Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients.

OBJECTIVE: The aim of this study was to evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. BACKGROUND: Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. METHODS: A retrospective analysis of prospective cohort including 8 trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18 to 90 years old with injury severity scores ≥9 transported from the scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and early mortality. RESULTS: A total of 33,511 were included with a median EMS agency volume of 374 patients annually (interquartile range: 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (adjusted odds ratio=0.95; 95% CI: 0.92-0.99, P =0.03) and 3% decreased odds of 24-hour mortality (adjusted odds ratio=0.97; 95% CI: 0.95-0.99, P =0.04). Prespecified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% vs 4.8%, P <0.01). CONCLUSIONS: A higher volume of trauma patients transported at the EMS agency level is associated with improved early mortality. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.

Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database.

BACKGROUND: Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours. METHODS: Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident. RESULTS: During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality. CONCLUSIONS: The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Plasma resuscitation improves and restores intestinal microcirculatory physiology following haemorrhagic shock.

BACKGROUND AND OBJECTIVES: Intestinal ischaemia-reperfusion injury following resuscitated haemorrhagic shock (HS) leads to endothelial and microcirculatory dysfunction and intestinal barrier breakdown. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell dysfunction, resulting in further ischaemia and organ injury. Resuscitation with fresh frozen plasma (FFP) improves blood flow, stabilizes the endothelial glycocalyx and alleviates organ injury. We postulate these improvements correlate with decreased tissue CO2 concentrations, improved microvascular oxygenation and attenuation of intestinal microvascular endothelial dysfunction. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to groups (n = 8/group): (1) sham, (2) HS (40% mean arterial blood pressure [MAP], 60 min) + crystalloid resuscitation (CR) (shed blood saline) and (3) HS + FFP (shed blood + FFP). MAP, heart rate (HR), ileal perfusion, pO2 and pCO2 were measured at intervals until 4 h post-resuscitation (post-RES). At 4 h post-RES, the ileum was rinsed in situ with Krebs solution. Topical acetylcholine and then nitroprusside were applied for 10 min each. Serum was obtained, and after euthanasia, tissues were harvested and snap-frozen in liquid N2 and stored at -80°C. RESULTS: FFP resuscitation resulted in sustained ileal perfusion as well as rapid sustained return to baseline microvascular pO2 and pCO2 values when compared to CR (p < 0.05). Endothelial function was preserved relative to sham in the FFP group but not in the CR group (p < 0.05). CONCLUSION: FFP-based resuscitation improves intestinal perfusion immediately following resuscitation, which correlates with improved tissue oxygenation and decreased tissue CO2 levels. CR resulted in significant damage to endothelial vasodilation response to acetylcholine, while FFP preserved this function.

The Geography of Injuries in Trauma Systems: Using Home as a Proxy for Incident Location.

INTRODUCTION: Effective trauma system organization is crucial to timely access to care and requires accurate understanding of injury and resource locations. Many systems rely on home zip codes to evaluate geographic distribution of injury; however, few studies have evaluated the reliability of home as a proxy for incident location after injury. METHODS: We analyzed data from a multicenter prospective cohort collected from 2017 to 2021. Injured patients with both home and incident zip codes were included. Outcomes included discordance and differential distance between home and incident zip code. Associations of discordance with patient characteristics were determined by logistic regression. We also assessed trauma center catchment areas based on home versus incident zip codes and variation regionally at each center. RESULTS: Fifty thousand one hundred seventy-five patients were included in the analysis. Home and incident zip codes were discordant in 21,635 patients (43.1%). Injuries related to motor vehicles (aOR: 4.76 [95% CI 4.50-5.04]) and younger adults 16-64 (aOR: 2.46 [95% CI 2.28-2.65]) were most likely to be discordant. Additionally, as injury severity score increased, discordance increased. Trauma center catchment area differed up to two-thirds of zip codes when using home versus incident location. Discordance rate, discordant distance, and catchment area overlap between home and incident zip codes all varied significantly by geographic region. CONCLUSIONS: Home location as proxy for injury location should be used with caution and may impact trauma system planning and policy, especially in certain populations. More accurate geolocation data are warranted to further optimize trauma system design.

High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

OBJECTIVES: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. METHODS: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. RESULTS: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). CONCLUSIONS: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.

Prehospital Blood Product and Crystalloid Resuscitation in the Severely Injured Patient: A Secondary Analysis of the Prehospital Air Medical Plasma Trial.

