The association between tranexamic acid (TXA) and fibrinolysis shutdown is unknown. We hypothesize that TXA is associated with fibrinolysis shutdown in critically injured trauma patients.
Two hundred ...eighteen critically injured adults admitted to the intensive care unit at an urban Level I trauma center from August 2011 to January 2015 who had thromboelastography performed upon intensive care unit admission were reviewed. Groups were stratified based on fibrinolysis shutdown, which was defined as LY30 of 0.8% or less. Continuous variables were expressed as mean ± standard deviation or median (interquartile range). Poisson regression analysis was used to determine predictors of shutdown.
Patients were age 46 ± 18 years, 81% male, 75% blunt trauma, Injury Severity Score of 28 ± 13, 16% received TXA, 64% developed fibrinolysis shutdown, and mortality was 15%. In the first 24 hours, 4 (2-9) units packed red blood cells and 2 (0-6) units fresh frozen plasma were administered. Those with shutdown had worse initial systolic blood pressure (114 ± 38 mm Hg vs. 129 ± 43 mm Hg, p = 0.006) and base deficit (-5 ± 6 mEq/L vs -3 ± 5 mEq/L, p = 0.013); received more packed red blood cells 6 (2-11) vs. 2 (1-5) units, p < 0.0001, and fresh frozen plasma 3 (0-8) vs. 0 (0-4) units, p < 0.0001; and more often received TXA (23% vs. 4%, p <0.0001). After controlling for confounders, TXA (relative risk, 1.35; 95% confidence interval, 1.10-1.64; p = 0.004) and cryoprecipitate transfusion (relative risk, 1.29; 95% confidence interval, 1.07-1.56; p = 0.007) were independently associated with fibrinolysis shutdown.
Patients who received TXA were at increased risk of fibrinolysis shutdown compared with patients who did not receive TXA. We recommend that administration of TXA be limited to severely injured patients with evidence of hyperfibrinolysis and recommend caution in those with evidence of fibrinolysis shutdown.
Therapeutic, level III.
Background Acute fibrinolysis shutdown is associated with early mortality after trauma; however, no previous studies have investigated the incidence of persistent fibrinolysis or its association with ...mortality. We tested the hypothesis that persistent fibrinolysis shutdown is associated with mortality in critically ill trauma patients. Study Design Thromboelastography was performed on ICU admission in 181 adult trauma patients and at 1 week in a subset of 78 patients. Fibrinolysis shutdown was defined as LY30 ≤ 0.8% and was considered transient if resolved by 1 week postinjury or persistent if not. Logistic regression adjusted for age, sex, hemodynamics, and Injury Severity Score (ISS). Results Median age was 52 years, 88% were male, and median ISS was 27, with 56% transient fibrinolysis shutdown, 44% persistent fibrinolysis shutdown and 12% mortality. Median LY30 was 0.23% (interquartile range IQR 0% to 1.20%) at admission and 0.10% (IQR 0% to 2.05%) at 1 week. Transient shutdown more often occurred after head injury (p = 0.019); persistent shutdown was more often associated with penetrating injury (29% vs 9%; p = 0.020), lower LY30 at ICU admission (0.10% vs 1.15%; p < 0.0001) and at 1 week (0% vs 1.68%; p < 0.0001), and higher mortality (21% vs 5%; p = 0.036). Persistent fibrinolysis shutdown was associated with admission LY30 (odds ratio OR 0.05; 95% CI 0.01 to 0.34; p = 0.002) and transfusion of packed RBCs (OR 0.81; 95% CI 0.68 to 0.97; p = 0.021) and platelets (OR 2.81; 95% CI 1.16 to 6.84; p = 0.022); moreover, it was an independent predictor of mortality (OR 8.48; 95% CI 1.35 to 53.18; p = 0.022). Conclusions Persistent fibrinolysis shutdown is associated with late mortality after trauma. A high index of suspicion should be maintained, especially in patients with penetrating injury, reduced LY30 on admission, and/or receiving blood product transfusion. Judicious use of tranexamic acid is advised in this cohort.
This study tested the hypothesis that early routine use of tranexamic acid (TXA) reduces mortality in a subset of the most critically injured trauma intensive care unit patients.
