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The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs). METHODS: Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization. RESULTS: Polytrauma patients (n = 180) had high Injury Severity Score (26 [20–34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78. CONCLUSION: Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation. LEVEL OF EVIDENCE: Diagnostic Tests/Criteria; Level II.

Background The incidence of underlying malignancy in appendicitis ranges between 0.5% and 1.7%. We sought to identify the subset of patients with appendicitis who are at increased risk of appendiceal malignancy. Methods Using the Eastern Association for the Surgery of Trauma Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, we included all patients from 28 centers undergoing immediate, delayed, or interval appendectomy between 2017 and 2018. Univariate then multivariable analyses were performed to compare patients with and without malignancy and to identify independent demographic, clinical, laboratory, and/or radiological predictors of malignancy. Akaike information criteria for regression models were used to evaluate goodness of fit. Results A total of 3,293 patients were included. The median age was 38 (27–53) years, and 46.5% were female patients. On pathology, 48 (1.5%) had an underlying malignancy (adenocarcinoma [60.4%], neuroendocrine [37.5%], and lymphoma [2.1%]). Patients with malignancy were older (56 [34.5–67] vs 37 [27–52] years, P 40 years with an appendiceal diameter >10 mm on computed tomography was 2.95% compared with 0.97% in patients ≤40 years old with appendiceal diameter ≤10 mm. The corresponding risk ratio for that population was 3.03 (95% confidence interval: 1.24–7.42; P = .02). Conclusion The combination of age >40 and an appendiceal diameter >10 mm is associated with a greater than 3-fold increased risk of malignancy in patients presenting with appendicitis.

Background Tranexamic acid (TXA) may be a useful adjunct for military patients with severe traumatic brain injury (TBI). These patients are often treated in austere settings without immediate access to neurosurgical intervention. The purpose of this study was to evaluate any association between TXA use and progression of intracranial hemorrhage (ICH), neurologic outcomes, and venous thromboembolism (VTE) in TBI. Methods This was a retrospective cohort study of military casualties from October 2010 to December 2015 who were transferred to a military treatment facility (MTF) in the United States. Data collected included: demographics, types of injuries, initial and interval head computerized tomography (CT) scans, Glasgow Coma Scores (GCS), and six-month Glasgow Outcome Scores (GOS). Results were stratified based on TXA administration, progression of ICH, and VTE. Results Of the 687 active duty service members reviewed, 71 patients had ICH (10.3%). Most casualties were injured in a blast (80.3%), with 36 patients (50.7%) sustaining a penetrating TBI. Mean ISS was 28.2 ± 12.3. Nine patients (12.7%) received a massive transfusion within 24 h of injury, and TXA was administered to 14 (19.7%) casualties. Patients that received TXA had lower initial reported GCS (9.2 ± 4.4 vs. 12.5 ± 3.4, p = 0.003), similar discharge GCS (13.3 ± 4.0 vs. 13.8 ± 3.2, p = 0.58), and a larger improvement between initial and discharge GCS (3.7 ± 3.9 vs. 1.3 ± 3.1, p = 0.02). However, there was no difference in mortality (7.1% vs. 7.0%, p = 1.00), progression of ICH (45.5% vs. 14.7%, p = 0.09), frequency of cranial decompression (50.0% vs. 42.1%, p = 0.76), or mean GOS (3.5 ± 0.9 vs. 3.8 ± 1.0, p = 0.13). Patients administered TXA had a higher rate of VTE (35.7% vs. 7.0%, p = 0.01). On multivariate analysis, however, TXA was not independently associated with VTE. Conclusions Patients that received TXA were associated with an improvement in GCS but not in progression of ICH or GOS. TXA was not independently associated with VTE, although this may be related to a paucity of patients receiving TXA. Decisions about TXA administration in military casualties with ICH should be considered in the context of the availability of neurosurgical intervention as well as severity of extracranial injuries and need for massive transfusion.

Introduction As combat-related trauma decreases, there remains an increasing need to maintain the ability to care for trauma victims from other casualty events around the world (e.g., terrorism, natural disasters, and infrastructure failures). During these events, military surgeons often work closely with their civilian counterparts, often in austere and expeditionary contexts. In these environments, the primary aim of the surgical team is to implement damage control principles to avert blood loss, optimize oxygenation, and improve survival. Upper-extremity vascular injuries are associated with high rates of morbidity and mortality resulting from exsanguination and ischemic complications; however, fatalities may be avoided if hemorrhage is rapidly controlled. In austere contexts, deployed surgical teams typically include one general surgeon and one orthopedic surgeon, neither of which have acquired the expertise to manage these vascular injuries. The purpose of this study was to examine the baseline capabilities of general surgeons and orthopedic surgeons to surgically expose and control axillary and brachial arteries and to determine if the abilities of both groups could be increased through a focused cadaver-based training intervention. Methods This study received IRB approval at our institution. Study methods included the use of cadavers for baseline assessment of procedural capabilities to expose and control axillary and brachial vessels, followed by 1:1 procedural training and posttraining re-assessment of procedural capabilities. Inferential analyses included ANOVA/MANOVA for within- and between-group effects (P Results Study outcomes demonstrated significant differences between the baseline performance abilities of the two groups, with general surgeons outperforming orthopedic surgeons. Before training, neither group reached performance benchmarks for overall or critical procedural abilities in exposing axillary and brachial vessels. Training led to increased abilities for both groups. There were statistically significant gains for overall procedural abilities, as well as for critical procedural elements that are directly associated with morbidity and mortality. These outcomes were consistent for both general and orthopedic surgeons. Effect sizes ranged between medium (general surgeons) and very large (orthopedic surgeons). Conclusion There was a baseline capability gap for both general surgeons and orthopedic surgeons to surgically expose and control the axillary and brachial vessels. Outcomes from the course suggest that the methodology facilitates the acquisition of accurate and independent vascular procedural capabilities in the management of upper-extremity trauma injuries. The impact of this training for surgeons situated in expeditionary or remote contexts has direct relevance for caring for victims of extremity trauma. These outcomes underscore the need to train all surgeons serving in rural, remote, expeditionary, combat, or global health contexts to be able to competently manage extremity trauma and concurrent vascular injuries to increase the quality of care in those settings.

