Severe trauma leads to sustained muscle loss, induced frailty, and distinct temporal changes in myokine and chemokine profiles of older patients.

INTRODUCTION: Sarcopenia is a known risk factor for adverse outcomes across multiple disease states, including severe trauma. Factors such as age, hyperinflammation, prolonged immobilization, and critical illness may not only exacerbate progression of this disease but may also contribute to the development of induced sarcopenia, or sarcopenia secondary to hospitalization. This study seeks to (1) determine the effects of severe traumatic injury on changes in skeletal muscle mass in older adults; (2) test whether changes in skeletal muscle mass are associated with clinical frailty, physical performance, and health-related quality of life; and (3) examine trauma-induced frailty and temporal changes in myokine and chemokine profiles. METHODS: A prospective, longitudinal cohort study of 47 critically ill, older (≥45 years) adults presenting after severe blunt trauma was conducted. Repeated measures of computed tomography-based skeletal muscle index, frailty, and quality of life were obtained in addition to selected plasma biomarkers over 6 months. RESULTS: Severe trauma was associated with significant losses in skeletal muscle mass and increased incidence of sarcopenia from 36% at baseline to 60% at 6 months. Severe trauma also was associated with a transient worsening of induced frailty and reduced quality of life irrespective of sarcopenia status, which returned to baseline by 6 months after injury. Admission biomarker levels were not associated with skeletal muscle index at the time points studied but demonstrated distinct temporal changes across our entire cohort. CONCLUSIONS: Severe blunt trauma in older adults is associated with increased incidence of induced sarcopenia and reversible induced frailty. Despite muscle wasting, functional decline is transient, with a return to baseline by 6 months, suggesting a need for holistic definitions of sarcopenia and further investigation into long-term functional outcomes in this population.

Retrospective evaluation of the neutrophil-to-lymphocyte ratio as a prognostic marker in cats with blunt trauma (2018-2021): 177 cases.

OBJECTIVE: To investigate the utility of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in cats with blunt trauma. DESIGN: Retrospective study from January 2018 to December 2021. SETTING: University teaching hospital. ANIMALS: Medical records of 177 cats admitted with blunt trauma were evaluated. History, clinical findings, blood cell count-based ratios, thoracic radiographs on presentation, and outcome were reviewed. The Animal Trauma Triage (ATT) score was assessed in each cat and classified as mild (1-3), moderate (4-7), and severe trauma (≥8). Forty-eight healthy blood donor cats served as the control population. NLR, neutrophil counts, and lymphocyte counts were compared between cats with blunt trauma and controls, and among trauma patients. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: NLR, neutrophil counts, and lymphocyte counts significantly differ in cats with blunt trauma compared to controls (p < 0.001), and NLR was higher in patients with thoracic trauma (p = 0.044). Nonsurvivors had lower lymphocyte counts (p = 0.041), although those values do not appear to be clinically relevant. A significant increase in NLR was observed with increasing severity of trauma (p < 0.001). The NLR was not associated with the length of hospitalization, intensive care assistance, or mortality. CONCLUSION: NLR is a widely available diagnostic tool, which can be used in addition to ATT to assess trauma severity, although in our study it was not predictive of the outcome.

Re-evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

INTRODUCTION: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI. The aim of this study was to determine the efficacy of the newly implemented protocol. METHODS: Patients diagnosed with a sternal fracture from March 2022 to April 2023 at our urban level-1 trauma center were retrospectively reviewed for EKG findings, hsTnI trend, echocardiogram changes, and clinical outcomes. The BCI cohort and non-BCI cohort ordinal measures were compared using Wilcoxon's two-tailed rank sum test and categorical measures were compared with Fisher's exact test. Youden indices were used to evaluate hsTnI sensitivity and specificity. RESULTS: Sternal fractures were identified in 206 patients, of which 183 underwent BCI screening. Of those screened, 103 underwent echocardiogram, 28 were diagnosed with clinically significant BCIs, and 15 received intervention. The peak hsTnI threshold of 76 ng/L was found to have a Youden index of 0.31. Rather, the Youden index was highest at 0.50 at 40 ng/L (sensitivity 0.79 and specificity 0.71) for clinically significant BCI. CONCLUSIONS: Screening patients with sternal fractures for BCI using hsTnI and EKG remains effective. To optimize the hsTnI threshold, this study determined the hsTnI threshold should be lowered to 40 ng/L. Further improvements to the institutional protocol may be derived from multicenter analysis.

