Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 348
Filtrar
3.
J Spinal Cord Med ; : 1-7, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043943

RESUMO

Context/Objective: Pneumonia is the leading cause of death after acute spinal cord injury (SCI). High tidal volume ventilation (HVtV) is used in SCI rehabilitation centers to overcome hypoventilation while weaning patients from the ventilator. Our objective was to determine if HVtV in the acute post-injury period in SCI patients is associated with lower incidence of ventilator-associated pneumonia (VAP) when compared to patients receiving standard tidal volume ventilation.Design: Cohort study.Setting: Red Duke Trauma Institute, University of Texas Health Science Center at Houston, TX, USA.Participants: Adult Acute Cervical SCI Patients, 2011-2018.Interventions: HVtV.Outcome measures: VAP, ventilator dependence at discharge, in-hospital mortality.Results: Of 181 patients, 85 (47%) developed VAP. HVtV was utilized in 22 (12%) patients. Demographics, apart from age, were similar between patients who received HVtV and standard ventilation; patients were younger in the HVtV group. VAP developed in 68% of patients receiving HVtV and in 44% receiving standard tidal volumes (P = 0.06). After adjustment, HVtV was associated with a 1.96 relative risk of VAP development (95% credible interval 1.55-2.17) on Bayesian analysis. These results correlate with a >99% posterior probability that HVtV is associated with increased VAP when compared to standard tidal volumes. HVtV was also associated with increased rates of ventilator dependence.Conclusions: While limited by sample size and selection bias, our data revealed an association between HVtV and increased VAP. Further investigation into optimal early ventilation settings is needed for SCI patients, who are at a high risk of VAP.

4.
J Burn Care Res ; 41(3): 604-611, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32011688

RESUMO

On August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation injury due to exposure from a fire environment, and in addition, address two more areas proposed by the American Burn Association Research Committee that are critical to burn care but may have current translational research gaps (inflammatory response and hypermetabolic response). Representatives from the Underwriters Laboratories Firefighter Safety Research Institute and the Bureau of Alcohol, Tobacco, Firearms and Explosives Fire Research Laboratory presented the state of the science in their fields, highlighting areas that required further investigation and guidance from the burn community. Four areas were discussed by the full 24 participant group and in smaller groups: Basic and Translational Understanding of Inhalation Injury, Thermal Contact and Resulting Injury, Systemic Inflammatory Response and Resuscitation, and Hypermetabolic Response and Healing. A primary finding was the need for validating historic models to develop a set of reliable data on contact time and temperature and resulting injury. The working groups identified common areas of focus across each subtopic, including gaining an understanding of individual response to injury that would allow for precision medicine approaches. Predisposed phenotype in response to insult, the effects of age and sex, and the role of microbiomes could all be studied by employing multi-omic (systems biology) approaches.

5.
J Am Coll Surg ; 230(4): 417-425, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954820

RESUMO

BACKGROUND: Occult hypoperfusion (OH), or global hypoperfusion with normal vital signs, is a risk factor for poor outcomes in elderly trauma patients. We hypothesized that OH is associated with worse outcomes than shock in both young and elderly trauma patients. METHODS: We conducted a single-center cohort study of adult (16 years or older) trauma patients from 2016 to 2018 with base excess measured on arrival. Perfusion states were defined as shock if heart rate was >120 beats/min or systolic blood pressure was <90 mmHg; OH if base excess was < -2 mmol/L, heart rate was <120 beats/min, and systolic blood pressure was >90 mmHg; and normal for all others. Patients were stratified as young (younger than 55 years) or elderly (55 years or older). Bayesian regression was used to assess the relationship between arrival perfusion state and mortality or serious complication. RESULTS: Of 3,126 included patients, 808 were elderly. Rates of shock (33% and 31%) and OH (25% and 23%) were similar in young and elderly patients, respectively. OH on arrival was associated with higher odds of mortality or serious complication than normal perfusion, regardless of age group. Compared with shock, OH was associated with an odds ratio of 1.21 (95% CI, 0.97 to 1.52, posterior probability 96%) for poor outcomes in elderly patients and an odds ratio of 0.52 (95% CI, 0.42 to 0.65, posterior probability <1%) for poor outcomes in younger patients. Findings were similar on sensitivity analysis, excluding shock patients with base excess ≥ -2 mmol/L. CONCLUSIONS: In elderly but not younger patients, OH is associated with worse outcomes than shock. Although shock parameters might need to be redefined in elderly patients, more attention is necessary for the diagnosis and treatment of all hypoperfused states in this age group.

