Cigarette Smoke Exposure and Acute Respiratory Distress Syndrome in Sepsis: Epidemiology, Clinical Features, and Biologic Markers.

Cigarette smoke exposure is associated with an increased risk of developing acute respiratory distress syndrome (ARDS) in trauma, transfusion, and nonpulmonary sepsis. It is unknown whether this relationship exists in the general sepsis population. Furthermore, it is unknown if patients with ARDS have differences in underlying biology based on smoking status.

Cigarette Smoking and ARDS After Blunt Trauma: The Influence of Changing Smoking Patterns and Resuscitation Practices.

Background: Cigarette smoking is associated with an increased risk of developing ARDS. However, whether changes in smoking patterns or processes of care impact this relationship is unclear.

Research Question: Are changes in smoking and resuscitation patterns associated with changes in the relationship between smoking and ARDS?

Study Design And Methods: We conducted a prospective cohort study of critically injured adults with blunt trauma from 2005 to 2015.

It's About Time: Transfusion effects on postinjury platelet aggregation over time.

Background: Impaired postinjury platelet aggregation is common, but the effect of transfusion on this remains unclear. Data suggest that following injury platelet transfusion may not correct impaired platelet aggregation, and impaired platelet aggregation may not predict the need for platelet transfusion. We sought to further investigate platelet aggregation responses to transfusions, using regression statistics to isolate the independent effects of transfusions given in discrete time intervals from injury on both immediate and longitudinal platelet aggregation.

End-tidal carbon dioxide underestimates plasma carbon dioxide during emergent trauma laparotomy leading to hypoventilation and misguided resuscitation: A Western Trauma Association Multicenter Study.

Background: End-tidal carbon dioxide (ETCO2) is routinely used during elective surgery to monitor ventilation. The role of ETCO2 monitoring in emergent trauma operations is poorly understood. We hypothesized that ETCO2 values underestimate plasma carbon dioxide (pCO2) values during resuscitation for hemorrhagic shock.

Dynamic multi-outcome prediction after injury: Applying adaptive machine learning for precision medicine in trauma.

Objective: Machine learning techniques have demonstrated superior discrimination compared to conventional statistical approaches in predicting trauma death. The objective of this study is to evaluate whether machine learning algorithms can be used to assess risk and dynamically identify patient-specific modifiable factors critical to patient trajectory for multiple key outcomes after severe injury.

Methods: SuperLearner, an ensemble machine-learning algorithm, was applied to prospective observational cohort data from 1494 critically-injured patients.

The why and how our trauma patients die: A prospective Multicenter Western Trauma Association study.

Background: Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality.

Is it time to measure complications from the National Trauma Data Bank? A longitudinal analysis of recent reporting trends.

Background: Payers have approached select complications as never events, yet there is rationale that achieving a zero incidence of these events is impractical. Prior 2005 National Trauma Data Bank (NTDB) analysis showed high rates (37%) of centers reporting no complications data making national estimates for determining standardized complication rates difficult to ascertain.

Methods: The 2008-2012 NTDB National Sample Program nationally weighted files were used to calculate yearly national estimates.

Dynamic coagulability after injury: Is delaying venous thromboembolism chemoprophylaxis worth the wait?

Background: Severely injured patients often progress from early hypocoagulable to normal and eventually hypercoagulable states, developing increased risk for venous thromboembolism (VTE). Prophylactic anticoagulation can decrease this risk, but its initiation is frequently delayed for extended periods due to concerns for bleeding. To facilitate timely introduction of VTE chemoprophylaxis, we characterized the transition from hypo- to hypercoagulability and hypothesized that trauma-induced coagulopathy resolves within 24 hours after injury.

Citrated kaolin thrombelastography (TEG) thresholds for goal-directed therapy in injured patients receiving massive transfusion.

Introduction: Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT.

Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.

Background: Complications after injury, such as acute respiratory distress syndrome (ARDS), are common after traumatic brain injury (TBI) and associated with poor clinical outcomes. The mechanisms driving non-neurologic organ dysfunction after TBI are not well understood. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) is a regulator of matrix metalloproteinase activity, inflammation, and vascular permeability, and hence has plausibility as a biomarker for the systemic response to TBI.

