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Background Repair of the orbital floor following trauma or tumor removal remains a challenge because of its complex three-dimensional shape. The purpose of the present study is to understand normal orbital floor anatomy by investigating its differences across four groups (Caucasian American and East Asian, males and females) via facial bone computed tomography (CT). Methods A total of 48 orbits in 24 patients between 20 and 60 years of age were evaluated. Although most patients underwent CT scanning following trauma, the orbital walls were intact in all patients. Linear and angular measurements of the orbital floor were obtained from CT images. Results Orbital floor width, length, angle between the orbital floor and medial wall, and distance from the inferior orbital rim to the lowest point of the orbital floor did not show a statistically significant difference between groups. Angles made by the infraorbital rim, the lowest point of the floor, and the anterior border of the infraorbital fissure were statistically significantly wider in East Asian females than in male groups. The floor depth in East Asian females was significantly smaller compared to all the other groups. Conclusion East Asian female population had smaller curvature and depth of an orbital floor than the other groups, which means racial and sex-related differences should be considered in the orbital floor reconstruction.

Progressive fibrosis of the dermal tissues is a challenging complication of radiotherapy whose underlying mechanism is not fully understood, and there are few available treatments. The canonical Wnt/β-catenin signaling pathway plays an important role in fibrosis as well as in the epithelial-to-mesenchymal transition (EMT). We investigated whether inhibition of Wnt/β-catenin signaling with sLRP6E1E2, a molecule that binds to extracellular Wnt ligands, ameliorated radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2 Gy not only facilitated fibrosis in cultured human dermal fibroblasts via activation of the Wnt/β-catenin pathway but also initiated EMT in cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic activity in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15 Gy was delivered to the dorsal skins of 36 mice randomized into three groups: those receiving PBS, those receiving control adenovirus, and those receiving decoy Wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and excessive deposition of type I collagen was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results demonstrate that the modulation of the Wnt/β-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis.

BACKGROUND Dickkopf 2 (DKK2) has important roles in vertebrate development; it inhibits Wnt signaling-related processes, such as axial patterning, limb development, somitogenesis, and eye formation. However, DKK2 also acts as a Wnt signaling agonist. Dickkopf 2, induced during endothelial cell morphogenesis, promotes angiogenesis in cultured human endothelial cells. In this study, we explored the effect of DKK2-expressing adenovirus on random-pattern flaps using a rodent model. METHODS A DKK2-expressing (dE1-RGD/DKK2) adenovirus was generated and 20 Sprague-Dawley rats were randomly divided into 2 groups: a DKK2 group and a control group. Each group was intradermally injected with 1 × 10 plaque-forming units of DKK2-expressing adenovirus (DKK2 group) or control virus (control group) 48 hours before and immediately before surgery. Then, random-pattern dorsal cutaneous flaps of 3 × 9 cm were elevated. Flap survival rates and cutaneous blood flow were measured over time, and immunohistochemical staining was performed 10 days after surgery to detect CD31 and vascular endothelial growth factor (VEGF). RESULTS Immunofluorescence staining confirmed the expression of DKK2 in the DKK2 group. The flap survival rate was higher in the DKK2 group (80.0 ± 4.49%) than in the control group (57.5 ± 4.21%; P < 0.05). Blood flow to the most distal compartment was higher in the DKK2 group than the control group during the early postoperative period. Although vascular density was greater in the DKK2 group, there was no difference in the VEGF concentration between groups. CONCLUSIONS The findings of the present study suggest that the DKK2-expressing adenovirus increases the survival of the random-pattern cutaneous flap independently of VEGF. The administration of the DKK2-expressing adenovirus into elevated skin flaps increased the number of capillaries and blood flow, thereby improving skin flap survival.