6.
Stem Cells Transl Med ; 9(4): 491-498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31903737

RESUMO

Clinical trials in trauma populations are exploring the use of clinical cellular therapeutics (CCTs) like human mesenchymal stromal cells (MSC) and mononuclear cells (MNC). Recent studies demonstrate a procoagulant effect of these CCTs related to their expression of tissue factor (TF). We sought to examine this relationship in blood from severely injured trauma patients and identify methods to reverse this procoagulant effect. Human MSCs from bone marrow, adipose, and amniotic tissues and freshly isolated bone marrow MNC samples were tested. TF expression and phenotype were quantified using flow cytometry. CCTs were mixed individually with trauma patients' whole blood, assayed with thromboelastography (TEG), and compared with healthy subjects mixed with the same cell sources. Heparin was added to samples at increasing concentrations until TEG parameters normalized. Clotting time or R time in TEG decreased relative to the TF expression of the CCT treatment in a logarithmic fashion for trauma patients and healthy subjects. Nonlinear regression curves were significantly different with healthy subjects demonstrating greater relative decreases in TEG clotting time. In vitro coadministration of heparin normalized the procoagulant effect and required dose escalation based on TF expression. TF expression in human MSC and MNC has a procoagulant effect in blood from trauma patients and healthy subjects. The procoagulant effect is lower in trauma patients possibly because their clotting time is already accelerated. The procoagulant effect due to MSC/MNC TF expression could be useful in the bleeding trauma patient; however, it may emerge as a safety release criterion due to thrombotic risk. The TF procoagulant effect is reversible with heparin.

8.
Thromb Res ; 187: 131-138, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31986476

RESUMO

BACKGROUND: The high incidence of venous thromboembolism (VTE) following trauma persists in spite of aggressive thromboprophylaxis strategies. Approximately half of VTE patients do not achieve the recommended anti-FXa response to enoxaparin anticoagulation (0.1-0.4 IU/mL), however, research to explain or correct this phenomenon is lacking. We hypothesized that antithrombin III (AT) deficiency is associated with poor enoxaparin responsiveness in trauma patients that develop VTE which can be reversed through supplementation with AT. METHODS AND FINDINGS: A retrospective cohort study was performed on plasma collected from trauma patients who did and did not develop pulmonary embolism (PE) as well as healthy volunteers. AT levels, thrombin generation, and anti-FXa levels were measured in the collected plasma at baseline and in response to supplementation with AT concentrate at 120-200% or plasma (30% volume). A total of 54 PE patients and 46 non-PE patients were enrolled in this study for analysis. Compared to healthy volunteers, trauma patients had lower levels of AT, elevated thrombin generation, and lower anti-FXa levels in response to enoxaparin. Moreover, thrombin generation was higher and responses to enoxaparin were lower in patients who developed PE compared to those who did not develop PE. We found that supplementation with AT, but not plasma, increased AT levels and improved enoxaparin-mediated inhibition of thrombin generation. CONCLUSIONS: Supplementation with AT may provide a novel adjunct therapy to increase the effectiveness of enoxaparin thromboprophylaxis and reduce the incidence of VTE in the trauma population.