Consecutive trauma ...patients (n = 1,217) who required emergency surgery (OR) and/or transfusions from August 2009 to January 2013 were reviewed. At surgeon discretion, TXA was administered at a median of 97 minutes (1-g bolus then 1-g over 8 hours) to 150 patients deemed high risk for hemorrhagic death. With the use of propensity scores based on age, sex, traumatic brain injury (TBI), mechanism of injury, systolic blood pressure, transfusion requirements, and Injury Severity Score (ISS), these patients were matched to 150 non-TXA patients.
The study population was 43 years old, 86% male, 54% penetrating mechanism of injury, 25% TBI, 28 ISS, with 22% mortality. OR was required in 78% at 86 minutes, transfusion was required in 97% at 36 minutes, and 75% received both. For TXA versus no TXA, more packed red blood cells and total fluid were required, and mortality was 27% versus 17% (all p < 0.05). The effects of TXA were similar in those with or without TBI, although ISS, fluid, and mortality were all higher in the TBI group. Mortality associated with TXA was influenced by the timing of administration (p < 0.05), but any benefit was eliminated in those who required more than 2,000-mL packed red blood cells, who presented with systolic blood pressure of less than 120 mm Hg or who required OR (all p < 0.05).
For the highest injury acuity patients, TXA was associated with increased, rather than reduced, mortality, no matter what time it was administered. This lack of benefit can probably be attributed to the rapid availability of fluids and emergency OR at this trauma center. Prospective studies are needed to further identify conditions that may override the benefits from TXA.
Therapeutic study, level IV.
Experimental Models of COVID-19 Caldera-Crespo, Luis A; Paidas, Michael J; Roy, Sabita ...
Frontiers in cellular and infection microbiology,
01/2022, Letnik:
11
Journal Article
Recenzirano
Odprti dostop
COVID-19 is the most consequential pandemic of the 21
century. Since the earliest stage of the 2019-2020 epidemic, animal models have been useful in understanding the etiopathogenesis of SARS-CoV-2 ...infection and rapid development of vaccines/drugs to prevent, treat or eradicate SARS-CoV-2 infection. Early SARS-CoV-1 research using immortalized
cell lines have aided in understanding different cells and receptors needed for SARS-CoV-2 infection and, due to their ability to be easily manipulated, continue to broaden our understanding of COVID-19 disease in
models. The scientific community determined animal models as the most useful models which could demonstrate viral infection, replication, transmission, and spectrum of illness as seen in human populations. Until now, there have not been well-described animal models of SARS-CoV-2 infection although transgenic mouse models (i.e. mice with humanized ACE2 receptors with humanized receptors) have been proposed. Additionally, there are only limited facilities (Biosafety level 3 laboratories) available to contribute research to aid in eventually exterminating SARS-CoV-2 infection around the world. This review summarizes the most successful animal models of SARS-CoV-2 infection including studies in Non-Human Primates (NHPs) which were found to be susceptible to infection and transmitted the virus similarly to humans (e.g., Rhesus macaques, Cynomolgus, and African Green Monkeys), and animal models that do not require Biosafety level 3 laboratories (e.g., Mouse Hepatitis Virus models of COVID-19, Ferret model, Syrian Hamster model). Balancing safety, mimicking human COVID-19 and robustness of the animal model, the Murine Hepatitis Virus-1 Murine model currently represents the most optimal model for SARS-CoV-2/COVID19 research. Exploring future animal models will aid researchers/scientists in discovering the mechanisms of SARS-CoV-2 infection and in identifying therapies to prevent or treat COVID-19.
We test the hypothesis that prehospital interventions (PHIs) performed by skilled emergency medical service providers during ground or air transport adversely affect outcome in severely injured ...trauma patients.
Consecutive trauma activations (March 2012 to June 2013) transported from the scene by air or ground emergency medical service providers were reviewed. PHI was defined as intubation, needle decompression, tourniquet, cricothyroidotomy, or advanced cardiac life support.
In 3,733 consecutive trauma activations (71% blunt, 25% penetrating, 4% burns), age was 39 years, 74% were male, Injury Severity Score (ISS) was 5, and Glasgow Coma Score (GCS) was 15, with 32% traumatic brain injury (TBI) and 7% overall mortality. Those who received PHI (n = 130, 3.5% of the trauma activations) were more severely injured: ISS (26 vs. 5), GCS (3 vs. 15), TBI (57% vs. 31%), Revised Trauma Score (RTS, 5.45 vs. 7.84), Trauma and Injury Severity Score (TRISS, 1.32 vs. 4.89), and mortality (56% vs. 5%) were different (all p < 0.05) than those who received no PHI. Air crews transported 22% of the patients; more had TBI, blunt injury, high ISS, and long prehospital times (all p < 0.05), but mortality was similar to those transported by ground. In the most severely injured patients with signs of life who received a PHI, the ISS, prehospital times, and proportions of TBI, blunt trauma, and air transport were similar, but mortality was significantly lower (43% vs. 23%, p= 0.021).
In our urban trauma system, PHIs are associated with a lower incidence of mortality in severely injured trauma patients and do not delay transport to definitive care.
Prognostic/epidemiologic study, level III; therapeutic study, level IV.
Hypertrophic scarring is a fibroproliferative process that occurs following a third-degree dermal burn injury, producing significant morbidity due to persistent pain, itching, cosmetic disfigurement, ...and loss of function due to contractures. Ablative fractional lasers have emerged clinically as a fundamental or standard therapeutic modality for hypertrophic burn scars. Yet the examination of their histopathological and biochemical mechanisms of tissue remodeling and comparison among different laser types has been lacking. In addition, deficiency of a relevant animal model limits our ability to gain a better understanding of hypertrophic scar pathophysiology. To evaluate the effect of ablative fractional lasers on hypertrophic third-degree burn scars, we have developed an in vivo Red Duroc porcine model. Third-degree burn wounds were created on the backs of animals, and burn scars were allowed to develop for 70 days before treatment. Scars received treatment with either CO2 or erbium: yttrium aluminum garnet (YAG) ablative fractional lasers. Here, we describe the effect of both lasers on hypertrophic third-degree burn scars in Red Duroc pigs. In this report, we found that Er:YAG has improved outcomes versus fractional CO2. Molecular changes noted in the areas of dermal remodeling indicated that matrix metalloproteinase 2, matrix metalloproteinase 9, and Decorin may play a role in this dermal remodeling and account for the enhanced effect of the Er:YAG laser. We have demonstrated that ablative fractional laser treatment of burn scars can lead to favorable clinical, histological, and molecular changes. This study provides support that hypertrophic third-degree burn scars can be modified by fractional laser treatment.
Background Venous duplex ultrasound (VDU) is the modality of choice for surveillance of venous thromboembolism (VTE), but there is controversy about its appropriate implementation as a screening ...method. We hypothesize that VDU surveillance in trauma patients at high risk for VTE decreases the rate of pulmonary embolism (PE). Study Design One thousand two hundred and eighty-two trauma ICU admissions were screened with Greenfield's Risk Assessment Profile from August 2011 to September 2014. Four hundred and two patients were identified as high risk for VTE (Risk Assessment Profile ≥10). Those who received weekly VDU to evaluate for deep vein thrombosis (n = 259 64%) were compared with those who did not (n = 143 36%). Parametric data are reported as mean ± SD and nonparametric data are reported as median (interquartile range). Statistical significance was determined at an α level of 0.05. Results The overall study population was 47 ± 19 years old and 75% were male, 78% of injuries were blunt mechanism, Injury Severity Score was 28 ± 13, Risk Assessment Profile was 14 ± 4, and mortality was 14.3%. Deep vein thrombosis rate was 11.6% (n = 30) in the surveillance group vs 2.1% (n = 3) in the non-surveillance group (p < 0.001). Deep vein thromboses detected in the surveillance group were managed with systemic anticoagulation (43%) or with IVC filter placement (57%). In the surveillance group, the PE rate was 1.9% (n = 5) vs 7.0% (n = 10) in the non-surveillance group (p = 0.014). Conclusions Trauma patients at high risk for VTE and who received VDU surveillance and early management of deep vein thrombosis have decreased rates of pulmonary embolism.
Abstract Introduction The objective of this study was to re-evaluate and simplify the Greenfield Risk Assessment Profile (RAP) for venous thromboembolism (VTE) in trauma using information readily ...available at the bedside. Methods Retrospective review of 1,233 consecutive admissions to the trauma intensive care unit from 08/2011-01/2015. Univariate were performed to determine which RAP risk factors were significant contributors to VTE. Multivariable logistic regression was employed to develop models for risk stratification. All results were considered statistically significant at p < 0.05. Results The study population was: age 44±19, 75% male, 72% blunt, Injury Severity Score (ISS) 21±13, RAP 9±5, and 8% mortality. Groups were separated into +VTE (n=104) and –VTE (n=1,129). They were similar in age, gender, mechanism, and mortality; but ISS and RAP were higher in the +VTE group (all p<0.0001). The +VTE group had more transfusions and longer time to prophylaxis (all p<0.05). Receiving 4+ transfusions in the first 24 hours (OR: 2.60, 95% CI: 1.64 – 4.13), Glasgow Coma Score <8 for >4 hours (OR: 2.13, 95% CI: 1.28 – 3.54), pelvic fracture (OR: 2.26, 95% CI: 1.44 – 3.57), age 40 – 59 years (OR: 1.70, 95% CI: 1.10 – 2.63), and >2-hour operation (OR: 1.80, 95% CI: 1.14 – 2.85) predicted VTE with an area under the receiver operator curve of 0.729, which was comparable to 0.740 for the RAP score alone. Conclusions VTE risk in trauma can be easily assessed using only five risk factors, which are all readily available at the bedside (transfusion, GCS, pelvic fracture, prolonged operation, age). This simplified model provides similar predictive ability to the more complicated RAP score. Prospective validation of a simplified risk assessment score is warranted.
The nuclear receptor superfamily includes receptors for steroids, retinoids, thyroid hormone and vitamin D, as well as many related proteins. An important feature of the action of the lipophilic ...hormones and vitamins is that the maintenance of homeostatic function requires both intrinsic positive and negative regulation. Here we provide in vitro and in vivo evidence that identifies the CREB-binding protein (CBP) and its homologue P300 (refs 6,7) as cofactors mediating nuclear-receptor-activated gene transcription. The role of CBP/P300 in the transcriptional response to cyclic AMP, phorbol esters, serum, the lipophilic hormones and as the target of the E1A oncoprotein suggests they may serve as integrators of extracellular and intracellular signalling pathways.
OBJECTIVES/GOALS: The objective of this presentation is to describe different recruitment tools implemented by the Miami Clinical and Translational Science Institute (CTSI) to facilitate participant ...recruitment into research studies. METHODS/STUDY POPULATION: Participant recruitment is critical to the success of all research studies. In the effort of advancing clinical and translational science and to help investigators recruit volunteers for research studies, the University of Miami has two recruitment tools: 1) Consent to Contact (CTC), an opt-in research registry where University of Miami Health System patients are asked for permission to be contacted about studies matching their demographic and/or health profiles; and 2) UMiamiHealthResearch.org (UMHR), implemented with the Michigan CTSA, a community-based registry for volunteers to sign up and be contacted about studies. Study investigators can use these tools once they have obtained IRB approval for their research. RESULTS/ANTICIPATED RESULTS: The CTC was launched in 2016; to date, over 130,000 patients have enrolled in CTC; 69 studies have been approved with over 75,000 patients’contact information released to study teams. UMHR was launched in 2020. To date, the site lists 237 studies. A total of 2,727 portal visitors have expressed interest in participating in specific studies. Study team members were successful in engaging interested participants, and enrolling participants into studies. Overall, teams reported a positive impact on recruitment. Data collection on utilization and satisfaction of these recruitments tools is ongoing. In addition, focus groups of study team members are being conducted to identify best practices for using these tools, and findings will be presented. DISCUSSION/SIGNIFICANCE: The CTC and UMHR recruitment tools have demonstrated positive impact in helping study teams identify potentially eligible research volunteers. The continued promotion of these tools at the University of Miami Health System and in the community will be crucial to the recruitment process and execution of research studies.
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