Sarcopenia Is Associated With Increased Mortality in Patients With Necrotizing Soft Tissue Infections.

INTRODUCTION: Necrotizing soft tissue infections (NSTIs) are surgical emergencies associated with high morbidity and mortality. Identifying risk factors for poor outcome is a critical part of preoperative decision-making and counseling. Sarcopenia, the loss of lean muscle mass, has been associated with an increased risk of mortality and can be measured using cross-sectional imaging. Our aim was to determine the impact of sarcopenia on mortality in patients with NSTI. We hypothesized that sarcopenia would be associated with an increased risk of mortality in patients with NSTI. METHODS: This is a retrospective cohort study of NSTI patients admitted from 1995 to 2015 to two academic institutions. Operative and pathology reports were reviewed to confirm the diagnosis in all cases. Average bilateral psoas muscle cross-sectional area at L4, normalized for height (Total Psoas Index [TPI]), was calculated using computed tomography (CT). Sarcopenia was defined as TPI in the lowest sex-specific quartile. Primary outcome was in-hospital mortality. Multivariate logistic regression was performed to assess the association between sarcopenia and in-hospital mortality. RESULTS: There were 115 patients with preoperative imaging, 61% male and a median age of 57 y interquartile range (IQR 46.6-67.0). Overall in-hospital mortality was 12.1%. There was no significant difference in sex, body mass index (BMI), comorbidities and American Society of Anesthesiologists classification (Table 1). After multivariate analysis, sarcopenia was independently associated with increased in-hospital mortality (Odds ratio, 3.5; 95% Confidence Interval [CI], 1.05-11.8). CONCLUSIONS: Sarcopenia is associated with increased risk of in-hospital mortality in patients with NSTIs. Sarcopenia identifies patients with higher likelihood of poor outcomes, which can possibly help surgeons in counseling their patients and families.

Mental Health Burden After Injury: It's About More than Just Posttraumatic Stress Disorder.

OBJECTIVE: Assess the prevalence of anxiety, depression, and posttraumatic stress disorder (PTSD) after injury and their association with long-term functional outcomes. BACKGROUND: Mental health disorders (MHD) after injury have been associated with worse long-term outcomes. However, prior studies almost exclusively focused on PTSD. METHODS: Trauma patients with an injury severity score ≥9 treated at 3 Level-I trauma centers were contacted 6-12 months post-injury to screen for anxiety (generalized anxiety disorder-7), depression (patient health questionnaire-8), PTSD (8Q-PCL-5), pain, and functional outcomes (trauma quality of life instrument, and short-form health survey)). Associations between mental and physical outcomes were established using adjusted multivariable logistic regression models. RESULTS: Of the 531 patients followed, 108 (20%) screened positive for any MHD: of those who screened positive for PTSD (7.9%, N = 42), all had co-morbid depression and/or anxiety. In contrast, 66 patients (12.4%) screened negative for PTSD but positive for depression and/or anxiety. Compared to patients with no MHD, patients who screened positive for PTSD were more likely to have chronic pain {odds ratio (OR): 8.79 [95% confidence interval (CI): 3.21, 24.08]}, functional limitations [OR: 7.99 (95% CI: 3.50, 18.25)] and reduced physical health [ß: -9.3 (95% CI: -13.2, -5.3)]. Similarly, patients who screened positive for depression/anxiety (without PTSD) were more likely to have chronic pain [OR: 5.06 (95% CI: 2.49, 10.46)], functional limitations [OR: 2.20 (95% CI: 1.12, 4.32)] and reduced physical health [ß: -5.1 (95% CI: -8.2, -2.0)] compared to those with no MHD. CONCLUSIONS: The mental health burden after injury is significant and not limited to PTSD. Distinguishing among MHD and identifying symptom-clusters that overlap among these diagnoses, may help stratify risk of poor outcomes, and provide opportunities for more focused screening and treatment interventions.

Traumatic Brain Injury: Does Admission Service Matter?

