Xeroform Stick-Down Dressing: A Novel Treatment for Pediatric Partial-Thickness Burns.

BACKGROUND: Burns traditionally require frequent, painful dressing changes to minimize infection risk and promote wound healing. To improve care for our pediatric population, our institution adapted a skin graft donor site dressing into a "stick-down" burn dressing consisting of a one-time application of bacitracin and 3% bismuth tribromophenate/vaseline impregnated gauze (Xeroform) that adheres to the burn and peels off as new epithelialized skin forms. The goal of which is to minimize dressing change frequency and patient discomfort in a cost-effective, widely available manner. This study aimed to compare clinical outcomes of the stick-down versus traditional topical dressings. METHODS: A retrospective cohort study of pediatric patients (age <18 year) with partial-thickness burns treated at a level I pediatric trauma center for 4 years was conducted. One hundred eleven patients were included: 74 patients treated with daily silver sulfadiazene (Silvadene) dressings matched to 37 patients treated with the Xeroform stick-down dressing using 2:1 propensity score matching. Univariate analyses used Wilcoxon rank sum and Fisher exact tests. RESULTS: The cohorts had similar demographics and burn characteristics. Both groups had similar hospitalization rates (31.1% Silvadene, 32.4% Xeroform), most commonly for pain control (54.5% Silvadene, 58.3% Xeroform), with similar average daily narcotic usage (7.7 ± 12.1 morphine milliequivalents Silvadene, 5.1 ± 9.5 Xeroform; P = 0.91). The Xeroform cohort had a shorter but statistically similar hospital stay (median, 1 vs 2 days). In addition, the Xeroform cohort required significantly less dressing changes with a median of 0.5 changes compared with 12 for the Silvadene cohort ( P < 0.0001). There was no difference in time to burn reepithelialization (median, 13.0 days for Silvadene and 12.0 days for Xeroform; P = 0.20) or wound healing complications (12.5% Silvadene, 2.7% Xeroform; P = 0.15). CONCLUSIONS: The Xeroform stick-down dressing has equivalent clinical outcomes to that of standard Silvadene dressings for the treatment of pediatric partial-thickness burns with the major advantages of decreasing dressing change frequency, minimizing patient distress and pain, and streamlining clinical care.

Rethinking Farkas: Updating Cephalic Index Norms in a Large, Diverse Population.

BACKGROUND: Cephalic index, the ratio of head width to length, is one normative indicator used by insurers to derive criteria for plagiocephaly helmet authorization. Current norms were established by a small sample of white children in the 1987 Farkas and Munro data set. This study establishes updated cephalic index values for infants and children in a large, diverse patient population. METHODS: Children aged 0 to 3 months, 3 to 6 months, 9 to 12 months, 2 to 3 years, and 12 to 14 years were recruited at their well-child appointment. Cephalic index was calculated for each age group and compared to previously established norms. RESULTS: Eight hundred seventy patients met inclusion criteria. The means for boys and girls between 0 and 6 months were 83.5 (n = 155, SD 6.01) and 83.5 (n = 191, SD 5.80), respectively. Established means for boys and girls between 0 and 6 months were 74.4 (n = 38, SD 5.2) and 74.3 (n = 49, SD 6.1), respectively. The difference between norms is highly statistically significant (p < 0.0001). For this age range, insurance criteria for a helmet is >83.7 for boys and >82.7 for girls. Using previous norms, 74 boys (44.6 percent) and 104 girls (54.5 percent) would meet criteria for a helmet under current guidelines. CONCLUSIONS: The mean cephalic index of children has changed. The reasons could include diversifying populations in the United States and the introduction of the Back to Sleep campaign. Over 50 percent of children may inappropriately meet criteria for a helmet based on prior norms. Updating norms could change the definition of plagiocephaly for a helmet orthosis.

Increasing Fat Graft Retention in Irradiated Tissue after Preconditioning with External Volume Expansion.