Plasma proteomics profile-based comparison of torso versus brain injury: A prospective cohort study.

BACKGROUND: Trauma-related deaths and posttraumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine. METHODS: This prospective observational single-center cohort study was conducted between August 2020 and September 2021 in the intensive care unit of Osaka University Hospital in Japan. Enrolling 59 consecutive patients with blunt trauma, we meticulously analyzed plasma proteomics profiles in participants with torso or head trauma, comparing them with those of controls (mild trauma). Using the Olink Explore 3072 instrument (Olink Proteomics AB, Uppsala, Sweden), we identified five endotypes (α-ε) via unsupervised hierarchical clustering. RESULTS: The median time from injury to blood collection was 47 minutes [interquartile range, 36-64 minutes]. The torso trauma subgroup exhibited 26 unique proteins with significantly altered expression, while the head trauma subgroup showed 68 unique proteins with no overlap between the two. The identified endotypes included α (torso trauma, n = 8), ß (young patients with brain injury, n = 5), γ (severe brain injury postsurgery, n = 8), δ (torso or brain trauma with mild hyperfibrinolysis, n = 18), and ε (minor trauma, n = 20). Patients with torso trauma showed changes in blood pressure, smooth muscle adaptation, hypermetabolism, and hypoxemia. Patients with traumatic brain injury had dysregulated blood coagulation and altered nerves regeneration and differentiation. CONCLUSION: This study identified unique plasma protein expression patterns in patients with torso trauma and traumatic brain injury, helping categorize five distinct endotypes. Our findings may offer new insights for clinicians, highlighting potential strategies for personalized medicine and improved trauma-related care. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Early prediction for massive fresh frozen plasma transfusion based on fibrinogen/fibrin degradation products and D-dimer in patients with blunt trauma: a single-center, retrospective cohort study.

PURPOSE: This study aimed to examine the association of fibrinogen/fibrin degradation product (FDP) values in comparison with D-dimer and fibrinogen (Fib) values and the need for massive fresh frozen plasma (FFP) transfusion in patients with blunt trauma. METHODS: This retrospective study included patients with blunt trauma aged ≥ 18 years who were transported directly to the tertiary care hospital between April, 2012, and March, 2021. Massive FFP transfusion was defined as a composite outcome of at least 10 units of FFP or death for any cause except for cerebral herniation, within 24 h after hospital arrival. We evaluated the diagnostic accuracy of predicting the need for massive FFP transfusions using FDP, D-dimer, and Fib levels at the time of hospital arrival. RESULTS: A total of 2160 patients were eligible for the analysis, of which 167 fulfilled the criteria for the composite outcome. The area under the curve and 95% confidence interval for FDP, D-dimer, and Fib levels were 0.886 (0.865-0.906), 0.885 (0.865-0.906), and 0.771 (0.731-0.810), respectively. When the cutoff values of FDP and D-dimer were set at 90 µg/mL and 45 µg/mL, the sensitivity values were 77% and 78%, the positive predictive values were 28% and 27%, and the negative predictive values were both 98%, respectively. In contrast, the sensitivity of Fib was low regardless of the cutoff value. CONCLUSION: FDP and D-dimer levels at the time of hospital arrival showed a higher predictive accuracy for the need for massive FFP transfusion than Fib.

Association between the initial serum phosphate level and 30-day mortality in blunt trauma patients.

BACKGROUND: Studies on patients with cardiac arrest or sepsis have reported that high initial phosphate levels are associated with poor outcomes. However, no previous study has investigated the association between initial phosphate levels and outcomes in blunt trauma patients. METHODS: This study was a retrospective observational study conducted on blunt trauma patients who had been treated at the single regional trauma center between January 2016 and December 2017. Patients' demographic data, initial vital signs, trauma scores, and laboratory parameters including phosphate levels were collected from the trauma registry. The primary outcome was set to 30-day mortality. The secondary outcomes were the total volume of blood transfused, 30-day hospital-free days, and 30-day intensive care unit-free days. RESULTS: Of the 1,907 included patients, 1,836 were in the survival group, and 71 were in the nonsurvival group. The nonsurvival group had a significantly higher phosphate level than the survival group. Patients in the hyperphosphatemia group had a higher 30-day mortality, fewer 30-day intensive care unit-free days, and higher transfusion volume than those in the other groups. In multivariable logistic regression analysis, hyperphosphatemia was independently associated with 30-day mortality. The receiver operating characteristic curve analysis showed that the area under the curve with the inclusion of phosphate in addition to Injury Severity Score, Revised Trauma Score, and age was 0.911. Area under the curve was also increased when phosphate was simply added to Injury Severity Score and Revised Trauma Score. CONCLUSION: In blunt trauma patients, hyperphosphatemia was associated with an increased 30-day mortality. LEVEL OF EVIDENCE: Prognostic, level III.