9.
Shock ; 53(2): 156-163, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31389906

RESUMO

BACKGROUND: Endothelial dysfunction during hemorrhagic shock (HS) is associated with loss of cell-associated syndecan-1 (Sdc1) and hyperpermeability. Fresh frozen plasma (FFP) preserves Sdc1 and reduces permeability following HS, although the key mediators remain unknown. Antithrombin III (ATIII) is a plasma protein with potent anti-inflammatory and endothelial protective activity. We hypothesized that the protective effects of FFP on endothelial Sdc1 and permeability are mediated, in part, through ATIII. METHODS: ATIII and Sdc1 were measured in severely injured patients upon admission (N = 125) and hospital day 3 (N = 90) for correlation analysis. In vitro effects of ATIII on human lung microvascular endothelial cells (HLMVECs) were determined by pretreating cells with vehicle, FFP, ATIII-deficient FFP, or purified ATIII followed by TNFα stimulation. Sdc1 expression was measured by immunostaining and permeability by electrical impedance. To determine the role of ATIII in vivo, male mice were subjected to a fixed pressure exsanguination model of HS, followed by resuscitation with FFP, ATIII-deficient FFP, or ATIII-deficient FFP with ATIII repletion. Lung Sdc1 expression was assessed by immunostaining. RESULTS: Pearson correlation analysis showed a significant negative correlation between plasma levels of Sdc1 and ATIII (R = -0.62; P < 0.0001) in injured patients on hospital day 3. Also, in vitro, FFP and ATIII prevented TNFα-induced permeability (P < 0.05 vs TNFα) in HLMVECs. ATIII-deficient FFP had no effect; however, ATIII restoration reestablished its protective effects in a dose-dependent manner. Similarly, FFP and ATIII prevented TNFα-induced Sdc1 shedding in HLMVECs; however, ATIII-deficient FFP did not. In mice, Sdc1 expression was increased following FFP resuscitation (1.7 ±â€Š0.5, P < 0.01) vs. HS alone (1.0 ±â€Š0.3); however, no improvement was seen following ATIII-deficient FFP treatment (1.3 ±â€Š0.4, P = 0.3). ATIII restoration improved Sdc1 expression (1.5 ±â€Š0.9, P < 0.05) similar to that of FFP resuscitation. CONCLUSIONS: ATIII plays a role in FFP-mediated protection of endothelial Sdc1 expression and barrier function, making it a potential therapeutic target to mitigate HS-induced endothelial dysfunction. Further studies are needed to elucidate the mechanisms by which ATIII protects the endothelium.

10.
Shock ; 53(3): 317-326, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31045988

RESUMO

OBJECTIVES: To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII); specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal intensive care unit. SUBJECTS: Thirty-six adult female sheep were surgically prepared and allocated into five groups (Sham (no SII), n = 6; 1 mg/kg/d CC10, n = 8; 3 mg/kg/d CC10, n = 7; 10 mg/kg/d CC10, n = 8; Control SII, n = 7). INTERVENTIONS: All groups except the sham group were subjected to SII with cooled cotton smoke. Then, the animals were placed on a ventilator, treated with 1, 3, and 10 mg/kg/d of intravenous rhCC10 or vehicle, divided evenly into two administrations per day every 12 h, fluid resuscitated, and monitored for 48 h in a conscious state. MEASUREMENTS AND MAIN RESULTS: The group treated with 10 mg/kg/d rhCC10 attenuated changes in the following variables: PaO2/FiO2 ratio, oxygenation index, and peak inspiratory pressure; neutrophil content in the airway and myeloperoxidase levels; obstruction of the large and small airways; systemic leakage of fluid and proteins, and pulmonary edema. CONCLUSIONS: In this study, high-dose rhCC10 significantly attenuated ARDS progression and lung dysfunction and significantly reduced systemic extravasation of fluid and proteins, normalizing fluid balance. Based on these results, rhCC10 may be considered a novel therapeutic option for the treatment of SII-induced ARDS.

