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Proceedings of the National Academy of... Feb 2019Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory...
Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo. The results reveal striking spatial regulation of platelet activation and fibrin formation that could not be inferred from studies performed ex vivo. As in the microcirculation, where previous studies have been performed, gradients of platelet activation are readily apparent, as is an asymmetrical distribution of fibrin deposition and thrombin activity. Both are oriented from the outer to the inner surface of the damaged vessel wall, with a greater extent of platelet activation and fibrin accumulation on the outside than the inside. Further, we show that the importance of P2Y signaling in establishing a competent hemostatic plug is related to the size of the injury, thus limiting its contribution to hemostasis to specific physiologic contexts. Taken together, these studies offer insights into the organization of hemostatic plugs, provide a detailed understanding of the adverse bleeding associated with a widely prescribed class of antiplatelet agents, and highlight differences between hemostasis and thrombosis that may suggest alternative therapeutic approaches.
Topics: Animals; Blood Coagulation; Blood Platelets; Disease Models, Animal; Fibrin; Hemostasis; Male; Mice; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis; Veins; Wounds and Injuries
PubMed: 30674670
DOI: 10.1073/pnas.1813642116 -
Journal of Cellular and Molecular... Jan 2020Prolonged and persistent hypermetabolism and excessive inflammatory response after severe trauma is detrimental and associated with poor outcome. The predisposing...
Prolonged and persistent hypermetabolism and excessive inflammatory response after severe trauma is detrimental and associated with poor outcome. The predisposing pathology or signals mediating this complex response are essentially unknown. As the liver is the central organ mediating the systemic metabolic responses and considering that adult hepatic stem cells are on top of the hierarchy of cell differentiation and may pass epigenetic information to their progeny, we asked whether liver progenitor cells are activated, signal hypermetabolism upon post-traumatic cellular stress responses, and pass this to differentiated progeny. We generated Sox9CreER : ROSA26 EYFP mice to lineage-trace the periportal ductal progenitor cells (PDPCs) and verify the fate of these cells post-burn. We observed increased proliferation of PDPCs and their progeny peaking around two weeks post-burn, concomitant with the hepatomegaly and the cellular stress responses. We then sorted out PDPCs, PDPC-derived hepatocytes and mature hepatocytes, compared their transcriptome and showed that PDPCs and their progeny present a significant up-regulation in signalling pathways associated with inflammation and metabolic activation, contributing to persistent hypermetabolic and hyper-inflammatory state. Furthermore, concomitant down-regulation of LXR signalling in PDPCs and their progeny implicates the therapeutic potential of early and short-term administration of LXR agonists in ameliorating such persistent hypermetabolism.
Topics: Animals; Burns; Cell Proliferation; Down-Regulation; Hepatomegaly; Hot Temperature; Inflammation; Liver; Liver X Receptors; Mice, Transgenic; Portal System; Receptors, Retinoic Acid; Signal Transduction; Stem Cells; Stress, Physiological; Transcriptome; Wounds and Injuries
PubMed: 31793707
DOI: 10.1111/jcmm.14845 -
Surgery Dec 2019Traumatic injury and the presence of a central venous catheter are 2 of the strongest risk factors for venous thromboembolism in children. The purpose of this study was... (Comparative Study)
Comparative Study
BACKGROUND
Traumatic injury and the presence of a central venous catheter are 2 of the strongest risk factors for venous thromboembolism in children. The purpose of this study was to determine the incidence of symptomatic, catheter-associated thrombosis in critically injured children. We hypothesized that femoral venous catheters are associated with a greater rate of thrombotic complications when compared with all other central venous access points.
METHODS
We reviewed a retrospective cohort (2006-2016) of injured children (≤18 years) admitted to a pediatric intensive care unit with central access placed ≤7 days from admission. Symptomatic, catheter-associated thrombosis was determined by radiographic evidence. Poisson regression was used to compare the incidence of catheter-associated thrombosis per 1,000 catheter days between femoral and nonfemoral catheters. All comparisons were 2-tailed with α = 0.05.
RESULTS
We examined 209 pediatric trauma patients with central access (65% femoral, 19% subclavian, 11% arm vein, and 5% internal jugular). Femoral catheters were removed earlier (median [interquartile range] 4 [2-7] vs 8 [3-12] days, P < .001) and were larger in diameter (5 Fr [4-7] vs 4 Fr [4-4], P < .001) when compared with all other catheters. Catheter-associated thrombosis was more frequent in femoral versus nonfemoral catheters (18.4 vs 3.5 per 1,000 catheter days, P = .01).