BACKGROUND: Fat grafting is an adjuvant that may improve the quality of radiation-damaged tissue. However, fat grafting for volume restoration in irradiated sites may be less effective because of a poorly vascularized fibrotic recipient bed. External volume expansion has emerged as a potential technique to prepare the recipient sites for improved survival of grafted fat. The authors previously demonstrated increased vasculature with external volume expansion stimulation of irradiated tissues. The authors now hypothesize that external volume expansion's improvements in recipient-site vascularity will increase the volume retention and quality of fat grafts in fibrotic irradiated sites. METHODS: Athymic mice were irradiated until development of chronic radiation injury. Then, the irradiated site was stimulated by external volume expansion (external volume expansion group), followed by subcutaneous fat grafting. Grafts in an irradiated site without external volume expansion stimulation (irradiated control group) and grafts in a healthy nonirradiated (nonirradiated control group) site were used as controls. All grafts were monitored for 8 weeks and evaluated both histologically and by micro-computed tomography for analysis of volume retention. RESULTS: Hyperspectral imaging confirmed a 25 percent decrease in vascularity of irradiated tissue (irradiated control group) compared with nonirradiated tissue (nonirradiated control group). Grafts in the irradiated control group retained 11 percent less volume than grafts in the nonirradiated control group. The experimental external volume expansion group achieved a 20 percent (p = 0.01) increase in retained graft volume compared with the irradiated control group. CONCLUSIONS: External volume expansion stimulation can mitigate the effects of irradiation at the recipient site and in turn help preserve fat graft volume retention. Possible mechanisms include increased vascularity, adipogenic conversion, and increased compliance of a fibrotic recipient site.

Experimental In-Vivo Models Used in Fat Grafting Research for Volume Augmentation in Soft Tissue Reconstruction.

As the popularity of fat grafting research increases, animal models are being used as the source of pre-clinical experimental information for discovery and to enhance techniques. To date, animal models used in this research have not been compared to provide a standardized model. We analyzed publications from 1968-2015 to compare published accounts of animal models in fat grafting research. Data collected included: species used, graft characteristics (donor tissue, recipient area, amount injected, injection technique), time of sacrifice and quantification methods. Mice were most commonly used (56% of studies), with the "athymic nude" strain utilized most frequently (44%). Autologous fat was the most common source of grafted tissue (52%). Subcutaneous dorsum was the most common recipient site (51%). On average, 0.80±0.60 mL of fat was grafted. A single bolus technique was used in 57% of studies. Fat volume assessment was typically completed at the end of the study, occurring at less than 1 week to one year. Graft volume was quantified by weight (63%), usually in conjunction with another analysis. The results demonstrate the current heterogeneity of animal models in this research. We propose that the research community reach a consensus to allow better comparison of techniques and results. One example is the model used in our laboratory and others; this model is described in detail. Eventually, larger animal models may better translate to the human condition but, given increased financial costs and animal facility capability, should be explored when data obtained from small animal studies is exhausted or inconclusive.

Hyperspectral Imaging Provides Early Prediction of Random Axial Flap Necrosis in a Preclinical Model.

BACKGROUND: Necrosis remains a significant complication in cutaneous flap procedures. Monitoring, and ideally prediction, of vascular compromise in the early postoperative period may allow surgeons to limit the impact of complications by prompt intervention. Hyperspectral imaging could be a reliable, effective, and noninvasive method for predicting flap survival postoperatively. In this preclinical study, the authors demonstrate that hyperspectral imaging is able to correlate early skin perfusion changes and ultimate flap survival in a preclinical model. METHODS: Thirty-one hairless, immunocompetent, adult male mice were used. Random pattern dorsal skin flaps were elevated and sutured back into place with a silicone barrier. Hyperspectral imaging and digital images were obtained 30 minutes, 24 hours, or 72 hours after flap elevation and before sacrifice on postoperative day 7. RESULTS: Areas of high deoxygenated hemoglobin change (124; 95 percent CI, 118 to 129) seen at 30 minutes after surgery were associated with greater than 50 percent flap necrosis at postoperative day 7. Areas demarcated by high deoxygenated hemoglobin at 30 minutes postoperatively had a statistically significant correlation with areas of macroscopic necrosis on postoperative day 7. Analysis of images obtained at 24 and 72 hours did not show similar changes. CONCLUSIONS: These findings suggest that early changes in deoxygenated hemoglobin seen with hyperspectral imaging may predict the region and extent of flap necrosis. Further clinical studies are needed to determine whether hyperspectral imaging is applicable to the clinical setting.

