A survey of low titer O whole blood use within the trauma quality improvement program registry.

INTRODUCTION: The use of low titer O whole blood (LTOWB) has expanded although it remains unclear how many civilian trauma centers are using LTOWB. METHODS: We analyzed data on civilian LTOWB recipients in the American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2020-2021. Unique facility keys were used to determine the number of centers that used LTOWB in that period. RESULTS: A total of 16,603 patients received LTOWB in the TQIP database between 2020 and 2021; 6600 in 2020, and 10,003 in 2021. The total number of facilities that reported LTOWB use went from 287/779 (37%) in 2020 to 302/795 (38%) in 2021. Between 2020 and 2021, among all level 1-3 designated trauma facilities that report to TQIP LTOWB use increased at level-1 centers (118 to 129), and level-2 centers (81 to 86), but decreased in level-3 facilities (9 to 4). Among pediatric and dual pediatric-adult designated hospitals there was a decrease in the number of pediatric level-1 centers (29 to 28) capable of administering LTOWB. Among centers with either single or dual level-1 trauma center designation with adult centers, the number that administered LTOWB to injured pediatric patients also decreased from 17 to 10, respectively. CONCLUSIONS: There was an increase in the number of facilities transfusing LTOWB between 2020 and 2021. The use of LTOWB is underutilized in children at centers that have it available. These findings inform the expansion of LTOWB use in trauma.

Burden of unintentional pediatric firearm injury: An examination of the Nationwide Readmission Database.

BACKGROUND: Significant increases in firearm-related mortality in the US pediatric population drive an urgent need to study these injuries to drive prevention policies. The purpose of this study was (1) to characterize those with and without readmissions, (2) to identify risk factors for 90-day unplanned readmission, and (3) to examine reasons for hospital readmission. METHODS: The 2016-2019 Nationwide Readmission Database of the Healthcare Cost and Utilization Project was used to identify hospital admissions with unintentional firearm injury in patients younger than 18 years. Ninety-day unplanned readmission characteristics were assessed and detailed. Multivariable regression analysis was used to assess factors associated with unplanned 90-day readmission. RESULTS: Over 4 years, 1,264 unintentional firearm injury admissions resulted in 113 subsequent readmissions (8.9%). There were no significant differences in age or payor, but more women (14.7% vs. 23%) and older children (13-17 years [80.5%]) had readmissions. The mortality rate during primary hospitalization was 5.1%. Survivors of initial firearm injury were more frequently readmitted if they had a mental health diagnosis (22.1% vs. 13.8%; p = 0.017). Readmission diagnosis included complications (15%), mental health or drug/alcohol (9.7%), trauma (33.6%), a combination of the prior three (28.3%), and chronic disease (13.3%). More than a third (38.9%) of the trauma readmissions were for new traumatic injury. Female children, those with longer lengths of stay, and those with more severe injuries were more likely to have unplanned 90-day readmissions. Mental health and drug/alcohol abuse diagnoses were not an independent predictor for readmission. CONCLUSION: This study provides insight into the characteristics of and risk factors for unplanned readmission in the pediatric unintentional firearm injury population. In addition to using prevention strategies, the utilization of trauma-informed care must be integrated into all aspects of care for this population to help minimize the long-term psychological impact of surviving firearm injury. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target.

The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, and there is an unmet demand for pharmacologic therapies targeting the underlying pathology of ARDS in patients suffering from the illness. The complement cascade (ComC) plays an integral role in the regulation of both innate and adaptive immune responses. ComC activation can prime an overzealous cytokine storm and tissue/organ damage. The ARDS and acute lung injury (ALI) have an established relationship with early maladaptive ComC activation. In this review, we have collected evidence from the current studies linking ALI/ARDS with ComC dysregulation, focusing on elucidating the new emerging roles of the extracellular (canonical) and intracellular (non-canonical or complosome), ComC (complementome) in ALI/ARDS pathobiology, and highlighting complementome as a vital nexus of the pathobiological connectome for ALI/ARDS via its crosstalking with other systems of the immunome, DAMPome, PAMPome, coagulome, metabolome, and microbiome. We have also discussed the diagnostic/therapeutic potential and future direction of ALI/ARDS care with the ultimate goal of better defining mechanistic subtypes (endotypes and theratypes) through new methodologies in order to facilitate a more precise and effective complement-targeted therapy for treating these comorbidities. This information leads to support for a therapeutic anti-inflammatory strategy by targeting the ComC, where the arsenal of clinical-stage complement-specific drugs is available, especially for patients with ALI/ARDS due to COVID-19.

