Alain Corcos

Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury

BACKGROUND Platelet transfusion is utilized increasingly for traumatic brain injury (TBI) for the reversal of aspirin (ASA) therapy. Assessment of platelet inhibition and reversal by platelet transfusion after TBI has not been adequately characterized. METHODS A retrospective cohort analysis of TBI patients at a level I trauma center (January 2008-December 2009) was performed. The Aspirin Response Test (ART; VerifyNow) was used to assess platelet inhibition in TBI patients and guide platelet transfusion in patients with ASA-induced suppression. A follow-up ART was obtained after platelet administration. Primary endpoints were progression of intracranial hemorrhage on computed tomography, need for craniotomy, and mortality. RESULTS We analyzed 84 patients (median age, 78 [interquartile range, 64-86)]; 54% male). ASA use was documented in 36 (42%) patients. Initial ART indicated platelet dysfunction in 54 (64%) patients, including 42% of patients without a documented history of ASA use. Of the patients with a documented history of ASA, 2.4% had a normal ART. Of those with an initial ART of <550 ASA response units, 45 received platelets. Repeat ART demonstrated reversal of inhibition in 29 patients (64.4%). Initial responders to transfusion received a greater volume of platelets, suggesting a dose-response relationship. Logistic regression revealed a trend toward higher mortality in nonresponders to transfusion (P = .09). Receiver operating characteristic curve analysis revealed that ART results increased prediction of poor outcome compared with ASA history alone (area under the curve = 0.760 and 0.775, respectively). CONCLUSION The ART should be used to better target and guide platelet transfusions in TBI patients with known or suspected ASA use history. Patients with occult platelet dysfunction can be identified, unnecessary platelet transfusions avoided, and the adequate volume of platelets administered to correct drug-induced dysfunction. A dose-response relationship between quantity of platelets transfused and reversal of ASA inhibition was observed.

Autologous skin cell spray-transplantation for a deep dermal burn patient in an ambulant treatment room setting.

Jorg C. Gerlach *, Christa Johnen , Eric McCoy , Kirsten Brautigam , Jorn Plettig , Alain Corcos c Departments of Surgery and Bioengineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA Charite, Campus Virchow, AG Experimental Surgery, University Medicine Berlin, Berlin, Germany University of Pittsburgh Medical Center, UPMC Mercy Hospital Burn Center, Pittsburgh, PA, USA Stem Cell Systems, Berlin, Germany b u r n s 3 7 ( 2 0 1 1 ) e 1 9 – e 2 3

Risk Factors for Hypothermia in EMS-treated Burn Patients

Abstract Objective. Hypothermia has been associated with increased mortality in burn patients. We sought to characterize the body temperature of burn patients transported directly to a burn center by emergency medical services (EMS) personnel and identify the factors independently associated with hypothermia. Methods. We utilized prospective data collected by a statewide trauma registry to carry out a nested case-control study of burn patients transported by EMS directly to an accredited burn center between 2000 and 2011. Temperature at hospital admission ≤36.5°C was defined as hypothermia. We utilized registry data abstracted from prehospital care reports and hospital records in building a multivariable regression model to identify the factors associated with hypothermia. Results. Forty-two percent of the sample was hypothermic. Burns of 20–39% total body surface area (TBSA) (OR 1.44; 1.17–1.79) and ≥40% TBSA (OR 2.39; 1.57–3.64) were associated with hypothermia. Hypothermia was also associated with age > 60 (OR 1.50; 1.30–1.74), polytrauma (OR 1.58; 1.19–2.09), prehospital Glasgow Coma Scale <8 (OR 2.01; 1.46–2.78), and extrication (OR 1.49; 1.30–1.71). Hypothermia was also more common in the winter months (OR 1.54; 1.33–1.79) and less prevalent in patients weighing over 90 kg (OR 0.63; 0.46–0.88). Conclusions. A substantial proportion of burn patients demonstrate hypothermia at hospital arrival. Risk factors for hypothermia are readily identifiable by prehospital providers. Maintenance of normothermia should be stressed during prehospital care.

Admission temperature and survival in patients admitted to burn centers.