Tools to assist clinicians in predicting pneumonia could lead to a significant decline in morbidity. Therefore, we sought to develop a model in combat trauma patients for identifying those at highest risk of pneumonia. This was a retrospective study of 73 primarily blast-injured casualties with combat extremity wounds. Binary classification models for pneumonia prediction were developed with measurements of injury severity from the Abbreviated Injury Scale (AIS), transfusion blood products received before arrival at Walter Reed National Military Medical Center (WRNMMC), and serum protein levels. Predictive models were generated with leave-one-out-cross-validation using the variable selection method of backward elimination (BE) and the machine learning algorithms of random forests (RF) and logistic regression (LR). BE was attempted with two predictor sets: (1) all variables and (2) serum proteins alone. Incidence of pneumonia was 12% (n = 9). Different variable sets were produced by BE when considering all variables and just serum proteins alone. BE selected the variables ISS, AIS chest, and cryoprecipitate within the first 24 h following injury for the first predictor set 1 and FGF-basic, IL-2R, and IL-6 for predictor set 2. Using both variable sets, a RF was generated with AUCs of 0.95 and 0.87—both higher than LR algorithms. Advanced modeling allowed for the identification of clinical and biomarker data predictive of pneumonia in a cohort of predominantly blast-injured combat trauma patients. The generalizability of the models developed here will require an external validation dataset.

BACKGROUND Surgical site infections (SSIs) are well-recognized complications after exploratory laparotomy for abdominal trauma; however, little is known about SSI development after exploration for battlefield abdominal trauma. We examined SSI risk factors after exploratory laparotomy among combat casualties. METHODS Military personnel with combat injuries sustained in Iraq and Afghanistan (June 2009 to May 2014) who underwent laparotomy and were evacuated to participating US military hospitals were included. Log-binominal regression was used to identify SSI risk factors. RESULTS Of 4,304 combat casualties, 341 patients underwent a total of 1,053 laparotomies. Abdominal SSIs were diagnosed in 49 patients (14.4%): 8% with organ space SSI, 4% with deep incisional SSI, and 4% with superficial SSIs (4 patients had multiple SSIs). Patients with SSIs had more colorectal (p < 0.001), small bowel (p = 0.010), duodenum (p = 0.006), pancreas (p = 0.032), and abdominal vascular injuries (p = 0.040), as well as prolonged open abdomen (p = 0.004) and more infections diagnosed before the SSI (or final exploratory laparotomy) versus non-SSI patients (p < 0.001). Sustaining colorectal injuries (risk ratio [RR], 3.20; 95% confidence interval [CI], 1.58-6.45), duodenum injuries (RR, 6.71; 95% CI, 1.73-25.58), and being diagnosed with prior infections (RR, 10.34; 95% CI, 5.05-21.10) were independently associated with any SSI development. For either organ space or deep incisional SSIs, non-intra-abdominal infections, fecal diversion, and duodenum injuries were independently associated, while being injured via an improvised explosive device was associated with reduced likelihood compared with penetrating nonblast (e.g., gunshot wounds) injuries. Non-intra-abdominal infections and hypotension were independently associated with organ space SSIs development alone, while sustaining blast injuries were associated with reduced likelihood. CONCLUSION Despite severity of injuries and the battlefield environment, the combat casualty laparotomy SSI rate is relatively low at 14%, with similar risk factors and rates reported following severe civilian trauma. LEVEL OF EVIDENCE Epidemiological, level III.

Background Surgeons in resource-limited environments often provide care outside the expected scope of current general surgery training. Geographically isolated patients may be unwilling or unable to travel for specialty care. These same patients also present with life-threatening emergencies beyond the typical breadth of a general surgeon's practice, in hospitals with limited professional and material support. This review characterizes the unique role of isolated surgeons, so individual surgeons and health care organizations may focus professional development resources more efficiently, with the ultimate goal of improved patient care. Methods We performed a scoping review of the isolated surgeon, reviewing 25 years of literature regarding isolated US civilian and military surgeons. We examined emerging themes regarding the definition of an isolated surgeon, the scope of surgical practice beyond current training norms, and training gaps identified by surgeons in an isolated role. Results From 904 articles identified, we included 91 for final review. No prior definition exists for the isolated surgeon, although multiple definitions describe rural surgeons, patients, or hospitals; we propose an initial definition from consistent themes in the literature. Isolated surgeons across varied practice settings consistently performed relatively large volumes of cases of, and identified training gaps in, orthopedic, obstetric and gynecologic, urologic, and vascular surgery subspecialties. Life-threatening, “rare-but-real” cases in the above and neurosurgical disciplines are uncommon, but consistent across practice settings. Conclusions This review represents the largest examination of the isolated surgeon in the current literature. Clarifying the identity, practice components, and training gaps of the isolated surgeon represent the first step in formalizing support for this small but critical group of surgeons and their patients.