Risk of Harm in Needle Decompression for Tension Pneumothorax.

INTRODUCTION: Tension pneumothorax (TPX) is the third most common cause of preventable death in trauma. Needle decompression at the fifth intercostal space at anterior axillary line (5th ICS AAL) is recommended by Tactical Combat Casualty Care (TCCC) with an 83-mm needle catheter unit (NCU). We sought to determine the risk of cardiac injury at this site. METHODS: Institutional data sets from two trauma centers were queried for 200 patients with CT chest. Inclusion criteria include body mass index of =30 and age 18-40 years. Measurements were taken at 2nd ICS mid clavicular line (MCL), 5th ICS AAL and distance from the skin to pericardium at 5th ICS AAL. Groups were compared using Mann-Whitney U and chi-squared tests. RESULTS: The median age was 27 years with median BMI of 23.8 kg/m2. The cohort was 69.5% male. Mean chest wall thickness at 2nd ICS MCL was 38-mm (interquartile range (IQR) 32-45). At 5th ICS AAL, the median chest wall thickness was 30-mm (IQR 21-40) and the distance from skin to pericardium was 66-mm (IQR 54-79). CONCLUSION: The distance from skin to pericardium for 75% of patients falls within the length of the recommended needle catheter unit (83-mm). The current TCCC recommendation to "hub" the 83mm needle catheter unit has potential risk of cardiac injury.

The impact of prehospital whole blood on hemorrhaging trauma patients: A multi-center retrospective study.

BACKGROUND: Whole blood (WB) use has become increasingly common in trauma centers across the United States for both in-hospital and prehospital resuscitation. We hypothesize that prehospital WB (pWB) use in trauma patients with suspected hemorrhage will result in improved hemodynamic status and reduced in-hospital blood product requirements. METHODS: The institutional trauma registries of two academic level I trauma centers were queried for all patients from 2015-2019 who underwent transfusion upon arrival to the trauma bay. Patients who were dead on arrival or had isolated head injuries were excluded. Demographics, injury and shock characteristics, transfusion requirements, including massive transfusion protocol (MTP) (>10 U in 24 hours) and rapid transfusion (CAT3+) and outcomes were compared between pWB and non-pWB patients. Significantly different demographic, injury characteristics and pWB were included in univariate followed by stepwise logistic regression analysis to determine the relationship with shock index (SI). Our primary objective was to determine the relationship between pWB and improved hemodynamics or reduction in blood product utilization. RESULTS: A total of 171 pWB and 1391 non-pWB patients met inclusion criteria. Prehospital WB patients had a lower median Injury Severity Score (17 vs. 21, p < 0.001) but higher prehospital SI showing greater physiologic disarray. Prehospital WB was associated with improvement in SI (-0.04 vs. 0.05, p = 0.002). Mortality and (LOS) were similar. Prehospital WB patients received fewer packed red blood cells, fresh frozen plasma, and platelets units across their LOS but total units and volumes were similar. Prehospital WB patients had fewer MTPs (22.6% vs. 32.4%, p = 0.01) despite a similar requirement of CAT3+ transfusion upon arrival. CONCLUSION: Prehospital WB administration is associated with a greater improvement in SI and a reduction in MTP. This study is limited by its lack of power to detect a mortality difference. Prospective randomized controlled trials will be required to determine the true impact of pWB on trauma patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Clinical Assessment of Low Calcium In traUMa (CALCIUM).

