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Background: Posttraumatic stress disorder (PTSD) is a common consequence of traumatic injury, yet certain biological factors contributing to PTSD are poorly understood. The gut microbiome may influence mental health outcomes, but its role in heterogeneous PTSD presentations requires elucidation., Methods: Bacterial composition was examined in adults 2-4 years post-trauma with probable PTSD (n = 24) versus trauma-exposed controls without probable PTSD (n = 24). 16S rRNA sequencing and bioinformatic tools assessed microbial diversity and abundance. Relationships between taxa and PTSD symptom clusters were evaluated., Results: No differences were found in overall microbial community structure between groups. The probable PTSD group exhibited significantly reduced Actinobacteriota and increased Verrucomicrobiota phylum abundance compared to controls. Specific taxa showed notable inverse associations with negative mood/cognition versus hyperarousal symptoms. Prevotella and Ruminococcaceae were negatively associated with negative mood but positively associated with hyperarousal., Conclusions: Results demonstrate microbial signatures of probable PTSD subtypes, highlighting the microbiome as a potential mediator of heterogeneous trauma psychopathology. Definition of PTSD microbial correlates provides a foundation for personalized psychobiotic interventions targeting predominant symptom profiles., Competing Interests: Declaration of competing interest This research was supported by a Medical College of Wisconsin Neuroscience Research Center Imagine More grant (PI: deRoon-Cassini). The authors have no other relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: The mortality rate for alimentary tract hemorrhage remains high due to a variety of contributing factors. In this report, we present a case of post-severe trauma patient with life-threatening gastrointestinal bleeding caused by cytomegalovirus (CMV)-induced damage to the terminal ileum., Case Report: A 76-year-old female with a history of hypertension and gastrointestinal bleeding developed CMV ileitis post-severe trauma. Despite negative CMV IgM antibodies, PCR testing confirmed CMV infection in the biopsy tissue. Histopathological examination revealed viral inclusion bodies, with immunohistochemistry confirming CMV presence., Results: Intravenous ganciclovir effectively managed symptoms and halted bleeding. CMV ileitis, typically seen in immunocompromised states, may occur sporadically in immunocompetent individuals, including post-orthopedic surgery patients. The exact mechanism remains unclear, possibly related to surgical stress. Diagnosis relies on histopathology and immunohistochemistry., Conclusion: Early recognition and treatment are vital for optimal outcomes, emphasizing the need for awareness among orthopedic surgeons regarding CMV as a potential cause of postoperative complications., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

General Purpose: To present current evidence regarding the physiology, assessment, and management of wound itch., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care., Learning Objectives/outcomes: After participating in this educational activity, the participant will:1. Summarize current understanding of itch physiology.2. Apply current evidence to the management of wound itch., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current literature demonstrates prophylactic enoxaparin to be efficacious in reducing venous thromboembolism (VTE) rates without significantly increasing risk for bleeding complications. Despite this evidence, prophylactic enoxaparin doses are frequently withheld for surgery or procedures. This exploratory study aims to quantify the risk of a VTE event in trauma patients associated with missed doses of prophylactic enoxaparin. Methods: This retrospective cohort study evaluated trauma patients admitted to our Level 1 trauma center from January 1, 2012 to January 31, 2021. A 1:1 propensity match with ten variables was performed to compare patients receiving prophylactic enoxaparin that had a VTE and those that did not. The primary outcome was a VTE event. Results: 493 patients met inclusion criteria; 1:1 propensity score matching was performed resulting in a cohort of 184 patients. The percentage of patients that missed a prophylactic enoxaparin dose in the VTE group was higher than the no VTE group (34.8% vs 21.7%, P = 0.049). This is consistent when examining total missed doses ( P = 0.038) and consecutively missed doses ( P = 0.035). The odds of having a VTE for patients that missed at least one dose or more of enoxaparin are nearly two times greater (OR 1.92, 95% CI 0.997, 3.7). Conclusion: Missing enoxaparin doses significantly increases the risk of VTE in matched populations. Most prophylactic enoxaparin doses were held for procedures, and not for bleeding events. Trauma teams should carefully weigh the risk of bleeding complications associated with continuing enoxaparin prophylaxis against the significant thromboembolic risk of withholding it., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Unveiling of the mechanism involved in the occurrence and development of trauma-induced heterotopic ossification (tHO) is highly demanding due to current ineffective clinical treatment for it. Previous studies proposed that hydrogen sulfide (H 2 S) was vital for fate determination of stem cells, suggesting a potential role in the regulation of tHO development. In the current study, We found that expression of metabolic enzyme within sulfur conversion pathway was enhanced after tendon injury, leading to H 2 S accumulation within the tHO region. Increased production of endogenous H 2 S was shown to promote aberrant osteogenic activity of tendon-derived stem cells (TDSCs), which accelerated tHO formation. The inhibition of metabolic enzyme of H 2 S production or directly absorption of H 2 S could abolished osteogenic induction of TDSCs and the formation of tHO. Mechanistically, through RNA sequencing combined with rescue experiments, we demonstrated that activation of Ca 2+ /ERK pathway was the downstream molecular event of H 2 S-induced osteogenic commitment of TDSCs and tHO. For treatment strategy exploration, zine oxide nanoparticles (ZnO) as an effective H 2 S elimination material was validated to ideally halt the tHO formation in this study. Furthermore, in terms of chirality of nanoparticles, D-ZnO or L-ZnO nanoparticles showed superiority over R-ZnO nanoparticles in both clearing of H 2 S and inhibition of tHO. Our study not only revealed the mechanism of tHO through the endogenous gas signaling event from a new perspective, but also presented a applicable platform for elimination of the inordinate gas production, thus aiding the development of clinical treatment for tHO., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: When an injured patient arrives in the Emergency Department (ED), timely and appropriate care is crucial. Shock Index Pediatric Age-Adjusted (SIPA) has been shown to accurately identify pediatric patients in need of emergency interventions. However, no study has evaluated SIPA against age-adjusted tachycardia (AT). This study aims to compare SIPA with AT in predicting outcomes such as mortality, severe injury, and the need for emergent intervention in pediatric trauma patients., Material and Methods: This is a retrospective cross-sectional analysis of patient data abstracted from the Trauma Quality Improvement Program Participant Use Files (TQIP PUFs) for years 2013-2020. Patients aged 4-16 with blunt mechanism of injury and injury severity score (ISS) > 15 were included. 