Impact of dermal matrix thickness on split-thickness skin graft survival and wound contraction in a single-stage procedure.

Optimal treatment of full-thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split-thickness skin graft (STSG) application. However, this two-stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single-stage reconstructions, with application of both STSG and dermal substitute at the index operation, we have little understanding of how the physical characteristics of dermal substitutes affects the success of a single-stage procedure. Here, we evaluated several dermal substitutes to optimise single-stage skin replacement in a preclinical porcine model. A porcine full-thickness excisional wound model was used to evaluate the following dermal substitutes: autologous dermal graft (ADG; thicknesses 0.15-0.60 mm), Integra (0.4-0.8 mm), Alloderm (0.9-1.6 mm), and chitosan-based hydrogel (0.1-0.2 mm). After excision, each wound was treated with either a dermal substitute followed by STSG or STSG alone (control). Endpoints included graft take at postoperative days (PODs) 7 and 14, wound closure at POD 28, and wound contracture from POD 28-120. Graft take was highest in the STSG alone and hydrogel groups at POD 14 (86.9% ± 19.5% and 81.3% ± 12.3%, respectively; P < .001). There were no differences in graft take at POD 7 or in wound closure at POD 28, though highest rates of wound closure were seen in the STSG alone and hydrogel groups (93.6% ± 9.1% and 99.8% ± 0.5%, respectively). ADG-treated wounds demonstrated the least amount of wound contracture at each time point. Increase dermal substitute thickness was associated with worse percent graft take at PODs 14 and 28 (Spearman ρ of -0.50 and -0.45, respectively; P < .001). In this preclinical single-stage skin reconstruction model, thinner ADG and hydrogel dermal substitutes outperformed thicker dermal substitutes. Both substitute thickness and composition affect treatment success. Further preclinical and clinical studies to optimise this treatment modality are warranted.

Preinjury statin use and thromboembolic events in trauma: a 10-year retrospective evaluation.

BACKGROUND: Traumatic injury is well known to increase the risk of venous thromboembolic events (VTEs), occurring in up to 58% of trauma patients. Statin medications have significant anti-inflammatory properties and have been shown to reduce the risk of VTE. We hypothesized that trauma patients who received statin medication before injury would have a lower incidence of VTE after injury. METHODS: A 10-y retrospective review identified all patients admitted to our trauma service with an injury severity score >9 and an intensive care unit stay of >3 d. This population was categorized as either "statin recipient" (SR) or "statin naïve," with subsequent categorical division by occurrence of VTE. Our primary outcome measure was the occurrence of documented VTE in both statin naïve and SR subjects. RESULTS: A total of 2519 trauma patients were included with 97 (3.8%) developing VTE. Pretrauma statin use in males remained as an independent predictor of VTE (odds ratio = 2.25, 95% confidence interval = 1.25-4.04, P < 0.01). The median time to VTE onset was 3 d longer in SRs (10.0 d; confidence interval = 7.3-12.7, P < 0.05). CONCLUSIONS: Pretrauma statin use does not appear to have a protective benefit of VTE prevention in trauma patients, as we have shown pretrauma SR male trauma patients to have a twofold increased incidence of VTE. However, when considering the 3 d longer median time to VTE onset found in SRs, we consider the protective benefit of statin use reported in the current literature as likely attributable to this observed delayed onset.

Accelerated epithelialization and improved wound healing metrics in porcine full-thickness wounds transplanted with full-thickness skin micrografts.

