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1.
Animal Model Exp Med ; 7(3): 367-376, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38860566

RESUMEN

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.


Asunto(s)
Anemia , Modelos Animales de Enfermedad , Traumatismo Múltiple , Ratas Sprague-Dawley , Choque Hemorrágico , Animales , Choque Hemorrágico/complicaciones , Masculino , Anemia/etiología , Anemia/patología , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/patología , Ratas , Médula Ósea/patología , Receptor Toll-Like 4/metabolismo , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Factor Estimulante de Colonias de Granulocitos/sangre , Hemoglobinas
2.
G Ital Nefrol ; 41(3)2024 06 28.
Artículo en Italiano | MEDLINE | ID: mdl-38943323

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda , Traumatismo Múltiple , Grupo de Atención al Paciente , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Humanos , Traumatismo Múltiple/terapia , Traumatismo Múltiple/complicaciones , Fluidoterapia , Terapia de Reemplazo Renal Continuo
3.
PeerJ ; 12: e17521, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903881

RESUMEN

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.


Asunto(s)
Altitud , Traumatismo Múltiple , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/epidemiología , Masculino , Femenino , Incidencia , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Factores de Riesgo , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/epidemiología , Traumatismo Múltiple/complicaciones , Mortalidad Hospitalaria , Puntaje de Gravedad del Traumatismo , China/epidemiología , Traumatismos Torácicos/mortalidad , Traumatismos Torácicos/epidemiología , Traumatismos Torácicos/complicaciones , Unidades de Cuidados Intensivos
4.
Sci Rep ; 14(1): 13308, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858394

RESUMEN

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.


Asunto(s)
Traumatismo Múltiple , Nomogramas , Curva ROC , Choque Hemorrágico , Humanos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/etiología , Choque Hemorrágico/terapia , Masculino , Femenino , Niño , Estudios Retrospectivos , Preescolar , Adolescente , Traumatismo Múltiple/diagnóstico , Traumatismo Múltiple/complicaciones , China/epidemiología , Puntaje de Gravedad del Traumatismo , Lactante , Modelos Logísticos
5.
World J Surg ; 48(2): 350-360, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38686758

RESUMEN

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.


Asunto(s)
Tiempo de Internación , Insuficiencia Multiorgánica , Traumatismo Múltiple , Humanos , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/etiología , Femenino , Masculino , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Estudios Retrospectivos , Adulto , Traumatismo Múltiple/cirugía , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/complicaciones , Factores de Tiempo , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo , Mortalidad Hospitalaria , Estudios Prospectivos , Anciano
6.
Injury ; 55(5): 111339, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38575396

RESUMEN

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.


Asunto(s)
Fracturas Óseas , Traumatismo Múltiple , Huesos Pélvicos , Enfermedades Uretrales , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Uretra/lesiones , Fracturas Óseas/cirugía , Traumatismo Múltiple/complicaciones , Huesos Pélvicos/lesiones
7.
J Trauma Acute Care Surg ; 97(1): 96-104, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548689

RESUMEN

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.


Asunto(s)
Anticoagulantes , Traumatismo Múltiple , Procedimientos Ortopédicos , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Tromboembolia Venosa/epidemiología , Femenino , Masculino , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/métodos , Anticoagulantes/administración & dosificación , Adulto , Anciano , Estados Unidos/epidemiología , Factores de Tiempo , Centros Traumatológicos , Fracturas del Fémur/cirugía , Fracturas del Fémur/complicaciones , Tiempo de Tratamiento/estadística & datos numéricos , Huesos Pélvicos/lesiones , Factores de Riesgo , Fracturas de Cadera/cirugía , Fracturas de Cadera/complicaciones , Embolia Pulmonar/prevención & control , Embolia Pulmonar/etiología
8.
Crit Care ; 28(1): 81, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491444

RESUMEN

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.