P-selectin antibody treatment after blunt thoracic trauma prevents early pulmonary arterial thrombosis without changes in viscoelastic measurements of coagulation.

INTRODUCTION: Previously, in a murine model of blunt thoracic trauma, we provided evidence of primary pulmonary thrombosis associated with increased expression of the cell adhesion molecule, P-selectin. In this study, mice are treated with P-selectin blocking antibody after injury to investigate the clinical viability of this antibody for the prevention of pulmonary thrombosis. In addition, viscoelastic testing is performed to investigate if P-selectin inhibition has a detrimental impact on normal hemostasis. METHODS: A murine model of thoracic trauma was used. Mice were divided into sham control and experimental injury groups. Thirty minutes after trauma, mice were treated with the following: P-selectin blocking antibody, isotype control antibody, low-dose heparin, high-dose heparin, or normal saline. At 90 minutes, whole blood was collected for characterization of coagulation by viscoelastic coagulation monitor (VCM Vet; Entegrion, Durham, NC). Mean clotting time, clot formation time, clot kinetics (α angle), and maximum clot firmness were compared between each treatment group. RESULTS: Mice that received P-selectin antibody 30 minutes after blunt thoracic trauma had four- to fivefold less (p < 0.001) arterial fibrin accumulation than those that received the isotype control. In both sham and trauma groups, compared with vehicle (normal saline) alone, no statistical difference was noted in any coagulation parameters after injection with P-selectin antibody, isotype control, or low-dose heparin. In addition, blinded histopathological evaluation yielded no difference in hemorrhage scores between injured mice treated with P-selectin blocking antibody and those treated with isotype antibody control. CONCLUSION: This study supports the clinical use of P-selectin blocking antibody for the prevention of pulmonary thrombosis by confirming its efficacy when given after a blunt thoracic trauma. In addition, we demonstrated that the administration of P-selectin antibody does not adversely affect systemic coagulation as measured by viscoelastic testing, suggesting that P-selectin antibody can be safely given during the acute posttraumatic period.

The Bitter and the Sweet: Relationship of Lactate, Glucose, and Mortality After Severe Blunt Trauma.

BACKGROUND: Hyperglycemia is associated with mortality after trauma; however, few studies have simultaneously investigated the association of depth of shock and acute hyperglycemia. We evaluated lactate, as a surrogate measure for depth of shock, and glucose levels on mortality following severe blunt trauma. We hypothesize that measurements of both lactate and glucose are associated with mortality when considered simultaneously. METHODS: This is a retrospective cohort study at a single academic trauma center. Inclusion criteria are age 18-89 years, blunt trauma, injury severity score (ISS) ≥15, and transferred from the scene of injury. All serum blood glucose and lactate values were analyzed within the first 24 hours of admission. Multiple metrics of glucose and lactate were calculated: first glucose (Glucadm) and lactate (Lacadm) at hospital admission, mean 24-hour after hospital admission glucose (Gluc24-hMean) and lactate (Lac24-hMean), maximum 24-hour after hospital admission glucose (Gluc24-hMax) and lactate (Lac24-hMax), and time-weighted 24-hour after hospital admission glucose (Gluc24-hTW) and lactate (Lac24-hTW). Primary outcome was in-hospital mortality. Multivariable logistic regression modeling assessed the odds ratio (OR) of mortality, after adjusting for confounding variables. RESULTS: A total of 1439 trauma patients were included. When metrics of both glucose and lactate were analyzed, after adjusting for age, ISS, and admission shock index, only lactate remained significantly associated with mortality: Lacadm (OR, 1.28; 95% confidence interval [CI], 1.13-1.44); Lac24-hMean (OR, 1.86; 95% CI, 1.52-2.28); Lac24-hMax (OR, 1.39; 95% CI, 1.23-1.56); and Lac24-hTW (OR, 1.86; 95% CI, 1.53-2.26). CONCLUSIONS: Lactate is associated with mortality in severely injured blunt trauma patients, after adjusting for injury severity, age, and shock index. However, we did not find evidence for an association of glucose with mortality after adjusting for lactate.