36,517 children met this criteria. Sensitivity, specificity, overtriage, and undertriage rates were calculated to compare the effectiveness of AT and elevated SIPA as predictors of severe injuries and need for emergent intervention. Emergent interventions included craniotomy, endotracheal intubation, thoracotomy, laparotomy, or chest tube placement within 24 h of arrival., Results: AT classified 59% of patients as "high risk," while elevated SIPA identified 26%. Compared to AT patients, a greater proportion of patients with elevated SIPA required a blood transfusion within 24 h (22% vs. 12%, respectively; p < 0.001). In-hospital mortality was higher for the elevated SIPA group than AT (10% vs. 5%, respectively; p < 0.001) as well as the need for emergent operative interventions (43% vs. 32% respectively; p < 0.001). Grade 3 or higher liver/spleen lacerations requiring blood transfusion were also more common among elevated SIPA patients than AT patients (8% vs. 4%, respectively; p < 0.001). AT demonstrated greater sensitivity but lower specificity compared to SIPA across all outcomes. AT showed improved overtriage and undertriage rates compared to SIPA, but this is attributed to identifying a large proportion of the sample as "high risk.", Conclusions: AT outperforms SIPA in sensitivity for mortality, injury severity and emergent interventions in pediatric trauma patients while the specificity of SIPA is high across these outcomes., Competing Interests: Declaration of competing interest The authors have no financial interests to disclose related to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Shock Index is used to predict injury severity and adverse outcomes in trauma patients, but pediatric age-adjusted shock index (SIPA) has superior performance in pediatric patients older than 1 year. Pediatric age-adjusted shock index scores younger than 1 year have not been well studied. This project aimed to establish and evaluate SIPA cut point data points for patients younger than 1 year., Methods: Using age-based vital signs, we developed cut point values for patients younger than 1 year using our institutional trauma data. All trauma patients younger than 12 months were included, and clinical outcomes were recorded. Pediatric age-adjusted shock index cut points were defined using age-specific vital sign limits (SIPA-VS) and tested against optimal cut points defined by receiver operating characteristic analysis (SIPA-ROC) and a cut point of 1.2 (SIPA-Nordin), which is used for patients aged 1 to 4 years. Student's t test, χ 2 tests, analysis of variance, and test characteristics were used to analyze groups., Results: A total of 609 pediatric trauma patients younger than 12 months were identified from 2018 to 2022. Pediatric age-adjusted shock index scores were calculated for 483 patients. There were 406 patients with blunt trauma and 17 with penetrating. SIPA-Nordin was elevated in 81.6% (n = 397) of patients, compared with SIPA-VS 21% (n = 101) and SIPA-ROC 31% (n = 150). In comparison with SIPA-Nordin, both SIPA-VS and SIPA-ROC score exhibited superior specificity and negative predictive values for multiple outcomes. Elevated SIPA-ROC scores had statistically significant associations with intensive care unit admission, mechanical ventilation, severe anemia, transfusion during hospital admission, and in-hospital mortality., Conclusion: Pediatric age-adjusted shock index is a useful tool in identifying patients at risk for several complications of severe traumatic injury. Pediatric age-adjusted shock index cut points had high negative predictive value and specificity for many outcomes. This study proposes cut point values that may aid in clinical decision making for trauma patients younger than 1 year., Level of Evidence: Diagnostic Test/Criteria; Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Timely identification of high-risk pediatric trauma patients and appropriate resource mobilization may lead to improved outcomes. We hypothesized that reverse shock index times the motor component of the Glasgow Coma Scale (GCS) (rSIM) would perform equivalently to reverse shock index times the total GCS (rSIG) in the prediction of mortality and the need for intervention following pediatric trauma., Methods: The 2017-2020 National Trauma Data Bank data sets were used. We included all patients 16 years or younger who had a documented prehospital and trauma bay systolic blood pressure, heart rate, and total GCS. We excluded all patients who arrived at the trauma center without vital signs and interfacility transport patients. Receiver operating characteristic curves were used to model the performance of each metric as a classifier with respect to our primary and secondary outcomes, and the area under the receiver operating characteristic curve (AUROC) was used for comparison. Our primary outcome was mortality before hospital discharge. Secondary outcomes included blood product administration or hemorrhage control intervention (surgery or angiography) <4 hours following hospital arrival and intensive care unit admission., Results: After application of exclusion criteria, 77,996 patients were included in our analysis. Reverse shock index times GCS-motor and rSIG performed equivalently as predictors of mortality in the 1- to 2- ( p = 0.05) and 3- to 5-year-old categories ( p = 0.28), but rSIM was statistically outperformed by rSIG in the 6- to 12- (AUROC, 0.96 vs. 0.95; p = 0.04) and 13- to 16-year-old age categories (AUROC, 0.96 vs. 0.95; p < 0.01). Reverse shock index times GCS-motor and rSIG also performed similarly with respect to prediction of secondary outcomes., Conclusion: Reverse shock index times GCS-total and rSIM are both outstanding predictors of mortality following pediatric trauma. Statistically significant differences in favor of rSIG were noted in some age groups. Because of the simplicity of calculation, rSIM may be a useful tool for pediatric trauma triage., Level of Evidence: Diagnostic Tests or Criteria; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The past century has seen many advances in the field of resuscitation. This is particularly true in the subset of patients who sustain major injuries causing hemorrhagic shock (HS) and require massive transfusion of more than 10 U of blood within the first 24 hours. Controversies on how best to resuscitate these patients include the role of fresh whole blood, stored whole blood, fresh frozen plasma, platelets, colloid solutions, balanced electrolytes solution, vasopressors, and diuretics. This review summarizes the often-contradictory recommendations observed and studied by a single trauma surgeon working in a busy urban acute care center for 65 years., Level of Evidence: Level I., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Whole blood can be ABO-type specific (type-specific whole blood (TSWB)) or low-titer O universal donor (low-titer O whole blood (LTOWB)). Having previously used LTOWB, the US Armed Forces Blood Program began using TSWB in 1965 as a method of increasing the donor pool. In contrast to military practice, the Association for the Advancement of Blood and Biotherapies formerly the American association of blood banks (AABB), from its first guidelines in 1958 until 2018, permitted only TSWB. Attempting to reduce time to transfusion, the US military reintroduced LTOWB in the deployed environment in 2015; this practice was endorsed by the AABB in 2018 and is progressively being implemented by military and civilian providers worldwide. Low-titer O whole blood is the only practical solution prehospital. However, there are several reasons to retain the option of TSWB in hospitals with a laboratory. These include (1) as-yet ill-defined risks of immunological complications from ABO-incompatible plasma (even when this has low titers of anti-A and -B), (2) risks of high volumes of LTOWB including published historical advice (based on clinical experience) not to transfuse type-specific blood for 2 to 3 weeks following a substantial LTOWB transfusion, (3) uncertainty as to the optimal definition of "low titer," and (4) expanding the potential donor pool by allowing type-specific transfusion. Several large randomized controlled trials currently underway are comparing LTOWB with component therapy, but none address the question of LTOWB versus TSWB. There are sufficient data to suggest that the additional risks of transfusing LTOWB to non-group O recipients should be avoided by using TSWB as soon as possible. Combined with the advantage of maintaining an adequate supply of blood products in times of high demand, this suggests that retaining TSWB within the civilian and military blood supply system is desirable. TSWB should be preferred when patient blood group is confirmed in facilities with a hematology laboratory, with LTOWB reserved for patients whose blood group is unknown., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Introduction: A 2003 landmark study identified the prevalence of early trauma-induced coagulopathy (eTIC) at 28% with a strong association with mortality of 8.9%. Over the last 20 years, there have been significant advances in both the fundamental understanding of eTIC and therapeutic interventions. Methods: A retrospective cohort study was performed from 2018 to 2022 on patients ≥18 using prospectively collected data from two level 1 trauma centers and compared to