OBJECTIVE: The aim of this study was to determine whether prehospital blood products reduce 30-day mortality in patients at risk for hemorrhagic shock compared with crystalloid only resuscitation. SUMMARY OF BACKGROUND DATA: Hemorrhage is the primary cause of preventable death after injury. Large volume crystalloid resuscitation can be deleterious. The benefits of prehospital packed red blood cells (PRBCs), plasma, or transfusion of both products among trauma patients is unknown compared with crystalloid. METHODS: Secondary analysis of the multicenter PAMPer trial was performed on hypotensive injured patients from the scene. The trial randomized 27 helicopter bases to prehospital plasma or standard resuscitation. Standard resuscitation at the sites was equally divided between crystalloid and crystalloid + PRBC. This led to 4 prehospital resuscitation groups: crystalloid only; PRBC; plasma; and PRBC+plasma. Cox regression determined the association between resuscitation groups and risk-adjusted 30-day mortality. The dose effect of resuscitation fluids was also explored. RESULTS: Four hundred seven patients were included. PRBC+plasma had the greatest benefit [hazard ratio (HR) 0.38; 95% confidence interval (95% CI) 0.26-0.55, P < 0.001], followed by plasma (HR 0.57; 95% CI 0.36-0.91, P = 0.017) and PRBC (HR 0.68; 95% CI 0.49-0.95, P = 0.025) versus crystalloid only. Mortality was lower per-unit of PRBC (HR 0.69; 95% CI 0.52-0.92, p = 0.009) and plasma (HR 0.68; 95% CI 0.54-0.88, P = 0.003). Crystalloid volume was associated with increased mortality among patients receiving blood products (HR 1.65; 95% CI 1.17-2.32, P = 0.004). CONCLUSION: Patients receiving prehospital PRBC+plasma had the greatest mortality benefit. Crystalloid only had the worst survival. Patients with hemorrhagic shock should receive prehospital blood products when available, preferably PRBC+plasma. Prehospital whole blood may be ideal in this population.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock.

BACKGROUND: After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting. METHODS: To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days. RESULTS: A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions. CONCLUSIONS: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427 .).

MicroRNA-203 suppresses proliferation in liver cancer associated with PIK3CA, p38 MAPK, c-Jun, and GSK3 signaling.

Primary liver cancer (hepatocellular carcinoma, HCC) is a leading cause of cancer-related deaths, and alternative ways to treat this disease are urgently needed. In recent years, novel approaches to cancer treatment have been based on microRNAs, small non-coding RNA molecules that play a crucial role in cancer progression by regulating gene expression. Overexpression of some microRNAs has shown therapeutic potential, but whether or not this was the case for microRNA-203 (miR-203) in liver cancer was unknown. Therefore, the aim of this study was to investigate the effect of miR-203 overexpression in liver cancer and explore the related mechanisms. Liver cancer cells from the HepG2 and Hep3B cell lines were transfected with either miR-203 mimics or negative control RNA, and then the cells were subjected to cell viability, cell proliferation, and Western blotting assays. As a result of microRNA-203 overexpression, HepG2 and Hep3B cell viability and cell proliferation significantly declined. Furthermore, microRNA-203 overexpression led to inhibited expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)/protein kinase B (Akt), c-Jun, and p38 mitogen-activated protein kinases (p38 MAPK), and restored glycogen synthase kinase 3 (GSK 3) activity in HepG2 cells. Our results suggest that c-Jun, p38 MAPK, PIK3CA/Akt, and GSK3 signaling involved in the effect of miR-203 on the proliferation of HCC cells.

Cell-specific regulation of iNOS by AMP-activated protein kinase in primary rat hepatocytes.

BACKGROUND: AMP-activated protein kinase (AMPK) regulates several metabolic pathways in hepatocytes that are critical to the hepatic response to sepsis and shock. Induction of nitric oxide synthesis is an important response to sepsis, inflammation and shock and many of the stimuli that upregulate inducible nitric oxide synthase (iNOS) also activate AMPK. AMPK inhibits nitric oxide (NO) production in skeletal and cardiac muscle cells, but the role of AMPK in regulating iNOS expression in hepatocytes has not been determined. MATERIALS AND METHODS: Primary cultured rat hepatocytes were preincubated with an AMPK inhibitor, AMPK activators, or transfected with AMPK siRNA before being treated with the proinflammatory cytokines interleukin-1ß (IL-1ß) and interferon-γ (IFNγ). The hepatocyte cell lysate and culture supernatants were collected for Western blot analysis and Griess assay. RESULTS: IL-1ß and IFNγ markedly upregulated iNOS expression and AMPK phosphorylation. IL-1ß + IFNγ-induced NO production and iNOS expression were significantly decreased in hepatocytes treated with the AMPK inhibitor compound C and AMPK knockdown by AMPK siRNA. Cytokine-induced iNOS expression was increased by AMPK activators 1-oxo-2-(2H-pyrrolium-1-yl)-1H-inden-3-olate, AMPK signaling activator III and AICA-riboside. Compound C upregulated Akt and c-Jun N-terminal kinase phosphorylation but decreased IκBα phosphorylation. AICA-riboside exerted opposite effects on these signaling pathways in hepatocytes. CONCLUSIONS: In contrast to other cell types, AMPK increased IL-1ß + IFNγ-induced NO production and iNOS expression through the Akt, c-Jun N-terminal kinase, and NF-κΒ signaling pathways in primary hepatocytes. These data suggest that AMPK-altering medications used clinically may have subsequent effects on iNOS expression and proinflammatory signaling pathways.