Analysis of the Plasma Metabolome after Trauma, Novel Circulating Sphingolipid Signatures, and In-Hospital Outcomes.

BACKGROUND: Trauma is the leading cause of death and disability for individuals under age 55. Many severely injured trauma patients experience complicated clinical courses despite appropriate initial therapy. We sought to identify novel circulating metabolomic signatures associated with clinical outcomes following trauma. STUDY DESIGN: Untargeted metabolomics and circulating plasma immune mediator analysis was performed on plasma collected during 3 post-injury time periods (<6 hours [h], 6 h-24h, day 2-day 5) in critically ill trauma patients enrolled between April 2004 and May 2013 at UPMC Presbyterian Hospital in Pittsburgh, PA. Inclusion criteria were age ≥ 18 years, blunt mechanism, ICU admission, and expected survival ≥ 24 h. Exclusion criteria were isolated head injury, spinal cord injury, and pregnancy. Exploratory endpoints included length of stay (overall and ICU), ventilator requirements, nosocomial infection, and Marshall organ dysfunction (MOD) score. The top 50 metabolites were isolated using repeated measures ANOVA and multivariate empirical Bayesian analysis for further study. RESULTS: Eighty-six patients were included for analysis. Sphingolipids were enriched significantly (chi-square, p < 10-6) among the top 50 metabolites. Clustering of sphingolipid patterns identified 3 patient subclasses: nonresponders (no time-dependent change in sphingolipids, n = 41), sphingosine/sphinganine-enhanced (n = 24), and glycosphingolipid-enhanced (n = 21). Compared with the sphingolipid-enhanced subclasses, nonresponders had longer mean length of stay, more ventilator days, higher MOD scores, and higher circulating levels of proinflammatory immune mediators IL-6, IL-8, IL-10, MCP1/CCL2, IP10/CXCL10, and MIG/CXCL9 (all p < 0.05), despite similar Injury Severity Scores (p = 0.12). CONCLUSIONS: Metabolomic analysis identified broad alterations in circulating plasma sphingolipids after blunt trauma. Circulating sphingolipid signatures and their association with both clinical outcomes and circulating inflammatory mediators suggest a possible link between sphingolipid metabolism and the immune response to trauma.

Vitamin D status is associated with hepcidin and hemoglobin concentrations in patients with severe traumatic injury.

BACKGROUND: Severe traumatic injury leads to persistent injury-associated anemia that is associated with hypercatecholaminemia, systemic inflammation, increased hepcidin, and a functional iron deficiency. Vitamin D has been shown to reduce proinflammatory cytokines and hepcidin concentrations. This study aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia following blunt trauma. METHODS: A prospective observational cohort study comparing blunt trauma patients (n = 45) with elective hip replacement patients (n = 22) and healthy controls (n = 8) was performed. Bone marrow ferroportin, transferrin receptor, and erythroferrone expression was measured using quantitative polymerase chain reaction (qPCR). Plasma was assessed for systemic inflammation, erythropoietin (EPO), iron regulation, and vitamin D (25-OH) concentrations using enzyme-linked immunosorbent assay. Hemoglobin was measured on the day of discharge. RESULTS: Compared with hip replacement, trauma patients had higher plasma interleukin-6 (90.1 vs. 3.8 pg/mL), C-reactive protein (6,223 vs. 2,612 ng/mL), and hepcidin (79.3 vs. 21.2 ng/mL) concentrations. Trauma patients had lower vitamin D (25-OH) (12.8 vs. 18.1 ng/mL) and iron (23.5 vs. 59.9 µg/mL) levels compared with hip replacement patients. Despite the higher hepcidin EPO levels, bone marrow erythroferrone expression was increased 69% following trauma. CONCLUSION: Following elective hip replacement, patients did have anemia and impaired iron homeostasis without a significant change in inflammatory biomarkers, EPO, and vitamin D status. Vitamin D status did correlate with systemic inflammation, iron dysfunction, and persistent injury-associated anemia following severe blunt trauma. Further research is needed to determine whether supplementation with vitamin D in the trauma population could improve the persistent injury-associated anemia. LEVEL OF EVIDENCE: Prospective study, prognostic, level III.

Association between cardiac troponin I concentrations and electrocardiographic abnormalities in dogs with blunt trauma.