Association between cumulative radiation dose, adverse skin reactions, and changes in surface hemoglobin among women undergoing breast conserving therapy.

INTRODUCTION: Radiation therapy is crucial to effective cancer treatment. Modern treatment strategies have reduced possible skin injury, but few clinical studies have addressed the dose relationship between radiation exposure and skin reaction. This prospective clinical study analyzes skin oxygenation/perfusion in patients undergoing fractionated breast conserving therapy via hyperspectral imaging (HSI). METHODS: Forty-three women undergoing breast conserving therapy were enrolled in this study. Optically stimulated luminescent dosimeters (OSLDs) measured radiation exposure in four sites: treatment breast, lumpectomy scar, medial tattoo and the control breast. The oxygenation/perfusion states of these sites were prospectively imaged before and after each treatment fraction with HSI. Visual skin reactions were classified according to the RTOG system. RESULTS: 2753 observations were obtained and indicated a dose-response relationship between radiation exposure and oxygenated hemoglobin (OxyHb) after a 600 cGy cumulative dose threshold. There was a relatively weak association between DeoxyHb and radiation exposure. Results suggest strong correlations between changes in mean OxyHb and skin reaction as well as between radiation exposure and changes in skin reaction. CONCLUSION: HSI demonstrates promise in the assessment of skin dose as well as an objective measure of skin reaction. The ability to easily identify adverse skin reactions and to modify the treatment plan may circumvent the need for detrimental treatment breaks.

External Volume Expansion in Irradiated Tissue: Effects on the Recipient Site.

BACKGROUND: External volume expansion prepares recipient sites to improve outcomes of fat grafting. For patients receiving radiotherapy after mastectomy, results with external volume expansion vary, and the relationship between radiotherapy and expansion remains unexplored. Thus, the authors developed a new translational model to investigate the effects in chronic skin fibrosis after radiation exposure. METHODS: Twenty-four SKH1-E mice received 50 Gy of ß-radiation to each flank and were monitored until fibrosis developed (8 weeks). External volume expansion was then applied at -25 mmHg to one side for 6 hours for 5 days. The opposite side served as the control. Perfusion changes were assessed with hyperspectral imaging. Mice were euthanized at 5 (n = 12) and 15 days (n = 12) after the last expansion application. Tissue samples were analyzed with immunohistochemistry for CD31 and Ki67, Masson trichrome for skin thickness, and picrosirius red to analyze collagen composition. RESULTS: All animals developed skin fibrosis 8 weeks after radiotherapy and became hypoperfused based on hyperspectral imaging. Expansion induced edema on treated sides after stimulation. Perfusion was decreased by 13 percent on the expansion side (p < 0.001) compared with the control side for 5 days after stimulation. Perfusion returned to control-side levels by day 15. Dermal vasculature increased 38 percent by day 15 (p < 0.01) in expansion versus control. No difference was found in collagen composition. CONCLUSIONS: External volume expansion temporarily reduces perfusion, likely because of transient ischemia or edema. Together with mechanotransduction, these effects encourage a proangiogenic and proliferative environment in fibrotic tissue after radiotherapy in the authors' mouse model. Further studies are needed to assess these changes in fat graft retention.

Induction of Adipogenesis by External Volume Expansion.

