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1.
PeerJ ; 12: e17521, 2024.
Article in English | MEDLINE | ID: mdl-38903881

ABSTRACT

Background: Acute respiratory distress syndrome (ARDS) is a severe complication that can lead to fatalities in multiple trauma patients. Nevertheless, the incidence rate and early prediction of ARDS among multiple trauma patients residing in high-altitude areas remain unknown. Methods: This study included a total of 168 multiple trauma patients who received treatment at Shigatse People's Hospital Intensive Care Unit (ICU) between January 1, 2019 and December 31, 2021. The clinical characteristics of the patients and the incidence rate of ARDS were assessed. Univariable and multivariable logistic regression models were employed to identify potential risk factors for ARDS, and the predictive effects of these risk factors were analyzed. Results: In the high-altitude area, the incidence of ARDS among multiple trauma patients was 37.5% (63/168), with a hospital mortality rate of 16.1% (27/168). Injury Severity Score (ISS) and thoracic injuries were identified as significant predictors for ARDS using the logistic regression model, with an area under the curve (AUC) of 0.75 and 0.75, respectively. Furthermore, a novel predictive risk score combining ISS and thoracic injuries demonstrated improved predictive ability, achieving an AUC of 0.82. Conclusions: This study presents the incidence of ARDS in multiple trauma patients residing in the Tibetan region, and identifies two critical predictive factors along with a risk score for early prediction of ARDS. These findings have the potential to enhance clinicians' ability to accurately assess the risk of ARDS and proactively prevent its onset.


Subject(s)
Altitude , Multiple Trauma , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/epidemiology , Male , Female , Incidence , Retrospective Studies , Middle Aged , Adult , Risk Factors , Multiple Trauma/mortality , Multiple Trauma/epidemiology , Multiple Trauma/complications , Hospital Mortality , Injury Severity Score , China/epidemiology , Thoracic Injuries/mortality , Thoracic Injuries/epidemiology , Thoracic Injuries/complications , Intensive Care Units
2.
Sci Rep ; 14(1): 13308, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38858394

ABSTRACT

The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer-Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.


Subject(s)
Multiple Trauma , Nomograms , ROC Curve , Shock, Hemorrhagic , Humans , Shock, Hemorrhagic/diagnosis , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/therapy , Male , Female , Child , Retrospective Studies , Child, Preschool , Adolescent , Multiple Trauma/diagnosis , Multiple Trauma/complications , China/epidemiology , Injury Severity Score , Infant , Logistic Models
3.
G Ital Nefrol ; 41(3)2024 06 28.
Article in Italian | MEDLINE | ID: mdl-38943323

ABSTRACT

The development of acute kidney injury (AKI) in polytrauma patients is a common and serious complication, with an incidence ranging from 6% to 50%. Polytrauma is a complex pathological condition that involves the collaboration of various specialists. On one hand, hemodynamic stabilization through fluid therapy and aminic support, with specific attack protocols, managed by anesthetists. On the other hand, if necessary, the initiation of renal replacement therapy such as Continuous Renal Replacement Therapy (CRRT), managed by nephrologists. CRRT is chosen both for managing fluid balance and ensuring the removal of toxic substances, as well as for proper control of electrolytes and acid-base balance.


Subject(s)
Acute Kidney Injury , Multiple Trauma , Patient Care Team , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Humans , Multiple Trauma/therapy , Multiple Trauma/complications , Fluid Therapy , Continuous Renal Replacement Therapy
4.
Animal Model Exp Med ; 7(3): 367-376, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860566

ABSTRACT

BACKGROUND: Severe trauma is associated with systemic inflammation and organ dysfunction. Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury. METHODS: Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or naïve controls. Weight, plasma toll-like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU-GEMM, BFU-E, and CFU-E) growth, plasma granulocyte colony-stimulating factor (G-CSF) and right lung histologic injury were assessed on day 7, with significance defined as p values <0.05 (*). RESULTS: Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS (p = 0.0002) along with elevated plasma TLR4 (p < 0.0001), lower hemoglobin (p < 0.0001), and enlarged spleen to body weight ratios (p = 0.004). Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naïve (p < 0.03, p < 0.01). Plasma G-CSF was elevated in PT compared to both naïve and LCHS (p < 0.0001, p = 0.02). LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema. CONCLUSIONS: Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia, splenic tissue enlargement, weight loss, and increased inflammatory activity compared to a less severe model. This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.