Perhaps it's not the platelet: Ristocetin uncovers the potential role of von Willebrand factor in impaired platelet aggregation following traumatic brain injury.

Background: Injury to the blood-brain barrier exposes endothelium rich in von Willebrand factor (vWF), which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance that induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole-blood multiple-electrode platelet aggregometry.

Health care utilization and the cost of posttraumatic acute respiratory distress syndrome care.

Background: Posttraumatic acute respiratory distress syndrome (ARDS) is associated with prolonged mechanical ventilation and longer hospitalizations. The relationship between posttraumatic ARDS severity and financial burden has not been previously studied. We hypothesized that increasing ARDS severity is associated with incrementally higher health care costs.

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background: Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury.

Exposing the bidirectional effects of alcohol on coagulation in trauma: Impaired clot formation and decreased fibrinolysis in rotational thromboelastometry.

Background: Alcohol has been associated with altered viscoelastic testing in trauma, indicative of impaired coagulation. Such alterations, however, show no correlation to coagulopathy-related outcomes. Other data suggest that alcohol may inhibit fibrinolysis.

Platelet aggregation after blunt trauma is associated with the acute respiratory distress syndrome and altered by cigarette smoke exposure.

Background: The risk of the acute respiratory distress syndrome (ARDS) is increased in passive and active smokers after blunt trauma. However, the mechanisms responsible, including the role of platelet aggregation, for this association are unknown.

Methods: We analyzed 215 patients with severe blunt trauma from a prospective observational cohort at a Level I trauma center between 2010 and 2015.

Characterization of distinct coagulopathic phenotypes in injury: Pathway-specific drivers and implications for individualized treatment.

Background: International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation.

Correlation between factor (F)XIa, FIXa and tissue factor and trauma severity.

Background: It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt, and penetrating injuries have active FIXa and FXIa in their plasma. In the current study, we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa, and FXIa in plasma from trauma patients.

Individual clotting factor contributions to mortality following trauma.

Background: Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma.

Methods: This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015.

The acute respiratory distress syndrome following isolated severe traumatic brain injury.

Background: Acute respiratory distress syndrome (ARDS) is common after traumatic brain injury (TBI) and is associated with worse neurologic outcomes and longer hospitalization. However, the incidence and associated causes of ARDS in isolated TBI have not been well studied.

Methods: We performed a subgroup analysis of 210 consecutive patients with isolated severe TBI enrolled in a prospective observational cohort at a Level 1 trauma center between 2005 and 2014.

Discovering the truth about life after discharge: Long-term trauma-related mortality.

Background: Outcome after traumatic injury has typically been limited to the determination at time of discharge or brief follow-up. This study investigates the natural history of long-term survival after trauma.

Methods: All highest-level activation patients prospectively enrolled in an ongoing cohort study from 2005 to 2012 were selected.

The Massive Transfusion Score as a decision aid for resuscitation: Learning when to turn the massive transfusion protocol on and off.

Background: Previous work proposed a Massive Transfusion Score (MTS) calculated from values obtained in the emergency department to predict likelihood of massive transfusion (MT). We hypothesized the MTS could be used at Hour 6 to differentiate who continues to require balanced resuscitation in Hours 7 to 24 and to predict death at 28 days.

Methods: We prospectively enrolled patients in whom the MT protocol was initiated from 2005 to 2011.

The found down patient: A Western Trauma Association multicenter study.

Background: Unconscious patients who present after being "found down" represent a unique triage challenge. These patients are selected for either trauma or medical evaluation based on limited information and have been shown in a single-center study to have significant occult injuries and/or missed medical diagnoses. We sought to further characterize this population in a multicenter study and to identify predictors of mistriage.

Differences in degree, differences in kind: characterizing lung injury in trauma.

Background: Acute lung injury following trauma remains a significant source of morbidity and mortality. Although multiple trauma studies have used hypoxemia without radiographic adjudication as a surrogate for identifying adult respiratory distress syndrome (ARDS) cases, the differences between patients with hypoxemia alone and those with radiographically confirmed ARDS are not well described in the literature. We hypothesized that nonhypoxemic, hypoxemic, and ARDS patients represent distinct groups with unique characteristics and predictors.