Asunto(s)
Traumatismo Múltiple , Heridas no Penetrantes , Adulto , Humanos , Estudios Retrospectivos , Heridas no Penetrantes/terapia , Puntaje de Gravedad del Traumatismo , Soluciones Cristaloides , Hospitales , Sistema de Registros , Alemania/epidemiología , Traumatismo Múltiple/complicaciones
9.
Mol Cell Probes ; 74: 101954, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452956

RESUMEN

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.


Asunto(s)
Exosomas , MicroARNs , Traumatismo Múltiple , Sepsis , Humanos , Exosomas/genética , Interleucina-6 , MicroARNs/genética , Sepsis/complicaciones , Sepsis/genética , Traumatismo Múltiple/complicaciones
10.
Injury ; 55(4): 111464, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452698

RESUMEN

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.


Asunto(s)
Traumatismos Craneocerebrales , Traumatismo Múltiple , Humanos , Accidentes de Tránsito/prevención & control , Ciudad de Roma/epidemiología , Ciclismo/lesiones , Traumatismos Craneocerebrales/epidemiología , Traumatismos Craneocerebrales/prevención & control , Traumatismos Craneocerebrales/etiología , Traumatismo Múltiple/complicaciones , Dispositivos de Protección de la Cabeza , Evaluación de Resultado en la Atención de Salud , Demografía
11.
J Proteome Res ; 23(4): 1163-1173, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38386921

RESUMEN

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.


Asunto(s)
Oclusión con Balón , Traumatismo Múltiple , Humanos , Animales , Porcinos , Multiómica , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/terapia , Aorta , Coagulación Sanguínea , Oclusión con Balón/métodos
12.
Thromb Haemost ; 124(1): 20-31, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37604188

RESUMEN

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.


Asunto(s)
Factor Xa , Traumatismo Múltiple , Pirazoles , Piridonas , Humanos , Masculino , Animales , Porcinos , Factor Xa/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Traumatismo Múltiple/complicaciones , Traumatismo Múltiple/tratamiento farmacológico , Traumatismo Múltiple/inducido químicamente , Proteínas Recombinantes/uso terapéutico , Anticoagulantes/uso terapéutico
13.
Shock ; 61(1): 150-156, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38010084

RESUMEN

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.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Traumatismo Múltiple , Choque Hemorrágico , Trombosis , Animales , Ratas , Masculino , Choque Hemorrágico/diagnóstico por imagen , Choque Hemorrágico/terapia , Ratas Sprague-Dawley , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Resucitación/métodos , Trastornos de la Coagulación Sanguínea/etiología , Músculo Esquelético/diagnóstico por imagen , Traumatismo Múltiple/complicaciones , Perfusión , Modelos Animales de Enfermedad
14.
J Trauma Acute Care Surg ; 96(1): 17-25, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37853556

RESUMEN

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.


Asunto(s)
Anemia , Contusiones , Traumatismo Múltiple , Ratas , Animales , Humanos , Masculino , Femenino , Médula Ósea , Ratas Sprague-Dawley , Anemia/etiología , Contusiones/complicaciones , Hemoglobinas , Traumatismo Múltiple/complicaciones , Eritropoyesis
15.
Int Immunopharmacol ; 127: 111377, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38104369

RESUMEN

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.


Asunto(s)
Ferroptosis , Linfopenia , Traumatismo Múltiple , Sepsis , Humanos , Linfocitos T CD4-Positivos , Traumatismo Múltiple/complicaciones
16.
BMC Emerg Med ; 23(1): 144, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053029

RESUMEN

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.


Asunto(s)
Traumatismo Múltiple , Trombosis , Trombosis de la Vena , Humanos , Estudios Prospectivos , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Medición de Riesgo , Factores de Riesgo , Trombosis/complicaciones , Traumatismo Múltiple/complicaciones , Extremidad Inferior/diagnóstico por imagen , Estudios Retrospectivos
17.
J Emerg Med ; 65(6): e551-e553, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37879971

RESUMEN

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.