Low-cost iron-based CO2 hydrogenation catalysts have shown promise as a viable route to the production of value-added hydrocarbon building blocks. It is envisioned that these hydrocarbons will be used to augment industrial chemical processes and produce drop-in replacement operational fuel. To this end, the U.S. Naval Research Laboratory (NRL) has been designing, testing, modeling, and evaluating CO2 hydrogenation catalysts in a laboratory-scale fixed-bed environment. To transition from the laboratory to a commercial process, the catalyst viability and performance must be evaluated at scale. The performance of a Macrolite&reg, supported iron-based catalyst in a commercial-scale fixed-bed modular reactor prototype was evaluated under different reactor feed rates and product recycling conditions. CO2 conversion increased from 26% to as high as 69% by recycling a portion of the product stream and CO selectivity was greatly reduced from 45% to 9% in favor of hydrocarbon production. In addition, the catalyst was successfully regenerated for optimum performance. Catalyst characterization by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), along with modeling and kinetic analysis, highlighted the potential challenges and benefits associated with scaling-up catalyst materials and processes for industrial implementation.

BACKGROUND: Tranexamic acid (TXA) may be a useful adjunct for military patients with severe traumatic brain injury (TBI). These patients are often treated in austere settings without immediate access to neurosurgical intervention. The purpose of this study was to evaluate any association between TXA use and progression of intracranial hemorrhage (ICH), neurologic outcomes, and venous thromboembolism (VTE) in TBI.METHODS: This was a retrospective cohort study of combat casualties from October 2010 to December 2015 who were transferred to a military treatment facility (MTF) in the United States. Data collected included: demographics, types of injuries, initial and interval head computerized tomography (CT) scans, Glasgow Coma Scores (GCS), and six-month Glasgow Outcome Scores (GOS). Results were stratified based on TXA administration, progression of ICH, and VTE.RESULTS: Of the 687 active duty service members reviewed, 71 patients had ICH (10.3%). Most casualties were injured in a blast (80.3%), with 36 patients (50.7%) sustaining a penetrating TBI. Mean ISS was 28.2 ± 12.3. Nine patients (12.7%) received a massive transfusion within 24 hours of injury, and TXA was administered to 14 (19.7%) casualties. Patients that received TXA had lower initial reported GCS (9.2 ± 4.4 vs. 12.5 ± 3.4, p=0.003), similar discharge GCS (13.3 ±4.0 vs. 13.8±3.2, p=0.58), and a larger improvement between initial and discharge GCS (3.7±3.9 vs. 1.3±3.1, p=0.02). However, there was no difference in mortality (7.1% vs. 7.0%, p=1.00), progression of ICH (45.5% vs. 14.7%, p=0.09), frequency of cranial decompression (50.0% vs. 42.1%, p=0.76), or mean GOS (3.5±0.9 vs. 3.8±1.0, p=0.13). Patients administered TXA had a higher rate of VTE (35.7% vs. 7.0%, p=0.01). On multivariate analysis, however, TXA was not independently associated with VTE.CONCLUSIONS: Patients that received TXA were associated with an improvement in GCS but not in progression of ICH or GOS. TXA was not independently associated with VTE, although this may be related to a paucity of patients receiving TXA. Decisions about TXA administration in combat casualties with ICH should be considered in the context of the availability of neurosurgical intervention as well as severity of extracranial injuries and need for massive transfusion.

Heterotopic ossification (HO) is defined as ectopic bone formation around joints and in soft tissues following trauma, particularly blast-related extremity injuries, thermal injuries, central nerve injuries, or orthopaedic surgeries, leading to increased pain and diminished quality of life. Current treatment options include pharmacotherapy with non-steroidal anti-inflammatory drugs, radiotherapy, and surgical excision, but these treatments have limited efficacy and have associated complication profiles. In contrast, small molecule inhibitors have been shown to have higher specificity and less systemic cytotoxicity. Previous studies have shown that bone morphogenetic protein (BMP) signaling and downstream non-canonical (SMAD-independent) BMP signaling mediated induction of TGF-β activated kinase-1 (TAK1) contributes to HO. In the current study, small molecule inhibition of TAK1, NG-25, was evaluated for its efficacy in limiting ectopic bone formation following a rat blast-associated lower limb trauma and a murine burn tenotomy injury model. A significant decrease in total HO volume in the rat blast injury model was observed by microCT imaging with no systemic complications following NG-25 therapy. Furthermore, tissue-resident mesenchymal progenitor cells (MPCs) harvested from rats treated with NG-25 demonstrated decreased proliferation, limited osteogenic differentiation capacity, and reduced gene expression of Tac1, Col10a1, Ibsp, Smad3, and Sox2 (P < 0.05). Single cell RNA-sequencing of murine cells harvested from the injury site in a burn tenotomy injury model showed increased expression of these genes in MPCs during stages of chondrogenic differentiation. Additional in vitro cell cultures of murine tissue-resident MPCs and osteochondrogenic progenitors (OCPs) treated with NG-25 demonstrated reduced chondrogenic differentiation by 10.2-fold (P < 0.001) and 133.3-fold (P < 0.001), respectively, as well as associated reduction in chondrogenic gene expression. Induction of HO in Tak1 knockout mice demonstrated a 7.1-fold (P < 0.001) and 2.7-fold reduction (P < 0.001) in chondrogenic differentiation of murine MPCs and OCPs, respectively, with reduced chondrogenic gene expression. Together, our in vivo models and in vitro cell culture studies demonstrate the importance of TAK1 signaling in chondrogenic differentiation and HO formation and suggest that small molecule inhibition of TAK1 is a promising therapy to limit the formation and progression of HO.