BACKGROUND: Traumatic brain injury (TBI) is common, and significant institutional variation exists with regards to structure and processes of care. Affected patients may be admitted to one of several different services, and this may drive differential care and outcomes. We sought to evaluate differential care and outcomes for patients with isolated mild-to-moderate traumatic brain injury based on admission service. MATERIALS AND METHODS: This is a single-institution retrospective study of all adult (≥18 y old) patients admitted with isolated TBI (AIS ≤1 in all other body regions) over a 3-year period (6/2015-6/2018). Patients who underwent neurosurgical intervention (craniectomy/craniotomy) and those with a head AIS ≥4 were excluded. Patients were assigned to one of three groups based upon admission service: Trauma Surgery, Neurology/Medicine or Neurosurgery. Outcomes evaluated included in-hospital mortality and markers of differential care. We performed multivariate analyses adjusting for patient demographics and clinical characteristics. RESULTS: A total of 401 isolated mild-to-moderate TBI patients were identified. Overall mortality was 1.7%. Adjusted multivariate logistic regression analysis demonstrated no difference in mortality. Patients admitted to Neurosurgery underwent more repeat head CTs and were more likely to receive antiseizure medication in the absence of seizure activity, and those admitted to Neurology/Medicine were less likely to receive venous thromboembolism chemoprophylaxis compared to those admitted to Trauma Surgery. CONCLUSIONS: We identify several important metrics of variation in care received by patients with an isolated mild-to-moderate TBI based upon admission service. These findings deserve further study, and this study may lay the foundation for future efforts at protocolizing care in an evidence-based fashion for this patient cohort.

The Association Between Medicare Eligibility and Gains in Access to Rehabilitative Care: A National Regression Discontinuity Assessment of Patients Ages 64 Versus 65 Years.

OBJECTIVES: The aims of this study were to assess for changes in uninsured rates among trauma patients at age 64 versus 65 years and whether there are associated changes in post-discharge rehabilitation; determine whether changes are driven by rehabilitation provided at home, skilled nursing facilities (SNFs), or acute inpatient facilities; and determine whether changes vary among stratified subgroups of trauma-related "best-practice" factors. SUMMARY BACKGROUND DATA: Rehabilitation is an important component of high-quality trauma systems with access heavily influenced by insurance status. In the wake of policy changes affecting insurance coverage, it remains unknown the extent to which insurance changes associate with variations in rehabilitation access/use among otherwise similar patients. METHODS: Regression discontinuity models were used to assess for changes in insurance status and rehabilitation at age 64 versus 65 years among adults ages 54 to 75 years (±10 years age-related Medicare eligibility). Data were extracted from the 2007-2012 National Trauma Data Bank. RESULTS: A total of 305,198 patients were included; 40.1% were discharged to rehabilitation. Medicare eligibility was associated with an abrupt 6.4 (95% confidence interval: 5.8-7.0) percentage-point decline in uninsured and a 9.6 (95% confidence interval: 6.5-12.6) percentage-point increase in rehabilitation at age 64 versus 65 years, enabling an additional 1-in-10 patients to access rehabilitation. Differences were driven by SNF use and were greatest among patients with less-severe clinical presentations. Restriction based on Medicare-payment eligibility to patients with length of stay ≥3days (SNF requirement) and ≥1 "presumptive diagnosis codes" (inpatient facilities' 60% rule) demonstrated abrupt gains in both SNF and inpatient care. CONCLUSIONS: The results reveal the magnitude of changes in access to rehabilitation associated with changes in insurance coverage at age 65 years. Use of quasiexperimental models enabled meaningful consideration of health-policy change.

Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach.