OBJECTIVE: To determine whether a normal cardiac troponin I (cTnI) concentration and normal ECG on entry rule out the development of a clinically significant cardiac arrhythmia (CSCA, defined as an arrhythmia requiring anti-arrhythmic treatment) in dogs that have sustained blunt trauma. DESIGN: Prospective, observational study. Client-owned dogs were enrolled between January 2015 and November 2016. SETTING: University teaching hospital. ANIMALS: Forty-seven client-owned dogs with a history of witnessed or suspected blunt trauma within 24 hours prior to presentation to the hospital. INTERVENTIONS: On admission to the emergency service, dogs had a standard 3-lead ECG and cTnI concentration (using a veterinary point-of-care device* ) performed. Animal Trauma Triage (ATT) scores, Modified Glasgow Coma Scale (MGCS), and the details regarding the nature and timing of the injury were recorded. The patients were monitored in the ICU for a minimum of 24 hours on continuous ECG telemetry. Cardiac rhythm was monitored every hour, and any abnormalities were noted. The need for anti-arrhythmic therapy was recorded. There were no treatment interventions. MEASUREMENTS AND MAIN RESULTS: Five of 47 dogs (10.6%) developed a CSCA during hospitalization after sustaining blunt trauma. A normal entry ECG and normal cardiac troponin concentration on entry had a 100% negative predictive value (NPV) for ruling out the development of a CSCA, although a normal cardiac troponin concentration alone also had an NPV of 100%. A normal entry ECG had an NPV of 95.3%. The prognosis for survival to discharge was 89.4% in this study population (42/47 dogs). CONCLUSIONS: In dogs with blunt trauma, an entry cTnI concentration or a combination of cTnI and ECG on entry may be useful in determining which patients are at a higher risk for the development of CSCA during the first 12 to 24 hours after the trauma.

The role of elevated high-sensitivity cardiac troponin on outcomes following severe blunt chest trauma.

BACKGROUND: Blunt cardiac injuries (BCI) result in poor outcomes following chest trauma. Admission ECG and troponin levels are frequently obtained in patients with suspected BCI, nevertheless, the prognostic value of cardiac troponins remains controversial. The purpose of the current study was to review the prognostic value of elevated high-sensitivity cardiac troponin T (hs-cTnT) in patients with severe blunt chest injuries. We hypothesized that elevated hs-cTnT result in poor outcomes in this subgroup of severe trauma patients. METHODS: After IRB approval, all consecutive patients with Injury Severity Score (ISS) > 15 and chest Abbreviated Injury Scale (AIS) score ≥3 admitted to the major trauma centers between 1/2015 and 6/2017 were retrospectively reviewed. Primary outcomes were in-hospital and one-year mortality. Secondary outcomes included ventilator days and Glasgow Outcome Scale (GOS) score at hospital discharge. RESULTS: Overall, 147 patients were included. Mean age was 49.0 (19.1) years and 75% were male. Serum troponin levels on admission were accrued in 82 (56%) patients with elevated and normal hs-cTnT levels found in 54 (66%) and in 28 (34%) patients, respectively. Elevated hs-cTnT group had significantly higher ISS and lactate level, and lower systolic blood pressure on admission. In-hospital mortality was significantly higher in patients with elevated hs-cTnT levels compared to patients with normal hs-cTnT levels (26% vs. 4%, p = 0.02). Hs-cTnT level > 14 ng/L was significantly associated with extended ventilator days and lower GOS score at hospital discharge. CONCLUSION: Blunt chest trauma victims with elevated hs-cTnT levels experience significantly poorer adjusted outcomes compared to patients with normal levels. Compliance with EAST practice management guidelines following severe blunt chest trauma was not fully complied in our study cohort that warrants prospective performance improvement measures.

Impact of Injury Severity on the Inflammatory State and Severe Anemia.