The nature of many combat wounds puts patients at a high risk of developing deep venous thrombosis (DVT) and pulmonary embolism (PE), which fall under the broader disease category of venous thromboembolism (VTE). In addition to the hypercoagulable state induced by trauma, massive injuries to the extremities, prolonged immobility, and long fixed wing transport times to higher echelons of care are unique risk factors for venous thromboembolism in the combat-injured patient. These risk factors mandate aggressive prophylaxis for DVT and PE that can effectively be achieved by the use of lower extremity sequential compression devices and low dose unfractionated heparin or low molecular weight heparin. In addition, inferior vena cava filters are often used for PE prophylaxis when chemical DVT prophylaxis fails or is contraindicated. The following Department of Defense (DoD) Joint Trauma System (JTS) Clinical Practice Guideline (CPG) discusses the current recommendations for the prevention of DVT and PE including the use of inferior vena cava filters (IVCFs).

Introduction Chest injuries occur in a significant portion of trauma patients and hemothorax is a common result. While the initial management of traumatic hemothorax is most commonly treated with tube thoracostomy, the management of retained hemothorax is a subject of debate. Recent literature has proposed different methods for treating or preventing retained hemothorax, yet the approach to this pathology is not straightforward. Methods The literature was reviewed for relevant studies regarding the prevention and management of post-traumatic retained hemothorax. What follows is a review of the recent literature and an algorithm for the approach to treating a traumatic retained hemothorax. Results Identifying a traumatic retained hemothorax and preventing subsequent complications such as pneumonia, empyema, and fibrothorax are significant issues faced by surgeons. Studies for preventing retained hemothorax have focused on initial chest tube size, location, and peri-procedural placement conditions, as well as thoracic lavage. Several treatment modalities exist, including second drainage procedure and intra-pleural fibrinolytic drug instillation, but video-assisted thoracoscopic surgery is the most common and successful approach. Regardless of the approach to evacuation, early intervention is paramount. Conclusion Further studies will help characterize appropriate candidates, timing, treatment modalities, and guide therapy for retained hemothorax.

Background Established animal trauma models are limited in recapitulating the pathophysiology of human traumatic injury. Herein, we characterize the physiologic insult and inflammatory response in two clinically relevant non-human primate (NHP) trauma models. Methods Mauritian Cynomolgus Macaques underwent either a laparoscopic closed abdomen liver injury (laparoscopic 60% left-lobe hepatectomy) in an established uncontrolled severe hemorrhage model (THM), or a polytrauma hemorrhage model (PHM) involving combined liver and bowel injury, uncontrolled severe hemorrhage as well as an open full-thickness cutaneous flank wound. Fixed volume resuscitation strategies were employed in the THM and goal directed resuscitation was used in the PHM. Complete peripheral blood and critical clinical chemistry parameters, serum biomarkers of systemic inflammation, tissue perfusion parameters, as well as survival, were compared between the models throughout the 2-week study period. Results NHPs in both the THM (n = 7) and the PHM (n = 21) demonstrated tissue hypoperfusion (peak lactate 6.3 ± 0.71 mmol/L) with end organ injury (peak creatinine 3.08 ± 0.69 mg/dL) from a similar liver injury (60% left hemi-hepatectomy), though the PHM NHPs had a significantly higher blood loss (68.1% ± 12.7% vs. 34.3% ± 2.3%, p = 0.02), lower platelet counts (59 ± 25 vs. 205 ± 46 K/uL, p = 0.03) and a trend towards higher mortality (90.5% vs. 33.3%, p = 0.09). The inflammatory response was robust in both models with peak cytokine (IL-6 > 6000-fold above baseline) and peak leukocyte values (WBC 27 K/uL) typically occurring around t = 240 min from the time of hepatic injury. A more robust systemic inflammatory response was appreciated in the PHM resulting in marked elevations in peak serum IL-6 (7887 ± 2521 pg/mL vs.1076 ± 4833 pg/mL, p = 0.02), IL-1ra (34,499 ± 5987 pg/mL vs. 2511 ± 1228 pg/mL, p

The remote military installation at Diego Garcia is used as an economic and strategic example of the many possible future naval or commercial sites and scenarios that could be utilized for the production of sustainable low carbon fuel from non-fossil electrical energy. In addition to photovoltaic (PV) and wind electrical sources, this analysis includes light water reactors (LWRs) on mobile platforms as the main electrical energy source. Using published capital cost estimates and a range of solar and wind renewable electrical energy scenarios, costs ranging between $6.40 and $12.57 per gallon of standard fuel are estimated for a 129,000 gallons/day fuel process. The cost estimate for a floating nuclear electrical scenario is between $4.66 and $9.47 per gallon. Larger area potential sites of strategic naval and/or commercial importance such as Guam and Djibouti provide additional operational scenarios. Most importantly these military examples provide a framework for how such a process could be used commercially to supply stored energy as a sustainable fuel source for remote countries poor in fossil fuel resources. This information may also be used by policy analysts to support alternative energy implementation strategies and greatly expand the naval and commercial role in nuclear and renewable energy aimed at sustainable production of low carbon fuel.