Introduction Traditionally, galeal flap or cranialization was often used to reconstruct the skull base defect caused by trauma or tumor removal. However, in the case of huge skull base defect, galeal flap is not enough to block the communication between nasal cavity and intracranial space. In this study, authors suggest combination flap of galea and reverse temporalis muscle as a method for reconstruction of huge skull base defect. Materials and methods From 2016 to 2019, retrospective review was conducted, assessing 7 patients with bone defect which is not just opening of frontal sinus but extends to frontal sinus and cribriform plate. Reconstructions were done by combination of galeal flap and reverse temporalis muscle flap transposition. Results Defects were caused by nasal cavity tumor with intracranial extension or brain tumor with nasal cavity extension. There was no major complication in every case. During the follow up period, no patient had signs of complication such as ascending infection, herniation and CSF rhinorrhea. Postoperative radiologic images of all patients that were taken at least 6 months after the surgery showed that flaps maintained the lining and the volume well. Discussion Conventional reconstruction of skull base defect with galeal flap is not effective enough to cover the large sized defect. In conclusion, galeal flap in combination with reverse temporalis muscle flap can effectively block the communication of nasal cavity and intracranium.

Aging-associated dermatological pigmentary diseases are associated with accumulation of senescence cells and the disruption of basement membrane due to chronic ultraviolet radiation (UVR) exposure. Our study is on the synergistic effect of the novel 300 μm needle-depth fractional microneedling radiofrequency (FMR) treatment and conventional Q-switched ND:YAG laser on aging-associated hyperpigmentation of the skin. The prospective controlled clinical trial of 25 Asian women revealed significantly higher improvements not only on wrinkles, but also on hyperpigmentation. Additional ex vivo study revealed significant reduction of pro-melanogenic markers as well as senescent keratinocytes, while increased expression of collagen type IV on the epidermal basement membrane, after additional FMR treatment on UV-irradiated human tissues. These results demonstrate that 300 μm needle-depth FMR might effectively remove senescent keratinocytes that secrete pro-melanogenic markers, and repair disrupted basement membrane, therefore preventing constant hyperpigmentation of the aged skin.

Background Face transplantation has naturally evolved from reconstructive procedures. However, few institutions perform face transplantations, because it is time-consuming and it is necessary to justify non-vital organ transplantation. We investigated the process of organ donation from brain-dead patients and the possibility of incorporating face transplantation into the donation process. Methods A retrospective review was performed of 1,074 brain-dead patients from January 2015 to December 2016 in Korea. We analyzed the time intervals from admission to brain death decisions (first, second, and final), the causes of brain death, and the state of the transplanted organs. Results The patient base (n=1,074) was composed of 747 males and 327 females. The average period between admission to the first brain death decision was 8.5 days (±15.3). The average time intervals between the first brain death decision and medical confirmation using electroencephalography and between the first brain death decision and the final determination of brain death were 16 hours 58 minutes (±14 hours 50 minutes) and 22 hours 57 minutes (±16 hours 16 minutes), respectively. The most common cause of brain death was cerebral hemorrhage/stroke (42.3%), followed by hypoxia (30.1%), and head trauma (25.2%). Conclusions When face transplantation is performed, the transplantation team has 22 hours 57 minutes on average to prepare after the first brain death decision. The cause of brain death was head trauma in approximately one-fourth of cases. Although head trauma does not always imply facial trauma, surgeons should be aware that the facial tissue may be compromised in such cases.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be psychosocially disfiguring for patients. Skin lesions in TSC, specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is important owing to its impact on patient cosmesis. Surgical treatment and laser therapy are the mainstream treatments for angiofibromas. Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. We describe an adult patient with an angiofibroma who had an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (CO2) laser ablation. The patient showed no sign of relapse or recurring lesions for a year. CO2 laser ablation may serve as a new paradigm of treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest a rather basic but highly effective approach for angiofibroma treatment that can be generally applied with the classic CO2 device.

Traditionally, a galeal flap has been used for skull base reconstruction. In addition to the galeal flap, several other flaps, such as the temporalis muscle flap or the free vascularized flap, can be options for skull base reconstruction, and each option has advantages and disadvantages. Certain cases, however, can be challengeable in the application of these flaps. We successfully managed to cover a skull base defect using an extended temporalis flap. Herein, we present the case and introduce this novel method.