OBJECTIVE: Trauma induces a complex immune response that requires a systems biology research approach. Here, we used a novel technology, mass cytometry by time-of-flight, to comprehensively characterize the multicellular response to trauma. DESIGN: Peripheral blood mononuclear cells samples were stained with a 38-marker immunophenotyping cytometry by time-of-flight panel. Separately, matched peripheral blood mononuclear cells were stimulated in vitro with heat-killed Streptococcus pneumoniae or CD3/CD28 antibodies and stained with a 38-marker cytokine panel. Monocytes were studied for phagocytosis and oxidative burst. SETTING: Single-institution level 1 trauma center. PATIENTS OR SUBJECTS: Trauma patients with injury severity scores greater than 20 (n = 10) at days 1, 3, and 5 after injury, and age- and gender-matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Trauma-induced expansion of Th17-type CD4 T cells was seen with increased expression of interleukin-17 and interleukin-22 by day 5 after injury. Natural killer cells showed reduced T-bet expression at day 1 with an associated decrease in tumor necrosis factor-ß, interferon-γ, and monocyte chemoattractant protein-1. Monocytes showed robust expansion following trauma but displayed decreased stimulated proinflammatory cytokine production and significantly reduced human leukocyte antigen - antigen D related expression. Further analysis of trauma-induced monocytes indicated that phagocytosis was no different from controls. However, monocyte oxidative burst after stimulation increased significantly after injury. CONCLUSIONS: Using cytometry by time-of-flight, we were able to identify several major time-dependent phenotypic changes in blood immune cell subsets that occur following trauma, including induction of Th17-type CD4 T cells, reduced T-bet expression by natural killer cells, and expansion of blood monocytes with less proinflammatory cytokine response to bacterial stimulation and less human leukocyte antigen - antigen D related. We hypothesized that monocyte function might be suppressed after injury. However, monocyte phagocytosis was normal and oxidative burst was augmented, suggesting that their innate antimicrobial functions were preserved. Future studies will better characterize the cell subsets identified as being significantly altered by trauma using cytometry by time-of-flight, RNAseq technology, and functional studies.

BWH emergency radiology--surgical correlation: sigmoid volvulus.

We describe the radiological and intraoperative correlation of large bowel obstruction due to sigmoid volvulus in a 52-year-old female. The purpose of this article is to emphasize the importance of recognizing sigmoid volvulus as a cause of bowel obstruction in patients presenting with abdominal pain, since it can lead to bowel ischemia and necrosis.

BWH emergency radiology-surgical correlation: torsion of Meckel's diverticulum.

We present the radiologic findings and intraoperative correlation of a torsed Meckel's diverticulum leading to small-bowel obstruction in a 65-year-old male without prior abdominal surgery. As this is a rare entity and difficult to diagnose, an understanding of the clinical presentation and radiologic findings correlated with this pathology can help to expedite diagnosis and treatment.

The Difficult Cholecystectomy: What You Need to Know.

ABSTRACT: This review discusses the grading of cholecystitis, the optimal timing of cholecystectomy, adopting a culture of safe cholecystectomy, understanding the common error traps that can lead to intraoperative complications and how to avoid them. The Tokyo Guidelines, AAST, Nassar and Parkland scoring systems are discussed. The patient factors, physiologic status and operative findings that predict a difficult cholecystectomy or conversion from laparoscopic to open cholecystectomy are reviewed. With laparoscopic expertise and patient conditions that are not prohibitive, early laparoscopic cholecystectomy is recommended. This is ideally within 72 hours of admission but supported up to the seventh hospital day. The majority of bile duct injuries (BDI) are due to misidentification of normal anatomy. Strasberg's four error traps and the zones of danger to avoid during a cholecystectomy are described. The review emphasizes the importance of a true critical view of safety (CVS) for identification of the anatomy. In up to 15% of operations for acute cholecystitis, a CVS cannot be achieved safely. Recognizing these conditions and changing your operative strategy are mandatory to avoid harm. The principles to follow for a safe cholecystectomy are discussed in detail. The cardinal message of this review is "under challenging conditions, BDI can be minimized via either a subtotal cholecystectomy or top-down cholecystectomy if dissection in the hepatocystic triangle is avoided." (28) The most severe biliary/vascular injuries usually occur after conversion from laparoscopic cholecystectomy. Indications and techniques for bailout procedures including the fenestrating and reconstituting subtotal cholecystectomy are presented. Seven to ten percent of cholecystectomies for acute cholecystitis currently result in subtotal cholecystectomy.

MACROPHAGE SWITCHING: POLARIZATION AND MOBILIZATION AFTER TRAUMA.