data from 2003. Demographics, laboratory data, and clinical outcomes were obtained. Results: There were 20,107 patients meeting criteria: 65% male, 85% blunt, mean age 54 ± 21 years, median Injury Severity Score 10 (10, 18), 8% of patients were hypotensive on arrival, with an all-cause mortality 6.0%. The prevalence of eTIC remained high at 32% in patients with an abnormal prothrombin time and 10% with an abnormal partial thromboplastin time, for an overall combined prevalence of 33.4%. Coagulopathy had a major impact on mortality over all injury severity ranges, with the greatest impact with lower Injury Severity Score. In a hybrid logistic regression/Classification and Regression Trees analysis, coagulopathy was independently associated with a 2.1-fold increased risk of mortality (95% confidence interval 1.5-2.9); the predictive quality of the model was excellent [area under the receiver operating characteristic curve (AUROC) 0.932]. Conclusion: The presence of eTIC conferred a higher risk of death across all disease severities and was independently associated with a greater risk of death. Biomarkers of coagulopathy associated with eTIC remain strongly predictive of poor outcome despite advances in trauma care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: The benefit of targeting high ratio fresh frozen plasma (FFP)/red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP/RBC transfusion and the association with outcomes in children presenting in shock., Methods: A post hoc analysis of a 24-institution prospective observational study (April 2018 to September 2019) of injured children younger than 18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (≥1:2) ratio FFP/RBC. Nonparametric Kruskal-Wallis and χ 2 were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths., Results: Of 135 children with median (interquartile range) age 10 (5-14) years and weight 40 (20-64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (low-38%, high-46%, p = 0.34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = 0.01); however, hospital mortality was similar (low-24%, high-20%, p = 0.65) as was the risk of extended ventilator, intensive care unit, and hospital days (all p > 0.05)., Conclusion: Despite increased injury severity, patients who received a high ratio of FFP/RBC had comparable rates of mortality. These data suggest high ratio FFP/RBC resuscitation is not associated with worst outcomes in children who present in shock. Massive transfusion protocol activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multimodal pain management has been shown to be effective in treating pain in acutely injured trauma patients. Our community-based, level 1 trauma center previously published in 2022 the efficacy of implementing multimodal pain control (MMPC) protocol in our inpatient trauma population which decreased the use of opioids while maintaining similar pain control. The MMPC group had a trend toward higher age and was significantly less injured. We hypothesize MMPC will reduce opioid consumption in both the advanced aged and more severely injured trauma populations while still providing adequate pain control., Methods: Defined by the year of admission, MMPC and physician managed pain control (PMPC) were compared in both advanced age groups and between the severely injured groups. The advanced age group included patients ≥55 years old. The severely injured group included ≥18 years old with ≥15 ISS. Primary outcomes were total opioid utilization per day, calculated in morphine milliequivalents (MME), and median daily pain scores., Results: For the severely injured population, the MMPC group showed a 3-fold decrease in opioid use (30 MME/d vs 90.3 MME/d, P < .001) and lower pain scores (5/10 vs 6/10, P < .001) than the PMPC group. In the advance age group, there was no significant difference between MMPC and PMPC groups in opioid use ( P = .974) or pain scores ( P = .553)., Conclusion: MMPC effectively reduces opioid consumption in a severely injured patient population while simultaneously improving pain control. Advanced age trauma patients can require complex pain management solutions and future research to determine their needs is recommended., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Trauma patients are at increased risk of venous thromboembolism (VTE), including deep venous thrombosis and/or pulmonary embolism. We conducted a systematic review and meta-analysis summarizing the association between prognostic factors and the occurrence of VTE following traumatic injury., Methods: We searched the Embase and Medline databases from inception to August 2023. We identified studies reporting confounding adjusted associations between patient, injury, or postinjury care factors and risk of VTE. We performed meta-analyses of odds ratios using the random-effects method and assessed individual study risk of bias using the Quality in Prognosis Studies tool., Results: We included 31 studies involving 1,981,946 patients. Studies were predominantly observational cohorts from North America. Factors with moderate or higher certainty of association with increased risk of VTE include older age, obesity, male sex, higher Injury Severity Score, pelvic injury, lower extremity injury, spinal injury, delayed VTE prophylaxis, need for surgery, and tranexamic acid use. After accounting for other important contributing prognostic variables, a delay in the delivery of appropriate pharmacologic prophylaxis for as little as 24 to 48 hours independently confers a clinically meaningful twofold increase in incidence of VTE., Conclusion: These findings highlight the contribution of patient predisposition, the importance of injury pattern, and the impact of potentially modifiable postinjury care on risk of VTE after traumatic injury. These factors should be incorporated into a risk stratification framework to individualize VTE risk assessment and support clinical and academic efforts to reduce thromboembolic events among trauma patients., Level of Evidence: Systematic Review and Meta-Analysis; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Trauma is the most common cause of morbidity and mortality in older people, and it is important to determine the predictors of outcomes after major trauma in older people., Methods: MEDLINE, Embase, and Web of Science were searched, and manual search of relevant papers since 1987 to February 2023 was performed. Random-effects meta-analyses were performed. The primary outcome of interest was mortality, and secondary outcomes were medical complications, length of stay, discharge destination, readmission, and intensive care requirement., Results: Among 6,064 studies in the search strategy, 136 studies qualified the inclusion criteria. Forty-three factors, ranging from demographics to patient factors, admission measurements, and injury factors, were identified as potential predictors. Mortality was the commonest outcome investigated, and increasing age was associated with increased risk of in-hospital mortality (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07) along with male sex (OR, 1.40; 95% CI, 1.24-1.59). Comorbidities of heart disease (OR, 2.59; 95% CI, 1.41-4.77), renal disease (OR, 2.52; 95% CI, 1.79-3.56), respiratory disease (OR, 1.40; 95% CI, 1.09-1.81), diabetes (OR, 1.35; 95% CI, 1.03-1.77), and neurological disease (OR, 1.42; 95% CI, 0.93-2.18) were also associated with increased in-hospital mortality risk. Each point increase in the Glasgow Coma Scale lowered the risk of in-hospital mortality (OR, 0.85; 95% CI, 0.76-0.95), while each point increase in Injury Severity Score increased the risk of in-hospital mortality (OR, 1.07; 95% CI, 1.04-1.09). There were limited studies and substantial variability in secondary outcome predictors; however, medical comorbidities, frailty, and premorbid living condition appeared predictive for those outcomes., Conclusion: This review was able to identify potential predictors for older trauma patients. The identification of these factors allows for future development of risk stratification tools for clinicians., Level of Evidence: Systematic Review and Meta-Analysis; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Conflicting evidence exists evaluating associations between cannabis (THC) and post-traumatic DVT., Methods: Retrospective analysis (2014-2023) of patients ≥15yrs from two Level I trauma centers with robust VTE surveillance and prophylaxis protocols. Multivariable hierarchical regression assessed the association between THC and DVT