Objectives: In combat casualty care, tranexamic acid (TXA) is administered as part of initial resuscitation effort; however, conflicting data exist as to whether TXA contributes to increased risk of venous thromboembolism (VTE). The purpose of this study is to determine what factors increase risk of pulmonary embolism after combat-related orthopaedic trauma and whether administration of TXA is an independent risk factor for major thromboembolic events. Setting: United States Military Trauma Centers. Patients: Combat casualties with orthopaedic injuries treated at any US military trauma center for traumatic injuries sustained from January 2011 through December 2015. In total, 493 patients were identified. Intervention: None. Main Outcome Measures: Occurrence of major thromboembolic events, defined as segmental or greater pulmonary embolism or thromboembolism-associated pulseless electrical activity. Results: Regression analysis revealed TXA administration, traumatic amputation, acute kidney failure, and hypertension to be associated with the development of a major thromboembolic event for all models. Injury characteristics independently associated with risk of major VTE were Injury Severity Score 23 or greater, traumatic amputation, and vertebral fracture. The best performing model utilized had an area under curve = 0.84, a sensitivity=0.72, and a specificity=0.84. Conclusions: TXA is an independent risk factor for major VTE after combat-related Orthopaedic injury. Injury factors including severe trauma, major extremity amputation, and vertebral fracture should prompt suspicion for increased risk of major thromboembolic events and increased threshold for TXA use if no major hemorrhage is present. Level of evidence: III, Prognostic Study

Background Abdominal injuries historically account for 13% of battlefield surgical procedures. We examined the occurrence of exploratory laparotomies and subsequent abdominal surgical site infections (SSIs) among combat casualties. Methods Military personnel injured during deployment (2009-2014) were included if they required a laparotomy for combat-related trauma and were evacuated to Landstuhl Regional Medical Center, Germany, before being transferred to participating US military hospitals. Results Of 4304 combat casualties, 341 (7.9%) underwent laparotomy. Including re-explorations, 1053 laparotomies (median, 2; interquartile range, 1-3; range, 1-28) were performed with 58% occurring within the combat zone. Forty-nine (14.4%) patients had abdominal SSIs (four with multiple SSIs): 27 (7.9%) with deep space SSIs, 14 (4.1%) with a deep incisional SSI, and 12 (3.5%) a superficial incisional SSI. Patients with abdominal SSIs had larger volume of blood transfusions (median, 24 versus 14 units), more laparotomies (median, 4 versus 2), and more hollow viscus injuries (74% versus 45%) than patients without abdominal SSIs. Abdominal closure occurred after 10 d for 12% of the patients with SSI versus 2% of patients without SSI. Mesh adjuncts were used to achieve fascial closure in 20.4% and 2.1% of patients with and without SSI, respectively. Survival was 98% and 96% in patients with and without SSIs, respectively. Conclusions Less than 10% of combat casualties in the modern era required abdominal exploration and most were severely injured with hollow viscus injuries and required massive transfusions. Despite the extensive contamination from battlefield injuries, the SSI proportion is consistent with civilian rates and survival was high.

For blunt trauma patients who have failed the NEXUS (National Emergency X-Radiography Utilization Study) low-risk criteria, the adequacy of computed tomography (CT) as the definitive imaging modality for clearance remains controversial. The purpose of this study was to prospectively evaluate the accuracy of CT for the detection of clinically significant cervical spine (C-spine) injury.This was a prospective multicenter observational study (September 2013 to March 2015) at 18 North American trauma centers. All adult (≥18 years old) blunt trauma patients underwent a structured clinical examination. NEXUS failures underwent a CT of the C-spine with clinical follow-up to discharge. The primary outcome measure was sensitivity and specificity of CT for clinically significant injuries requiring surgical stabilization, halo, or cervical-thoracic orthotic placement using the criterion standard of final diagnosis at the time of discharge, incorporating all imaging and operative findings.Ten thousand seven hundred sixty-five patients met inclusion criteria, 489 (4.5%) were excluded (previous spinal instrumentation or outside hospital transfer); 10,276 patients (4,660 [45.3%] unevaluable/distracting injuries, 5,040 [49.0%] midline C-spine tenderness, 576 [5.6%] neurologic symptoms) were prospectively enrolled: mean age, 48.1 years (range, 18-110 years); systolic blood pressure 138 (SD, 26) mm Hg; median, Glasgow Coma Scale score, 15 (IQR, 14-15); Injury Severity Score, 9 (IQR, 4-16). Overall, 198 (1.9%) had a clinically significant C-spine injury requiring surgery (153 [1.5%]) or halo (25 [0.2%]) or cervical-thoracic orthotic placement (20 [0.2%]). The sensitivity and specificity for clinically significant injury were 98.5% and 91.0% with a negative predictive value of 99.97%. There were three (0.03%) false-negative CT scans that missed a clinically significant injury, all had a focal neurologic abnormality on their index clinical examination consistent with central cord syndrome, and two of three scans showed severe degenerative disease.For patients requiring acute imaging for their C-spine after blunt trauma, CT was effective for ruling out clinically significant injury with a sensitivity of 98.5%. For patients with an abnormal neurologic examination as the trigger for imaging, there is a small but clinically significant incidence of a missed injury, and further imaging with magnetic resonance imaging is warranted.Diagnostic tests, level II.

Introduction Trauma, hemorrhage, and peritonitis have widely varying impacts on endocrine response in the injured patient. We sought to examine cortisol response in established non-human primate models of traumatic hemorrhage and intra-abdominal contamination. Methods Cynomologus Macaques were separated into two experimental groups, the polytrauma and hemorrhage model, involving a laparoscopic liver resection with uncontrolled hemorrhage, cecal perforation, and soft tissue excision; and the traumatic hemorrhage model, involving only liver resection and uncontrolled hemorrhage. Cortisol levels were measured pre-operatively, at the time of injury, and at regular intervals until post-operative day 1. Results Cortisol levels increased 600% from the pre-operative value in the polytrauma and hemorrhage model, with minimal changes (20%) in the hemorrhage only model. Conclusion Cortisol levels increase dramatically in response to polytrauma and intra-abdominal contamination as compared to hemorrhage only. The lack of response in the hemorrhage only group may be due to relative adrenal insufficiency caused by the shock state or lack of enticing stimuli from fecal peritonitis.