ABSTRACT: Introduction: Trauma alters the immune response in numerous ways, affecting both the innate and adaptive responses. Macrophages play an important role in inflammation and wound healing following injury. We hypothesize that macrophages mobilize from the circulation to the site of injury and secondary sites after trauma, with a transition from proinflammatory (M1) shortly after trauma to anti-inflammatory (M2) at later time points. Methods: C57Bl6 mice (n = 6/group) underwent a polytrauma model using cardiac puncture/hemorrhage, pseudofemoral fracture, and liver crush injury. The animals were killed at several time points: uninjured, 24 h, and 7 days. Peripheral blood mononuclear cells, spleen, liver nonparenchymal cells, and lung were harvested, processed, and stained for flow cytometry. Macrophages were identified as CD68 + ; M1 macrophages were identified as iNOS + ; M2 macrophages as arginase 1 + . Results: We saw a slight presence of M1 macrophages at baseline in peripheral blood mononuclear cells (6.6%), with no significant change at 24 h and 7 days after polytrauma. In contrast, the spleen has a larger population of M1 macrophages at baseline (27.7%), with levels decreasing at 24 h and 7 days after trauma (20.6% and 12.6%, respectively). A similar trend is seen in the lung where at baseline 14.9% of CD68 + macrophages are M1, with subsequent continual decrease reaching 8.7% at 24 h and 4.4% at 7 days after polytrauma. M1 macrophages in the liver represent 14.3% of CD68 + population in the liver nonparenchymal cells at baseline. This percentage increases to 20.8% after trauma and decreases at 7 days after polytrauma (13.4%). There are few M2 macrophages in circulating peripheral blood mononuclear cells and in spleen at baseline and after trauma. The percentage of M2 macrophages in the lungs remains constant after trauma (7.2% at 24 h and 9.2% at 7 days). In contrast, a large proportion of M2 macrophages are seen in the liver at baseline (36.0%). This percentage trends upward and reaches 45.6% acutely after trauma and drops to 21.4% at 7 days. The phenotypic changes in macrophages seen in the lungs did not correlate with a functional change in the ability of the macrophages to perform oxidative burst, with an increase from 2.0% at baseline to 22.1% at 7 days after polytrauma ( P = 0.0258). Conclusion: Macrophage phenotypic changes after polytrauma are noted, especially with a decrease in the lung M1 phenotype and a short-term increase in the M2 phenotype in the liver. However, macrophage function as measured by oxidative burst increased over the time course of trauma, which may signify a change in subset polarization after injury not captured by the typical macrophage phenotypes.

Quantifying the Prognostic Value of Preoperative Surgeon Intuition: Comparing Surgeon Intuition and Clinical Risk Prediction as Derived from the American College of Surgeons NSQIP Risk Calculator.

BACKGROUND: Surgical risk prediction models traditionally use patient attributes and measures of physiology to generate predictions about postoperative outcomes. However, the surgeon's assessment of the patient may be a valuable predictor, given the surgeon's ability to detect and incorporate factors that existing models cannot capture. We compare the predictive utility of surgeon intuition and a risk calculator derived from the American College of Surgeons (ACS) NSQIP. STUDY DESIGN: From January 10, 2021 to January 9, 2022, surgeons were surveyed immediately before performing surgery to assess their perception of a patient's risk of developing any postoperative complication. Clinical data were abstracted from ACS NSQIP. Both sources of data were independently used to build models to predict the likelihood of a patient experiencing any 30-day postoperative complication as defined by ACS NSQIP. RESULTS: Preoperative surgeon assessment was obtained for 216 patients. NSQIP data were available for 9,182 patients who underwent general surgery (January 1, 2017 to January 9, 2022). A binomial regression model trained on clinical data alone had an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI 0.80 to 0.85) in predicting any complication. A model trained on only preoperative surgeon intuition had an AUC of 0.70 (95% CI 0.63 to 0.78). A model trained on surgeon intuition and a subset of clinical predictors had an AUC of 0.83 (95% CI 0.77 to 0.89). CONCLUSIONS: Preoperative surgeon intuition alone is an independent predictor of patient outcomes; however, a risk calculator derived from ACS NSQIP is a more robust predictor of postoperative complication. Combining intuition and clinical data did not strengthen prediction.