BACKGROUND: Severe traumatic injury is a major cause of morbidity and mortality. Our goal was to analyze blunt traumatic injury by injury severity score (ISS) and compare with elective hip repair, as a transient injury, and healthy control with the hypothesis that more severe injury would lead to an increase in neuroendocrine activation, systemic inflammation, and worse anemia. MATERIALS AND METHODS: A prospective observational cohort study was performed at a level 1 trauma center, comparing blunt trauma patients (n = 37), elective hip replacement patients (n = 26), and healthy controls (n = 8). Bone marrow and plasma were assessed for hyperadrenergic state, erythropoiesis, and systemic inflammation. Trauma patient's ISS ranged from 4 to 41 and were broken down into quartiles for analysis. The ISS quartiles were 4-13, 14-20, 21-26, and 27-41. RESULTS: Plasma norepinephrine, interleukin-6, tumor necrosis factor-alpha, and hepcidin increased progressively as ISS increased. Hemoglobin significantly decreased as ISS increased and packed red blood cell (pRBC) transfusion increased as ISS increased. Elective hip replacement patients had an appropriate increase in the bone marrow expression of erythropoietin and the erythropoietin receptor, which was absent in all trauma patient groups. CONCLUSIONS: Increased neuroendocrine activation, systemic inflammation, and anemia correlated with worsening injury severity, lower age, and increased pRBC transfusions. Elective hip replacement patients have only minimal systemic inflammation with an appropriate bone marrow response to anemia. This study demonstrates a link between injury severity, neuroendocrine activation, systemic inflammation, and the bone marrow response to anemia.

Trends in hematologic markers after blunt splenic trauma: Risk factor or Epiphenomenon?

BACKGROUND: Most blunt splenic injuries (BSI) are treated with nonoperative management (NOM) or embolization (EMBO). Little is known about the hematologic changes associated with these treatments. We aim to assess the temporal changes of hematologic markers in trauma patients who undergo splenectomy (SPL), packing and splenorrhaphy (P/S), EMBO, or NOM. We hypothesize that differences in trends of hematologic markers exist in patients undergoing EMBO or SPL, compared to NOM. METHODS: An 8-year review of adult patients with BSI and underwent SPL, EMBO, P/S, or NOM. White blood cell count (WBC), hematocrit (HCT) and platelet count (PLT) at presentation to 14 days post-admission were analyzed; post-procedural complications were reviewed. Temporal trends were compared using linear mixed-effects models. RESULTS: 478 patients sustained BSI, 298 (62.3%) underwent NOM, 100 (29.2%) SPL, 42 (8.8%) EMBO, and 38 (8.0%) P/S. After adjustment for age, ISS and splenic injury grade, SPL patients had a significantly higher upward trend compared to other management strategies (p < 0.05). Infection further increased this trend. Starting on day 6, SPL patients with infections had significantly higher WBC than those without infection. SPL and P/S were more likely than NOM to develop infections after adjustment for confounders (HR = 3.64; 95%CI: 1.79-7.39 and HR = 2.59; 95%CI: 1.21-5.55, respectively). Day 6 WBC>16,000 cells/ml post-SPL had a positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 76.9% for infections. Among P/S, Day 6 WBC >10,200 cells/ml had a PPV = 50% and NPV = 86.7% for infections. CONCLUSIONS: We observed distinct patterns of hematologic markers following BSI managed with SPL, EMBO, P/S, and NOM. Day 6 WBC increases after SPL or P/S should raise suspicion of infections and trigger a diagnostic investigation.

Diurnal Variation in Systemic Acute Inflammation and Clinical Outcomes Following Severe Blunt Trauma.

Animal studies suggest that the time of day is a determinant of the immunological response to both injury and infection. We hypothesized that due to this diurnal variation, time of injury could affect the systemic inflammatory response and outcomes post-trauma and tested this hypothesis by examining the dynamics of circulating inflammatory mediators in blunt trauma patients injured during daytime vs. nighttime. From a cohort of 472 blunt trauma survivors, two stringently matched sub-cohorts of moderately/severely injured patients [injury severity score (ISS) >20] were identified. Fifteen propensity-matched, daytime-inured ("mDay") patients (age 43.6 ± 5.2, M/F 11/4, ISS 22.9 ± 0.7) presented during the shortest local annual period (8:00 am-5:00 pm), and 15 propensity-matched "mNight" patients (age 43 ± 4.3, M/F 11/4, ISS 24.5 ± 2.5) presented during the shortest night period (10:00 pm-5:00 am). Serial blood samples were obtained (3 samples within the first 24 h and daily from days 1-7) from all patients. Thirty-two plasma inflammatory mediators were assayed. Two-way Analysis of Variance (ANOVA) was used to compare groups. Dynamic Network Analysis (DyNA) and Dynamic Bayesian Network (DyBN) inference were utilized to infer dynamic interrelationships among inflammatory mediators. Both total hospital and intensive care unit length of stay were significantly prolonged in the mNight group. Circulating IL-17A was elevated significantly in the mNight group from 24 h to 7 days post-injury. Circulating MIP-1α, IL-7, IL-15, GM-CSF, and sST2 were elevated in the mDay group. DyNA demonstrated elevated network complexity in the mNight vs. the mDay group. DyBN suggested that cortisol and sST2 were central nodes upstream of TGF-ß1, chemokines, and Th17/protective mediators in both groups, with IL-6 being an additional downstream node in the mNight group only. Our results suggest that time of injury affects clinical outcomes in severely injured patients in a manner associated with an altered systemic inflammation program, possibly implying a role for diurnal or circadian variation in the response to traumatic injury.