11.
Ann Surg ; 271(2): 375-382, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30067544

RESUMO

OBJECTIVE: To establish a trauma preventable/potentially preventable death rate (PPPDR) within a heavily populated county in Texas. SUMMARY: The National Academies of Sciences estimated the trauma preventable death rate in the United States to be 20%, issued a call for zero preventable deaths, while acknowledging that an accurate preventable death rate was lacking. In this absence, effective strategies to improve quality of care across trauma systems will remain difficult. METHODS: A retrospective review of death-related records that occurred during 2014 in Harris County, TX, a diverse population of 4.4 million. Patient demographics, mechanism of injury, cause, timing, and location of deaths were assessed. Deaths were categorized using uniform criteria and recorded as preventable, potentially preventable or nonpreventable. RESULTS: Of 1848 deaths, 85% had an autopsy and 99.7% were assigned a level of preventability, resulting in a trauma PPPDR of 36.2%. Sex, age, and race/ethnicity varied across preventability categories (P < 0.01). Of 847 prehospital deaths, 758 (89.5%) were nonpreventable. Among 89 prehospital preventable/potentially preventable (P/PP) deaths, hemorrhage accounted for 55.1%. Of the 657 initial acute care setting deaths, 292 (44.4%) were P/PP; of these, hemorrhage, sepsis, and traumatic brain injury accounted for 73.3%. Of 339 deaths occurring after initial hospitalization, 287 (84.7%) were P/PP, of these 117 resulted from sepsis and 31 from pulmonary thromboembolism, accounted for 51.6%. CONCLUSIONS: The trauma PPPDR was almost double that estimated by the National Academies of Sciences. Data regarding P/PP deaths offers opportunity to target research, prevention, intervention, and treatment corresponding to all phases of the trauma system.

12.
J Surg Res ; 246: 605-613, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668435

RESUMO

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.


Assuntos
Transtornos Plaquetários/diagnóstico , Plaquetas/fisiologia , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/fisiologia , Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Transtornos Plaquetários/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Tromboelastografia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Adulto Jovem
13.
Pediatr Surg Int ; 36(2): 179-189, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31701301

RESUMO

PURPOSE: Although trauma is the leading cause of death for the pediatric population, few studies have addressed the preventable/potentially preventable death rate (PPPDR) attributable to trauma. METHODS: This is a retrospective study of trauma-related death records occurring in Harris County, Texas in 2014. Descriptive and Chi-squared tests were conducted for two groups, pediatric and adult trauma deaths in relation to demographic characteristics, mechanism of injury, death location and survival time. RESULTS: There were 105 pediatric (age < 18 years) and 1738 adult patients. The PPPDR for the pediatric group was 21.0%, whereas the PPPDR for the adult group was 37.2% (p = 0.001). Analysis showed fewer preventable/potentially preventable (P/PP) deaths resulting from any blunt trauma mechanism in the pediatric population than in the adult population (19.6% vs. 48.4%, p < 0.001). Amongst the pediatric population, P/PP traumatic brain injury (TBI) were more common in the youngest age range (age 0-5) vs. the older (6-12 years) pediatric and adolescent (13-17 years) patients. CONCLUSION: Our results identify areas of opportunities for improving pediatric trauma care. Although the overall P/PP death rate is lower in the pediatric population than the adult, opportunities for improving initial acute care, particularly TBI, exist.

14.
Neurogastroenterol Motil ; 32(3): e13757, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31722447

RESUMO

BACKGROUND: Although the development of ileus is widespread and negatively impacts patient outcomes, the mechanism by which ileus develops remains unclear. The purpose of our study was to examine the contribution of myogenic mechanisms to postoperative ileus development and the involvement of inflammation in mediating intestinal smooth muscle dysfunction. METHODS: Contractile activity and the effects of CXCL1 were studied in a gut manipulation model. KEY RESULTS: Contraction amplitude in the ileum decreased significantly, while tone increased significantly in response to gut manipulation. Differences in contraction amplitude were affected by tetrodotoxin at earlier time points, but not at later time points. Agonist-induced contractions in the small intestine decreased significantly with ileus development. Intestinal transit slowed significantly after the induction of ileus. Myosin light chain phosphorylation was significantly decreased and edema increased significantly in the intestinal wall. Conditioned media from mechanically activated macrophages depressed intestinal contractile activity. CXCL1 (GroA) was significantly increased in the mechanically activated macrophages and intestinal smooth muscle within 1 hour after induction of ileus compared with control cells and sham animals, respectively. Treatment with CXCL1 significantly decreased contraction amplitude and agonist-induced contractile activity and increased tone in the small intestine. In the gut manipulation model, treatment with a CXCR2 antagonist prevented the decrease in agonist-induced contractile activity but not contraction amplitude. CONCLUSIONS & INFERENCES: These data suggest that CXCL1, released from macrophages during intestinal wall stress, can suppress intestinal contractile activity. CXCL1 is a potential target for preventing or treating ileus in trauma patients.