Split-thickness skin grafting (STSG) is the current gold standard for treatment of extensive burn and traumatic skin injuries. However, STSG is limited by donor-site morbidity and availability, and often leads to scarring and wound contracture. Furthermore, these thin grafts lack dermal elements such as nerves and adnexa which are important in recapitulating normal skin function. Methods of fractional skin replacement either as minced STSGs or microscopic skin tissue columns have been proposed, though these techniques have not been fully characterized and lack evidence of regenerated adnexal structures. Here, we describe an alternative method of fractional skin replacement using full-thickness skin micrografts containing deep dermal components and intact adnexa. Full-thickness wounds measuring 3 cm in diameter and 2 cm apart were created on adult female Yorkshire swine. Full-thickness skin tissue columns (FTSTCs) 1.5 mm in diameter with intact adnexa and subcutaneous tissue were obtained using a suction-assisted device. Explant culture was initiated to demonstrate the capacity of FTSTCs to act as reservoirs of viable and proliferative epidermal and dermal cells. FTSTCs were applied directly to excisional wounds at three different expansion ratios (1:16, 1:40, 1:100) in fibrin sealant. Biopsies were collected at defined time points postwounding and processed for histology and immunohistochemistry. Wounds grafted with FTSTCs showed enhanced reepithelialization and epidermal differentiation over untreated control wounds in a dosage dependent manner. Adnexal structures such as hair follicles and sweat glands were only evident in FTSTC-treated wounds. Furthermore, whereas ungrafted wounds were marked by extensive infiltration of α-Smooth Muscle Actin+ (α-SMA+ ) myofibroblasts at POD 60, α-SMA expression was sparse and largely limited to perivascular cells in FTSTC-treated wounds. The number of Ki67+ cells was also greatly reduced in FTSTC-treated wounds. Transplantation of FTSTCs containing intact adnexa improved wound healing parameters in porcine full-thickness wounds and may have implications for the treatment of large, traumatic wounds.

Ultrahigh dose gentamicin alters inflammation and angiogenesis in vivo and in vitro.

Skin quality outcome after skin grafting is adversely affected by wound bed inflammation. Neomycin, gentamicin, and other aminoglycoside antibiotics are known to modulate inflammation, and topical application affords the use of higher doses than are possible to use systemically. Previous data suggest that clinically relevant doses of neomycin, but not gentamicin, may impair angiogenesis, which is critical to the durable survival of skin grafts. The role of gentamicin at ultrahigh doses compared with clinically relevant neomycin doses in regulating inflammatory expression and angiogenesis has been examined. In a porcine skin replacement excisional wound model, continuous exposure to gentamicin increased anti-angiogenic and inflammatory expression at 7 days postgrafting. In in vitro studies, gentamicin also impaired angiogenesis in a human umbilical vein endothelial cell (HUVEC) tube formation model, increased the expression of the anti-angiogenic gene C-X-C motif chemokine 10 (CXCL10) in HUVECs and macrophages, and increased pro-inflammatory cytokine expression of macrophages in a dose-dependent manner. Neomycin exerted similar effects in vitro at clinically relevant doses on HUVEC tube formation and macrophage pro-inflammatory expression. CXCL10 was upregulated in macrophages, but did not exhibit a change in HUVECs with neomycin treatment. Ultrahigh doses of gentamicin and clinically relevant doses of neomycin affect inflammation and angiogenesis in in vivo and in vitro models. These findings suggest that topical administration of aminoglycosides have the potential to adversely influence early skin graft survival.

Pediatric trauma surgery in Iraq and Afghanistan: Mortality, indicators, and most common operating room interventions from 2007 to 2016.

BACKGROUND: The wars in Afghanistan and Iraq produced thousands of pediatric casualties, using substantial military medical resources. We sought to describe characteristics of pediatric casualties who underwent operative intervention in Iraq and Afghanistan. METHODS: This is a retrospective analysis of pediatric casualties treated by US Forces in the Department of Defense Trauma Registry with at least one operative intervention during their course. We report descriptive, inferential statistics, and multivariable modeling to assess associations for receiving an operative intervention and survival. We excluded casualties who died on arrival to the emergency department. RESULTS: During the study period, there were a total of 3,439 children in the Department of Defense Trauma Registry, of which 3,388 met inclusion criteria. Of those, 2,538 (75%) required at least 1 operative intervention totaling 13,824 (median, 4; interquartile range, 2-7; range, 1-57). Compared with nonoperative casualties, operative casualties were older and male and had a higher proportion of explosive and firearm injuries, higher median composite injury severity scores, higher overall blood product administration, and longer intensive care hospitalizations. The most common operative procedures were related to abdominal, musculoskeletal, and neurosurgical trauma; burn management; and head and neck. When adjusting for confounders, older age (unit odds ratio, 1.04; 1.02-1.06), receiving a massive transfusion during their initial 24 hours (6.86, 4.43-10.62), explosive injuries (1.43, 1.17-1.81), firearm injuries (1.94, 1.47-2.55), and age-adjusted tachycardia (1.45, 1.20-1.75) were all associated with going to the operating room. Survival to discharge on initial hospitalization was higher in the operative cohort (95% vs. 82%, p < 0.001). When adjusting for confounders, operative intervention was associated with improved mortality (odds ratio, 7.43; 5.15-10.72). CONCLUSION: Most children treated in US military/coalition treatment facilities required at least one operative intervention. Several preoperative descriptors were associated with casualties' likelihood of operative interventions. Operative management was associated with improved mortality. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300µm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been demonstrated. Future research to enhance quality of skin replacement therapies should be directed toward modulation of inflammation and assessments for complete excision.