Asunto(s)
Reanimación Cardiopulmonar , Traumatismo Múltiple , Fracturas de las Costillas , Masculino , Humanos , Persona de Mediana Edad , Hombro , Reanimación Cardiopulmonar/métodos , Fracturas de las Costillas/complicaciones , Servicio de Urgencia en Hospital , Traumatismo Múltiple/complicaciones
18.
Injury ; 54(12): 111078, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37865011

RESUMEN

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.


Asunto(s)
Traumatismo Múltiple , Embolia Pulmonar , Tromboembolia Venosa , Adulto , Humanos , Tromboembolia Venosa/etiología , Enoxaparina , Fondaparinux , Metaanálisis en Red , Anticoagulantes/uso terapéutico , Embolia Pulmonar/prevención & control , Hemorragia/complicaciones , Traumatismo Múltiple/complicaciones
19.
BMC Musculoskelet Disord ; 24(1): 848, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891518

RESUMEN

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.


Asunto(s)
Fracturas Óseas , Fracturas de Cadera , Traumatismo Múltiple , Huesos Pélvicos , Fracturas de la Columna Vertebral , Masculino , Humanos , Femenino , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones , Estudios de Seguimiento , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Acetábulo/lesiones , Pelvis/lesiones , Fracturas de Cadera/complicaciones , Fracturas de la Columna Vertebral/complicaciones , Traumatismo Múltiple/complicaciones , Estudios Retrospectivos
20.
Immun Inflamm Dis ; 11(9): e1031, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37773708

RESUMEN

OBJECTIVE: This study aimed to explore potential risk factors for the occurrence of multiple organ dysfunction syndrome (MODS) in patients with multiple injuries by evaluating neutrophil-to-lymphocyte ratio (NLR)-associated trauma severity. METHODS: This retrospective case-control study included 95 patients with multiple injuries, who were admitted to our hospital (between January 2018 and December 2020). Clinical data including gender, age, underlying disease, number of injury sites (NIS), injury severity score (ISS), hemoglobin level within 24 h of admission (HL-24h), neutrophil count (NC), white blood cell count, platelet count (PC), NLR, d-dimer level, activated partial thromboplastin time (APTT), complicated shock within 24 h of admission (CS-24h), length of stay, as well as prognostic outcome was systematically analyzed. According to MODS occurrence, patients were divided into a MODS group (n = 27) and a non-MODS group (n = 68). The risk factors affecting patients with multiple injuries complicated by MODS were identified using univariate and multivariate logistic regression analyses. Candidate risk factors were further analyzed using receiver operating characteristic (ROC) curves. RESULTS: Univariate analysis revealed a significant difference between the MODS and non-MODA groups in terms of NIS, ISS, HL-24h, PC, APTT, d-dimer level, CS-24h, NLR, NC, prognostic outcome, and other indicators (p < .05). Multivariate logistic regression analysis showed that  d-dimer levels within 24 h of admission and ISS, NLR, and CS-24h were significantly associated with multiple injuries complicated by MODS. Compared with the non-MODS controls, the NLR in the MODS group showed a much higher level and tended to rise with the increase in ISS score, indicating a significant intergroup difference (p < .05). The ROC curve analysis results suggested that the NLR had good sensitivity and specificity for predicting the prognosis of patients with MODS with multiple injuries. CONCLUSION: d-dimer level, ISS, NLR, and CS-24h are important risk factors for MODS in patients with multiple injuries. Notably, NLR expression may be a good indicator of injury severity and predictor of the occurrence of MODS in patients with multiple injuries. Therefore, assessment of injury severity and coagulation function, active resuscitation, as well as prevention of infection should be emphasized during treatment of multiple injuries, to reduce and prevent the risk of MODS in patients with multiple injuries.


Asunto(s)
Traumatismo Múltiple , Neutrófilos , Humanos , Insuficiencia Multiorgánica/epidemiología , Insuficiencia Multiorgánica/etiología , Estudios Retrospectivos , Estudios de Casos y Controles , Linfocitos , Traumatismo Múltiple/complicaciones , Pronóstico
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