Orbital Exenteration Reconstruction for Medically Complex Patients: Bilaminate Dermal Substitute as an Alternative to Major Surgery.

Reconstructive strategies after orbital exenteration range from the use of skin grafts to tissue flaps, depending on the classification of the defect, patient's goals, and tolerance for surgery. We present a case of a 68-year-old, medically complex patient who underwent orbital exenteration, radiation therapy, and reconstruction with a bilaminate dermal substitute. Despite the placement in an irradiated area without periosteum, the bilaminate dermal substitute graft demonstrated acceptable integration and provided an adequate base for subsequent split thickness skin grafting, sparing a medically fragile patient from a morbid operation. This case highlights the advantages of a less invasive reconstructive modality when managing a patient with multiple comorbidities and a significant chance of cancer recurrence.

Pseudogout: A Rare Cause of Acute Carpal Tunnel Syndrome and Acute Guyon Canal Syndrome.

Pseudogout is an acute inflammatory arthropathy that often presents as a hot, swollen, painful joint. Rarely, the inflammatory response caused by pseudogout has led to acute neuropathic symptoms of the hand. We present a case of pseudogout causing acute neuropathic symptoms in the median and ulnar nerves, ultimately necessitating urgent surgical decompression. The patient's symptoms were alleviated after surgical decompression. Pseudogout should be considered a rare cause of acute neuropathic compression of the hand. Its management may require surgical intervention and should involve postoperative follow-up with a rheumatologist.

The Use of Visible-Light Hyperspectral Imaging in Evaluating Burn Wounds: A Case Report.

Burn depth is a critical factor in determining the healing potential of a burn as the extent of injury ultimately guides overall treatment. Visible-Light Hyperspectral Imaging is an FDA-approved, noninvasive, and noncontrast imaging technology that uses light waves within the visible spectrum to evaluate skin and superficial soft tissue perfusion. In this case report, visible-light hyperspectral imaging was used to evaluate a 37-year-old male who presented to the Emergency Department with a thermal burn of the trunk, back, and right upper extremity. Images were taken at initial evaluation, 6 hours postinjury, and again during daily dressing changes until hospital day 5 when the patient underwent surgical debridement. In this patient, operative treatment was postponed until 89.7 hours postinjury, at which point the clinical examination showed clear visual demarcation in regions of irreversible damage. Comparatively, visible-light hyperspectral imaging analysis of the permanently injured tissue demonstrated acute but varying changes in both oxygenated hemoglobin and deoxygenated hemoglobin at the time of initial evaluation. The most dramatic change in tissue oxygenation occurred between 6.5 and 39.3 hours, demonstrating visible-light hyperspectral imaging's ability to detect significant differences in oxygenation values between areas of second-degree superficial burns and areas of second-degree deep and third-degree burns in the acute period. The data suggest that the utilization of visible-light hyperspectral imaging in this 6.5- to 39.3-hour window may help predict final burn depth before clinical assessment, potentially allowing for surgical intervention within the first 48 hours following injury.

Microsurgical Replantation of Completely Avulsed Scalp Segment Recovered From Under Snow.

Complete scalp avulsion is a devastating injury resulting in permanent disfigurement. Replantation is the procedure of choice whenever possible. This report describes a successful case of microsurgical reattachment of complete scalp avulsion of temporoparietal segment in a 72-year-old female patient after her hair was tangled in the hoof crack of a horse when the animal slipped on ice and fell on a cold New England night. The amputated segment could be recovered from under snow only after 4 hours following the incident. The procedure involved microvascular anastomoses of superficial temporal artery and vein. The recovery was uneventful, with complete survival of the replant, including the severely crushed segment. There was no need for any transfusion. Long term follow up revealed excellent aesthetic outcome with complete hair growth. This report presents a case experience of successful scalp replantation even after the amputated part was exposed to freezing conditions for 4 hours.

Rapidly Progressive Soft Tissue Infection of the Upper Extremity With Aeromonas veronii Biovar sobria.