15.
J Trauma Acute Care Surg ; 88(1): 87-93, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31464874

RESUMO

PURPOSE: Following US military implementation of a cold-stored whole blood program, several US trauma centers have begun incorporating uncrossmatched, group O cold-stored whole blood into civilian trauma resuscitation. We set out to evaluate the safety profile, transfusion reactions events, and impact of low-titer group O whole blood (LTO-WB) at our center. METHODS: In November 2017, we added LTO-WB to each of our helicopters and to our emergency department (ED) refrigerator, alongside that of existing red blood cells and plasma. We collected information on all patients with trauma receiving prehospital or ED transfusion of uncrossed, emergency release blood products between November 2017 and June 2018. Patients were divided into those receiving any LTO-WB and those receiving only red blood cell and or plasma (COMP). Serial hemolysis panels were obtained at 3 hours, 24 hours, and 48 hours. All data were run using STATA 12.1. Statistical significance was set at p < 0.05. RESULTS: One hundred ninety-eight patients received LTO-WB and 152 patients received COMP. There were no differences in age, sex, or mechanism. The LTO-WB patients had higher chest Abbreviated Injury Scale scores (median, 3 vs. 2; p = 0.027), as well as worse arrival base excess (median, -7 vs. -5; p = 0.014) and lactate (5.1 vs. 3.5; p < 0.001). The LTO-WB patients received less post-ED blood products than the COMP patients (median, 0 vs. 3; p = 0.001). There was no difference in survival (LTO-WB, 73%; COMP, 74%; p = 0.805). There were only two suspected transfusion reactions, both in the COMP group (p = 0.061). There was no difference in hemolysis panel values. Controlling for age, severity of injury, and prehospital physiology, LTO-WB was associated with a 53% reduction in post-ED blood product transfusion (odds ratio, 0.47; 0.23-0.94 95% CI; p = 0.033) and two-fold increase in likelihood of survival (odds ratio, 2.19; 1.01-4.76 95% CI; p = 0.047). CONCLUSION: Low-titer group O whole blood has similar evidence of laboratory hemolysis, similar transfusion reaction rates, and is associated with a reduction in post-ED transfusions and increase likelihood of survival. LEVEL OF EVIDENCE: Therapeutic, Level II.

16.
Am J Surg ; 219(1): 140-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31076074

RESUMO

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct used to temporize uncontrolled abdominopelvic hemorrhage. No published clinical data exist that describe average catheter lengths or balloon fill volumes necessary to occlude the aorta. METHODS: A prospective, single-institution registry was queried for patients who underwent placement of a Prytime ER-REBOA™ catheter. Demographic, catheter, hemodynamic, and morphometric data were measured. Linear regression analyses were performed to identify variables associated with insertion distances and balloon volumes. RESULTS: 45 patients underwent supraceliac REBOA: median catheter insertion distance 45 cm [IQR 42-46], balloon inflation volume 14 mL [IQR 8-19], systolic blood pressure (SBP) augmentation 50 mmHg [IQR 35-55]. 14 patients underwent infrarenal deployment: median catheter insertion distance 28.5 cm [IQR 26.5-32.5], balloon volume 10 mL [IQR 5-15]; SBP augmentation 55 mmHg [IQR 40-65]. Patient body metrics were not associated with catheter length or balloon volume. CONCLUSION: A wide range of catheter insertion distances and balloon fill volumes were necessary for correct REBOA positioning and occlusion. No single patient metric accurately correlated with catheter distance or balloon volume. LEVEL OF EVIDENCE: Level IV, Prognostic.