Impact of Anticoagulant and Antiplatelet Use on Outcomes in Blunt Chest Injury.

The aim of this study was to evaluate the impact of prehospital antiplatelet and/or anticoagulant (APAC) use on treatment and outcomes in patients with severe blunt chest injury. Patients with three or more rib fractures and a hospital length of stay (LOS) > three days admitted from 2014 to 2015 were included. Demographics, mortality, complications, injuries, hospital and ICU LOS, use of blood products, and thoracostomy were studied. Of 383 patients, 27.4 per cent were on APAC medication. Patients on APAC were older (P < 0.0001), had higher Glasgow Coma Score (P < 0.0001), and had lower Injury Severity Score (P < 0.0001) and total number of fractures (P = 0.0013) than the non-APAC group. APAC was not a predictor of mortality with or without age adjustment. In multiple linear regressions, APAC did not predict an increased LOS. APAC patients did not demonstrate an increase in admission diagnosis or complication of hemothorax, blood transfusions, tube thoracostomy, tracheostomy, LOS, or mortality rates. Similar findings are present in the subgroup of patients studied with high kinetic energy mechanism of injury. Our study does not support the perceived morbidity of APAC therapy in patients with severe blunt chest injury.

Not all in your head (and neck): Stroke after blunt cerebrovascular injury is associated with systemic hypercoagulability.

BACKGROUND: Stroke secondary to blunt cerebrovascular injury (BCVI) most often occurs before initiation of antithrombotic therapy. Earlier treatment, especially in multiply injured patients with relative contraindications to antithrombotic agents, could be facilitated with improved risk stratification; furthermore, the relationship between BCVI-attributed stroke and hypercoagulability remains unknown. We hypothesized that patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who do not stroke. METHODS: Rapid thromboelastography (TEG) was evaluated for patients with BCVI-attributed stroke at an urban Level I trauma center from 2011 to 2018. Contemporary controls who had BCVI but did not stroke were selected for comparison using propensity-score matching with 20% caliper that accounted for age, sex, injury severity, and BCVI location and grade. RESULTS: During the study period, 15,347 patients were admitted following blunt trauma. Blunt cerebrovascular injury was identified in 435 (3%) patients, of whom 28 experienced associated stroke and had a TEG within 24 hours of arrival. Forty-nine patients who had BCVI but did not suffer stroke served as matched controls. Stroke patients formed clots faster as evident in their larger angle (77.5 degrees vs. 74.6 degrees, p = 0.03) and had greater clot strength as indicated by their higher maximum amplitude (MA) (66.9 mm vs. 61.9 mm, p < 0.01). Activated clotting time was shorter among stroke patients but not significantly (113 seconds vs. 121 seconds, p > 0.05). Increased angle and elevated MA were significant predictors of stroke with odds ratios of 2.97 for angle greater than 77.3 degrees and 4.30 for MA greater than 63.0 mm. CONCLUSION: Patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who remain asymptomatic. Increased angle or MA should be considered when assessing the risk of thrombosis and determining the optimal time to initiate antithrombotic therapy in patients with BCVI. LEVEL OF EVIDENCE: Prognostic, Level III.

Is early chemical thromboprophylaxis in patients with solid organ injury a solid decision?