risk. THC ​+ ​patients were direct matched to other drug use categories on VTE risk markers and hospital length of stay., Results: Of 7365 patients, 3719 were drug-, 575 were THC ​+ ​only, 2583 were other drug+, and 488 were TCH+/other drug+. DVT rates by exposure group did not differ. TCH ​+ ​only patients had higher GCS scores, shorter hospital length of stay, and the lowest pelvic fracture and mortality rates. A total of 458 drug-, 453 other drug+, and 232 THC+/other drug ​+ ​patients were matched to 458, 453, and 232 THC ​+ ​only patients. There were no differences in DVT event rates in any paired sub-cohort set. Additionally, iteratively adjusted paired models did not show an association between THC and DVT., Conclusions: THC does not appear to be associated with increased DVT risk in patients with strict trauma chemoprophylaxis. Toxicology testing is useful for identifying substance abuse intervention opportunities, but not for DVT risk stratification in THC ​+ ​patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or funding to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Whole blood (WB) resuscitation has reemerged as a resuscitation strategy for injured patients. However, the effect of WB-based resuscitation on outcomes has not been established. The primary objective of this guideline was to develop evidence-based recommendations on whether WB should be considered in civilian trauma patients receiving blood transfusions., Methods: An Eastern Association for the Surgery of Trauma working group performed a systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation methodology. One Population, Intervention, Comparison, and Outcomes question was developed to analyze the effect of WB resuscitation in the acute phase on mortality, transfusion requirements, infectious complications, and intensive care unit length of stay. English language studies including adult civilian trauma patients comparing in-hospital WB to component therapy were included. Medline, Embase, Cochrane CENTRAL, CINAHL Plus, and Web of Science were queried. GRADEpro (McMaster University; Evidence Prime, Inc.; Ontario) was used to assess quality of evidence and risk of bias. The study was registered on International Prospective Register of Systematic Reviews (CRD42023451143)., Results: A total of 21 studies were included. Most patients were severely injured and required blood transfusion, massive transfusion protocol activation, and/or a hemorrhage control procedure in the early phase of resuscitation. Mortality was assessed separately at the following intervals: early (i.e., emergency department, 3 hours, or 6 hours), 24 hours, late (i.e., 28 days or 30 days), and in-hospital. On meta-analysis, WB was not associated with decreased mortality. Whole blood was associated with decreased 4-hour red blood cell (mean difference, -1.82; 95% confidence interval [CI], -3.12 to -0.52), 4-hour plasma (mean difference, -1.47; 95% CI, -2.94 to 0), and 24-hour red blood cell transfusions (mean difference, -1.22; 95% CI, -2.24 to -0.19) compared with component therapy. There were no differences in infectious complications or intensive care unit length of stay between groups., Conclusion: We conditionally recommend WB resuscitation in adult civilian trauma patients receiving blood transfusions, recognizing that data are limited for certain populations, including women of childbearing age, and therefore this guideline may not apply to these populations., Level of Evidence: Systematic Review/Meta-Analysis; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hypothermia increases mortality in trauma populations and frequently occurs in military casualties due to the nature of combat environments. The association between hypothermia and the time of year when injured remains unclear. We sought to determine the association between seasonal changes in temperature and hypothermia among combat casualties., Materials and Methods: This observational study was a secondary analysis of a previously described Department of Defense Trauma Registry dataset which included U.S. military and Coalition casualties who received prehospital care from January 2007 to March 2020 in Afghanistan and Iraq. We tested for associations between hypothermia (<36.2°C) and seasonal ambient temperatures by constructing multivariable logistic regression models. Summer was defined as June through August and winter as December through February. We assumed that the combat operations occurred in the area near the point of first contact with the deployed military treatment facilities. This study was determined to be exempt from Institutional Review Board oversight., Results: There were 5,821 that met inclusion for this study. Within the multivariable logistic regression model, we adjusted for injury severity score, mechanism of injury, and imputed transport time, finding that combat casualties were 2.28 (odds ratio, 95% confidence interval 1.93-2.69) times more likely to develop hypothermia in the winter versus summer. When using temperature as a continuous outcome, casualties had a lower emergency department temperature during the winter (parameter estimate -0.133°C, P < 0.001) after adjusting for confounders. In casualties experiencing hypothermia, mortality was higher (4% versus 1%, P < 0.001), and composite median injury severity score values were higher (10 versus 5, P < 0.001). Among hypothermic casualties, serious injuries were significantly more common (all P < 0.001) to the head (15% versus 7%), thorax (15% versus 7%), abdomen (9% versus 6%), extremities (35% versus 22%), and skin (4% versus 2%)., Conclusions: We found a seasonal variation in the occurrence of hypothermia in a large cohort of trauma casualties. Despite adjustment for multiple known confounders, our findings substantiate probable ambient temperature variations to trauma-induced hypothermia. Furthermore, our findings, when taken in the context of other studies on the efficacy of current hypothermia prevention and treatment strategies, support the need for better methods to mitigate hypothermia in future cold-weather operations., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Trauma poses a significant global health challenge. Despite advancements in the management of severely injured patients, (poly)trauma continues to be a primary contributor to morbidity and mortality worldwide. In the context of trauma resuscitation, supplemental oxygen is commonly administered generously as suggested by guidelines. Yet, it remains uncertain whether the trauma population might derive advantages from a more conservative approach to supplemental oxygen., Methods: In this retrospective cohort study from two Swiss trauma centers, severely injured adult (> 16 years) trauma patients with an Injury Severity Score (ISS) ≥ 16 were divided into four groups according to the first blood gas analysis taken: hypoxaemia (PaO 2  < 10.7 kPa/80 mmHg), normoxaemia (PaO 2 10.7-16.0 kPa/80-120 mmHg), which served as reference, moderate hyperoxaemia (PaO 2  > 16.0-40 kPa/120-300 mmHg) and severe hyperoxaemia (PaO 2  > 40 kPa/300 mmHg). The primary outcome was 28-day mortality. Length of hospital stay (LOS) and length of intensive care unit stay (LOS-ICU) were analyzed as secondary outcomes., Results: Of 1,189 trauma patients, 41.3% had hyperoxaemia (18.8% with severe hyperoxaemia) and 19.3% had hypoxaemia. No difference was found for 28-day mortality (hypoxaemia: 15.7%, normoxaemia: 14.1%, hyperoxaemia: 13.8%, severe hyperoxaemia: 16.0%, p = 0.846). Patients with severe hyperoxaemia had a significant prolonged LOS (median 12.5 [IQR 7-18.5] days vs. 10 [7-17], p = 0.040) and extended LOS-ICU (3.8 [1.8-9] vs. 2 [1-5] days, p = 0.149) compared to normoxaemic patients. In multivariable analysis, oxygen group was not associated with the primary outcome 28-day mortality or LOS-ICU. Severe hyperoxaemia patients had a tendency towards longer hospital stay (adjusted coefficient 2.23 days [95% CI: - 0.32; 4.79], p = 0.087)., Conclusion: Hyperoxaemia was not associated with an increased 28-day mortality when compared to normoxaemia. However, both moderate and severe hyperoxaemia is frequently observed in trauma patients, and the presence of severe hyperoxaemia showed a tendency with extended hospital stay compared to normoxaemia patients. Robust randomized controlled trials are imperative to thoroughly evaluate the potential correlation between hyperoxaemia and outcomes in trauma patients . Trial Registration Retrospectively registered., (© 2024. The Author(s).)