It is commonly believed that hypothermia occurring during burn resuscitation is associated with poor outcome, but there is little direct supporting evidence. The authors conducted an analysis of a statewide trauma registry to determine whether hypothermia (T ⩽36.5°C) was associated with mortality when controlling for clinical confounders. They included all patients treated at an accredited burn center from 2000 to 2011 where the trauma registrar recorded the primary injury type as a burn. They excluded records with missing data and nonphysiologic temperature (<26°C or >42°C). The primary exposure of interest was hypothermia. The authors constructed a hierarchical, multivariable logistic regression model to examine the effect of hypothermia on survival, controlling for potentially confounding variables. Predictors of mortality are presented as odds ratio (95% confidence interval). Primary burn injury was coded 17,098 times during the study period. Of these, 3809 were not treated at a burn center and 1192 were excluded for missing data. Admission hypothermia was independently associated with mortality (1.91 [1.58–2.29]) when adjusting for age, sex, total second- and third-degree burn surface area (TBSA), comorbid conditions, injury severity score, direct transport vs referral, method of temperature measurement, year, and the hospital providing care. Increasing age, female sex, TBSA >40%, presence of multiple comorbid conditions, and increasing injury severity score were associated with mortality. Other variables in the model were not independently associated with outcome. There was a weak correlation between TBSA and admission temperature (r = .18). Hypothermia at hospital admission is independently associated with mortality in burn patients when controlling for clinical confounders. Future studies should address potential causes underlying this observation.

Radiographic assessment of ground-level falls in elderly patients: Is the “PAN-SCAN” overdoing it?

INTRODUCTION Routine, whole-body computed tomography imaging (PAN-SCAN) has been shown to identify unexpected injuries and alter the management of patients presenting with blunt trauma. We sought to characterize the changes in practice over time and the utility of PAN-SCAN imaging in elderly patients who fall and require admission to a trauma center. METHODS We performed a retrospective analysis by using data derived from a Pennsylvania state-wide trauma registry (2007-2010). All hemodynamically stable patients (>65 years) who had a ground-level fall and were admitted for >24 hours were selected. Patients who underwent a combination of all three scans within 2 hours of arrival were considered to have underwent PAN-SCAN imaging. Clinical outcomes were compared across PAN-SCAN patients relative to less diagnostic imaging. Regression analysis was used to determine whether PAN-SCAN imaging was an independent determinate of mortality and resource use. RESULTS Over the period of study, 13,043 patients met inclusion criteria. The annual rate of PAN-SCAN imaging after ground-level falls increased over time. After we controlled for important confounders, PAN-SCAN imaging was not associated with mortality (odds ratio 0.97, P = .74, 95% confidence interval 0.80-1.18). Despite greater injury severity, PAN-SCAN imaging was independently associated with significantly lesser intensive care unit requirements, step-down days, and a lesser overall duration of stay. CONCLUSION PAN-SCAN imaging has become more common over time in elderly patients having a ground-level fall. Although PAN-SCAN imaging during the initial trauma evaluation was not associated with an independent decrease in the risk of mortality, it was independently associated with lesser hospital resource use. These data suggest that whole-body computed tomography imaging may benefit trauma center resource use for patients with ground-level falls.

Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting.

Partial and deep partial-thickness burn wounds present a difficult diagnosis and prognosis that makes the planning for a conservative treatment versus mesh grafting problematic. A non-invasive treatment strategy avoiding mesh grafting is often chosen by practitioners based on their clinical and empirical evidence. However, a delayed re-epithelialization after conservative treatment may extend the patients hospitalization period, increase the risk of infection, and lead to poor functional and aesthetic outcome. Early spray grafting, using non-cultured autologous cells, is under discussion for partial and deep partial-thickness wounds to accelerate the re-epithelialization process, reducing the healing time in the hospital, and minimizing complications. To address planning for future clinical studies on this technology, suitable indications will be interesting. We present case information on severe second-degree injuries after gas, chemical, electrical, gasoline, hot water, and tar scalding burns showing one patient per indication. The treatment results with autologous non-cultured cells, support rapid, uncomplicated re-epithelialization with aesthetically and functionally satisfying outcomes. Hospital stays averaged 7.6±1.6 days. Early autologous cell-spray grafting does not preclude or prevent simultaneous or subsequent traditional mesh autografting when indicated on defined areas of full-thickness injury.