Aeromonas veronii, a bacterium found in freshwater, is an unusual pathogen in healthy patients. We present a case report of a rare, aggressive subtype in a young, immunocompetent individual. History of injury in an aquatic environment and culture data are key for identification of the causal agent and should dictate acute clinical management and antibiotic therapy. Coverage should include cephalosporins, quinolones, or sulfas if Aeromonas is suspected, and adjusted depending on culture and sensitivity. Early surgical exploration, incision and drainage, and appropriate antimicrobial therapy are the cornerstones for successful treatment of these aggressive, sometimes life-threatening infections.

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.

Generation of Functional Human Adipose Tissue in Mice from Primed Progenitor Cells.

IMPACT STATEMENT: This research describes the use of human mesenchymal progenitor cells for generating functional adipose tissue in vivo in a nude mouse model. Further preclinical development of the methods and insights described in this article can lead to therapeutic use of these cells in regenerative and reconstructive medicine.

International Medical Graduates and the Integrated Plastic Surgery Residency Match.

Plastic surgery continues to be one of the most competitive programs into which medical students attempt to match. The reasons for this include the complexity and diversity of cases, the opportunity to interact with multiple specialties, patient and surgeon satisfaction, and the potential for higher compensation compared with other specialties. The disparity between the relatively small number of plastic surgery residency positions and the large number of highly competitive candidates has created challenges for both the applicant and the residency program director. This challenge is even greater for international medical graduates because of traditional preconceived notions about the quality of the applicants. The authors sought to determine existing beliefs about international medical graduates among plastic surgeons.

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.

Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model.

BACKGROUND: Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. METHODS: Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis. RESULTS: Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at -25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes. CONCLUSION: Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.

Blockade of IgM-Mediated Inflammation Alters Wound Progression in a Swine Model of Partial-Thickness Burn.

In a mouse model, a second-degree burn elicits a severe inflammatory response that is mediated by circulating autoantibody specific for a neoantigen (nonmuscle myosin). Nonmuscle myosin is expressed by injured tissue, leading to amplified ulceration and scarring. We hypothesize that a synthetic peptide (N2) can mimic the neoantigen and competitively inhibit the autoantibody, decreasing inflammation, and reducing the extent of burn injury in a preclinical swine model of burn. Second-degree burns were created on young swine using brass cylinders, warmed to varying temperatures before skin contact. Animals were treated in double-blind fashion with normal saline, control peptide, or blocking peptide. Biopsies were taken at 2 hours, 1, 4, 7, and 14 days after burn injury. Burn wound healing parameters were assessed. Immunohistochemical staining for Ki-67, immunoglobulin (Ig)M, and interleukin (IL)-8 were also performed. N2 blocking peptide administration decreased dermal injury at 4 days with increased reepithelization, indicating more rapid healing. N2 normalized skin histology by 14 days and showed improved epidermal healing. Granulation tissue thickness was decreased, and there was an accompanying decrease in neutrophil infiltration. The basal layer of epidermis in N2-treated animals displayed more cells positive for Ki-67, suggesting a prompter regenerative capacity. Immunohistochemical staining demonstrated decreased deposition of immunoglobulin M and interleukin-8 after thermal injury in animals treated with N2 peptide, in comparison to controls. The findings of this study identify N2 blocking a specific inflammatory pathway, as a novel therapeutic approach, preventing the evolution of cutaneous burn injuries in a preclinical animal model.

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.

Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a.

Wound healing is a physiological reparative response to injury and a well-orchestrated process that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, and wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. Herein, we investigate the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to high glucose in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~3.5-fold) four days post-wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to ~80%), increased granulation tissue thickness (by 2.5-fold) and accelerated wound closure (53% after nine days) compared to scrambled anti-miR controls in db/db mice. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene SMAD1 in ECs nine days post-wounding of diabetic mice. In addition, high glucose reduced activity of the SMAD1-3'-UTR. Diabetic dermal wounds treated with LNA-anti-miR-26a had increased expression of ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.

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.