Introduction: The association between hypothermia, coagulopathy, and acidosis in trauma is well described. Hypothermia mitigation starts in the prehospital setting; however, it is often a secondary focus after other life-saving interventions. The deployed environment further compounds the problem due to prolonged evacuation times in rotary wing aircraft, resource limitations, and competing priorities. This analysis evaluates hypothermia in combat casualties and the relationship to resuscitation strategy with blood products., Methods: Using the data from the Department of Defense Joint Trauma Registry from 2003 to 2021, a retrospective analysis was conducted on adult trauma patients. Inclusion criteria was arrival at the first military treatment facility (MTF) hypothermic (<95ºF). Study variables included: mortality, year, demographics, battle vs non-battle injury, mechanism, theater of operation, vitals, and labs. Subgroup analysis was performed on severely injured (15 < ISS < 75) hypothermic trauma patients resuscitated with whole blood (WB) vs only component therapy., Results: Of the 69,364 patients included, 908 (1.3%) arrived hypothermic; the vast majority of whom (N = 847, 93.3%) arrived mildly hypothermic (90-94.9°F). Overall mortality rate was 14.8%. Rates of hypothermia varied by year from 0.7% in 2003 to 3.9% in 2014 (P <0.005). On subgroup analysis, mortality rates were similar between patients resuscitated with WB vs only component therapy; though base deficit values were higher in the WB cohort (-10 vs -6, P < 0.001)., Conclusion: Despite nearly 20 years of combat operations, hypothermia continues to be a challenge in military trauma and is associated with a high mortality rate. Mortality was similar between hypothermic trauma patients resuscitated with WB vs component therapy, despite greater physiologic derangements on arrival in patients who received WB. As the military has the potential to conduct missions in environments where the risk of hypothermia is high, further research into hypothermia mitigation techniques and resuscitation strategies in the deployed setting is warranted., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated., Methods: European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes., Results: The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin - alpha 2-antiplasmin (PAP) - and tPA levels and lower alpha2 - antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes., Conclusions: Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation., (© 2024. The Author(s).)

Purpose: Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP., Methods: This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality., Results: The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality., Conclusion: Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Trauma patients in the emergency department experience severe pain that is not always easy to manage. The risk of acute compartment syndrome further complicates the analgesic approach. The purpose of this review is to discuss relevant bibliography and highlight current guidelines and recommendations for the safe practice of peripheral nerve blocks in this special group of patients. According to the recent bibliography, peripheral nerve blocks are not contraindicated in patients at risk of acute compartment syndrome, as long as there is surveillance and certain recommendations are followed.

Importance: Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma., Objective: To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma., Design, Setting, and Participants: This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024., Main Outcomes and Measures: The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality., Results: The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT., Conclusions and Relevance: In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

Background: Antibiotics are frequently administered prophylactically to trauma patients with various injury patterns to prevent infectious complications. Trauma patients may also require large volume resuscitation with blood products. Limited data are available to support antibiotic dosing recommendations in this population. We hypothesized that we would be able to develop a population pharmacokinetic model of cefazolin, a frequently used antibiotic in the trauma scenario, from remnant blood samples by pharmacokinetic analysis of trauma patients. Methods: Remnant plasma from standard of care chemistry/hematology assessments was retrieved within 48 h of collection and assayed to determine cefazolin concentrations. Population pharmacokinetic analyses were conducted in Pmetrics using R. Linear regression was conducted to assess the effect of blood product resuscitation volume on cefazolin pharmacokinetic parameters. Results: Cefazolin concentrations best fitted a two-compartment model (Akaike information criterion: 443.9). The mean ± standard deviation parameters were total body clearance (4.3 ± 1.9L), volume of the central compartment (V c : 7.7 ± 6.9L), and intercompartment transfer constants (k 12 : 1.3 ± 0.98 h -1 , k 21 : 0.6 ± 0.45 h -1 ). No statistical relationships were observed between blood products, volume of blood products, and cefazolin clearance or V c ( R 2 : 0.0004-0.21, p = 0.08-0.95). Using a 5,000-patient Monte Carlo simulation, 2 g with repeated dosing every 2 h until end of surgery was required to achieve 93.2% probability of 100% free time above the minimum inhibitory concentration (MIC) ( f T > MIC) at the ECOFF value for Staphylococcus aureus (2 mg/L). Conclusions: In these 15 trauma patients receiving blood transfusion, no relationship with blood volume resuscitation and cefazolin pharmacokinetics was observed. On the basis of this pharmacokinetic model, frequent cefazolin doses are required to maintain 100% f T > MIC.

This chapter delves into uncommon wounds including pyoderma gangrenosum, sickle cell disease ulcers, vasculitic wounds, Martorell hypertensive ischemic leg ulcers, and malignant ulcers. Emphasizing a multidisciplinary approach, it covers diagnostics, treatments, and challenges, with case studies illustrating complexities in managing these conditions. The discussion extends to radiation-related wounds, underscoring the need for patient-centered care, interdisciplinary collaboration, and realistic goal setting. Overall, the chapter navigates the intricacies of uncommon wounds, emphasizing the importance of tailored approaches for improved outcomes in patients with diverse underlying conditions., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chronic wound-related pain is a complex biopsychosocial experience that is experienced spontaneously at rest and exacerbated during activities. Tissue debridement, trauma at dressing change, increased bioburden or infection, exposure of periwound skin to moisture, and related treatment can modulate chronic wound-related pain. Clinicians should consider multimodal and multidisciplinary management approach that take into account the biology, emotions, cognitive thinking, social environment, and other personal determinants of pain. Unresolved pain can have a significant impact on wound healing, patients' adherence to treatment, and individual's quality of life., Competing Interests: Disclosure The author has nothing to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Malnutrition is a collective term that includes both undernutrition and malnutrition. Malnutrition presents with and without inflammation, is reported in underweight, normal weight, and overweight individuals, and is associated with undesirable alterations in body composition, and diminished functional status. Older adults commonly experience dwindling nutritional status as evidenced by insidious weight loss, insufficient dietary intake, loss of muscle mass, quality, and strength, declining functional status, and other physical and emotional decline indicators. Sustained pressure, acute trauma, malnutrition, and inflammatory-driven chronic conditions increase the risk for skin integrity issues., Competing Interests: Disclosure The authors have nothing to disclose., (Published by Elsevier Inc.)