Major trauma frequently occurs in the deployed, combat setting and is especially applicable in the recent conflicts with explosives dominating the combat wounded. In future near-peer conflicts, we will likely face even more profound weapons including mortars and artillery. As such, the number of severely wounded will likely increase. Hypocalcemia frequently occurs after blood transfusions, secondary to the preservatives in the blood products; however, recent data suggests major trauma in and of itself is a risk factor for hypocalcemia. Calcium is a major ion involved in heart contractility; thus, hypocalcemia can lead to poor contractility. Smaller studies have linked hypocalcemia to worse outcomes, but it remains unclear what causes hypocalcemia and if intervening could potentially save lives. The objective of this study is to determine the incidence of hypocalcemia on hospital arrival and the association with survival. We are seeking to address the following scientific questions, (1) Is hypocalcemia present following traumatic injury prior to transfusion during resuscitation? (2) Does hypocalcemia influence the amount of blood products transfused? (3) To what extent is hypocalcemia further exacerbated by transfusion? (4) What is the relationship between hypocalcemia following traumatic injury and mortality? We will conduct a multicenter, prospective, observational study. We will gather ionized calcium levels at 0, 3, 6, 12, 18, and 24 hours as part of scheduled calcium measurements. This will ensure we have accurate data to assess the early and late effects of hypocalcemia throughout the course of resuscitation and hemorrhage control. These data will be captured by a trained study team at every site. Our findings will inform clinical practice guidelines and optimize the care delivered in the combat and civilian trauma setting. We are seeking 391 patients with complete data to meet our a priori inclusion criteria. Our study will have major immediate short-term findings including risk prediction modeling to assess who is at risk for hypocalcemia, data assessing interventions associated with the incidence of hypocalcemia, and outcome data including mortality and its link to early hypocalcemia.

The regional whole blood program in San Antonio, TX: A 3-year update on prehospital and in-hospital transfusion practices for traumatic and non-traumatic hemorrhage.

Low titer type O Rh-D + whole blood (LTO + WB) has become a first-line resuscitation medium for hemorrhagic shock in many centers around the World. Showing early effectiveness on the battlefield, LTO + WB is used in both the pre-hospital and in-hospital settings for traumatic and non-traumatic hemorrhage resuscitation. Starting in 2018, the San Antonio Whole Blood Collaborative has worked to provide LTO + WB across Southwest Texas, initially in the form of remote damage control resuscitation followed by in-hospital trauma resuscitation. This program has since expanded to include pediatric trauma resuscitation, obstetric hemorrhage, females of childbearing potential, and non-traumatic hemorrhage. The objective of this manuscript is to provide a three-year update on the successes and expansion of this system and outline resuscitation challenges in special populations.

Compensatory reserve and pulse character: Enhanced potential to predict urgency for transfusion and other life-saving interventions after traumatic injury.

BACKGROUND: Field triage of trauma patients requires timely assessment of physiologic status to determine resuscitative needs. Vital signs and rudimentary assessments such as pulse character (PC) are used by first responders to guide decision making. The compensatory reserve measurement (CRM) has demonstrated utility as an easily interpretable method for assessing patient status. We hypothesized that the ability to identify injured patients requiring transfusion and other life-saving interventions (LSI) using a measurement of pulse character could be enhanced by the addition of the CRM. METHODS: We performed a prospective observational study on 300 trauma patients admitted to a level I trauma center. CRM was recorded continuously after device placement on arrival. Patient demographics, field and trauma resuscitation unit vital signs, therapeutic interventions, and outcomes were collected. A field SBP <100 mmHg was utilized as a surrogate for abnormal PC as previously validated. A patient with a CRM threshold value of <60% was considered clinically compromised with a risk of onset of decompensated shock. Data were analyzed to assess the capacity of CRM and pulse character separately or in combination to predict LSI defined as need for transfusion, intubation, tube thoracostomy, or operative/ angiographic hemorrhage control. RESULTS: An improvement in the predictive capability for LSI, transfusion, or a composite outcome was demonstrated by the combination of CRM and PC compared to either measure alone. CONCLUSIONS: Combining PC assessment with CRM has the potential to enhance the recognition of injured patients requiring life-saving intervention thus improving sensitivity of decision support for prehospital providers.

An Analysis of the Incidence of Hypocalcemia in Wartime Trauma Casualties.