CONCLUSION
Femoral venous catheters are associated with a greater incidence of symptomatic, catheter-associated thrombosis in pediatric trauma patients. When central venous access is indicated for injured children, the femoral site should be avoided. If a femoral venous catheter is necessary, use of a smaller catheter should be considered.
Topics: Age Factors; Catheterization, Central Venous; Central Venous Catheters; Child; Child, Preschool; Female; Femoral Vein; Humans; Incidence; Infant; Male; Retrospective Studies; Risk Factors; Thrombosis; Wounds and Injuries
PubMed: 31526580
DOI: 10.1016/j.surg.2019.05.018 -
Journal of Vascular Surgery. Venous and... May 2019Portal vein injury is uncommon, and the optimal treatment is controversial. We compared the outcomes of ligation vs repair of portal injury using the National Trauma... (Comparative Study)
Comparative Study
BACKGROUND
Portal vein injury is uncommon, and the optimal treatment is controversial. We compared the outcomes of ligation vs repair of portal injury using the National Trauma Data Bank.
METHODS
Adult patients who suffered portal injury were identified from the National Trauma Data Bank (2002-2014) by International Classification of Diseases, Ninth Revision diagnosis codes. Patients were stratified by treatment modality into no surgery, ligation, and surgical repair using International Classification of Diseases procedure codes. Outcomes including hospital mortality, bowel resection, and length of stay between ligation and surgical repair were compared by Kruskal-Wallis or Fisher exact test as appropriate. Multivariable analyses were performed with logistic regression.
RESULTS
Among 752 patients with portal vein injury, 345 patients (45.9%) underwent no surgery, 103 patients (13.7%) had ligation, and 304 (40.4%) underwent surgical repair. Overall mortality was 49%. Age, sex, Injury Severity Score, Glasgow Coma Scale score, presenting blood pressure, and heart rate were similar between groups that underwent ligation and surgical repair. The hospital mortality (59.2% vs 47.7%; P = .08), bowel resection (1.9% vs 1.0%; P = .55), and length of stay (12.5 vs 15.0 days; P = .08) were also comparable between ligation and repair in univariate analysis. In multivariable analysis, hospital mortality for surgical repair was similar to ligation (risk ratio, 0.69; 95% confidence interval, 0.41-1.16; P = .16).
CONCLUSIONS
Portal vein injury is associated with significant mortality and morbidity. Surgical repair showed a trend for lower postoperative mortality than ligation, but this was not statistically significant on multivariate analysis. Repair of a traumatic portal vein injury should be attempted, but ligation is an acceptable alternative without an increase in bowel resection rates or a statistically significant increase in mortality.
Topics: Adult; Databases, Factual; Female; Hospital Mortality; Humans; Ligation; Male; Middle Aged; Portal Vein; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Vascular System Injuries; Young Adult
PubMed: 30477977
DOI: 10.1016/j.jvsv.2018.08.007 -
Journal of Vascular Surgery Sep 1998Morbidly obese patients who sustained popliteal vascular injury after spontaneous knee dislocation (KD) were studied.
PURPOSE
Morbidly obese patients who sustained popliteal vascular injury after spontaneous knee dislocation (KD) were studied.
METHODS
Seven morbidly obese patients (body mass index [BMI] >35 kg/m2 and >100 lb over ideal body weight) who sustained spontaneous KD while upright were reviewed.
RESULTS
Severe popliteal arterial injury accompanied all spontaneous KD. The mean age of patients was 34.1 +/- 6.7 years; the mean weight was 354 +/- 150 lb (range, 220-702 lb); and mean BMI was 53 +/- 21 kg/m2 (range, 37-98.4). All had arterial avulsion and thrombosis. Three had concomitant venous injury. All underwent operative repair. Morbid obesity presented unique challenges to surgical management. Limited positioning, specialized operative tables, large incisions, deep exposure, special retraction, long operative times (mean, 537 +/- 134 minutes), and major blood loss (mean, 2.5 +/- 3 L) were standard. Five arterial injuries were repaired with interposition vein grafts, and 2 required tibial bypass. Venous repairs included thrombectomy and primary repair (n = 2) and interposition grafting (n = 1). Many complications were related to morbid obesity, including deep wound infection (n = 3), diabetic ketoacidosis (n = 2), and cor pulmonale from sleep apnea (n = 1). Despite patent grafts in all patients, 2 above-knee amputations were required for extensive neuromuscular loss.