Purpose The aim of this study was to investigate the effects of relaxin (RLN) expression on fibrosis inhibition in synovial fibroblasts. Materials and methods Tissue cells from patients with knee osteoarthritis and > 30° flexion contractures were utilised. Synovial fibroblasts were activated by TGF-β1 (two nanograms per millilitre) and then exposed to Ad-RLN as a therapeutic gene, adenovirus-lacZ construct as a marker gene, and SB505124 as an inhibitor for TGF-β1 signal for 48 h. The mRNA expression levels of collagens and MMPs were analysed by reverse transcription-polymerase chain reaction. Also, fibronectin, phosphorylation of Smad2 and ERK1/2, alpha smooth muscle actin, TIMP-1, TIMP-2, MMP-1 and MMP-13 levels were estimated using western blotting, and the total collagen synthesis was assayed. Results Ad-RLN-transduced synovial fibroblasts demonstrated 17%, 13%, and 48% reduction in collagen I, III and IV mRNA expression levels, respectively, and a 40% decrease in MMP-3, MMP-8, 20% decrease in MMP-9, MMP-13 mRNA expression, compared to non-Ad-RLN-transduced cells. In protein expression, Ad-RLN-transduced synovial fibroblasts demonstrated 46% increase in MMP-1, 5% decrease in MMP-2, 51% increase in MMP-9, and 22% increase in MMP-13, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts showed a 25% decrease in TIMP-1 and 65% decrease in TIMP-2 protein expression at 48 h, compared to non-Ad-RLN-transduced cells. Ad-RLN-transduced synovial fibroblasts demonstrated a 45% inhibition of fibronectin in protein expression level and 38% decrease in total collagen synthesis at 48 h, compared to non-Ad-RLN-transduced cells. Conclusion Relaxin expression exerted anti-fibrogenic effects on synovial fibroblasts from patients with knee osteoarthritis and flexion contractures. Therefore, relaxin could be an alternative therapeutic agent during the initial stage of osteoarthritis with flexion contracture by exerting its anti-fibrogenic effects.

Accumulation of excessive extracellular matrix (ECM) and aberrant transforming growth factor β (TGF-β) signaling pathway function can be potential therapeutic targets for keloid treatment. In this study, we examined the antifibrotic effect of metformin as a suppressor of TGF-β signaling pathways in human dermal fibroblasts (HDFs) and keloid spheroids. Human dermal fibroblasts were stimulated with TGF-β (10 ng/mL) and treated with metformin (10 mM). The mRNA and protein expression of ECM components were evaluated by quantitative polymerase chain reaction, western blot, and immunofluorescence assay. In addition, we immunohistochemically examined the expression levels of ECM proteins in keloid spheroids. After addition of metformin (10 mM), collagen types I and III and elastin mRNA levels were significantly decreased in HDFs, and collagen type I protein level was significantly decreased. In addition, the expression levels of collagen types I and III, fibronectin, and elastin were significantly reduced in keloid spheroids after treatment with metformin (100 mM). Collagen types I and III and p-Smad2/3 complex proteins were decreased in metformin-treated keloid spheroids. These findings indicated that metformin inhibits the expression of ECM components in TGF-β-stimulated HDFs and keloid spheroids. Therefore, we suggest the potential of metformin as an effective agent for the treatment of keloids.

Background Fractional microneedle radiofrequency (FMRF) systems are popular options for treating acne scars. However, treatment efficacy when used in combination with traditional ablative fractional laser (AFL) and the safety profile with concomitant use of isotretinoin remain unknown. Objective The aim of this study was to assess the safety and efficacy of an early intervention combination treatment protocol for inflammatory acne and acne scars. Materials and methods The electronic records of 71 patients with inflammatory acne and acne scars were included in this retrospective observational study. Data were collected for all patients who received combination FMRF and AFL. Within the study group, 43 patients were receiving low-dose isotretinoin or had completed isotretinoin within the past 3 weeks. Results The mean Scar Global Assessment score significantly decreased after 3 sessions of combination treatment (n = 71). Patients with inflammatory acne showed a significant decrease in the number of inflammatory lesions (n = 30). Patients with concomitant low-dose isotretinoin use reported a further decrease in Scar Global Assessment score (n = 43). There were no reported persistent side effects, including prolonged inflammatory reaction or scarring. Conclusion Combination treatment with FMRF and AFL is an effective and well-tolerated treatment modality for acne scars and inflammatory acne.