Glycogen synthase kinase 3 regulates IL-1ß mediated iNOS expression in hepatocytes by down-regulating c-Jun.

Excessive nitric oxide from the inducible nitric oxide synthase (iNOS) increases shock-induced hepatic injury, hepatic dysfunction, inflammation, and mortality in animal models. Cytokines increase the expression of iNOS in hepatocytes, but the signaling mechanisms involved are not completely understood. We have previously demonstrated that Akt mediates the inhibitory effect of cAMP and insulin on cytokine-induced hepatocyte iNOS expression. We hypothesized that glycogen synthase kinase 3 (GSK3), a target of Akt phosphorylation, would regulate hepatocyte iNOS expression. In cultured rat hepatocytes, GSK3 inhibitors decreased IL-1ß mediated nitric oxide (NO) production and iNOS protein expression, while the phosphatidylinositol 3-kinase (PI3K)/Akt pathway inhibitor LY294002 increased the cytokine-mediated NO production and iNOS expression. Over-expression of the constitutively active form of GSK3ß enhanced IL-1ß-mediated iNOS expression. GSK3 catalyzes the phosphorylation of c-Jun at the c-terminal Thr239 that facilitates c-Jun degradation. Inhibition of GSK3 with SB216763 and lithium chloride significantly reduced, whereas blocking PI3K/Akt increased phosphorylation of c-Jun at Thr239. The levels of total-c-Jun and c-Jun phosphorylated at Ser63 inversely correlated with c-Jun phosphorylated at Thr239, GSK3 activation and iNOS expression. Over-expression of a dominant negative c-Jun not only caused an increase in IL-1ß-mediated iNOS promoter activity and iNOS protein expression but was also able to reverse the SB216763-mediated suppression of iNOS. These results demonstrate that GSK3, a downstream target of Akt, regulates IL-1ß-stimulated iNOS expression in hepatocytes by directly phosphorylating c-Jun in an inhibitory manner.

Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

BACKGROUND: Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. MATERIALS AND METHODS: Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. RESULTS: The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. CONCLUSIONS: These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines.

Taking the Blood Bank to the Field: The Design and Rationale of the Prehospital Air Medical Plasma (PAMPer) Trial.

Hemorrhage and trauma induced coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. Interest in the use of prehospital plasma in hemorrhaging patients as a primary resuscitation agent has grown recently. Trauma center-based damage control resuscitation using early and aggressive plasma transfusion has consistently demonstrated improved outcomes in hemorrhaging patients. Additionally, plasma has been shown to have several favorable immunomodulatory effects. Preliminary evidence with prehospital plasma transfusion has demonstrated feasibility and improved short-term outcomes. Applying state-of-the-art resuscitation strategies to the civilian prehospital arena is compelling. We describe here the rationale, design, and challenges of the Prehospital Air Medical Plasma (PAMPer) trial. The primary objective is to determine the effect of prehospital plasma transfusion during air medical transport on 30-day mortality in patients at risk for traumatic hemorrhage. This study is a multicenter cluster randomized clinical trial. The trial will enroll trauma patients with profound hypotension (SBP ≤ 70 mmHg) or hypotension (SBP 71-90 mmHg) and tachycardia (HR ≥ 108 bpm) from six level I trauma center air medical transport programs. The trial will also explore the effects of prehospital plasma transfusion on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research with an investigational new drug approval from the U.S. Food and Drug Administration utilizing a multipronged community consultation process. It is one of three ongoing Department of Defense-funded trials aimed at expanding our understanding of the optimal therapeutic approaches to coagulopathy in the hemorrhaging trauma patient.

Predictors of oliguria in post-traumatic acute kidney injury.

BACKGROUND: Acute kidney injury is classified by urine output into non-oliguric and oliguric variants. Non-oliguric acute kidney injury has lower morbidity and mortality and accounts for up to 64% of acute kidney injury in hospitalized patients. However, the incidence of non-oliguric acute kidney injury in the trauma population and whether the 2 variants of acute kidney injury share the same risk factors is unknown. We hypothesized that oliguria would be present in the majority of acute kidney injury in severely injured trauma patients and that unique risk factors would predispose patients to the development of oliguria. METHODS: Patients admitted to the trauma intensive care unit and diagnosed with an acute kidney injury between 2016 to 2021 were identified. Cases were categorized based on urine output into oliguric (<400 mL per day) and non-oliguric (>400 mL per day) disease. Risk factors, management, and outcomes were compared. Logistic regression was used to identify risk factors associated with oliguria. RESULTS: A total of 227 patients met inclusion criteria. Non-oliguric acute kidney injury accounted for 74% of all cases and was associated with greater survival (78% vs 35.6%, P < .001). Using logistic regression, female sex, vasopressor use, and a greater net fluid balance at 48 hours were all predictive of oliguria (while controlling for age, race, shock index, massive transfusion, operative intervention, cardiac arrest, and nephrotoxic medication exposure). CONCLUSION: Non-oliguria accounts for the majority of post-traumatic acute kidney injury and is associated with improved survival. Specific risk factors for the development of oliguric acute kidney injury include female sex, vasopressor use, and a higher net fluid balance at 48 hours.