Assuntos
Aorta Abdominal , Oclusão com Balão , Cateteres , Hemorragia/terapia , Ressuscitação/instrumentação , Ressuscitação/métodos , Abdome , Adulto , Cateterismo/métodos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pelve , Estudos Prospectivos , Adulto Jovem
17.
Shock ; 53(1): 24-34, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939502

RESUMO

INTRODUCTION: Traumatic brain injury (TBI) is associated with secondary injury to the central nervous system (CNS) via inflammatory mechanisms. The combination of polytrauma and TBI further exacerbates the inflammatory response to injury; however, combined injury phenomena have not been thoroughly studied. In this study, we examined the inflammatory differences between patients with TBI versus patients with polytrauma, but no TBI (polytrauma). We hypothesize that patients with TBI have a heightened early inflammatory response compared with polytrauma. METHODS: We conducted a single-center retrospective study of a cohort of patients with polytrauma, who were enrolled in the PROPPR study. These patients had blood samples prospectively collected at eight time points in the first 3 days of admission. Using radiological data to determine TBI, our polytrauma cohort was dichotomized into TBI (n = 30) or polytrauma (n = 54). Inflammatory biomarkers were measured using ELISA. Data across time were compared for TBI versus polytrauma groups using Wilcoxon rank-sum test. Network analysis techniques were used to systematically characterize the inflammatory responses at admission. RESULTS: Patients with TBI (51.6%) had a higher 30-day mortality compared with polytrauma (16.9%) (P <0.001). Expression levels of IL6, IL8, and CCL2 were elevated from the 2-h through 24-h time points, becoming significant at the 6-h time point (IL6, IL8, and CCL2; P <0.05) (). CSF3 showed a similar pattern, but did not attain significance. TBI and polytrauma networks underwent diverging trends from admission to the 6-h time point. CONCLUSION: Patients with TBI demonstrated upregulations in proinflammatory cytokines IL6, IL8, and CCL2. Utilizing informatics methods, we were able to identify temporal differences in network trends, as well as uncharacterized cytokines and chemokines in TBI. These data suggest TBI induces a distinct inflammatory response and pathologically heightened inflammatory response in the presence of polytrauma and may propagate worsened patient outcomes including mortality.

18.
Burns ; 46(2): 386-393, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866179

RESUMO

Shedding of syndecan-1 from the endothelial glycocalyx layer (EGL), referred to as endotheliopathy of trauma (EoT), is associated with poorer outcomes. This study aims to determine if EoT is also present in the burn population. We enrolled 458 burn and non-burn trauma patients at a Level 1 trauma center and defined EoT by a syndecan-1 level of ≥40 ng/mL. Sixty-eight of the enrolled patients had burns with a median TBSA of 19%, with 27.9% also suffering inhalational injury (II). Mortality was similar between the burn and non-burn group, also for patients with EoT. The incidence of II was significantly greater in the EoT+ burn group compared to the EoT- group (p = 0.038). Patients with II received significantly larger amounts of i.v. fluids (p = 0.001). The incidence of EoT was significantly different between the II-groups, as was mortality (pEoT = 0.038, pmortality < 0.001). EoT is attributed to the shock rather than the mechanism of trauma and may in burns be associated to II rather than TBSA. Patients with burns and II had worse outcomes and higher mortality compared to patients with burns alone. Burn injury induces EGL shedding similar to that in non-burn patients with EoT, and results in similar higher rate of mortality.