OBJECTIVE: Background: Massive transfusion protocols implement the use of blood products to restore homeostasis. Citrated blood products are required for massive transfusions and can induce hypocalcemia, resulting in decreased cardiac contractility. Recent data suggests that major trauma alone is associated with hypocalcemia. This phenomenon remains poorly described. We seek to characterize the incidence and risk factors for early hypocalcemia in the setting of combat trauma. MATERIALS AND METHODS: This is a secondary analysis of previously described data from the Department of Defense Trauma Registry from January 2007 to March 2020. In this sub-analysis, we selected only casualties that had at least one ionized calcium measurement. We defined hypocalcemia as an ionized calcium level of less than 1.2mmol/L. RESULTS: Within our study database, there were 142 adult casualties that met inclusion with at least one calcium value documented. We found 72 (51%) experienced at least one episode of hypocalcemia. Median composite injury severity score (ISS) was significantly lower in the control cohort compared to those with hypocalcemia (9 versus 15, p=0.010). Survival was similar between the two groups (97% versus 90%, p=0.166). On multivariable analysis when evaluating serious injuries by body region, only serious injuries to the extremities were significantly associated with developing hypocalcemia (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00-2.21). When comparing prehospital interventions, only intravenous (IV) fluid administration was associated with high proportions experiencing hypocalcemia (25% versus 43%, p=0.029). In the multivariable model adjusted for ISS, mechanism of injury, and patient category, IV fluids were associated with the development of hypocalcemia (OR 2.48, 95% CI 1.03-5.94). When comparing vital signs, only respiratory rates were noted to be higher in the hypocalcemia cohort (18.6 versus 20.4, p=0.048). CONCLUSIONS: Approximately half of combat casualties with available ionized calcium (iCa) level were hypocalcemic. Prehospital IV fluid use was associated with the development of hypocalcemia. Our study has implications for forward-staged medical teams with limited laboratory analysis capabilities. Additional research is needed to determine whether calcium replacement improves survival from traumatic injury and to identify the specific indications and timing for calcium replacement. This study will help inform a clinical study intended to aid in the development of clinical practice guidelines for deployed medical personnel.

The Use of Whole Blood Transfusion During Non-Traumatic Resuscitation.

BACKGROUND: Evidence from military populations showed that resuscitation using whole blood (WB), as opposed to component therapies, may provide additional survival benefits to traumatically injured patients. However, there is a paucity of data available for the use of WB in uninjured patients requiring transfusion. We sought to describe the use of WB in non-trauma patients at Brooke Army Medical Center (BAMC). MATERIALS AND METHODS: Between January and December 2019, the BAMC ClinComp electronic medical record system was reviewed for all patients admitted to the hospital who received at least one unit of WB during this time period. Patients were sorted based on their primary admission diagnosis. Patients with a primary trauma-based admission were excluded. RESULTS: One hundred patients were identified who received at least one unit of WB with a primary non-trauma admission diagnosis. Patients, on average, received 1,064 mL (750-2,458 mL) of WB but received higher volumes of component therapy. Obstetric/gynecologic (OBGYN) indications represented the largest percentage of non-trauma patients who received WB (23%), followed by hematologic/oncologic indications (16%). CONCLUSION: In this retrospective study, WB was most commonly used for OBGYN-associated bleeding. As WB becomes more widespread across the USA for use in traumatically injured patients, it is likely that WB will be more commonly used for non-trauma patients. More outcome data are required to safely expand the indications for WB use beyond trauma.

Whole blood resuscitation restores intestinal perfusion and influences gut microbiome diversity.