Introduction Endocrine dysregulation's role in heterotopic ossification (HO) remains unexplored. We sought to examine corticosterone and testosterone in established rat models of ectopic bone formation, and correlate to HO formation with CT analysis. Methods Fifteen rats were placed into three groups of traumatic injury patterns: Blast and injury (120 kPa blast, femoral fracture and quadriceps crush), injury only, and blast only. Serum corticosterone and testosterone levels were drawn until post-operative day 40. HO was analyzed using CT. Results Corticosterone levels peaked in the blast and injury group in the shortest time post injury, followed by injury only and blast only groups. Testosterone levels reached nadir in similar fashion. Volume of HO was highest in the blast and injury group, followed by the injury only group. Conclusion Corticosterone and testosterone's contribution to HO formation requires further characterization, but this study suggests that high peaks in corticosterone and a low nadir in testosterone are associated with higher volumes of HO.

Objective. Ischemia-reperfusion injury (IRI) produces systemic inflammation with the potential for causing organ failure in tissues peripheral to the initial site of injury. We speculate that treatment strategies that dampen inflammation may be therapeutically beneficial to either the initial site of injury or peripheral organs. To test this, we evaluated the impact of FTY720-induced sequestration of circulating mature lymphocytes on renal IRI and secondary organ injury. Methods. A microvascular clamp was surgically placed around the left renal pedicle of anesthetized male Sprague-Dawley rats with either vehicle or FTY720 treatment (0.3 mg/kg) intravenously injected after 15 min of ischemia. Blood flow was restored after 60 min. Cohorts of anesthetized rats were euthanized at 6, 24, or 72 hrs with tissue samples collected for analysis. Results. FTY720 treatment resulted in profound T lymphocyte reduction in peripheral blood. Histopathologic examination, clinical chemistries, and gene transcript expression measurements revealed that FTY720 treatment reduced hepatocellular degeneration, reduced serum markers of liver injury (ALT/AST), and reduced the expression of gene targets associated with IRI. Conclusion. These findings support an anti-inflammatory effect of FTY720 in the liver where the expression of genes associated with apoptosis, chemotaxis, and the AP-1 transcription factor was reduced. Findings presented here provide the basis for future studies evaluating FTY720 as a potential therapeutic agent to treat complications resulting from renal IRI.

In the original article, the units indicated on the y-axes of Fig. 3 are incorrectly labelled. The correct label is pg/mL. Following is the corrected Fig. 3.

Background The Joint Trauma System has demonstrated improved outcomes through coordinated research and process improvement programs. With fewer combat trauma patients, our military American College of Surgeons level 2 trauma center’s ability to maintain a strong trauma Process Improvement (PI) program has become difficult. As emergency general surgery (EGS) patients are similar to trauma patients, our Trauma and Acute Care Surgery (TACS) service developed an EGS PI program analogous to what is done in trauma. We describe the implementation of our novel EGS PI program and its effect on institutional PI proficiency. Methods An EGS registry was developed in 2013. Inclusion criteria were based on AAST published literature. In 2015, EGS registrar and PI coordinator positions were developed and filled with existing trauma staff. A formal EGS PI program began January 1, 2016. Pre- and post-program data was compared to determine the effect including EGS PI events had on increasing yield into our trauma PI program. Results In 2016, TACS saw 1001 EGS consults. Four hundred forty-four met criteria for registry inclusion. Eighty-two patients had 131 PI events; re-admission within 30 days, unplanned therapeutic intervention, and unplanned ICU admission were the most common events. Capture of EGS PI events yielded a 49% increase compared with 2015. Conclusion Overall patient volume and PI events post EGS PI program initiation exceeded those prior to implementation. These data suggest that extending trauma PI principles to EGS may be beneficial in maintaining inter-war military and/or lower volume trauma center readiness.

Beyond its anti-fibrinolytic mechanism, tranexamic acid has been suggested to have anti-inflammatory properties which may contribute to the survival benefit it provides to trauma patients. The objective of this study was to assess possible immunomodulatory effects of tranexamic acid as well as potential amelioration of end-organ injury in a rodent hemorrhagic shock model. Controlled hemorrhagic shock was induced in adult Sprague Dawley rats to a mean arterial pressure of 30 mmHg. Groups of 10 rats were administered intravenous tranexamic acid (300mg/kg) or vehicle control (normal saline) intravenously 15 minutes after the induction of shock. After 60 minutes of hemorrhagic shock, resuscitation was started. Animals were euthanized at six, 24, or 72 hours from the start of shock. Serum laboratory values to include inflammatory biomarkers were measured, and end organ histology was evaluated. Tranexamic acid treatment was associated with a significant decrease in serum IL-1β at six and 24 hours and IL-10 at 24 hours from start of shock compared to vehicle control. Histologic analysis demonstrated mild decreases in both perivascular pulmonary edema and follicular mesenteric lymph node hyperplasia in the tranexamic acid treatment group but also increased myocardial lymphocytic infiltration with necrosis and degeneration. Tranexamic acid was also associated with a small but significant increase in peripheral neutrophil count as well as a significant decrease in neutrophil aggregation in pulmonary tissue at six hours post-injury. These data thus demonstrate a mixed effect of tranexamic acid. While there was an improvement in pulmonary edema and a suppressive effect on several key inflammatory mediators, there was also increased myocardial degeneration and necrosis, which is possibly related to the pro-thrombotic effect of tranexamic acid.