Abstract: Tranexamic acid is an inexpensive antifibrinolytic treatment that reduces morbidity and mortality in civilian and military trauma patients. It must be administered within 3 hours of the injury, and its efficacy is greater the earlier it is given. It is already used preventively in the civilian environment in a number of indications to reduce bleeding and bleeding-related mortality. We wondered about the potential benefits of preventive oral administration of tranexamic acid prior to an assault for military personnel with a potential risk of injury., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Introduction: Augmented renal clearance (ARC) is prevalent in trauma populations. Identification is underrecognized by calculated creatinine clearance or estimated glomerular filtration rate equations. Predictive scores may assist with ARC identification. The goal of this study was to evaluate validity of the ARCTIC score and ARC Predictor to predict ARC in critically ill trauma patients., Methods: This single center, retrospective study was performed at an academic level 1 trauma center. Critically ill adult trauma patients undergoing 24-h urine-collection were included. Patients with serum creatinine >1.5 mg/dL, kidney replacement therapy, suspected rhabdomyolysis, chronic kidney disease, or inaccurate urine collection were excluded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ARCTIC Score and ARC Predictor were calculated. Receiver operating characteristic curves were created for ARCTIC score and ARC Predictor models., Results: One-hundred and twenty-two patients with ARC and 78 patients without ARC were included. The ARCTIC score sensitivity, specificity, PPV, and NPV were 89%, 54%, 75%, and 75%, respectively. The ARC Predictor demonstrated sensitivity, specificity, PPV, and NPV of 77%, 88%, 91%, and 71%, respectively. Regression analyses revealed both ARCTIC score ≥6 and ARC Predictor threshold >0.5 as significant risk factors for ARC in presence of traumatic brain injury, obesity, injury severity score, and negative nitrogen balance (ARCTIC ≥6: odds ratio 8.59 [95% confidence interval 3.90-18.92], P < 0.001; ARC Predictor >0.5: odds ratio 20.07 [95% confidence interval 8.53-47.19], P < 0.001)., Conclusions: These findings corroborate validity of two pragmatic prediction tools to identify patients at high risk of ARC. Future studies evaluating correlations between ARCTIC score, ARC Predictor, and clinical outcomes are warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Fat embolism is a life-threatening complication often occurring in patients with traumatic injuries. However, temporal trends and perioperative outcomes of fat embolism remain understudied. Using a nationally representative cohort, we aimed to characterize temporal trends of fat embolism and its associated resource utilization in operatively managed trauma patients., Methods: All patients (≥18 years) undergoing any major operations after traumatic injuries were tabulated using the 2005 to 2020 National Inpatient Sample. Patients were stratified into those with fat embolism and those without. Multivariable logistic and linear regressions were developed to assess the association between fat embolism and outcomes of interest., Results: Of an estimated 10,600,000 hospitalizations, 7,479 (0.07%) patients had fat embolism. Compared to the non-fat embolism cohort, the fat embolism cohort was younger (55 [26-79] vs 69 [49-82] years, standard mean difference = 0.46) and more likely to receive treatment at a high-volume trauma center (42.9 vs 33.7%, standard mean difference = 0.19). Over the study period, there was an increase in annual mortality and hospitalization costs among the fat embolism group (nptrend <0.001). After risk adjustment, fat embolism was associated with greater odds of mortality (adjusted odds ratio: 2.65, 95% confidence interval: 2.24-3.14) compared to others. Additionally, fat embolism was associated with increased odds of cerebrovascular, infectious, and renal complications., Conclusion: Among all operatively managed trauma patients, those who developed fat embolism had increased mortality, rates of complications, length of stay, and costs. Optimization of early and accurate identification of fat embolism is warranted to mitigate complications and improve resource allocation among trauma patients., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study presents data on pre-trauma steroid use, a topic underrepresented in the trauma literature. Long-term steroid use has been linked to impaired wound healing, compromised immune responses, and hindrance of bone healing, alongside the potential for adrenal insufficiency during traumatic events. The aim of this study was to conduct a retrospective analysis of clinical outcomes for trauma patients with chronic steroid use. Examining adult trauma cases with pre-trauma steroid use at a level 1 trauma center (January 2016-September 2023), we identified 18 patients (58.6 ± 19.4 years, 55.6% males). All were on prednisone prior to trauma activation and 66.7% had autoimmune disease. Complications included orthopedic fractures (72.2%), ICU admissions (16.7%), and low mortality (5.6%). Future larger, multi-center studies are needed to determine the impact of immunosuppression and pre-trauma steroids on clinical outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Admission hypocalcemia has been associated with poor outcomes in injured adults. The impact of hypocalcemia on mortality has not been widely studied in pediatric trauma., Methods: A pediatric trauma center database was queried retrospectively (2013-2022) for children younger than 18 years who received blood transfusion within 24 hours of injury and had ionized calcium (iCal) level on admission. Children who received massive transfusion (>40 mL/kg) prior to hospital arrival or calcium prior to laboratory testing were excluded. Hypocalcemia was defined by the laboratory lower limit (iCal <1.00). Main outcomes were in-hospital mortality and 24-hour blood product requirements. Logistic regression analysis was performed to adjust for Injury Severity Score (ISS), admission shock index, Glasgow Coma Scale (GCS) score, and weight-adjusted total transfusion volume., Results: In total, 331 children with median (IQR) age of 7 years (2-3 years) and median (IQR) ISS 25 (14-33) were included, 32 (10%) of whom were hypocalcemic on arrival to the hospital. The hypocalcemic cohort had higher ISS (median (IQR) 30(24-36) vs. 22 (13-30)) and lower admission GCS score (median (IQR) 3 (3-12) vs. 8 (3-15)). Age, sex, race, and mechanism were not significantly different between groups. On univariate analysis, hypocalcemia was associated with increased in-hospital (56% vs. 18%; p < 0.001) and 24-hour (28% vs. 5%; p < 0.001) mortality. Children who were hypocalcemic received a median (IQR) of 22 mL/kg (7-38) more in total weight-adjusted 24-hour blood product transfusion following admission compared to the normocalcemic cohort ( p = 0.005). After adjusting for ISS, shock index, GCS score, and total transfusion volume, hypocalcemia remained independently associated with increased 24-hour (odds ratio, 4.93; 95% confidence interval, 1.77-13.77; p = 0.002) and in-hospital mortality (odds ratio, 3.41; 95% confidence interval, 1.22-9.51; p = 0.019)., Conclusion: Hypocalcemia is independently associated with mortality and receipt of greater weight-adjusted volumes of blood product