OBJECTIVE: Gut dysbiosis, an imbalance in the gut microbiome, occurs after trauma, which may be ameliorated with transfusion. We hypothesized that gut hypoperfusion following trauma causes dysbiosis and that whole blood (WB) resuscitation mitigates these effects. METHODS: Anesthetized rats underwent sham (S; laparotomy only, n = 6); multiple injuries (T; laparotomy, liver and skeletal muscle crush injuries, and femur fracture, n = 5); multiple injuries and 40% hemorrhage (H; n = 7); and multiple injuries, hemorrhage, and WB resuscitation (R; n = 7), which was given as 20% estimated blood volume from donor rats 1 hour posttrauma. Baseline cecal mesenteric tissue oxygen (O2) concentration was measured following laparotomy and at 1 hour and 2 hours posttrauma. Fecal samples were collected preinjury and at euthanasia (2 hours). 16S rRNA sequencing was performed on purified DNA, and diversity and phylogeny were analyzed with QIIME (Knight Lab, La Jolla, CA; Caporaso Lab, Flagstaff, AZ) using the Greengenes 16S rRNA database (operational taxonomic units; 97% similarity). α and ß diversities were estimated using observed species metrics. Permutational analysis of variance was performed for overall significance. RESULTS: In H rats, an average decline of 36% ± 3.6% was seen in the mesenteric O2 concentration at 1 hour without improvement by 2 hours postinjury, which was reversed following resuscitation at 2 hours postinjury (4.1% ± 3.1% difference from baseline). There was no change in tissue O2 concentration in the S or T rats. ß Diversity differed among groups for all measured indices except Bray-Curtis, with the spatial median of the S and R rats more similar compared with S and H rats (p < 0.05). While there was no difference in α diversity found among the groups, indices were significantly correlated with mesenteric O2 concentration. Members of the family Enterobacteriaceae were significantly enriched in only 2 hours. CONCLUSION: Mesenteric perfusion after trauma and hemorrhage is restored with WB resuscitation, which influences ß diversity of the gut microbiome. Whole blood resuscitation may also mitigate the effects of hemorrhage on intestinal dysbiosis, thereby influencing outcomes.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.

More sophisticated than a drink cooler or an old sphygmomanometer but still not adequate for prehospital blood: A market review of commercially available equipment for prehospital blood transport and administration.

BACKGROUND: Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care-this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting-especially in combat-presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. STUDY DESIGN AND METHODS: We conducted a market review of available technology through subject-matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. RESULTS: We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. CONCLUSIONS: The risk of on-scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock.

BACKGROUND: Low titer O+ whole blood (LTOWB) is being increasingly used for resuscitation of hemorrhagic shock in military and civilian settings. The objective of this study was to identify the impact of prehospital LTOWB on survival for patients in shock receiving prehospital LTOWB transfusion. STUDY DESIGN AND METHODS: A single institutional trauma registry was queried for patients undergoing prehospital transfusion between 2015 and 2019. Patients were stratified based on prehospital LTOWB transfusion (PHT) or no prehospital transfusion (NT). Outcomes measured included emergency department (ED), 6-h and hospital mortality, change in shock index (SI), and incidence of massive transfusion. Statistical analyses were performed. RESULTS: A total of 538 patients met inclusion criteria. Patients undergoing PHT had worse shock physiology (median SI 1.25 vs. 0.95, p < .001) with greater reversal of shock upon arrival (-0.28 vs. -0.002, p < .001). In a propensity-matched group of 214 patients with prehospital shock, 58 patients underwent PHT and 156 did not. Demographics were similar between the groups. Mean improvement in SI between scene and ED was greatest for patients in the PHT group with a lower trauma bay mortality (0% vs. 7%, p = .04). No survival benefit for patients in prehospital cardiac arrest receiving LTOWB was found (p > .05). DISCUSSION: This study demonstrated that trauma patients who received prehospital LTOWB transfusion had a greater improvement in SI and a reduction in early mortality. Patient with prehospital cardiac arrest did not have an improvement in survival. These findings support LTOWB use in the prehospital setting. Further multi-institutional prospective studies are needed.

Prehospital shock index and systolic blood pressure are highly specific for pediatric massive transfusion.