Acute ischemia-reperfusion injury (IRI) of the extremities leads to local and systemic inflammatory changes which can hinder limb function and can be life threatening. This study examined whether the administration of the T-cell sequestration agent, FTY720, following hind limb tourniquet-induced skeletal muscle IRI in a rat model would attenuate systemic inflammation and multiple end organ injury. Sprague-Dawley rats were subjected to 1 hr of ischemia via application of a rubber band tourniquet. Animals were randomized to receive an intravenous bolus of either vehicle control or FTY720 15 min after band placement. Rats (n=10/time point) were euthanized at 6, 24, and 72 hr post-IRI. Peripheral blood as well as lung, liver, kidney, and ischemic muscle tissue was analyzed and compared between groups. FTY720 treatment markedly decreased the number of peripheral blood T cells (p<0.05) resulting in a decreased systemic inflammatory response and lower serum creatinine levels and had a modest but significant effect in decreasing the transcription of injury-associated target genes in multiple end organs. These findings suggest that early intervention with FTY720 may benefit the treatment of IRI of the limb. Further preclinical studies are necessary to characterize the short-term and long-term beneficial effects of FTY720 following tourniquet-induced IRI.

Background Multi-organ failure (MOF) following trauma remains a significant cause of morbidity and mortality related to a poorly understood abnormal inflammatory response. We characterized the inflammatory response in a non-human primate soft tissue injury and closed abdomen hemorrhage and sepsis model developed to assess realistic injury patterns and induce MOF. Methods Adult male Mauritan Cynomolgus Macaques underwent laparoscopy to create a cecal perforation and non-anatomic liver resection along with a full-thickness flank soft tissue injury. Treatment consisted of a pre-hospital phase followed by a hospital phase after 120 minutes. Blood counts, chemistries, and cytokines/chemokines were measured throughout the study. Lung tissue inflammation/apoptosis was confirmed by mRNA quantitative real-time PCR (qPCR), H&E, myeloperoxidase (MPO) and TUNEL staining was performed comparing age-matched uninjured controls to experimental animals. Results Twenty-one animals underwent the protocol. Mean percent hepatectomy was 64.4 ± 5.6; percent blood loss was 69.0 ± 12.1. Clinical evidence of end-organ damage was reflected by a significant elevation in creatinine (1.1 ± 0.03 vs. 1.9 ± 0.4, p=0.026). Significant increases in systemic levels of IL-10, IL-1ra, IL-6, G-CSF, and MCP-1 occurred (11-2986-fold) by 240 minutes. Excessive pulmonary inflammation was evidenced by alveolar edema, congestion, and wall thickening (H&E staining). Concordantly, amplified accumulation of MPO leukocytes and significant pulmonary inflammation and pneumocyte apoptosis (TUNEL) was confirmed using qRT-PCR. Conclusion We created a clinically relevant large animal multi-trauma model using laparoscopy that resulted in a significant systemic inflammatory response and MOF. With this model, we anticipate studying systemic inflammation and testing innovative therapeutic options.

Importance Since publication of the CRASH-2 and MATTERs studies, the US military has included tranexamic acid (TXA) in clinical practice guidelines. While TXA was shown to decrease mortality in trauma patients requiring massive transfusion, improper administration and increased risk of venous thromboembolism remain a concern. Objective To determine the appropriateness of TXA administration by US military medical personnel based on current Joint Trauma System clinical practice guidelines and to determine if TXA administration is associated with venous thromboembolism. Design, Setting, and Participants This cohort study of US military casualties in US military combat support hospitals in Afghanistan and a single US-based tertiary military treatment facility within the continental United States was conducted from 2011 to 2015, with follow-up through initial hospitalization and readmissions. Exposures Data collected for all patients included demographic information as well as Injury Severity Score; receipt of blood products, TXA, and/or a massive transfusion; and admission hemodynamics. Main Outcomes and Measures Variance from guidelines in TXA administration and venous thromboembolism. Tranexamic acid overuse was defined as a hemodynamically stable patient receiving TXA but not a massive transfusion, underuse was defined as a patient receiving a massive transfusion but not TXA, and TXA administration was considered delayed when given more than 3 hours after injury. Results Of the 455 identified patients, 443 (97.4%) were male, and the mean (SD) age was 25.3 (4.8) years. A total of 173 patients (38.0%) received a massive transfusion, and 139 (30.5%) received TXA in theater. Overuse occurred in 18 of 282 patients (6.4%) and underuse in 46 of 173 (26.6%) receiving massive transfusions, and delayed administration was found in 6 of 145 patients (4.3%) receiving TXA. Overuse increased at 3.3% per quarter (95% CI, 4.0-9.9; P R 2 = 0.340) and underuse decreased at −4.4% per quarter (95% CI, −4.5 to −3.6; P R 2 = 0.410). Tranexamic acid administration was an independent risk factor for venous thromboembolism (odds ratio, 2.58; 95% CI, 1.20-5.56; P = .02). Conclusions and Relevance Military medical personnel decreased missed opportunities to appropriately use TXA but also increased overuse. In addition, TXA administration was an independent risk factor for venous thromboembolism. A reevaluation of the use of TXA in combat casualties should be undertaken.

Iron-based CO2 catalysts have shown promise as a viable route to the production of olefins from CO2 and H2 gas. However, these catalysts can suffer from low conversion and high methane selectivity, as well as being particularly vulnerable to water produced during the reaction. In an effort to improve both the activity and durability of iron-based catalysts on an alumina support, copper (10–30%) has been added to the catalyst matrix. In this paper, the effects of copper addition on the catalyst activity and morphology are examined. The addition of 10% copper significantly increases the CO2 conversion, and decreases methane and carbon monoxide selectivity, without significantly altering the crystallinity and structure of the catalyst itself. The FeCu/K catalysts form an inverse spinel crystal phase that is independent of copper content and a metallic phase that increases in abundance with copper loading (>10% Cu). At higher loadings, copper separates from the iron oxide phase and produces metallic copper as shown by SEM-EDS. An addition of copper appears to increase the rate of the Fischer–Tropsch reaction step, as shown by modeling of the chemical kinetics and the inter- and intra-particle transport of mass and energy.