Calculations for reproducible autologous skin cell-spray grafting

Non-cultured, autologous cell-spray grafting is an alternative to mesh grafting for larger partial- and deep partial-thickness burn wounds. The treatment uses a suspension of isolated cells, from a patients donor site skin tissue, and cell-spray deposition onto the wound that facilitates re-epithelialization. Existing protocols for therapeutic autologous skin cell isolation and cell-spray grafting have defined the donor site area to treatment area ratio of 1:80, substantially exceeding the coverage of conventional mesh grafting. However, ratios of 1:100 are possible by maximizing the wound treatment area with harvested cells from a given donor site skin tissue according to a given burn area. Although cell isolation methods are very well described in the literature, a rational approach addressing critical aspects of these techniques are of interest in planning clinical study protocols. We considered in an experimental study the cell yield as a function of the donor site skin tissue, the cell density for spray grafting, the liquid spray volume, the sprayed distribution area, and the percentage of surface coverage. The experimental data was then used for the development of constants and mathematical equations to give a rationale for the cell isolation and cell-spray grafting processes and in planning for clinical studies.

In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population

An alternative approach for traditional clinical mesh grafting in burn wound treatment is the use of expanded autologous keratinocytes in suspension or sheets that are cultured over 2-4 weeks in a remote service facility. While a wound reepithelialization has been described, the functional and aesthetic outcome is under debate. Cell isolation from split-skin donor tissue aims to preserve the valuable stem cell progenitors from the basal epidermal layer and to provide patients with a rapid wound reepithelialization and a satisfying outcome. While the presence of epidermal progenitors in the cell graft is thought to enable an improved epidermal surface post reepithelialization, we investigated a feasible clinical approach involving cultured versus noncultured epidermal cells comparing the α6int(high)/K15(high)/FSC(low)/SSC(low) and α6int(high)/K5(high)/FSC(low)/SSC(low) keratinocyte progenitor subpopulations before and after in vitro culture process. Our results show a significant increase of cell size during in vitro passaging and a decrease of progenitor markers linked to a gradual differentiation. A provision of the regenerative epidermal progenitors, isolated from the split-skin biopsy and applied directly onto the wound in an on-site setting of isolation and cell spray grafting in the operation room, could be of interest when choosing options for skin wound care with autologous cells.

Effects of wound dressings on cultured primary keratinocytes

Autologous cell-spray grafting of non-cultured epidermal cells is an innovative approach for the treatment of severe second-degree burns. After treatment, wounds are covered with dressings that are widely used in wound care management; however, little is known about the effects of wound dressings on individually isolated cells. The sprayed cells have to actively attach, spread, proliferate, and migrate in the wound for successful re-epithelialization, during the healing process. It is expected that exposure to wound dressing material might interfere with cell survival, attachment, and expansion. Two experiments were performed to determine whether some dressing materials have a negative impact during the early phases of wound healing. In one experiment, freshly isolated cells were seeded and cultured for one week in combination with eight different wound dressings used during burn care. Cells, which were seeded and cultured with samples of Adaptic(®), Xeroform(®), EZ Derm(®), and Mepilex(®) did not attach, nor did they survive during the first week. Mepitel(®), N-Terface(®), Polyskin(®), and Biobrane(®) dressing samples had no negative effect on cell attachment and cell growth when compared to the controls. In a second experiment, the same dressings were exposed to pre-cultured cells in order to exclude the effects of attachment and spreading. The results confirm the above findings. This study could be of interest for establishing skin cell grafting therapies in burn medicine and also for wound care in general.

Safety profile of uncrossmatched, cold-stored, low-titer, group O+ whole blood in civilian trauma patients

The use of cold‐stored low‐titer group O whole blood (LTOWB) for civilian trauma patients is gaining popularity. However, hemolysis might occur among non–group O recipients. This study evaluated the serologic safety of transfusing up to 4 units of LTOWB.