BACKGROUND: While massive transfusion protocols (MTPs) are associated with decreased mortality in adult trauma patients, there is limited research on the impact of MTP on pediatric trauma patients. The purpose of this study was to compare pediatric trauma patients requiring massive transfusion with all other pediatric trauma patients to identify triggers for MTP activation in injured children. METHODS: Using our level I trauma center's registry, we retrospectively identified all pediatric trauma patients from January 2015 to January 2018. Massive transfusion (MT) was defined as infusion of 40 mL/kg of blood products in the first 24 hours of admission. Patients missing prehospital vital sign data were excluded from the study. We retrospectively collected data including demographics, blood utilization, variable outcome data, prehospital vital signs, prehospital transport times, and Injury Severity Scores. Statistical significance was determined using Mann-Whitney U test and χ2 test. p Values of less than 0.05 were considered significant. RESULTS: Thirty-nine (1.9%) of the 2,035 pediatric patients met the criteria for MT. All-cause mortality in MT patients was 49% (19 of 39 patients) versus 0.01% (20 of 1996 patients) in non-MT patients. The two groups significantly differed in Injury Severity Score, prehospital vital signs, and outcome data.Both systolic blood pressure (SBP) of <100 mm Hg and shock index (SI) of >1.4 were found to be highly specific for MT with specificities of 86% and 92%, respectively. The combination of SBP of <100 mm Hg and SI of >1.4 had a specificity of 94%. The positive and negative predictive values of SBP of <100 mm Hg and SI of >1.4 in predicting MT were 18% and 98%, respectively. Based on positive likelihood ratios, patients with both SBP of <100 mm Hg and SI of >1.4 were 7.2 times more likely to require MT than patients who did not meet both of these vital sign criteria. CONCLUSION: Pediatric trauma patients requiring early blood transfusion present with lower blood pressures and higher heart rates, as well as higher SIs and lower pulse pressures. We found that SI and SBP are highly specific tools with promising likelihood ratios that could be used to identify patients requiring early transfusion. LEVEL OF EVIDENCE: Therapeutic/care management, level V.

Trauma-induced lung injury is associated with infiltration of activated TLR expressing myeloid cells.

INTRODUCTION: Traumatic injury with hemorrhage (TH) induces an inflammatory response in the lung resulting in lung injury involving activation of immune cells including myeloid cells (i.e., monocytes, granulocytes and macrophages), in part through TLRs. TLRs, via the recognition of damage associated molecular patterns (DAMPs), are a key link between tissue injury and inflammation. Nonetheless, the role of TLRs in myeloid cell activation and TH-induced lung injury remains ill defined. METHODS: C57BL/6 male mice were subjected to TH or sham treatment (n = 4-6 /group). Lung tissues were collected two hrs. after injury. Single cells were isolated from the lungs by enzymatic digestion and myeloid cell TLR expression and activation (i.e., cytokine production) were assessed using flow cytometry techniques. RESULTS: The injury was associated with a profound change in the lung myeloid cell population. TH markedly increased lung CD11b+ monocyte numbers and Gr1+ granulocyte numbers as compared to sham mice. The number of cells expressing TLR2, TLR4, and TLR9 were increased 4-7 fold in the TH mice. Activation for elevated cytokine (TNFα, IL-10) production was observed in the lung monocyte population of the TH mice. CONCLUSIONS: Trauma-induced lung injury is associated with infiltration of the lungs with TLR expressing myeloid cells that are activated for elevated cytokine responses. This elevation in TLR expression may contribute to DAMP-mediated pulmonary complications of an inflammatory nature and warrants further investigation.

Burn resuscitation strategy influences the gut microbiota-liver axis in swine.

Fluid resuscitation improves clinical outcomes of burn patients; however, its execution in resource-poor environments may have to be amended with limited-volume strategies. Liver dysfunction is common in burn patients and gut dysbiosis is an understudied aspect of burn sequelae. Here, the swine gut microbiota and liver transcripts were investigated to determine the impact of standard-of-care modified Brooke (MB), limited-volume colloid (LV-Co), and limited-volume crystalloid (LV-Cr) resuscitation on the gut microbiota, and to evaluate its' potential relationship with liver dysfunction. Independent of resuscitation strategy, bacterial diversity was reduced 24 h post-injury, and remained perturbed at 48 h. Changes in community structure were most pronounced with LV-Co, and correlated with biomarkers of hepatocellular damage. Hierarchical clustering revealed a group of samples that was suggestive of dysbiosis, and LV-Co increased the risk of association with this group. Compared with MB, LV-Co and LV-Cr significantly altered cellular stress and ATP pathways, and gene expression of these perturbed pathways was correlated with major dysbiosis-associated bacteria. Taken together, LV-Co resuscitation exacerbated the loss of bacterial diversity and increased the risk of dysbiosis. Moreover, we present evidence of a linkage between liver (dys)function and the gut microbiota in the acute setting of burn injury.

From battlefront to homefront: creation of a civilian walking blood bank.