CONCLUSION
Morbid obesity is a specific risk factor for spontaneous KD and vascular injury. In addition, morbid obesity presents unique challenges to operative repair and predisposes patients to unusual major postoperative complications.
Topics: Adult; Body Mass Index; Female; Humans; Joint Dislocations; Knee Injuries; Male; Middle Aged; Obesity, Morbid; Popliteal Artery; Postoperative Complications; Retrospective Studies; Risk Factors; Treatment Outcome; Veins
PubMed: 9737455
DOI: 10.1016/s0741-5214(98)70131-4 -
Journal of Vascular Surgery Oct 2020Firearm injuries have traditionally been associated with worse outcomes compared with other types of penetrating trauma. Lower extremity trauma with vascular injury is a... (Comparative Study)
Comparative Study
OBJECTIVE
Firearm injuries have traditionally been associated with worse outcomes compared with other types of penetrating trauma. Lower extremity trauma with vascular injury is a common presentation at many centers. Our goal was to compare firearm and non-firearm lower extremity penetrating injuries requiring vascular repair.
METHODS
We analyzed the National Inpatient Sample from 2010 to 2014 for all penetrating lower extremity injuries requiring vascular repair based on International Classification of Diseases, Ninth Revision codes. Our primary outcomes were in-hospital lower extremity amputation and death.
RESULTS
We identified 19,494 patients with lower extremity penetrating injuries requiring vascular repair-15,727 (80.7%) firearm injuries and 3767 (19.3%) non-firearm injuries. The majority of patients were male (91%), and intent was most often assault/legal intervention (64.3%). In all penetrating injuries requiring vascular repair, the majority (72.9%) had an arterial injury and 43.8% had a venous injury. Location of vascular injury included iliac (19.3%), femoral-popliteal (60%), and tibial (13.2%) vascular segments. Interventions included direct vascular repair (52.1%), ligation (22.1%), bypass (19.4%), and endovascular procedures (3.6%). Patients with firearm injuries were more frequently younger, black, male, and on Medicaid, with lower household income, intent of assault or legal action, and two most severe injuries in the same body region (P < .0001 for all). Firearm injuries compared with non-firearm injuries were more often reported to be arterial (75.5% vs 61.9%), to involve iliac (20.6% vs 13.7%) and femoral-popliteal vessels (64.7% vs 39.9%), to undergo endovascular repair (4% vs 2.1%), and to have a bypass (22.5% vs 6.5%; P < .05 for all). Firearm-related in-hospital major amputation (3.3% vs 0.8%; P = .001) and mortality (7.6% vs 4.2%; P = .001) were higher compared with non-firearm penetrating trauma. Multivariable analysis showed that injury by a firearm source was independently associated with postoperative major amputation (odds ratio, 4.78; 95% confidence interval, 2.07-11.01; P < .0001) and mortality (odds ratio, 1.74; 95% confidence interval, 1.14-2.65; P = .01).
CONCLUSIONS
Firearm injury is associated with a higher rate of amputation and mortality compared with non-firearm injuries of the lower extremity requiring vascular repair. These data can continue to guide public health discussions about morbidity and mortality from firearm injury.
Topics: Adolescent; Adult; Amputation, Surgical; Arteries; Child; Child, Preschool; Databases, Factual; Female; Hospital Mortality; Humans; Infant; Infant, Newborn; Injury Severity Score; Lower Extremity; Male; Medicaid; Middle Aged; Retrospective Studies; Risk Factors; Sex Factors; Socioeconomic Factors; Treatment Outcome; United States; Vascular System Injuries; Veins; Wounds, Gunshot; Wounds, Penetrating; Young Adult
PubMed: 32115320
DOI: 10.1016/j.jvs.2019.12.036 -
Annals of Saudi Medicine 2009The brachial artery is the most frequently injured artery in the upper extremity due to its vulnerability. The purpose of our study was to review our experience with...
BACKGROUND AND OBJECTIVE
The brachial artery is the most frequently injured artery in the upper extremity due to its vulnerability. The purpose of our study was to review our experience with brachial artery injuries over a 9-year period, describing the type of injury, surgical procedures, complications, and associated injuries.
PATIENTS AND METHODS
Forty-nine patients with brachial artery injury underwent surgical repair procedures at our hospital, from the beginning of May 1999 to the end of June 2008. The brachial artery injuries were diagnosed by physical examination and Doppler ultrasonography. Depending on the mode of presentation, patients were either taken immediately to the operating room for bleeding control and vascular repair or were assessed by preoperative duplex ultrasonography.
RESULTS
This study group consisted of 43 males and 6 females, ranging in age from 6 to 65 years with a mean (SD) age of 27.9 (6.7) years. The mechanism of trauma was penetrating in 45 patients and blunt in the remaining 4 patients. Stab injury was the most frequent form of penetrating trauma (24 of 45). Treatment included primary arterial repair in 5 cases, end-to-end anastomosis in 28 cases, interposition vein graft in 15 cases, and interposition-ringed polytetrafluoroethylene graft in 1 case. Associated injuries were common and included venous injury (14), bone fracture (5), and peripheral nerve injury (11). Fifteen patients developed postoperative complications. One patient underwent an above-elbow amputation.
CONCLUSIONS
Prompt and appropriate management of the brachial artery injuries, attention to associated injuries, and a readiness to revise the vascular repair early in the event of failure will maximize patient survival and upper extremity salvage.
Topics: Adolescent; Adult; Aged; Brachial Artery; Child; Female; Humans; Male; Middle Aged; Physical Examination; Treatment Outcome; Ultrasonography, Doppler; Vascular Surgical Procedures; Wounds and Injuries
PubMed: 19318753
DOI: 10.4103/0256-4947.51797 -
Clinical and Applied... 2013
Topics: Humans; Orthopedic Procedures; Venous Thromboembolism; Wounds and Injuries
PubMed: 23529482
DOI: 10.1177/1076029612474840f -
Scientific Reports Mar 2018This study aimes to determine the complication rates, possible risk factors and outcomes of emergency procedures performed during resuscitation of severely injured...
This study aimes to determine the complication rates, possible risk factors and outcomes of emergency procedures performed during resuscitation of severely injured patients. The medical records of patients with an injury severity score (ISS) >15 admitted to the University Hospital Leipzig from 2010 to 2015 were reviewed. Within the first 24 hours of treatment, 526 patients had an overall mechanical complication rate of 26.2%. Multivariate analysis revealed out-of-hospital airway management (OR 3.140; 95% CI 1.963-5.023; p < 0.001) and ISS (per ISS point: OR 1.024; 95% CI 1.003-1.045; p = 0.027) as independent predictors of any mechanical complications. Airway management complications (13.2%) and central venous catheter complications (11.4%) were associated with ISS >32.5 (p < 0.001) and ISS >33.5 (p = 0.005), respectively. Chest tube complications (15.8%) were associated with out-of-hospital insertion (p = 0.002) and out-of-hospital tracheal intubation (p = 0.033). Arterial line complications (9.4%) were associated with admission serum lactate >4.95 mmol/L (p = 0.001) and base excess <-4.05 mmol/L (p = 0.008). In multivariate analysis, complications were associated with an increased length of stay in the intensive care unit (p = 0.019) but not with 24 hour mortality (p = 0.930). Increasing injury severity may contribute to higher complexity of the individual emergency treatment and is thus associated with higher mechanical complication rates providing potential for further harm.
Topics: Adult; Aged; Female; Humans; Injury Severity Score; Intensive Care Units; Male; Middle Aged; Resuscitation; Retrospective Studies; Risk Factors; Wounds and Injuries
PubMed: 29507415
DOI: 10.1038/s41598-018-22457-9 -
Acta Cirurgica Brasileira Oct 2011To investigate the effects of a new electrocautery device to provoke endovascular venous thermal injury.
PURPOSE
To investigate the effects of a new electrocautery device to provoke endovascular venous thermal injury.
METHODS
An experimental endovascular electrocautery was placed inside eight ex-vivo bovine saphenous veins models. Each one was divided in eight segments and progressive intensities of electric energy liberated. The macroscopic and microscopic effects were analyzed.
RESULTS
Forty bovine saphenous veins segments were studied. The higher the electric energy applied the greater the nuclear picnosis and more intense the cytoplasmatic shrinkage and electrocoagulation effects.
CONCLUSION
The experimental endovascular electrocautery device demonstrated to be both capable of inducing the destruction of the intimal layers of the studied vein model and provoke endovascular thermal injury.
Topics: Animals; Burns, Electric; Cattle; Electrocoagulation; Endovascular Procedures; Models, Theoretical; Saphenous Vein; Thermal Conductivity; Time Factors
PubMed: 21952653
DOI: 10.1590/s0102-86502011000500001