Persistent long-term opioid use after trauma: Incidence and risk factors.

BACKGROUND: The opioid epidemic in the United States continues to lead to a substantial number of preventable deaths and disability. The development of opioid dependence has been strongly linked to previous opioid exposure. Trauma patients are at particular risk since opioids are frequently required to control pain after injury. The purpose to this study was to examine the prevalence of opioid use before and after injury and to identify risk factors for persistent long-term opioid use after trauma. METHODS: Records for all patients admitted to a Level 1 trauma center over a 1-year period were analyzed. Demographics, injury characteristics, and hospital course were recorded. A multistate Prescription Drug Monitoring Program database was queried to obtain records of all controlled substances prescribed from 6 months before the date of injury to 12 months after hospital discharge. Patients still receiving narcotics at 1 year were defined as persistent long-term users and were compared against those who were not. RESULTS: A total of 2,992 patients were analyzed. Of all patients, 20.4% had filled a narcotic prescription within the 6 months before injury, 53.5% received opioids at hospital discharge, and 12.5% had persistent long-term use after trauma with the majority demonstrating preinjury use. Univariate risk factors for long-term use included female sex, longer length of stay, higher Injury Severity Score, anxiety, depression, orthopedic surgeries, spine injuries, multiple surgical locations, discharge to acute inpatient rehab, and preinjury opioid use. On multivariate analysis, the only significant predictors of persistent long-term prescription opioid use were preinjury use and a much smaller effect associated with use at discharge. CONCLUSION: During a sustained opioid epidemic, concerns and caution are warranted in the use of prescription narcotics for trauma patients. However, persistent long-term opioid use among opioid-naive patients is rare and difficult to predict after trauma. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Six Square Miles of Urban America: Association Between Firearm Discharge, Injury, and Fatality.

BACKGROUND: Despite the increase in firearm injury observed across the country, significant gaps remain relevant to our understanding of how firearm exposure translates to injury. Using acoustic gunshot detection and a collaborative hospital and law enforcement firearm injury database, we sought to identify the relationship between firearm discharge and injury over time. STUDY DESIGN: From 2018-2021, instances of firearm discharge captured via acoustic detection in six-square miles of Louisville, KY was merged with data from the collaborative firearm injury database. Key outcomes included the total number of rounds fired, injury and fatality rates per round, and the percentage of rounds discharged from automatic weapons and high-capacity magazines. RESULTS: Over the study period, 54,397 rounds of ammunition were discharged resulting in 914 injuries, 435 hospital admissions, 2,442 hospital days, 155 emergent operations, and 180 fatalities. For each round of ammunition fired, the risk of injury and fatality was 1.7% and 0.3% respectively. The total number of rounds fired per month nearly tripled (614 vs. 1,623, p < 0.001) leading to increased injury (15 vs. 37, p < 0.001) and fatality (3 vs. 7, p < 0.001). The percentage of rounds fired from automatic weapons (0 vs. 6.8%, p < 0.001) and high-capacity magazines (7.6 vs. 28.9%, p < 0.001) increased over time. CONCLUSIONS: The increased burden of firearm injury is related to an overall increase in firearm exposure as measured by the total number of rounds discharged. High-capacity magazines and automatic weaponry are being used with increasing frequency in urban American.

Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials.

Background: The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods: We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results: We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention. Conclusions: AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers: NCT01818427, NCT02086500 and NCT03477006. Level of evidence: II.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Traumatic injury may be a predisposing factor for cerebrovascular accident.

The purpose of the study was to assess whether trauma may be an independent risk factor for stroke. Evidence has shown that trauma patients experience a hypercoagulable state postinjury, increasing the risk of thrombotic events. A case-controlled, retrospective analysis was performed on admitted trauma patients over a 2-year period. Results revealed that trauma patients are 1.6 times more likely to have a cerebrovascular accident (CVA) during their hospital admission, when compared with nontrauma patients with similar CVA risk factors. Several statistically significant differences between the groups were identified. On the basis of these results, trauma appears to be an independent, nonmodifiable risk factor for CVA.