Hemorrhagic shock remains the leading cause of preventable death on the battlefield, despite major advances in trauma care. Early initiation of balanced resuscitation has been shown to decrease mortality in the hemorrhaging patient. To address transfusion limitations in austere environments or in the event of multiple casualties, walking blood banks have been used in the combat setting with great success. Leveraging the success of the region-wide whole blood program in San Antonio, Texas, we report a novel plan that represents a model response to mass casualty incidents.

The gut microbiome distinguishes mortality in trauma patients upon admission to the emergency department.

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier, decreased gut perfusion, and inflammation. While recent studies indicate that the gut microbiome (GM) is altered early following traumatic injury, the impact of GM changes on clinical outcomes remains unknown. Our objective of this follow-up study was to determine if the GM is associated with clinical outcomes in critically injured patients. METHODS: We conducted a prospective, observational study in adult patients (N = 67) sustaining severe injury admitted to a level I trauma center. Fecal specimens were collected on admission to the emergency department, and microbial DNA from all samples was analyzed using the Quantitative Insights Into Microbial Ecology pipeline and compared against the Greengenes database. α-Diversity and ß-diversity were estimated using the observed species metrics and analyzed with t tests and permutational analysis of variance for overall significance, with post hoc pairwise analyses. RESULTS: Our patient population consisted of 63% males with a mean age of 44 years. Seventy-eight percent of the patients suffered blunt trauma with 22% undergoing penetrating injuries. The mean body mass index was 26.9 kg/m. Significant differences in admission ß-diversity were noted by hospital length of stay, intensive care unit hospital length of stay, number of days on the ventilator, infections, and acute respiratory distress syndrome (p < 0.05). ß-Diversity on admission differed in patients who died compared with patients who lived (mean time to death, 8 days). There were also significantly less operational taxonomic units in samples from patients who died versus those who survived. A number of species were enriched in the GM of injured patients who died, which included some traditionally probiotic species such as Akkermansia muciniphilia, Oxalobacter formigenes, and Eubacterium biforme (p < 0.05). CONCLUSION: Gut microbiome diversity on admission in severely injured patients is predictive of a variety of clinically important outcomes. While our study does not address causality, the GM of trauma patients may provide valuable diagnostic and therapeutic targets for the care of injured patients. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

The Effect of Burn Resuscitation Volumes on the Gut Microbiome in a Swine Model.

INTRODUCTION: While recent reports underscore the significance of the gut microbiome (GM) in health and disease, its importance in burn outcomes remains unclear. Moreover, aggressive intravenous (IV) fluid resuscitation of patients may alter intestinal flora. Herein, we describe GM changes following a large burn in swine randomized to different volumes of IV Lactated Ringers' (LR). METHODS: Anesthetized Yorkshire swine sustained 40% total body surface area full-thickness burns and were randomized to different volumes of IV LR: none (n = 5), 15 mL/kg/d (low; n = 6), or 80 mL/kg/d (high; n = 6). At baseline and days 1 and 2, fecal swabs were collected for 16s rDNA sequencing. Proximal jejunum was collected immediately after euthanasia (day 2) for western blot, histopathology, and cytokine analyses. RESULTS: Burns produced significant shifts in ß-diversity and non-significant reductions in α-diversity that did not recover regardless of treatment group. Burn-induced increases in Proteobacteria and decreases in Firmicutes were attenuated by IV fluids in a dose-dependent manner, and also correlated with α-diversity. IV fluids caused a dose-dependent increase in Bacteroides and prevented a transient increase in the opportunistic pathogen Haemophilus parainfluenzae. While high volumes of IV fluids increased intestinal Hsp70 levels (P = 0.0464), they reduced SGLT1 (P = 0.0213) and caspase3 (P = 0.0139) levels. IV fluids elicited a non-specific cytokine response; however, Bacteroidetes levels correlated with intestinal IL18 levels (P = 0.0166, R = 0.4201). CONCLUSIONS: We present the first report on the gut microbiome in a porcine burn model, and present data to suggest that IV fluids may influence GM and gut functional proteins following a burn. Overall, burn-induced GM diversity shifts may expose diagnostic and/or therapeutic targets to improve outcomes.