19.
Sci Rep ; 9(1): 17676, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776369

RESUMO

Every year more than 500,000 deaths are attributed to trauma worldwide and severe hemorrhage is present in most of them. Transfused platelets have been shown to improve survival in trauma patients, although its mechanism is only partially known. Platelet derived-extracellular vesicles (PEVs) are small vesicles released from platelets upon activation and/or mechanical stimulation and many of the benefits attributed to platelets could be mediated through PEVs. Based on the available literature, we hypothesized that transfusion of human PEVs would promote hemostasis, reduce blood loss and attenuate the progression to hemorrhagic shock following severe trauma. In this study, platelet units from four different donors were centrifuged to separate platelets and PEVs. The pellets were washed to obtain plasma-free platelets to use in the rodent model. The supernatant was subjected to tangential flow filtration for isolation and purification of PEVs. PEVs were assessed by total count and particle size distribution by Nanoparticle Tracking Analysis (NTA) and characterized for cells of origin and expression of EV specific-surface and cytosolic markers by flow cytometry. The coagulation profile from PEVs was assessed by calibrated automated thrombography (CAT) and thromboelastography (TEG). A rat model of uncontrolled hemorrhage was used to compare the therapeutic effects of 8.7 × 108 fresh platelets (FPLT group, n = 8), 7.8 × 109 PEVs (PEV group, n = 8) or Vehicle (Control, n = 16) following severe trauma. The obtained pool of PEVs from 4 donors had a mean size of 101 ± 47 nm and expressed the platelet-specific surface marker CD41 and the EV specific markers CD9, CD61, CD63, CD81 and HSP90. All PEV isolates demonstrated a dose-dependent increase in the rate and amount of thrombin generated and overall clot strength. In vivo experiments demonstrated a 24% reduction in abdominal blood loss following liver trauma in the PEVs group when compared with the control group (9.9 ± 0.4 vs. 7.5 ± 0.5 mL, p < 0.001>). The PEV group also exhibited improved outcomes in blood pressure, lactate level, base excess and plasma protein concentration compared to the Control group. Fresh platelets failed to improve these endpoints when compared to Controls. Altogether, these results indicate that human PEVs provide pro-hemostatic support following uncontrolled bleeding. As an additional therapeutic effect, PEVs improve the outcome following severe trauma by maintaining hemodynamic stability and attenuating the development of ischemia, base deficit, and cardiovascular shock.

20.
J Am Coll Surg ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31733328

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in severely injured trauma patients and is associated with poor outcomes. A positive fluid balance is associated with AKI and poor long-term renal outcomes among general ICU and cardiac surgery patients. Currently, the optimal endpoint of resuscitation of severely injured trauma patients is unknown, which may result in excess fluid administration. We hypothesized that positive fluid balance is common after severe trauma and is associated with increased AKI development. STUDY DESIGN: A cohort study of adult (≥16 years old) trauma patients requiring ICU admission from January 2017 to June of 2017 was conducted. Patients were excluded for early death, rhabdomyolysis, or previous history of end-stage renal disease or congestive heart failure. Acute kidney injury within 7 days of admission was defined according to Kidney Disease Improving Global Outcomes creatinine-based criteria. Univariate and multivariable analyses were performed. RESULTS: Of 364 patients, 74% were male. The median age was 41 years (interquartile range [IQR] 27 to 59 years), and the median Injury Severity Score (ISS) was 18 (IQR 10 to 29). Positive fluid balance (>2 L) was observed in 49% of patients. Acute kidney injury was diagnosed in 105 (29%) patients. After adjustment, there was an increased risk of AKI with a positive fluid balance >2 L (relative risk [RR] 1.98 [95% CI 1.24 to 3.17]). Additionally, the risk of AKI incrementally increased by 1.22 with each liter fluid positive above a zero balance (95% CI 1.11 to 1.34). CONCLUSIONS: Positive fluid balance in excess of 2 L at 48 hours occurs in half of severely injured trauma patients, and fluid positivity is independently and incrementally associated with AKI development. Fluid responsiveness should be investigated as an end point of post-traumatic resuscitation to prevent unnecessary fluid administration and subsequent AKI.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA