The transfusion of cold-stored uncrossmatched whole blood (WB) has not been extensively used in civilian trauma resuscitation. This report details the initial experience with the safety and ...feasibility of using WB in this setting after a change of practice at a Level 1 trauma center was instituted.
Up to two units of uncrossmatched group O positive WB that was leukoreduced using a platelet-sparing filter from male donors were transfused to male trauma patients with hypotension secondary to bleeding. Hemolytic marker haptoglobin and reports of transfusion reactions in these patients were followed. Additionally, transfusion volumes and outcomes were compared to a historical cohort of male trauma patients who received at least one red blood cell (RBC) unit, but not WB, during the first 24 hours of admission.
There were 47 WB patients who were transfused with a mean (SD) of 1.74 (0.61) WB units. The median haptoglobin concentration on post-WB transfusion Day 1 was 25.1 (9.3) mg/dL in 7 of 30 non-group O recipients. No adverse reactions in temporal relation to the WB transfusions were reported. There were 145 male historical control patients identified who were resuscitated with component therapy; the median volume of incompatible plasma transfused to the WB versus component therapy group was not significantly different (1,000 vs. 800 mL, respectively; p = 0.38); the mean plasma:RBC (0.99 0.47 vs. 0.77 0.73, respectively; p = 0.006) and platelet:RBC (0.72 0.40 vs. 0.51 0.734, respectively; p < 0.0001) ratios were significantly higher in the WB group.
Transfusion of two units of cold-stored uncrossmatched WB is feasible and seems to be safe in civilian trauma resuscitation. Determining the efficacy of WB with regard to reducing the number of blood products transfused in the first 24 hours or improving recipient survival will require a larger randomized trial.
Therapeutic study, level IV.
ABSTRACTToward the end of World War I and during World War II, whole-blood transfusions were the primary agent in the treatment of military traumatic hemorrhage. However, after World War II, the ...fractionation of whole blood into its components became widely accepted and replaced whole-blood transfusion to better accommodate specific blood deficiencies, logistics, and financial reasons. This transition occurred with very few clinical trials to determine which patient populations or scenarios would or would not benefit from the change. A smaller population of patients with trauma hemorrhage will require massive transfusion (>10 U packed red blood cells in 24 h) occurring in 3% to 5% of civilian and 10% of military traumas. Advocates for hemostatic resuscitation have turned toward a ratio-balanced component therapy using packed red blood cells–fresh frozen plasma–platelet concentration in a 1:1:1 ratio due to whole-blood limited availability. However, this “reconstituted” whole blood is associated with a significantly anemic, thrombocytopenic, and coagulopathic product compared with whole blood. In addition, several recent military studies suggest a survival advantage of early use of whole blood, but the safety concerns have limited is widespread civilian use. Based on extensive military experience as well as recent published literature, low-titer leukocyte reduced cold-store type O whole blood carries low adverse risks and maintains its hemostatic properties for up to 21 days. A prospective randomized trial comparing whole blood versus ratio balanced component therapy is proposed with rationale provided.
Abstract
Background
Restorative Eye Treatment with TriHex Technology (RET) is a topical eye product with peptides and botanicals that reduce the appearance of crow's feet, under-eye bags, and dark ...circles. INhance with TriHex Technology (IH) is a topical product that has been clinically proven to accelerate the clearance of bruises and aid in the reduction of swelling. TriHex Technology has been shown to regenerate collagen and elastin.
Objectives
Evaluate the use of RET compared to a bland moisturizer prior to blepharoplasty and the bilateral use of INhance postoperatively.
Methods
Blepharoplasty patients were randomized to use either RET or a bland moisturizer, twice daily, on the designated periocular skin for 4 weeks prior to the procedure. Postoperatively, participants applied IH bilaterally, at least 4 times a day, and returned for follow-up on Days 1 or 3, 7, and 14. The removed upper-eyelid skin (13 patients) underwent independent dermatopathological evaluation.
Results
Investigators noted no differences in peri-operative complications but observed faster improvement in swelling, bruising, discomfort on the treated side. 85% of participants had less edema and bruising on the RET pretreated side. Biopsy results revealed improved extracellular matrix appearance on the RET pretreated side. Participants agreed that IH alleviated their swelling and noted that their skin felt and appeared more hydrated.
Conclusions
A regimen designed for eyelid surgery employing a pretreatment product component and a post treatment product appear to have a positive impact on measured outcomes in blepharoplasty patients including effects on bruising, swelling and patient comfort.
Level of Evidence: 4
Guidelines for management of intracranial hemorrhage do not account for bleed location. We hypothesize that parafalcine subdural hematoma (SDH), as compared to convexity SDH, is a distinct clinical ...entity and these patients do not benefit from critical care monitoring or repeat imaging.
We identified patients presenting to a single level I trauma center with isolated head injuries from February 2016 to August 2017. We identified 88 patients with isolated blunt traumatic parafalcine SDH and 228 with convexity SDH.
Demographics, comorbidities, and use of antiplatelet and anticoagulant agents were similar between the groups. As compared to patients with convexity SDH, patients with parafalcine SDH had a significantly lower incidence of radiographic progression, and had no cases of neurologic deterioration, neurosurgical intervention, or mortality (all P < 0.005). Compared to patients admitted to the intensive care unit, patients with parafalcine SDH admitted to the floor had a shorter length of stay (2.0 ± 1.6 versus 3.8 ± 2.9 d, P < 0.005) with no difference in outcomes.
Patients presenting with a parafalcine SDH are a distinct and relatively benign clinical entity as compared to convexity SDH and do not benefit from repeat imaging or intensive care unit admission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Single-center experience has shown that American College of Surgeons (ACS) trauma verification can improve outcomes. The current objective was to compare mortality between ACS-verified and ...state-designated centers in a national sample.
Subjects 16 years or older from ACS-verified or state-designated Level I and II centers were identified in the National Trauma Databank 2007 to 2008. A predictive mortality model was constructed using Trauma Quality Improvement Project methodology. Imputation was used for missing data. Probability of mortality in the model determined expected deaths. Observed-to-expected (O/E) mortality ratios with 90% confidence interval (CI) and outliers (90% CI more than or less than 1.0) were compared across ACS and state Level I and II centers. The mortality model was repeated with ACS versus state included.
There were 900,274 subjects. The model had an area under the curve of 0.92 to predict death. Level I ACS centers had a lower median O/E ratio compared with state centers (0.95 interquartile range, 0.82-1.05 vs. 1.02 interquartile range, 0.87-1.15; p < 0.01), with no difference in Level II centers. Level II state centers had more high O/E outliers. ACS verification was an independent predictor of survival in Level II centers (odds ratio, 1.26; 95% CI, 1.20-1.32; p < 0.01) but not in Level I centers (p = 0.84).
Level II centers have a disproportionate number of high mortality outliers, and ACS verification is a predictor of survival. Level I ACS centers have lower O/E ratios overall, but no difference in outliers. ACS verification seems beneficial. These data suggest that Level II centers benefit most, and promoting Level II ACS verification may be an opportunity for improved outcomes.
Prognostic study, level III.
Background: Inadequate nitric oxide (NO) availability may underlie vascular smooth muscle overgrowth that contributes to vascular occlusive diseases including atherosclerosis and restenosis. NO ...possesses a number of properties that should inhibit this hyperplastic healing response, such as promoting reendothelialization, preventing platelet and leukocyte adherence, and inhibiting cellular proliferation.
Study Design: We proposed that shortterm but sustained increases in NO synthesis achieved with inducible NO synthase (iNOS) gene transfer at sites of vascular injury would prevent intimal hyperplasia. We constructed an adenoviral vector, AdiNOS, carrying the human iNOS cDNA and used it to express iNOS at sites of arterial injury in vivo.
Results: AdiNOS-treated cultured vascular smooth muscle cells produced up to 100-fold more NO than control cells. In vivo iNOS gene transfer, using low concentrations of AdiNOS (2 × 10
6 plaque forming units PFU/rat) to injured rat carotid arteries, resulted in a near complete (>95%) reduction in neointima formation even when followed longterm out to 6 weeks post-injury. This protective effect was reversed by the continuous administration of an iNOS selective inhibitor L-N
6-(1-iminoethyl)-lysine. However, iNOS gene transfer did not lead to regression of preestablished neointimal lesions. In an animal model more relevant to human vascular healing, iNOS gene transfer (5 × 10
8 PFU/pig) to injured porcine iliac arteries in vivo was also efficacious, reducing intimal hyperplasia by 51.8%.
Conclusions: These results indicate that shortterm overexpression of the iNOS gene initiated at the time of vascular injury is an effective method of locally increasing NO levels to prevent intimal hyperplasia.
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IJS, NUK, SBCE, SBJE, UL, UM, UPUK
The injury response is a complex set of events, which represents the reaction of a biological system to a perceived change in its environment in an attempt to maintain system integrity. Isolation of ...individual events or components of this response cannot describe the overall process, but may reflect general mechanisms that have evolved over time to solve the complex requirements of the injury response. The process, generally termed the acute phase response, is a series of organ-specific responses that begin shortly after a systemic injury. In the liver, this response involves both dramatic inductions and reductions in specific sets of genes, and an overall widespread global change in proteins produced. This can be thought of as a phenotypic change or 'reprogramming' of the liver. These changes in protein production are modulated and regulated at the level of transcription and involve significant manipulations of transcriptional regulatory mechanisms. Hepatocyte nuclear factor 4 (HNF-4) is a liver enriched transcription factor that regulates a large number of liver-specific genes, which play important roles in the critical pathways modulated by the response to injury. HNF-4 also performs an essential role in overall development and is critical for the normal expression of multiple genes in the developed liver, as well as being upstream of HNF-1 in a transcriptional hierarchy that drives hepatocyte differentiation. The role of HNF-4 in regulating liver-specific transcriptional changes directed by injury remains to be defined. In our cell-culture and whole-animal models, we demonstrate that the binding activity of HNF-4 decreases quickly after injury due to post-translational modification by phosphorylation. The mechanisms by which HNF-4 is modified after injury involve the activation of Janus kinase 2 (JAK2) signal transduction pathways, but the direct or indirect interaction of JAK2 with HNF-4 remains to be defined.
Transplant rejection and toxicity associated with chronic immunosuppressive therapy remain a major problem. Mixed hematopoietic chimerism has been shown to produce tolerance to solid organ ...transplants. However, currently available protocols to induce mixed hematopoietic chimerism invariably require toxic pre-conditioning. In this study, we investigated a non-toxic CTLA4-Ig-based protocol to induce donor-specific tolerance to cardiac allografts in rats.
Fully mismatched, 4 to 6 week old ACI (RT1.A
a) and Wistar Furth (RT1.A
u) rats were used as cell/organ donors and recipients, respectively. Recipients were treated with CTLA4-Ig 2 mg/kg/day (on days 0, 2, 4, 6, 8), tacrolimus 1 mg/kg/day (daily, from days 0 to 9), and a single dose of anti-lymphocyte serum (10 mg) on day 10, soon after total body irradiation (300 cGy) and donor bone marrow (100 × 10
6 T-cell depleted cells) transplantation (BMT). Six weeks after BMT, chimeric animals received heterotopic heart transplants.
Hematopoietic chimerism was 18.8 ± 10.6% at day 30, and was stable (24 ± 10%) at 1 year post-BMT; there was no graft
versus host disease. Chimeric recipients (RT1.A
u) permanently accepted (>360 days) donor-specific (RT1.A
a;
n = 6) hearts, yet rapidly rejected (<9 days) third-party hearts (RT1.A
l;
n = 5). Graft (heart) tolerant (>100 days) recipients accepted donor-specific secondary skin grafts (>200 days) while rejected the third-party skin grafts (<9 days). Lymphocytes of graft tolerant animals demonstrated hyporesponsiveness in mixed lymphocyte cultures in a donor-specific manner. Tolerant graft histology showed no obliterative arteriopathy or chronic rejection.
The CTLA4-Ig based conditioning regimen with donor BMT produced mixed chimerism and induced donor- specific tolerance to cardiac allografts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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