Subject(s)
Anemia , Disease Models, Animal , Multiple Trauma , Rats, Sprague-Dawley , Shock, Hemorrhagic , Animals , Shock, Hemorrhagic/complications , Male , Anemia/etiology , Anemia/pathology , Multiple Trauma/complications , Multiple Trauma/pathology , Rats , Bone Marrow/pathology , Toll-Like Receptor 4/metabolism , Lung Injury/etiology , Lung Injury/pathology , Granulocyte Colony-Stimulating Factor/blood , Hemoglobins
5.
J Neurotrauma ; 41(13-14): e1708-e1718, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38623766

ABSTRACT

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 µg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.


Subject(s)
Brain Injuries, Traumatic , Disease Models, Animal , Granulocyte-Macrophage Colony-Stimulating Factor , Multiple Trauma , Rats, Sprague-Dawley , Animals , Male , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/immunology , Rats , Multiple Trauma/immunology , Multiple Trauma/complications , Immunosuppression Therapy/methods
6.
World J Surg ; 48(2): 350-360, 2024 02.
Article in English | MEDLINE | ID: mdl-38686758

ABSTRACT

BACKGROUND: Postinjury multiple organ failure (MOF) is the leading cause of late trauma deaths, with primarily non-modifiable risk factors. Timing of surgery as a potentially modifiable risk factor is frequently proposed, but has not been quantified. We aimed to compare mortality, hospital length of stay (LOS), and ICU LOS between MOF patients who had surgery that preceded MOF with modifiable timings versus those with non-modifiable timings. METHODS: Retrospective analysis of an ongoing 17-year prospective cohort study of ICU polytrauma patients at-risk of MOF. Among MOF patients (Denver score>3), we identified patients who had surgery that preceded MOF, determined whether the timing of these operation(s) were modifiable(M) or non-modifiable (non-M), and evaluated the change in physiological parameters as a result of surgery. RESULTS: Of 716 polytrauma patients at-risk of MOF, 205/716 (29%) developed MOF, and 161/205 (79%) had surgery during their ICU admission. Of the surgical MOF patients, 147/161 (91%) had one or more operation(s) that preceded MOF, and 65/161 (40%) of them had operation(s) with modifiable timings. There were no differences in age (mean (SD) 52 (19) vs 53 (21)years), injury severity score (median (IQR) 34 (26-41)vs34 (25-44)), admission physiological and resuscitation parameters, between M and non-M-patients. M patients had longer ICU LOS (median (IQR) 18 (12-28)versus 11 (8-16)days, p < 0.0001) than non-M-patients, without difference in mortality (14%vs16%, p = 0.7347), or hospital LOS (median (IQR) 32 (18-52)vs27 (17-47)days, p = 0.3418). M-patients had less fluids and transfusions intraoperatively. Surgery did not compromise patient physiology. CONCLUSION: Operations preceding MOF are common in polytrauma and seem to be safe in maintaining physiology. The margin for improvement from optimizing surgical timing is modest, contrary to historical assumptions.


Subject(s)
Length of Stay , Multiple Organ Failure , Multiple Trauma , Humans , Multiple Organ Failure/mortality , Multiple Organ Failure/etiology , Female , Male , Middle Aged , Length of Stay/statistics & numerical data , Retrospective Studies , Adult , Multiple Trauma/surgery , Multiple Trauma/mortality , Multiple Trauma/complications , Time Factors , Intensive Care Units/statistics & numerical data , Risk Factors , Hospital Mortality , Prospective Studies , Aged
7.
Injury ; 55(5): 111339, 2024 May.
Article in English | MEDLINE | ID: mdl-38575396

ABSTRACT

INTRODUCTION: Male urethral injuries are uncommon, and the ideal timing of the definitive treatment remains controversial. This study aimed to compare the outcomes of early and delayed interventions (1 month or more after the injury) for male urethral injuries. PATIENT AND METHODS: We conducted a retrospective review of the medical records of 67 male patients with urethral injuries treated at our institution between 2011 and 2020. We examined patient age, injury severity score (ISS), abbreviated injury scale, mechanism, location and severity of injury, presence of pelvic fractures, surgical interventions, timing of treatment, and complications. We analysed factors associated with urinary complications based on the location of urethral injury. Additionally, we performed a subset analysis of patients with severe injuries (ISS≥16) to assess the impact of delayed surgery. RESULTS: Overall, 47 %, 37 %, and 27 % of patients in the delayed treatment group (N = 30) had urethral stricture (US), erectile dysfunction (ED), and/or urinary incontinence (UI). These rates were greater than the 22 % US, 3 % ED, and 11 % UI rates in the early treatment group (N = 37). The subgroup analysis revealed that patients with anterior urethral injury (AUI) who underwent delayed treatment (N = 18) tended to be more severely injured (ISS, 19 vs 9, p = 0.003) and exhibited higher rates of US (44% vs 21 %, p = 0.193) and ED (39% vs 0 %, p = 0.002) than those who received early treatment (N = 24). In the case of posterior urethral injury (PUI), the delayed treatment group (N = 13) had higher rates of US (50% vs 23 %, p = 0.326), ED (33% vs 8 %, p = 0.272), and UI (42% vs 0 %, p = 0.030) than the early treatment group. Regarding study limitations, more than 45 % of the enrolled patients were severely injured (ISS≥16), which may have potentially influenced the timing of urethral injury repair. CONCLUSIONS: The treatment of male urethral injuries may be delayed due to concurrent polytrauma and other associated injuries. However, delayed treatment is associated with higher rates of urinary complications. Early treatment of urethral injuries may be beneficial to male patients with urethral trauma, even in cases of severe injury.


Subject(s)
Fractures, Bone , Multiple Trauma , Pelvic Bones , Urethral Diseases , Humans , Male , Retrospective Studies , Treatment Outcome , Urethra/injuries , Fractures, Bone/surgery , Multiple Trauma/complications , Pelvic Bones/injuries
8.
Mol Cell Probes ; 74: 101954, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38452956

ABSTRACT

Sepsis as a severe systemic inflammation leads oftentimes to organ dysfunction and subsequently to death. In polytrauma patients, septic complications represent with 45% the predominant cause of late death and are responsible for extremely high costs in the healthcare system. Therefore, clinicians have to detect as early as possible the begin of sepsis to improve the patient's outcome. One new promising diagnostic tool to diagnose septic complications in polytraumatized patients are exosomes. Plasma samples from polytraumatized patients (Injury Severity Score (ISS) ≥16) which developed sepsis (n = 10) and without sepsis (n = 10), were collected at emergency room (ER), 24h and 5 days after trauma. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with plasma EVs from healthy controls (n = 10). Moreover, exosomal cytokine concentrations were measured via high-sensitive ELISA and were correlated with systemic concentrations. For miRNA cargo analysis, we analysed the miRNAs miR-1298-5p, miR-1262, miR-125b-5p, miR-92a-3p, miR-93-5p, miR-155-5p and miR-21-5p and compared their exosomal concentrations by means of RT-qPCR. CD62p + exosomes were significantly increased in septic polytrauma-patients (p ≤ 0.05), while CD40+exosomes, as well as CD49e + exosomes were diminished (p ≤ 0.05). Furthermore, we observed that the exosomal IL-6 concentration reflects the systemic IL-6 concentration (r2 = 0.63) and did not significantly alter between patients with and without sepsis. The exosomal IL-10 concentration seemed to be constant in all patients and healthy controls. We observed that a decrease of miR-21-5p in exosomes was associated with the development of sepsis (p ≤ 0.05), while exosomal miR-93-5p, miR-155-5p and miR-92a-3p were not specifically altered in septic patients. Taken together, the present study in polytraumatized patients demonstrated that the development of sepsis is associated with an increase of CD62p + exosomes. Furthermore, the exosomal cargo was changed in septic patients: miR-21-5p was diminished.


Subject(s)
Exosomes , MicroRNAs , Multiple Trauma , Sepsis , Humans , Exosomes/genetics , Interleukin-6 , MicroRNAs/genetics , Sepsis/complications , Sepsis/genetics , Multiple Trauma/complications
9.
J Trauma Acute Care Surg ; 97(1): 96-104, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38548689

ABSTRACT

INTRODUCTION: There are no clear recommendations for the perioperative timing and initiation of venous thromboembolism pharmacologic prophylaxis (VTEp) among polytrauma patients undergoing high-risk bleeding orthopedic operative intervention, leading to variations in VTEp administration. Our study examined the association between the timing of VTEp and VTE complications in polytrauma patients undergoing high-risk operative orthopedic interventions nationwide. METHODS: We performed a retrospective cohort study of trauma patients 18 years or older who underwent high-risk bleeding operative orthopedic interventions for pelvic, hip, and femur fractures within 24 hours of admission at American College of Surgeons-verified trauma centers using the 2019-2020 American College of Surgeons Trauma Quality Improvement Program databank. We excluded patients with a competing risk of nonorthopedic surgical bleeding. We assessed operative orthopedic polytrauma patients who received VTEp within 12 hours of orthopedic surgical intervention compared with VTEp received beyond 12 hours of intervention. The primary outcome assessed was overall VTE events. Secondary outcomes were orthopedic reinterventions within 72 hours after primary orthopedic surgery, deep venous thromboembolism, and pulmonary embolism rates. RESULTS: The study included 2,229 patients who underwent high-risk orthopedic operative intervention. The median time to VTEp initiation was 30 hours (interquartile range, 18-44 hours). After adjustment for baseline patient, injury, and hospital characteristics, VTEp initiated more than 12 hours from primary orthopedic surgery was associated with increased odds of VTE (adjusted odds ratio, 2.02; 95% confidence interval, 1.08-3.77). Earlier initiation of prophylaxis was not associated with an increased risk for surgical reintervention (hazard ratio, 0.90; 95% confidence interval, 0.62-1.34). CONCLUSION: Administering VTEp within 24 hours of admission and within 12 hours of major orthopedic surgery involving the femur, pelvis, or hip demonstrated an associated decreased risk of in-hospital VTE without an accompanying elevated risk of bleeding-related orthopedic reintervention. Clinicians should reconsider delays in initiating or withholding perioperative VTEp for stable polytrauma patients needing major orthopedic intervention. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.


Subject(s)
Anticoagulants , Multiple Trauma , Orthopedic Procedures , Venous Thromboembolism , Humans , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/epidemiology , Female , Male , Multiple Trauma/complications , Multiple Trauma/surgery , Retrospective Studies , Middle Aged , Orthopedic Procedures/adverse effects , Orthopedic Procedures/methods , Anticoagulants/administration & dosage , Adult , Aged , United States/epidemiology , Time Factors , Trauma Centers , Femoral Fractures/surgery , Femoral Fractures/complications , Time-to-Treatment/statistics & numerical data , Pelvic Bones/injuries , Risk Factors , Hip Fractures/surgery , Hip Fractures/complications , Pulmonary Embolism/prevention & control , Pulmonary Embolism/etiology
10.
Injury ; 55(4): 111464, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38452698

ABSTRACT

INTRODUCTION: This study aims to analyze the clinical characteristics, demographic features, and injury circumstances of patients admitted to the Emergency Department (ED) at Fondazione Policlinico Universitario A. Gemelli (IRCCS) in Rome, Italy, due to bicycle accidents. METHODS: Data on clinical characteristics, accident timing, injury circumstances, and helmet use were collected for ED patients involved in bicycle accidents from January 2019 to December 2022. Subsequently, Abbreviated Injury Scale codes of all diagnoses were recorded and the Injury Severity Score was calculated. RESULTS: Over the study period, 763 patients were admitted to the ED following bicycle accidents, with a 0.3 % fatality rate and a 30.4 % frequency of multitrauma. Multivariate analysis revealed that collisions with other vehicles increased trauma severity and the risk of ICU admission. Conversely, helmet use was associated with reduced severity of head trauma and a lower likelihood of ICU admission. Notably, toxicological investigations were not conducted for any ED-admitted patients. CONCLUSIONS: Although a low mortality rate and a low incidence of multi-trauma have been shown in comparison to other nations, it is necessary to adopt prevention strategies like safety devices, more cycle paths, and better infrastructures on the one hand, and stricter laws on the other. It is essential to require toxicological testing in Italy for all accidents involving this means of transport, and to make helmet use compulsory for all ages.


Subject(s)
Craniocerebral Trauma , Multiple Trauma , Humans , Accidents, Traffic/prevention & control , Rome/epidemiology , Bicycling/injuries , Craniocerebral Trauma/epidemiology , Craniocerebral Trauma/prevention & control , Craniocerebral Trauma/etiology , Multiple Trauma/complications , Head Protective Devices , Outcome Assessment, Health Care , Demography
11.
Crit Care ; 28(1): 81, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38491444

ABSTRACT

INTRODUCTION: Fluid resuscitation has long been a cornerstone of pre-hospital trauma care, yet its optimal approach remains undetermined. Although a liberal approach to fluid resuscitation has been linked with increased complications, the potential survival benefits of a restrictive approach in blunt trauma patients have not been definitively established. Consequently, equipoise persists regarding the optimal fluid resuscitation strategy in this population. METHODS: We analysed data from the two largest European trauma registries, the UK Trauma Audit and Research Network (TARN) and the German TraumaRegister DGU® (TR-DGU), between 2004 and 2018. All adult blunt trauma patients with an Injury Severity Score > 15 were included. We examined annual trends in pre-hospital fluid resuscitation, admission coagulation function, and mortality rates. RESULTS: Over the 15-year study period, data from 68,510 patients in the TARN cohort and 82,551 patients in the TR-DGU cohort were analysed. In the TARN cohort, 3.4% patients received pre-hospital crystalloid fluids, with a median volume of 25 ml (20-36 ml) administered. Conversely, in the TR-DGU cohort, 91.1% patients received pre-hospital crystalloid fluids, with a median volume of 756 ml (750-912 ml) administered. Notably, both cohorts demonstrated a consistent year-on-year decrease in the volume of pre-hospital fluid administered, accompanied by improvements in admission coagulation function and reduced mortality rates. CONCLUSION: Considerable variability exists in pre-hospital fluid resuscitation strategies for blunt trauma patients. Our data suggest a trend towards reduced pre-hospital fluid administration over time. This trend appears to be associated with improved coagulation function and decreased mortality rates. However, we acknowledge that these outcomes are influenced by multiple factors, including other improvements in pre-hospital care over time. Future research should aim to identify which trauma populations may benefit, be harmed, or remain unaffected by different pre-hospital fluid resuscitation strategies.


Subject(s)
Multiple Trauma , Wounds, Nonpenetrating , Adult , Humans , Retrospective Studies , Wounds, Nonpenetrating/therapy , Injury Severity Score , Crystalloid Solutions , Hospitals , Registries , Germany/epidemiology , Multiple Trauma/complications
12.
J Proteome Res ; 23(4): 1163-1173, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38386921

ABSTRACT

Trauma-induced coagulopathy (TIC) is a leading contributor to preventable mortality in severely injured patients. Understanding the molecular drivers of TIC is an essential step in identifying novel therapeutics to reduce morbidity and mortality. This study investigated multiomics and viscoelastic responses to polytrauma using our novel swine model and compared these findings with severely injured patients. Molecular signatures of TIC were significantly associated with perturbed coagulation and inflammation systems as well as extensive hemolysis. These results were consistent with patterns observed in trauma patients who had multisystem injuries. Here, intervention using resuscitative endovascular balloon occlusion of the aorta following polytrauma in our swine model revealed distinct multiomics alterations as a function of placement location. Aortic balloon placement in zone-1 worsened ischemic damage and mitochondrial dysfunction, patterns that continued throughout the monitored time course. While placement in zone-III showed a beneficial effect on TIC, it showed an improvement in effective coagulation. Taken together, this study highlights the translational relevance of our polytrauma swine model for investigating therapeutic interventions to correct TIC in patients.


Subject(s)
Balloon Occlusion , Multiple Trauma , Humans , Animals , Swine , Multiomics , Multiple Trauma/complications , Multiple Trauma/therapy , Aorta , Blood Coagulation , Balloon Occlusion/methods
13.
Thromb Haemost ; 124(1): 20-31, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37604188

ABSTRACT

BACKGROUND: Andexanet alfa (andexanet) is a reversal agent for use in patients with life-threatening or uncontrolled bleeding treated with oral factor Xa (FXa) inhibitors. There are limited data on the dose-response relationship of andexanet and FXa inhibitor-related bleeding. OBJECTIVE: The aim of this study was to assess the dose-related effectiveness of andexanet in reducing blood loss, improving survival, and reversing apixaban anticoagulation in a porcine polytrauma model. METHODS: Apixaban was given orally to 40 male pigs for 3 days at a dose of 20 mg/d. On day 3, following bilateral femur fractures and blunt liver injury, animals (n = 8/group) received andexanet (250-mg bolus, 250-mg bolus + 300-mg 2-hour infusion, 500-mg bolus, or 500-mg bolus + 600-mg 2-hour infusion) or vehicle (control). Total blood loss was the primary endpoint. Coagulation parameters were assessed for 300 minutes or until death. Data were analyzed with a mixed-model analysis of variance. RESULTS: Administration of 250-mg bolus + 300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus + 600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all p < 0.0001), with 100% survival. Andexanet 250-mg bolus was ineffective in reducing total blood loss (6%) and mortality (63% survival) versus controls. Andexanet 500-mg bolus ± infusion neutralized anti-FXa activity to less than 50 ng/mL. Andexanet neutralization of thrombin generation and thromboelastometry parameters was dose and infusion time dependent. CONCLUSION: In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (<50 ng/mL) with andexanet 500-mg bolus ± infusion were correlated with 60% less blood loss and 100% survival versus controls.


Subject(s)
Factor Xa , Multiple Trauma , Pyrazoles , Pyridones , Humans , Male , Animals , Swine , Factor Xa/therapeutic use , Factor Xa Inhibitors/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Multiple Trauma/complications , Multiple Trauma/drug therapy , Multiple Trauma/chemically induced , Recombinant Proteins/therapeutic use , Anticoagulants/therapeutic use
14.
Shock ; 61(1): 150-156, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38010084

ABSTRACT

ABSTRACT: Background: After severe injury, optical measures of microvascular blood flow (MBF) decrease and do not normalize with resuscitation to normal blood pressure. These changes are associated with organ dysfunction, coagulopathy, and death. However, the pathophysiology is not well understood. Several possible pathways could also contribute to the development of trauma-induced coagulopathy (TIC). A small-animal model of trauma-related MBF derangement that persists after resuscitation and includes TIC would facilitate further study. Parametric contrast-enhanced ultrasound (CEUS) is particularly advantageous in this setting, because it noninvasively assesses MBF in large, deep vascular beds. We sought to develop such a model, measuring MBF with CEUS. Methods: Sixteen male Sprague-Dawley rats were anesthetized, ventilated, and cannulated. Rats were subjected to either no injury (sham group) or a standardized polytrauma and pressure-targeted arterial catheter hemorrhage with subsequent whole blood resuscitation (trauma group). At prespecified time points, CEUS measurements of uninjured quadriceps muscle, viscoelastic blood clot strength, and complete blood counts were taken. Results: After resuscitation, blood pressure normalized, but MBF decreased and remained low for the rest of the protocol. This was primarily driven by a decrease in blood volume with a relative sparing of blood velocity. Viscoelastic blood clot strength and platelet count also decreased and remained low throughout the protocol. Conclusion: We present a rat model of MBF derangement in uninjured skeletal muscle and coagulopathy after polytrauma that persists after resuscitation with whole blood to normal macrohemodynamics. Parametric CEUS analysis shows that this change is primarily due to microvascular obstruction. This platform can be used to develop a deeper understanding of this important process.


Subject(s)
Blood Coagulation Disorders , Multiple Trauma , Shock, Hemorrhagic , Thrombosis , Animals , Rats , Male , Shock, Hemorrhagic/diagnostic imaging , Shock, Hemorrhagic/therapy , Rats, Sprague-Dawley , Hemorrhage/diagnostic imaging , Hemorrhage/etiology , Resuscitation/methods , Blood Coagulation Disorders/etiology , Muscle, Skeletal/diagnostic imaging , Multiple Trauma/complications , Perfusion , Disease Models, Animal
15.
J Trauma Acute Care Surg ; 96(1): 17-25, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37853556

ABSTRACT

INTRODUCTION: Pneumonia is a common complication after severe trauma that is associated with worse outcomes with increased mortality. Critically ill trauma patients also have persistent inflammation and bone marrow dysfunction that manifests as persistent anemia. Terminal erythropoiesis, which occurs in bone marrow structures called erythroblastic islands (EBIs), has been shown to be impacted by trauma. Using a preclinical model of polytrauma (PT) and pneumonia, we sought to determine the effect of infection on bone marrow dysfunction and terminal erythropoiesis. METHODS: Male and female Sprague-Dawley rats aged 9 to 11 weeks were subjected to either PT (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofracture) or PT with postinjury day 1 Pseudomonas pneumonia (PT-PNA) and compared with a naive cohort. Erythroblastic islands were isolated from bone marrow samples and imaged via confocal microscopy. Hemoglobin, early bone marrow erythroid progenitors, erythroid cells/EBI, and % reticulocytes/EBI were measured on day 7. Significance was defined as p < 0.05. RESULTS: Day 7 hemoglobin was significantly lower in both PT and PT-PNA groups compared with naive (10.8 ± 0.6 and 10.9 ± 0.7 vs. 12.1 ± 0.7 g/dL [ p < 0.05]). Growth of bone marrow early erythroid progenitors (colony-forming units-granulocyte, erythrocyte, monocyte, megakaryocyte; erythroid burst-forming unit; and erythroid colony-forming unit) on day 7 was significantly reduced in PT-PNA compared with both PT and naive. Despite a peripheral reticulocytosis following PT and PT-PNA, the percentage of reticulocytes/EBI was not different between naive, PT, and PT-PNA. However, the number of erythroblasts/EBI was significantly lower in PT-PNA compared with naive (2.9 ± 1.5 [ p < 0.05] vs. 8.9 ± 1.1 cells/EBI macrophage). In addition to changes in EBI composition, EBIs were also found to have significant structural changes following PT and PT-PNA. CONCLUSION: Multicompartmental PT altered late-stage erythropoiesis, and these changes were augmented with the addition of pneumonia. To improve outcomes following trauma and pneumonia, we need to better understand how alterations in EBI structure and function impact persistent bone marrow dysfunction and anemia.


Subject(s)
Anemia , Contusions , Multiple Trauma , Rats , Animals , Humans , Male , Female , Bone Marrow , Rats, Sprague-Dawley , Anemia/etiology , Contusions/complications , Hemoglobins , Multiple Trauma/complications , Erythropoiesis
16.
Int Immunopharmacol ; 127: 111377, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38104369

ABSTRACT

BACKGROUND: Immunological disorder remains a great challenge in severe poly-trauma, in which lymphopenia is an important contributor. The purpose of present study is to explore whether ferroptosis, a new manner of programmed cell death (PCD), is involved in the lymphocyte depletion and predictive to the adverse prognosis of severe injuries. PATIENTS AND METHODS: Severe polytrauma patients admitted from January 2022 to December 2022 in our trauma center were prospectively investigated. Peripheral blood samples were collected at admission (day 1), day 3 and day 7 from them. Included patients were classified based on whether they developed sepsis or not. Clinical outcomes, systematic inflammatory response, lymphocyte subpopulation, CD4 + T cell ferroptosis were collected, detected and analyzed. RESULTS: Notable lymphopenia was observed on the first day after severe trauma and failed to normalize on the 7th day if patients were complicated with sepsis, in which CD4 + T cell was the subset of lymphocyte that depleted most pronouncedly. Lymphocyte loss was significantly correlated with the acute and biphasic systemic inflammatory response. Ferroptosis participated in the death of CD4 + T cells, potentially mediated by the downregulation of xCT-GSH-GPX4 pathway. CD4 + T cells ferroptosis had a conducive predicting value for the development of sepsis following severe trauma. CONCLUSIONS: CD4 + T cells ferroptosis occurs early in the acute stage of severe polytrauma, which may become a promising biomarker and therapeutic target for post-traumatic sepsis.


Subject(s)
Ferroptosis , Lymphopenia , Multiple Trauma , Sepsis , Humans , CD4-Positive T-Lymphocytes , Multiple Trauma/complications
17.
BMC Emerg Med ; 23(1): 144, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38053029

ABSTRACT

BACKGROUND: Deep vein thrombosis (DVT) is a common complication in orthopedic patients. Previous studies have focused on major orthopedic surgery.There are few studies with multiple trauma. We aimed to describe the prevalence of DVT and compare the predictive power of the different risk assessment scales in patients with multiple trauma. METHODS: This prospective cohort study involved multiple trauma patients admitted to our hospital between October 2021 and December 2022. Data were prospectively collected for thrombotic risk assessments using the Risk Assessment Profile for thromboembolism(RAPT), the DVT risk assessment score (DRAS), and the Trauma Embolic Scoring System (TESS), respectively. The receiver operation characteristic (ROC) curve and the area under the curve (AUC) were evaluated to compare the predictive power. The whole leg duplex ultrasound of both lower extremities Doppler ultrasound was used to determine DVT incidence. RESULTS: A total of 210 patients were included, and the incidence of DVT was 26.19%. Distal DVT accounted for 87.27%; postoperative DVT, 72.73%; and bilateral lower extremity thrombosis, 30.91%. There were significant differences in age, education degree, pelvic fracture, surgery, ISS, D-dimer level, length of hospital stay and ICU stay between the thrombosis group and the non-thrombosis group. The AUCs for RAPT, DRAS, and TESS were 0.737, 0.710, and 0.683, respectively. There were no significant differences between the three ROC curves. CONCLUSIONS: The incidence of DVT was relatively high during hospitalization. We prospectively validated the tests to predict risk of DVT among patients with multiple trauma to help trauma surgeons in the clinical administration of DVT prophylaxis.