transfusion after injury in children. The benefit of timely calcium administration in pediatric trauma needs further exploration., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Combat casualties receiving damage-control laparotomy at forward deployed, resource-constrained US military Role 2 (R2) surgical units require multiple evacuations, but the added risk of venous thromboembolism (VTE) in this population has not been defined. To fill this gap, we retrospectively analyzed 20 years of Department of Defense Trauma Registry data to define the VTE rate in this population., Methods: Department of Defense Trauma Registry from 2002 to 2023 was queried for US military combat casualties requiring damage-control laparotomy at R2. All deaths were excluded in subsequent analysis. Rates of VTE were assessed, and subgroup analysis was performed on patients requiring massive transfusion., Results: Department of Defense Trauma Registry (n = 288) patients were young (mean age, 25 years) and predominantly male (98%) with severe (mean Injury Severity Score, 26), mostly penetrating injury (76%) and high mortality. Venous thromboembolism rate was high: 15.8% (DVT, 10.3%; pulmonary embolism, 7.1%). In the massively transfused population, the VTE rate was even higher (26.7% vs. 10.2%, p < 0.001)., Conclusion: This is the first report that combat casualties requiring damage-control laparotomy at R2 have such high VTE rates. Therefore, for military casualties, we propose screening ultrasound upon arrival to each subsequent capable echelon of care and low threshold for initiating thromboprophylaxis., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objective: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock., Background: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury., Methods: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality., Results: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups., Conclusions and Relevance: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences., Trial Registration: ClinicalTrials.gov identifier: NCT04667468., Competing Interests: J.L.S. reports grants from the DoD; F.X.G. reports grants from the DoD; S.R.W. reports grants from the DoD; L.Z.K. reports grants and consulting fees from University of Maryland/BARDA, personal fees from Gamma Diagnostics, Coagulant Therapeutics, Haemonetics, other from Cerus, outside the submitted work; A.E.K. reports being founder of CaptureDx; J.C. reports participates on the steering committee for Faraday Pharmaceuticals; M.D.N. has received grants from National Institutes of Health, Department of Defense, DARPA, Haemonetics, Alexion and Instrumentation Laboratories, honoraria for lectures from Haemonetics and Takeda, support for attending meetings and/or travel from Takeda; participates on a Data Safety Monitoring Board or Advisory Board from NHLBI CONNECTS Steering Committee; is the Chief Medical Officer, Haima Therapeutics, and has Patents planned, issued or pending (US Patent 11,408.844; US Patent 9.072,760), outside the submitted work; P.C.S. reports personal fees from Hemanext, Cerus, participates in advisory board for Octapharma,and Haima, and is the Co-Founder and Chief Medical Officer of Kalocyte, outside the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Considering resources for comprehensive geriatric care, it would be beneficial for geriatric trauma patients (GTPs) and medical patients to be comanaged in one program focusing on ancillary therapeutics (AT): physical therapy, occupational therapy, speech language pathology, respiratory therapy, and sleep wake hygiene. This pilot study describes outcomes of GTPs in a hospital-wide program focused on geriatric-specific AT., Methods: Geriatric trauma patients and geriatric patients were screened by program coordinator for enrollment at one Level II trauma center from August 2021 to December 2022. Enrolled patients (EPs) were admitted to trauma or medicine floors and received repetitive AT with attention to sleep wake hygiene throughout hospitalization and compared with similar nonenrolled patients (NEPs). Excluded patients had any of the following: indication of geriatric syndrome with a fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) score of 5, no frailty with a FRAIL score of 0, comfort focused plans, or arrived from skilled care. Retrospective chart review of demographics and outcomes was completed for both EPs and NEPs., Results: A total of 224 EPs (28 trauma [TR]) were compared with 574 NEPs (148 TR). Enrolled patients showed shorter length of stay (mean, 3.8 vs. 6.1; p = 0.0001), less delirium (3.1% vs. 9.6%, p = 0.00222), less time to ambulation (13 hours vs. 39 hours, p = 0.0005), and higher likelihood to discharge home (56% vs. 27%, p < 0.0001) as compared with NEPs. The median FRAIL score was 3 for both groups. Enrolled medical patients ambulated the soonest at 11 average hours, compared with 23 hours for enrolled trauma patients and 39 hours for NEPs. There were zero delirium events among enrolled trauma patients; 25% was found among nonenrolled trauma patients ( p = 0.00288)., Conclusion: Despite a small trauma cohort, results support feasibility to include GTPs in hospital-wide programs with geriatric-specific AT. Mobility and cognitive strategies may improve opportunities to avoid delirium, decrease length of stay, and influence more frequent disposition to home., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Background: Despite improving understanding of trauma-induced coagulopathy (TIC), mortality and morbidity due to exsanguinating trauma remain high. Increased complications due to hemorrhage have been reported in blood group O, possibly due to reduced levels of von Willebrand factor (vWF)., Methods: An urban level 1 adult trauma center registry was retrospectively queried. Patients receiving ≥6 units of pRBC within 4 ​h of presentation were included. Patient demographics, admission labs and outcomes were obtained. Univariate and multiple logistic regression analyses were performed., Results: 562 patients were identified. There were no significant differences in demographics, admission labs, or outcome between different ABO groups. After adjustment, Type A patients were more likely to be hypocoagulable compared to Type O patients (p ​= ​0.014). No mortality differences were seen between ABO types in multiple regression analysis., Conclusions: No outcome or mortality differences were seen between ABO types, therefore factors other than vWF expression should be considered to explain coagulopathy in trauma patients., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Precision and personalized medicine remain an elusive but illustrious goal in the realm of critical care, particularly in the areas of trauma and sepsis. These aims specifically refer to data gathering, interpretation, and treatment application on an individualized basis in the clinical care of patients. Until now, personalized medicine has mainly remained focused on genetics and epigenetic phenomena and has propelled clinical care forward, especially in the field of oncology. Advances in technology and methodology continue to proliferate in early-phase research, and some of these advancements are well poised to break into the clinical sphere of critical care. Here, we describe 2 topics at the forefront of investigation with potent and imminent potential for clinical application., (Copyright © 2024. Published by Elsevier Inc.)