Revascularization and rescue of a failed kidney transplant in a case of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is a cause of end-stage renal disease associated with abdominal aortic aneurysms. We report a patient with autosomal dominant polycystic kidney disease who received an allograft kidney and subsequently underwent treatment of an abdominal aortic aneurysm with aortic ligation and axillary-bifemoral bypass. After years of graft function, bypass thrombosis resulted in dialysis-dependent renal failure. Aortobifemoral bypass resulted in immediate restoration of allograft function despite 6 months of prior renal failure. Aortic reconstruction restored renal function to a hibernating allograft long after clinical graft failure from arterial ischemia, a phenomenon not previously reported in the literature.

The emerging therapeutic potential of extracellular vesicles in trauma.

Traumatic injury is a major cause of morbidity and mortality worldwide, despite significant advances in treatments. Most deaths occur either very early, through massive head trauma/CNS injury or exsanguination (despite advances in transfusion medicine), or later after injury often through multiple organ failure and secondary infection. Extracellular vesicles (EVs) are known to increase in the circulation after trauma and have been used to limited extent as diagnostic and prognostic markers. More intriguingly, EVs are now being investigated as both causes of pathologies post trauma, such as trauma-induced coagulopathy, and as potential treatments. In this review, we highlight what is currently known about the role and effects of EVs in various aspects of trauma, as well as exploring current literature from investigators who have begun to use EVs therapeutically to alter the physiology and pathology of traumatic insults. The potential effectiveness of using EVs therapeutically in trauma is supported by a large number of experimental studies, but there is still some way to go before we understand the complex effects of EVs in what is already a complex disease process.

Rhabdomyolysis: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Rhabdomyolysis is a clinical condition characterized by destruction of skeletal muscle with release of intracellular contents into the bloodstream. Intracellular contents released include electrolytes, enzymes, and myoglobin, resulting in systemic complications. Muscle necrosis is the common factor for traumatic and non-traumatic rhabdomyolysis. The systemic impact of rhabdomyolysis ranges from asymptomatic elevations in bloodstream muscle enzymes to life-threatening acute kidney injury and electrolyte abnormalities. The purpose of this clinical consensus statement is to review the present-day diagnosis, management, and prognosis of patients who develop rhabdomyolysis.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Prevention of alcohol withdrawal syndrome in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Alcohol withdrawal syndrome is a common and challenging clinical entity present in trauma and surgical intensive care unit (ICU) patients. The screening tools, assessment strategies, and pharmacological methods for preventing alcohol withdrawal have significantly changed during the past 20 years. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews the best practices for screening, monitoring, and prophylactic treatment of alcohol withdrawal in the surgical ICU.

EFFECT OF IRRIGATION FLUID COMPOSITION ON HEMOSTASIS IN MOUSE BLEEDING MODELS.

ABSTRACT: Introduction: Intraoperative irrigation, usually with normal saline (NS), aids in bleeding identification and management. We investigated the effect of different irrigation fluids, with additives, on hemostasis using two bleeding models. Methods: C57BL/6 J mice were subjected to a tail bleed model or uncontrolled abdominal hemorrhage via liver laceration followed by abdominal cavity irrigation. We compared NS, lactated Ringer's (LR), and PlasmaLyte. We examined NS and LR at different temperatures. Normal saline or LR with calcium (Ca 2+ ) or tranexamic acid (TXA) was studied. Results: Compared with room temperature (RT), increasing the temperature of the irrigation fluid to 37°C and 42°C reduced tail vein bleeding times substantially in both NS and LR (all P < 0.001), with no significant differences between the two fluids. At RT, LR, but not PlasmaLyte, substantially reduced bleeding times in comparison to NS ( P < 0.0001). Liver injury blood loss was lower with LR ( P < 0.01). Normal saline supplemented with 2.7 mEq/L of Ca 2+ decreased bleeding time and blood loss volume ( P < 0.001 and P < 0.01, respectively) to similar levels as LR. Normal saline with 150 mg/mL of TXA markedly reduced bleeding time ( P < 0.0001), and NS with 62.5 mg/mL TXA decreased blood loss ( P < 0.01). Conclusion: Whereas Ca 2+ - and TXA-supplemented NS reduced bleeding, LR remained superior to all irrigation fluid compositions. As LR contains Ca 2+ , and Ca 2+ -supplemented NS mirrored LR in response, Ca 2+ presence in the irrigation fluid seems key to improving solution's hemostatic ability. Because warming the fluids normalized the choice of agents, the data also suggest that Ca 2+ -containing fluids such as LR may be more suitable for hemostasis when used at RT.