BACKGROUND: External volume expansion by suction is used to prepare the recipient site for fat grafting by increasing its compliance and vascularity. The authors previously developed a mouse model for external volume expansion and demonstrated its pro-proliferative and angiogenic effects. Increased thickness of the subcutaneous tissue was also observed. This study was thus designed to assess the adipogenic potential of external volume expansion stimulation. METHODS: A miniaturized external volume expansion device consisting of a rubber dome connected to a -25 mmHg suction source was applied to the dorsum of mice for a single 2-hour stimulation or for 2 hours daily for 5 days. Tissues were harvested up to 48 hours after the last stimulation and analyzed for edema, inflammation, and adipocyte content by staining for hematoxylin and eosin, CD45, and perilipin-A. Expression of peroxisome proliferator-activated receptor-γ (proadipogenic factor) and preadipocyte factor 1 (preadipocyte marker) was evaluated by Western blot analysis. RESULTS: Both a 2-hour stimulation and cyclical 2-hour stimulation for 5 days induced 1.5- and 1.9-fold increases in the number of adipocytes per millimeter. Edema was present in the immediate poststimulation period, and inflammation was seen 2 days later. Peroxisome proliferator-activated receptor-γ was increased at the end of stimulation. CONCLUSIONS: Stretch is known to stimulate proliferation, whereas edema and inflammation are both emerging proadipogenic factors. Their combination in external volume expansion seems to produce proadipogenic effects, seen even after a single 2-hour stimulation.

Hyperspectral Imaging as an Early Biomarker for Radiation Exposure and Microcirculatory Damage.

BACKGROUND: Radiation exposure can lead to detrimental effects in skin microcirculation. The precise relationship between radiation dose received and its effect on cutaneous perfusion still remains controversial. Previously, we have shown that hyperspectral imaging (HSI) is able to demonstrate long-term reductions in cutaneous perfusion secondary to chronic microvascular injury. This study characterizes the changes in skin microcirculation in response to varying doses of ionizing radiation and investigates these microcirculatory changes as a possible early non-invasive biomarker that may correlate with the extent of long-term microvascular damage. METHODS: Immunocompetent hairless mice (n = 66) were exposed to single fractions of superficial beta-irradiation in doses of 0, 5, 10, 20, 35, or 50 Gy. A HSI device was utilized to measure deoxygenated hemoglobin levels in irradiated and control areas. HSI measurements were performed at baseline before radiation exposure and for the first 3 days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at 4 weeks post-irradiation was performed in harvested tissue by CD31 immunohistochemistry. RESULTS: CD31 immunohistochemistry demonstrated a significant correlation (r = 0.90, p < 0.0001) between dose and vessel density reduction at 4 weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first 3 days post-irradiation in all groups. These deoxygenated hemoglobin changes varied proportionally with dose (r = 0.98, p < 0.0001) and skin reactions (r = 0.98, p < 0.0001). There was a highly significant correlation (r = 0.91, p < 0.0001) between these early changes in deoxygenated hemoglobin and late vascular injury severity assessed at the end of 4 weeks. CONCLUSION: Radiation dose is directly correlated with cutaneous microvascular injury severity at 4 weeks in our model. Early post-exposure measurement of cutaneous deoxygenated hemoglobin levels may be a useful biomarker for radiation dose reconstruction and predictor for chronic microvascular injury.

Hyperspectral Imaging for Burn Depth Assessment in an Animal Model.

UNLABELLED: Differentiating between superficial and deep-dermal (DD) burns remains challenging. Superficial-dermal burns heal with conservative treatment; DD burns often require excision and skin grafting. Decision of surgical treatment is often delayed until burn depth is definitively identified. This study's aim is to assess the ability of hyperspectral imaging (HSI) to differentiate burn depth. METHODS: Thermal injury of graded severity was generated on the dorsum of hairless mice with a heated brass rod. Perfusion and oxygenation parameters of injured skin were measured with HSI, a noninvasive method of diffuse reflectance spectroscopy, at 2 minutes, 1, 24, 48 and 72 hours after wounding. Burn depth was measured histologically in 12 mice from each burn group (n = 72) at 72 hours. RESULTS: Three levels of burn depth were verified histologically: intermediate-dermal (ID), DD, and full-thickness. At 24 hours post injury, total hemoglobin (tHb) increased by 67% and 16% in ID and DD burns, respectively. In contrast, tHb decreased to 36% of its original levels in full-thickness burns. Differences in deoxygenated and tHb among all groups were significant (P < 0.001) at 24 hours post injury. CONCLUSIONS: HSI was able to differentiate among 3 discrete levels of burn injury. This is likely because of its correlation with skin perfusion: superficial burn injury causes an inflammatory response and increased perfusion to the burn site, whereas deeper burns destroy the dermal microvasculature and a decrease in perfusion follows. This study supports further investigation of HSI in early burn depth assessment.