BACKGROUND: The optimal time to initiate chemical thromboprophylaxis (CTP) in patients who have undergone nonoperative management (NOM) of blunt solid organ injuries (SOI) remains controversial. The aim of our study was to assess the impact of early initiation of CTP in patients with blunt abdominal SOIs. METHODS: We performed a 2-year (2013-2014) retrospective analysis of American College of Surgeons Trauma Quality Improvement Program. We included all adult trauma patients (age, ≥ 18 years) with blunt SOI who underwent NOM. Patients were stratified into three groups based on timing of CTP (early, ≤48 hours of injury; late, >48 hours of injury,; and no prophylaxis group). Our primary outcomes were rates of failure of NOM, pRBC transfusion, and mortality. Our secondary outcomes were the rate of venous thromboembolic (VTE) events (i.e., deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) and length of stay. RESULTS: A total of 36,187 patients met the inclusion criteria. Mean age was 49.5 ± 19 years and 36% of patients received CTP (early, 37% (n = 4,819) versus late, 63% (n = 8,208)). After controlling for confounders, patients receiving early CTP had lower rates of DVT (p = 0.01) and PE (p = 0.01) compared with the no prophylaxis and late CTP groups. There was no difference between the three groups regarding the postprophylaxis pRBC transfusions, failure of NOM, and mortality. CONCLUSION: Our results suggest that in patients undergoing NOM of blunt abdominal SOI, early initiation of CTP should be considered. It is associated with decreased rates of DVT and PE, with no significant difference in post prophylaxis pRBC transfusion, failure of nonoperative management, and mortality. LEVEL OF EVIDENCE: Therapeutic, level V.

Elevations in Circulating sST2 Levels Are Associated With In-Hospital Mortality and Adverse Clinical Outcomes After Blunt Trauma.

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2), a decoy receptor for interleukin (IL)-33, has emerged as a novel biomarker in various disease processes. Recent studies have elucidated the role of the sST2/IL-33 complex in modulating the balance of Th1/Th2 immune responses after tissue stress. However, the role of sST2 as a biomarker after traumatic injury remains unclear. To address this, we evaluated serum sST2 correlations with mortality and in-hospital adverse outcomes as endpoints in blunt trauma patients. METHODS: We retrospectively analyzed clinical and biobank data of 493 blunt trauma victims 472 survivors (mean age: 48.4 ± 0.87; injury severity score [ISS]: 19.6 ± 0.48) and 19 nonsurvivors (mean age: 58.8 ± 4.5; ISS: 23.3 ± 2.1) admitted to the intensive care unit. Given the confounding impact of age on the inflammatory response, we derived a propensity-matched survivor subgroup (n = 19; mean age: 59 ± 3; ISS: 23.4 ± 2) using an IBM SPSS case-control matching algorithm. Serial blood samples were obtained from all patients (3 samples within the first 24 h and then once daily from day [D] 1 to D5 after injury). sST2 and twenty-nine inflammatory biomarkers were assayed using enzyme-linked immunosorbent assay and Luminex, respectively. Two-way analysis of variance on ranks was used to compare groups (P < 0.05). Spearman rank correlation was performed to determine the association of circulating sST2 levels with biomarker levels and in-hospital clinical outcomes. RESULTS: Circulating sST2 levels of the nonsurvivor cohort were statistically significantly elevated at 12 h after injury and remained elevated up to D5 when compared either to the overall 472 survivor cohort or a matched 19 survivor subcohort. Admission sST2 levels obtained from the first blood draw after injury in the survivor cohort correlated positively with admission base deficit (correlation coefficient [CC] = 0.1; P = 0.02), international normalized ratio (CC = 0.1, P = 0.03), ISS (CC = 0.1, P = 0.008), and the average Marshall multiple organ dysfunction score between D2 and D5 (CC = 0.1, P = 0.04). Correlations with ISS revealed a positive correlation of ISS with plasma sST2 levels across the mild ISS (CC = 0.47, P < 0.001), moderate ISS (CC = 0.58, P < 0.001), and severe ISS groups (CC = 0.63, P < 0.001). Analysis of biomarker correlations in the matched survivor group over the initial 24 h after injury showed that sST2 correlates strongly and positively with IL-4 (CC = 0.65, P = 0.002), IL-5 (CC = 0.57, P = 0.01), IL-21 (CC = 0.52, P = 0.02), IL-2 (CC = 0.51, P = 0.02), soluble IL-2 receptor-α (CC = 0.5, P = 0.02), IL-13 (CC = 0.49, P = 0.02), and IL-17A (CC = 0.48, P = 0.03). This was not seen in the matched nonsurvivor group. sST2/IL-33 ratios were significantly elevated in nonsurvivors and patients with severe injury based on ISS ≥ 25. CONCLUSIONS: Elevations in serum sST2 levels are associated with poor clinical trajectories and mortality after blunt trauma. High sST2 coupled with low IL-33 associates with severe injury, mortality, and worse clinical outcomes. These findings suggest that sST2 could serve as an early prognostic biomarker in trauma patients and that sustained elevations of sST2 could contribute to a detrimental suppression of IL-33 bioavailability in patients with high injury severity.