Iron-based CO2 catalysts have shown promise as a viable route to the production of olefins from CO2 and H2 gas. However, these catalysts can suffer from low conversion and high methane selectivity, as well as being particularly vulnerable to water produced during the reaction. In an effort to improve both the activity and durability of iron-based catalysts on an alumina support, copper (10–30%) has been added to the catalyst matrix. In this paper, the effects of copper addition on the catalyst activity and morphology are examined. The addition of 10% copper significantly increases the CO2 conversion, and decreases methane and carbon monoxide selectivity, without significantly altering the crystallinity and structure of the catalyst itself. The FeCu/K catalysts form an inverse spinel crystal phase that is independent of copper content and a metallic phase that increases in abundance with copper loading (>10% Cu). At higher loadings, copper separates from the iron oxide phase and produces metallic copper as shown by SEM-EDS. An addition of copper appears to increase the rate of the Fischer–Tropsch reaction step, as shown by modeling of the chemical kinetics and the inter- and intra-particle transport of mass and energy.

Trauma remains an enormous burden on the American medical system. While patients of all ages sustain severe trauma, it remains the most common cause of death in young adults. Exsanguination from uncontrolled hemorrhage is the leading cause of preventable death among the traumatically injured. The lethal triad of trauma is a culmination of coagulopathy, acidosis, and hypothermia that can rapidly deteriorate and lead to a patient’s demise if not treated accordingly. The goal of trauma resuscitation is to prevent or halt this triad while minimizing iatrogenic injury. The provider has many options available in his armamentarium for resuscitation, but each carries its own risks and benefits. Over the past two decades, trauma research has given us a better understanding of and improved management strategies for this triad. This chapter will explore the various resuscitative options available and summarize the most recent literature regarding their use.

BackgroundA key component of a process improvement program is the institution of hospital-specific protocols to address certain disparities and streamline patient care. In that regard, we evaluated the implementation of an outpatient laparoscopic appendectomy (OLA) protocol at a tertiary military hospital. We hypothesized that OLA would reduce length of stay (LOS) without increasing complications.MethodsIn August 2016, our institution implemented an OLA protocol—defined as discharge within 24 hours of surgery. Exclusion criteria included age ResultsIn 2017, the first full year of protocol implementation, 44 of 59 (75%) patients met the inclusion criteria, and all but 2 (42 of 44, 95%) stayed for less than 24 hours. Of the two outliers, one developed acute on chronic kidney disease and one had a slow return of bowel function following grade 3 appendicitis. Complications were low across all years (one per year). In 2017, the readmission was for percutaneous drainage of an abscess. Overall, protocol implementation produced a significant decrease in LOS.DiscussionOLA protocol decreased LOS at a military hospital and should be expanded to other department of defense (DoD) facilities. Further research is needed to identify cost benefit to the military health system.Level of evidenceIII.

Background After adequate operative debridement and antimicrobial therapies, combat-related extremity wounds that either heal or fail are both associated with a distinct inflammatory response. Short-term use of nonsteroidal anti-inflammatory drugs in postoperative pain management may affect this response and, by consequence, the healing potential of these wounds. We investigated whether patients treated with nonsteroidal anti-inflammatory drugs had a distinct inflammatory response; different rates of critical colonization, defined as >105 colony forming units on quantitative bacteriology; and healing potential. Methods We retrospectively reviewed the records of 73 patients with combat-related extremity wounds. Patients were separated into 2 groups: those who received nonsteroidal anti-inflammatory drugs during the debridement period (nonsteroidal anti-inflammatory drugs group, N = 17) and those who did not (control group; N = 56). Serum and wound tissue samples collected during each operative debridement were measured for 32 known cytokines and tested for quantitative bacteriology, respectively. We compared cytokine concentrations between groups and then designed a logistic regression model to identify variables associated with successful wound healing, while controlling for known confounders. Results Despite similar demographics and wound characteristics, the nonsteroidal anti-inflammatory drugs group had significant lesser concentrations of inflammatory cytokines, interleukin-2, interleukin-6, interleukin-8, and monocyte chemoattractant protein-1. On multivariate analysis, nonsteroidal anti-inflammatory drug treatment emerged as a predictor of successful wound healing after controlling for known confounders such as wound size, tobacco use, Acute Physiology and Chronic Health Evaluation II score, and critical colonization. Conclusion Treatment with nonsteroidal anti-inflammatory drugs for postoperative pain management after major combat-related extremity trauma is associated with lesser concentrations of inflammatory cytokines and may contribute to a more favorable inflammatory response leading to successful wound healing.

Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A, and PDCD4 knockout mice have a high penetrance for B-cell lymphomas. Here, we show that on B-cell receptor (BCR)-mediated p70s6K activation, PDCD4 is degraded, and eIF4A activity is greatly enhanced. We identified a subset of genes involved in BCR signaling, including CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives. Expression of these known oncogenic proteins is enhanced on BCR activation and is attenuated by the eIF4A inhibitor Silvestrol. Antigen-experienced immunoglobulin (Ig)G(+) splenic B cells, from which most DLBCLs are derived, have higher levels of eIF4A cap-binding activity and protein translation than IgM(+) B cells. Our results suggest that eIF4A-mediated enhancement of oncogene translation may be a critical component for lymphoma progression, and specific targeting of eIF4A may be an attractive therapeutic approach in the management of human B-cell lymphomas.