Venous thromboembolism (VTE) in pediatric trauma patients is under-investigated. The purpose of this study was to perform an evaluation of the risk factors for VTE after pediatric trauma, including readmissions across the United States. The Nationwide Readmissions Database for 2016-2020 was queried for all patients under the age of 18 years admitted for trauma. 276 670 patients were identified; 2063 (.8%) were diagnosed with VTE. Among those with VTE, 300 (15%) were identified during a readmission. Higher rates of VTE were seen in ages 15-17 years (n = 1,294, 1.3%, P < .001), penetrating injuries (n = 478, .9%, P < .001), and assault (n = 271, 2.7%, P < .001). The strongest risk factor for VTE was prolonged mechanical ventilation (OR 5.5 [4.9-6.3] P < .001). Our study found that a significant portion of post-traumatic VTE in children and teenagers occur during readmissions. A deeper understanding of the risk factors outlined here can guide enhanced clinical protocols, ensuring early detection and prevention of this complication., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While epilepsy-related injuries (ERIs) are frequent in people with epilepsy (PWE), factors associated with hospitalization because of ERIs remain relatively unknown., Methods: We conducted a cross-sectional anonymous survey at a tertiary epilepsy clinic among adult outpatients with epilepsy. Participants indicated their demographic, clinical characteristics, adverse effects of antiseizure medications (ASMs), somatic comorbidities and whether they were hospitalized because of ERIs in the past. For variables with significantly different distributions between participant subgroups (positive vs negative history of past hospitalisation because of ERI), the association with ERI-linked hospitalization was assessed using univariable and multivariable regression models., Results: Among 600 PWE (312, 52.0 % female) included, 405 (67.5 %) reported at least one ERI in the past and 104 (25.7 %) had been hospitalised because of at least one of the injuries. Age, seizures in the street, focal unaware seizures and adverse ASM effects were associated with ERI-linked hospitalization only in univariable regression models. Male sex (OR = 1.677, 95 % CI = 1.022-2.753), loss of consciousness during seizures (OR = 2.294, 95 % CI = 1.166-4.513), seizure frequency (OR = 1.264, 95 % CI = 1.024-1.559) and ASM-related loss of coordination (OR = 3.496, 95 % CI = 1.670-7.320) were statistically significant predictors in the multivariable model (Nagelkerke R 2  = 0.106)., Conclusion: Our study indicates that, beyond seizure-related factors, adverse effects of ASMs and somatic comorbidities need to be considered when estimating the odds of previous ERI-linked hospitalisations. Alternative determinants of a higher risk of serious ERI, such as lifestyle or occupational variables, should be explored in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Computed tomography pulmonary angiography (CTPA) is a standard imaging technique employed for the detection of pulmonary embolism (PE). This systematic review and meta-analysis aims to examine the prevalence of PE among the trauma patients undergoing CTPA., Methods: A comprehensive search across PubMed, Scopus, Google Scholar, and Web of Science yielded 13 studies encompassing 5,570 individuals conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline. Studies that used CTPA for the detection of PE among the trauma patients were selected. This resulted in an evaluation of prevalence, trauma types, clinical manifestations, radiological findings, and mortality rates of PE among traumatic patients undergoing CTPA., Results: The overall prevalence of PE among trauma patients undergoing CTPA was 18% (95% CI = 13-24%). After pooling the existing data, femur fractures were determined to be the most prevalent trauma type (12%). The most prevalent clinical manifestations of PE among trauma patients included shortness of breath, chest pain, and altered vital signs. Radiological findings encompassed various pulmonary abnormalities, such as opacity, ground-glass opacities, and pleural effusions. Mortality rates of PE among the trauma patients ranged from 0% to 29.4% across the included studies., Conclusion: This study provides comprehensive insights into the prevalence, clinical manifestations, radiological findings and mortality of PE among trauma patients undergoing CTPA. According to our findings, lower threshold for CTPA is recommended in patients with lower extremity or spine fractures., (© 2024. The Author(s).)

Competing Interests: Competing interests: IR was the chief investigator of the CRASH-2 and CRASH-3 trials and coauthor on studies of intramuscular tranexamic acid in trauma and the development of the BATT score.

Background: Tranexamic acid (TXA) decreases mortality in injured patients and should be administered as soon as possible. Despite international guidelines recommending TXA in the prehospital setting, its use remains low. The aim of this study was to assess the prehospital administration of TXA for injured patients in a Swiss region., Methods: We conducted a retrospective observational study in Switzerland between 2018 and 2021. Inclusion criteria were injured patients ≥18 years for whom an ambulance or helicopter was dispatched. The exclusion criterion was minor injury defined by a National Advisory Committee for Aeronautics score <3. The primary outcome was the proportion of patients treated with TXA according to guidelines. The European guidelines were represented by the risk of death from bleeding (calculated retrospectively using the Bleeding Audit for Trauma and Triage (BATT) score). Factors impacting the likelihood of receiving TXA were assessed by multivariate analysis., Results: Of 13 944 patients included in the study, 2401 (17.2%) were considered at risk of death from bleeding. Among these, 257 (11%) received prehospital TXA. This represented 38% of those meeting US guidelines. For European guidelines, the treatment rate increased with the risk of death from bleeding: 6% (95% CI 4.4% to 7.0%) for low risk (BATT score 3-4); 13% (95% CI 11.1% to 15.9%) for intermediate risk (BATT score 5-7); and 21% (95% CI 17.6% to 25.6%) for high risk (BATT score ≥8) (p<0.01). Women and the elderly were treated less often than men and younger patients, irrespective of the risk of death from bleeding and the mechanism of injury., Conclusion: The proportion of injured patients receiving TXA in the prehospital setting of the State of Vaud in Switzerland was low, with even lower rates for women and older patients. The reasons for this undertreatment are probably multifactorial and would require specific studies to clarify and correct them., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The endothelial glycocalyx, a gel-like layer that lines the luminal surface of blood vessels, is composed of proteoglycans, glycoproteins, and glycosaminoglycans. The endothelial glycocalyx plays an essential role in vascular homeostasis, and its degradation in trauma and sepsis can lead to microvascular dysfunction and organ injury. While there are no proven therapies for preventing or treating endothelial glycocalyx degradation, some initial literature suggests that plasma may have a therapeutic role in trauma and sepsis patients. Overall, the literature suggesting the use of plasma as a therapy for endothelial glycocalyx degradation is non-clinical basic science or exploratory. Plasma is an established therapy in the resuscitation of patients with hemorrhage for restoration of coagulation factors. However, plasma also contains other bioactive components, including sphingosine-1 phosphate, antithrombin, and adiponectin, which may protect and restore the endothelial glycocalyx, thereby helping to maintain or restore vascular homeostasis. This narrative review begins by describing the endothelial glycocalyx in health and disease: we discuss the overlapping disease mechanisms in trauma and sepsis that lead to its damage and introduce plasma transfusion as a potential therapy for prevention and treatment of endothelial glycocalyx degradation. Second, we review the literature on plasma as an exploratory therapy for endothelial glycocalyx degradation in trauma and sepsis. Third, we discuss the safety of plasma transfusion by reviewing the adverse events associated with plasma and other blood product transfusions, and we examine modern transfusion precautions that have enhanced the safety of plasma transfusion. We conclude that the literature proposes that plasma may have the potential to prevent and treat endothelial glycocalyx degradation in trauma and sepsis, indicating the need for further research., (© 2024. The Author(s).)

Background and Objective: Deep vein thrombosis (DVT) is a common complication after trauma and mostly without specific symptoms. Timely diagnosis and early appropriate treatment measures can prevent further development of thrombosis for patients with traumatic lower extremity fractures. Although extracellular vesicles (EVs) are confirmed as promising disease biomarkers, little is known about the role of altered levels and composition in the diagnosis of post-traumatic DVT., Method: The levels of circulating EVs subgroups were measured using flow cytometry. Isolated EVs were characterized and subjected to proteomics analysis to screen for differentially expressed proteins (DEPs) between DVT and non-DVT patients. Regularized logistic regression analysis based on L2 penalty terms using R's caret package was applied to build a model for DVT diagnosis., Results: Compared to non-DVT patients, DVT patients had higher circulating hepatocyte-derived EVs (hEVs) with good predictive value for post-traumatic DVT diagnosis. The results of the proteomic analysis showed that differentially expressed proteins (DEPs) of circulating EVs between the DVT group and non-DVT group were enriched in the complement and coagulation cascade. Finally, an integrated model of five biomarkers including SERPING1, C8G, CFH, FIX, and hEVs level was established for post-traumatic DVT diagnosis with robust identification of the traumatic patients with and without DVT (AUC 0.972)., Conclusion: Post-traumatic DVT patients had changed levels and composition of circulating EVs compared to non-DVT patients and healthy controls. Circulating EVs may acquire pathological protein signatures and become potential biomarkers for identifying subjects' post-traumatic DVT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.