, Page(s) 673–683

Abstract: Objectives: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database.: Background: ... ...

Abstract	Objectives: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. Background: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. Methods: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. Results: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). Conclusions: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.
MeSH term(s)	Brain Injuries, Traumatic/therapy ; Emergency Medical Services/methods ; Humans ; Multiple Trauma/therapy ; Plasma ; Proteomics
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000005610
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Article ; Online: Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

Air medical journal

2023 Volume 43, Issue 1, Page(s) 47–54

Abstract: Objective: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) ... ...

Abstract	Objective: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Methods: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. Results: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. Conclusion: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Emergency Medical Services ; Air Ambulances ; Multiple Trauma/therapy ; Hospitals ; Injury Severity Score ; Wounds and Injuries/therapy ; Trauma Centers
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2072853-0
ISSN	1532-6497 ; 1067-991X
ISSN (online)	1532-6497
ISSN	1067-991X
DOI	10.1016/j.amj.2023.09.013
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Article: Microbial population structure in a stratified, acidic pit lake in the Iberian Pyrite Belt

Grettenberger, Christen L / Mccauley Rench, Rebecca L / Gruen, Danielle S / Mills, Daniel B / Carney, Colin / Brainard, Jamie / Hamasaki, Hiroshi / Ramirez, Ramses / Watanabe, Yumiko / Amaral-Zettler, Linda A / Ohmoto, Hiroshi / Macalady, Jennifer L

Geomicrobiology journal. 2020 July 1, v. 37, no. 7

2020

Abstract: We examined the geochemistry and bacterial and archaeal community structure in the acidic (pH < 2.4) pit lake at Peña de Hierro, near the headwaters of the Río Tinto. The lake has strong vertical gradients in light, O₂, pH, conductivity, and dissolved ... ...

Abstract	We examined the geochemistry and bacterial and archaeal community structure in the acidic (pH < 2.4) pit lake at Peña de Hierro, near the headwaters of the Río Tinto. The lake has strong vertical gradients in light, O₂, pH, conductivity, and dissolved ions. Bacterial and archaeal communities between 0 and 32 m displayed low species richness and evenness. Relatives of iron cycling taxa accounted for 60-90% of the operational taxonomic units (OTUs) throughout the water column. Relatives of heterotrophic, facultative Fe(III)-reducing species made up more than a third of the bacterial and archaeal community in the photic zone. Taxa related to Fe(II) oxidizers Ferrithrix thermotolerans and Acidithix ferrooxidans were also abundant in the photic zone. Below the photic zone, relatives of the lithoautotrophic Fe(II) oxidizers Leptospirillum ferrooxidans and Ferrovum myxofaciens bloomed at different depths within or just below the oxycline. Thermoplasmatales predominated in the deep, microoxic zone of the lake. The microbial population structure of the lake appears to be influenced by the production of oxygen and organic matter by phototrophs in a narrow zone at the lake surface and by strong geochemical gradients present in the water column that create distinct niches for separate Fe(II) oxidizers.
Keywords	Leptospirillum ferrooxidans ; Thermoplasmatales ; autotrophs ; community structure ; euphotic zone ; geochemistry ; lakes ; organic matter ; oxygen ; pH ; population structure ; pyrite ; species richness
Language	English
Dates of publication	2020-0701
Size	p. 623-634.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1482560-0
ISSN	1521-0529 ; 0149-0451
ISSN (online)	1521-0529
ISSN	0149-0451
DOI	10.1080/01490451.2020.1751748
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Article ; Online: Characterization of unexpected survivors following a prehospital plasma randomized trial.

Gruen, Danielle S / Guyette, Francis X / Brown, Joshua B / Daley, Brian J / Miller, Richard S / Harbrecht, Brian G / Claridge, Jeffrey A / Phelan, Herb A / Yazer, Mark H / Neal, Matthew D / Zuckerbraun, Brian S / Sperry, Jason L

The journal of trauma and acute care surgery

2020 Volume 89, Issue 5, Page(s) 908–914

Abstract: Background: Prehospital plasma improves survival for severely injured trauma patients transported by air ambulance. We sought to characterize the unexpected survivors, patients who survived despite having high predicted mortality after traumatic injury.! ...

Abstract	Background: Prehospital plasma improves survival for severely injured trauma patients transported by air ambulance. We sought to characterize the unexpected survivors, patients who survived despite having high predicted mortality after traumatic injury. Methods: The Prehospital Air Medical Plasma trial randomized severely injured patients (n = 501) to receive either standard care (crystalloid) or two units of prehospital plasma followed by standard care fluid resuscitation. We built a generalized linear model to estimate patient mortality. Area under the receiver operating characteristic curve was used to evaluate model performance. We defined unexpected survivors as patients who had a predicted mortality greater than 50% and survived to 30 days. We characterized patient demographics, clinical features, and outcomes of the unexpected survivors. Observed to expected (O/E) ratios and Z-statistics were calculated using model-estimated mortality for each cohort. Results: Our model predicted mortality better than Injury Severity Score or Revised Trauma Score parameters and identified 36 unexpected survivors. Compared with expected survivors, unexpected survivors were younger (33 years [24, 52 years] vs. 47 years [32, 59 years], p = 0.013), were more severely injured (Injury Severity Score 34 [22, 50] vs. 18 [10, 27], p < 0.001), had worse organ dysfunction and hospital resource outcomes (multiple organ failure, intensive care unit, hospital length of stay, and ventilator days), and were more likely to receive prehospital plasma (67 vs. 46%, p = 0.031). Nonsurvivors with high predicted mortality were more likely to receive standard care resuscitation (p < 0.001). Unexpected survivors who received prehospital plasma had a lower observed to expected mortality than those that received standard care resuscitation (O/E 0.56 [0.33-0.84] vs. 1.0 [0.73-1.32]). The number of prehospital plasma survivors (24) exceeded the number of predicted survivors (n = 10) estimated by our model (p < 0.001). Conclusion: Prehospital plasma is associated with an increase in the number of unexpected survivors following severe traumatic injury. Prehospital interventions may improve the probability of survival for injured patients with high predicted mortality based on early injury characteristics, vital signs, and resuscitation measures. Level of evidence: Therapeutic Level III.
MeSH term(s)	Adult ; Air Ambulances/statistics & numerical data ; Blood Component Transfusion/methods ; Blood Component Transfusion/statistics & numerical data ; Crystalloid Solutions/administration & dosage ; Female ; Fluid Therapy/methods ; Fluid Therapy/statistics & numerical data ; Hospital Mortality ; Humans ; Injury Severity Score ; Male ; Middle Aged ; Plasma ; Resuscitation/methods ; Resuscitation/statistics & numerical data ; Standard of Care ; Survival Analysis ; Survivors/statistics & numerical data ; Time Factors ; Time-to-Treatment ; Treatment Outcome ; Wounds and Injuries/diagnosis ; Wounds and Injuries/mortality ; Wounds and Injuries/therapy ; Young Adult
Chemical Substances	Crystalloid Solutions
Language	English
Publishing date	2020-05-29
Publishing country	United States
Document type	Clinical Trial, Phase III ; Equivalence Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000002816
Database	MEDical Literature Analysis and Retrieval System OnLINE

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