Reverse posterior interosseous flap for defects of the dorsal ulnar wrist using previously burned and recently grafted skin.

BACKGROUND: In the severely burned patient, coverage of exposed bone in the dorsal ulnar wrist can be a difficult problem. This is especially challenging in patients with a high percentage total body surface area (TBSA) where donor flaps can be scarce. The use of previously burned and/or recently grafted skin as flaps is an option. It has been postulated that use of previously burned skin can result in higher rates of local or distant flap failures. The reverse posterior interosseous flap (PIF) is an axial flap, based on the retrograde posterior interosseous artery, to provide coverage of the hand. Here we describe utilization of the PIF, using previously burned and/or recently grafted skin for coverage of dorsal ulnar wrist defects. METHODS: This is a case series of three patients, with extensive burns (range 35-83%TBSA), where defects of the dorsal ulnar wrist necessitated coverage. Each patient underwent PIF(s) utilizing previously burned and/or grafted skin, all within three months after their initial burn event. RESULTS: Case 1: 28 year old male who suffered 35% TBSA via blast mechanism developed a chronic open wound over the dorsal ulnar wrist with exposed tendon. The patient successfully underwent a left PIF using previously grafted skin. Case 2: 23 year old male with 83% TBSA. Bilateral ulnar styloids were exposed. PIFs were performed bilaterally, using previously burned and recently grafted skin. Coverage was successful but received leech therapy post-operatively for venous congestion. Case 3: 37 year old male with 52% TBSA, with the most severe burns isolated to his bilateral upper extremities; the ulnar head was exposed. The posterior interroseous artery was explored and PIF was attempted, but there was no retrograde flow in the distal artery due to a deeper injury than previously recognized. The patient ultimately underwent a pedicled abdominal flap for coverage. CONCLUSIONS: Defects of the distal ulnar wrist after deep and extensive burns can be problematic. Use of the reverse PIF using previously burned skin, even those that has just been recently grafted is a viable option for this difficult patient population. However, it may not be possible in all patients. Vigilance and early intervention for post-operative venous congestion are important.

Inability to determine tissue health is main indication of allograft use in intermediate extent burns.

INTRODUCTION: Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns. METHODS: Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted. RESULTS: In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, p<0.001) than non-allografted patients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use. CONCLUSIONS: Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed suitability for autograft application. Allograft application can be utilized to test recipient site viability in cases of autograft failure or uncertain depth of excision.

Characterization of skin allograft use in thermal injury.

This study provides objective data on the practice of allograft usage in severely burned patients. Furthermore, gaps in our knowledge are identified, and areas for further research are delineated. Using an institutional review board-approved protocol, active duty military patients injured while deployed in support of overseas contingency operations and treated at our burn center between March 2003 and December 2010 were identified. Their electronic medical records were reviewed for allograft use, TBSA burned, injury severity score, anatomic distribution of burns, operative burden, length of stay, transfusions, and outcome. Among 844 patients, 112 (13.3%) received allograft and 732 (86.7%) did not. The amount of allograft used per patient varied and was not normally distributed (median, 23.5; interquartile range, 69.5). Patients received allograft skin an average of 12.75 times during their admission. Allografted patients sustained severe burns (µ, 53.8% TBSA); most were transfused (71.2%) and grafted frequently, averaging every 7.45 days. Most commonly, allograft was placed on the extremities (66.5%) followed by the trunk (44.2%); however, the vast majority of allografted patients also had concomitant burns of the head (91.1%) and hands (87.5%). All-cause mortality among the allografted patients was 19.1%. In conclusion, allograft is commonly used in the surgical treatment of severe burns. Although there are no anatomic limitations to allograft placement, there are distinct patterns of use. Given the role of allograft in the acute management of large burns, there is need for further investigation of its effect on mortality, morbidity, and antigenicity.