Seroma Formation in Rat Latissimus Dorsi Resection in the Presence of Biologics: The Role of Quilting.

BACKGROUND: Seroma formation is a well-recognized complication associated with many operative procedures. Despite its ubiquity, a lack of definitive scientific understanding of the etiology, natural history, and biochemistry of seromas remains. We endeavored to create and examine seromas in a rat model in the setting of commonly used biologic implants and to examine the role of quilting sutures/mechanical fixation in mitigating seroma development. METHODS: Female Sprague-Dawley rats were assigned to either Quilting or Nonquilting groups then subdivided into one of 3 porcine dermal implant groups (Permacol Surgical Implant, Strattice Reconstructive Tissue Matrix, or XCM Biologic Tissue Matrix) or control group. A 5-cm midline back incision was made, the skin reflected and the latissimus dorsi muscle resected bilaterally. Implants were sutured into the surgical bed using a running suture. The skin of nonquilted rats was closed with a running subcuticular suture. Quilted rats underwent placement of absorbable quilting sutures spaced 2 cm apart between the skin and underlying implant or muscle before skin closure. Postoperatively, rats were monitored for seroma formation with fluid aspirated as needed. At 28 or 90 days, rats were euthanized. Seroma and implants were examined grossly and under light microscopy. RESULTS: Of nonquilted rats, 42/54 (78%) developed seromas compared with 19/46 (41%) of quilted rats (P < 0.05), defined by bursa cavity present at necropsy. When a biologic implant was present, 28/35 (80%) of nonquilted rats developed seromas compared with 12/33 (36%) of quilted rats (P < 0.05). In the control group, 14/19 (74%) of nonquilted rats developed seromas compared with 7/13 (54%) of quilted rats. This difference was not statistically significant. Bursa presence was confirmed histologically in all cases, with no difference in bursa character seen between groups. CONCLUSIONS: This study confirms a reliable rat model of seroma formation, with most of the rats exhibiting at least subclinical seromas. There was no difference in seroma formation rate in the presence of biologic implants, and no differences in bursa character between implants. Mechanical fixation with quilting sutures decreased seroma rate significantly in all subgroups. All rats with seromas at necropsy had histological evidence of a bursa with no difference in appearance between groups.

Mechanisms of action of external volume expansion devices.

BACKGROUND: External volume expansion by suction has been proposed to improve the survival of fat grafting by preparing the recipient site. In previous experimental work, external volume expansion demonstrated the capacity to stimulate cell proliferation, vessel remodeling, and adipogenesis. This study investigated possible mechanisms underlying these observed changes. METHODS: A miniaturized external volume expansion device was applied to the dorsum of mice for 2 hours. Hypoxia during stimulation was assessed with pimonidazole hydrochloride, and tissue perfusion was measured for up to 2 days using hyperspectral imaging. Treated tissues were evaluated by microscopy for edema, inflammation, and the effects on cell proliferation and vessel remodeling. RESULTS: External volume expansion-treated tissues were grossly expanded with 2 hours of stimulation, developing a macroscopic swelling that regressed slowly over the course of hours following stimulus cessation. This gross swelling was reflective of histologic signs of intense edema, persistent for at least 1 hour after external volume expansion. Tissues were hypoxic during stimulation, and hyperspectral imaging demonstrated decreased tissue content of both oxygenated and deoxygenated hemoglobin in the first hour after external volume expansion release. The onset of inflammation was already apparent by the end of stimulation and remained elevated through 2 days after external volume expansion. At this time point, epidermal and dermal cell proliferation and vascular density were significantly increased. CONCLUSION: External volume expansion sets in motion various mechanisms, including mechanical stimulation, edema, ischemia, and inflammation, that over distinct time periods maintain an environment conducive to cell proliferation and angiogenesis, which can be elicited even by a single 2-hour external volume expansion cycle.