Subject(s)
Multiple Trauma , Thrombosis , Venous Thrombosis , Humans , Prospective Studies , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Risk Assessment , Risk Factors , Thrombosis/complications , Multiple Trauma/complications , Lower Extremity/diagnostic imaging , Retrospective Studies
18.
J Emerg Med ; 65(6): e551-e553, 2023 12.
Article in English | MEDLINE | ID: mdl-37879971

ABSTRACT

BACKGROUND: There are multiple reported injuries associated with cardiopulmonary resuscitation, most of them caused by the force of compressions, like sternal and rib fractures, abdominal organ injuries like splenic rupture, liver lacerations, and injuries to the upper airway and skin. Injuries related to defibrillation and cardioversion are rare, mostly related to skin and muscle injuries on where the defibrillation paddles were placed. CASE REPORT: A 52-year-old man presented to the Emergency Department with crushing chest pain. The patient was suffering from a myocardial infarction, and during percutaneous coronary intervention, had to be defibrillated on the angioplasty table. This resulted in fracture-dislocations on both shoulders. The patient was transferred to our orthopedics clinic and was operated on within 5 days of angioplasty. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early diagnosis and treatment are important, and can prevent long-term morbidity. However, cardiopulmonary resuscitation and defibrillation are acts that are most commonly performed in the emergency department. Injury prevention by controlling the patient's position, in this case, positions of the shoulders, is an important factor that emergency physicians can control and effect.


Subject(s)
Cardiopulmonary Resuscitation , Multiple Trauma , Rib Fractures , Male , Humans , Middle Aged , Shoulder , Cardiopulmonary Resuscitation/methods , Rib Fractures/complications , Emergency Service, Hospital , Multiple Trauma/complications
19.
Injury ; 54(12): 111078, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37865011

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines. METHODS: A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393. RESULTS: Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients. CONCLUSION: Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.


Subject(s)
Multiple Trauma , Pulmonary Embolism , Venous Thromboembolism , Adult , Humans , Venous Thromboembolism/etiology , Enoxaparin , Fondaparinux , Network Meta-Analysis , Anticoagulants/therapeutic use , Pulmonary Embolism/prevention & control , Hemorrhage/complications , Multiple Trauma/complications
20.
BMC Musculoskelet Disord ; 24(1): 848, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37891518

ABSTRACT

BACKGROUND: Surgical treatment of pelvic and acetabular fractures is an advanced intervention with a high risk of subsequent complications. These patients are often polytrauma patients with multiple injuries in several organ systems. The optimal timing for the definitive surgery of these fractures has been debated. The primary aim of this study was to investigate the influence of timing of definitive surgery on the rate of unplanned reoperations. Secondary aims included its influence on the occurrence of adverse events and mortality. METHODS: All patients from 18 years with a surgically treated pelvic or acetabular fracture operated at the Karolinska University Hospital in Sweden during 2010 to 2019 were identified and included. Data was collected through review of medical records and radiographs. Logistic regression analysis was performed to evaluate factors associated with unplanned reoperations and other adverse events. RESULTS: A total of 419 patients with definitive surgical treatment within 1 month of a pelvic (n = 191, 46%) or an acetabular (n = 228, 54%) fracture were included. The majority of the patients were males (n = 298, 71%) and the mean (SD, range) age was 53.3 (19, 18-94) years. A total of 194 (46%) patients had their surgery within 72 h (early surgery group), and 225 (54%) later than 72 h (late surgery group) after the injury. 95 patients (23%) had an unplanned reoperation. There was no difference in the reoperation rate between early (n = 44, 23%) and late (n = 51, 23%) surgery group (p = 1.0). A total of 148 patients (35%) had any kind of adverse event not requiring reoperation. The rate was 32% (n = 62) in the early, and 38% (n = 86) in the late surgery group (p = 0.2). When adjusting for relevant factors in regression analyses, no associations were found that increased the risk for reoperation or other adverse events. The 30-day mortality was 2.1% (n = 4) for the early and 2.2% (n = 5) for the late surgery group (p = 1.0). The 1-year mortality was 4.1% (n = 8) for the early and 7.6% (n = 17) for the late surgery group (p = 0.2). CONCLUSIONS: Early (within 72 h) definitive surgery of patients with pelvic or acetabular fractures seems safe with regard to risk for reoperation, other adverse events and mortality.


Subject(s)
Fractures, Bone , Hip Fractures , Multiple Trauma , Pelvic Bones , Spinal Fractures , Male , Humans , Female , Pelvic Bones/diagnostic imaging , Pelvic Bones/surgery , Pelvic Bones/injuries , Follow-Up Studies , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Fractures, Bone/complications , Acetabulum/diagnostic imaging , Acetabulum/surgery , Acetabulum/injuries , Pelvis/injuries , Hip Fractures/complications , Spinal Fractures/complications , Multiple Trauma/complications , Retrospective Studies
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