Venous thromboembolism prophylaxis in the trauma intensive care unit: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Venous thromboembolism (VTE) is a potential sequela of injury, surgery, and critical illness. Patients in the Trauma Intensive Care Unit are at risk for this condition, prompting daily discussions during patient care rounds and routine use of mechanical and/or pharmacologic prophylaxis measures. While VTE rightfully garners much attention in clinical patient care and in the medical literature, optimal strategies for VTE prevention are still evolving. Furthermore, trauma and surgical patients often have real or perceived contraindications to prophylaxis that affect the timing of preventive measures and the consistency with which they can be applied. In this Clinical Consensus Document, the American Association for the Surgery of Trauma Critical Care Committee addresses several practical clinical questions pertaining to specific or unique aspects of VTE prophylaxis in critically ill and injured patients.

Trauma induces expansion and activation of a memory-like Treg population.

CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44high /CD62Llow subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII-/- ) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII-/- mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.

Circulating Factors in Trauma Plasma Activate Specific Human Immune Cell Subsets.

BACKGROUND: Trauma causes tissue injury that results in the release of damage associated molecular patterns (DAMPs) and other mediators at the site of injury and systemically. Such mediators disrupt immune system homeostasis and may activate multicellular immune responses with downstream complications such as the development of infections and sepsis. To characterize these alterations, we used time-of-flight mass cytometry to determine how trauma plasma affects normal peripheral blood mononuclear cell (PBMC) activation to gain insights into the kinetics and nature of trauma-induced circulating factors on human immune cell populations. A better understanding of the components that activate cells in trauma may aid in the discovery of therapeutic targets. METHODS: PBMCs from healthy volunteers were cultured with 5% plasma (healthy, trauma-1day, or trauma-3day) or known DAMPs for 24 h. Samples were stained with a broad immunophenotyping CyTOF antibody panel. Multiplex (Luminex) cytokine assays were used to measure differences in multiple cytokine levels in healthy and trauma plasma samples. RESULTS: Plasma from day 1, but not day 3 trauma patients induced the acute expansion of CD11c+ NK cells and CD73+/CCR7+ CD8 T cell subpopulations. Additionally, trauma plasma did not induce CD4+ T cell expansion but did cause a phenotypic shift towards CD38+/CCR7+ expressing CD4+ T cells. Multiplex analysis of cytokines by Luminex showed increased levels of IL-1RA, IL-6 and IL-15 in trauma-1day plasma. Similar to trauma day 1 plasma, PBMC stimulation with known DAMPs showed activation and expansion of CD11c+ NK cells. CONCLUSIONS: We hypothesized that circulating factors in trauma plasma would induce phenotypic activation of normal human immune cell subsets. Using an unbiased approach, we identified specific changes in immune cell subsets that respond to trauma plasma. Additionally, CD11c+ NK cells expanded in response to DAMPs and LPS, suggesting they may also be responding to similar components in trauma plasma. Collectively, our data demonstrate that the normal PBMC response to trauma plasma involves marked changes in specific subsets of NK and CD8+ T cell populations. Future studies will target the function of these trauma plasma reactive immune cell subsets. These findings have important implications for the field of acute traumatic injuries.

Altered monocyte and NK cell phenotypes correlate with posttrauma infection.

BACKGROUND: Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection. METHODS: Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons. RESULTS: The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection. CONCLUSION: This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients. LEVEL OF EVIDENCE: Prognostic study, level II.