An adenoviral vector (Ad) expressing a Wnt decoy receptor (sLRP6E1E2) is known to induce an anti-fibrotic effect by inhibiting Wnt signaling. We evaluated its effects in vivo using pig models and attempted to introduce an alginate gel-matrix system to prolong the effect of the Ad. Transduction efficiency as to the biological activity of Ad in different forms was evaluated. Then, 50 days after the formation of full-thickness skin defects on the backs of Yorkshire pigs, scars were treated with each form of Ad. Therapeutic efficacy and various factors influencing scar formation and collagen rearrangement were analyzed. Inflammatory cell infiltration within the scar tissues was also evaluated. Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus treatment improved scar quality in a pig model. Loading this construct in alginate gel allows sustained virus release into local tissues and prolongs Ad activity, thus maintaining its therapeutic effect longer in vivo.

Summary Introduction The effect of radiation on uncomplicated postoperative scars is unclear. This study aimed to analyze irradiated and non-irradiated scars in patients with unilateral breast cancer, who underwent oncoplastic breast reduction surgery and radiation therapy (RT), to identify how postoperative scar changes with radiation. Methods Twenty breast scars in 10 patients were analyzed after unilateral breast-conserving surgery, oncoplastic breast reduction, and RT. Scars were assessed using the Vancouver scar scale (VSS) by two independent blinded observers and three-dimensional scar analysis camera. Paired t-test between irradiated and non-irradiated scars in each patient and correlation of scar score differences with potential contributing factors were analyzed. Results The VSS was significantly lower for the irradiated scar than that for the non-irradiated contralateral scar (1.40 vs. 4.05, p = 0.001), although time interval from the last radiation to scar assessment had a negative correlation with paired differences of VSS (Spearman's correlation coefficient: –0.637, p = 0.048). Compared with the non-irradiated scar, the irradiated scar showed a significantly high level of hemoglobin (1.04 vs. 1.26, p = 0.017) and melanin (0.55 vs. 0.63, p = 0.03). Conclusions Postoperative scars with radiation showed better results in objective and subjective assessments than scars without radiation. These findings suggest that radiation has a positive effect on general scar maturation.

Background Infantile hemangioma (IH) is a common vascular tumor in pediatric patients, and is commonly treated with propranolol. We describe our experiences with dosage, response to treatment, and side effects in 23 IH patients treated with propranolol. Methods For this nonrandomized comparative cohort study, the authors enrolled 23 patients treated with propranolol. Photographs were taken before propranolol administration and at 3, 6, 9, and 12 months after treatment. Treatment responses were objectively analyzed with a computer program. Results There were three male and 20 female patients. Common tumor locations were the head and neck (13 cases, 56.5%), trunk (four cases, 17.4%), extremities (three cases, 13.0%), and combined locations (three cases, 13.0%). The response to propranolol was significantly lower in patients with two or more lesions than in patients with a single lesion in terms of both color fading (P Conclusions Propranolol is an efficacious treatment with a good safety profile. In patients with a single lesion, the response to treatment was better in terms of color fading and size reduction. Furthermore, male patients responded better to propranolol treatment in terms of color fading than female patients, and starting treatment before 6 months after birth was more advantageous for size reduction.

We evaluated the efficacy and safety of a povidone-iodine (PVP-I) foam dressing (Betafoam) for donor site dressing versus a hydrocellular foam dressing (Allevyn) and petrolatum gauze. This prospective Phase 4 study was conducted between March 2016 and April 2017 at eight sites in Korea. A total of 106 consenting patients (aged ≥ 19 years, scheduled for split-thickness skin graft) were randomised 1:1:1 to PVP-I foam, hydrocellular, or petrolatum gauze dressings for up to 28 days after donor site collection. We assessed time to complete epithelialisation, proportion with complete epithelialisation at Day 14, and wound infection. Epithelialisation time was the shortest with PVP-I foam dressing (12.74 ± 3.51 days) versus hydrocellular foam dressing (16.61 ± 4.45 days; P = 0.0003) and petrolatum gauze (15.06 ± 4.26 days, P = 0.0205). At Day 14, 83.87% of PVP-I foam dressing donor sites had complete epithelialisation, versus 36.36% of hydrocellular foam dressing donor sites (P = 0.0001) and 55.88% of petrolatum gauze donor sites (P = 0.0146). There were no wound infections. Incidence rates of adverse events were comparable across groups (P = 0.1940). PVP-I foam dressing required less time to complete epithelialisation and had a good safety profile.

Fibrous dysplasia (FD) is a rare, benign bone disease with abnormal bone maturation and fibroblastic proliferation. Optimal treatment of zone 1 craniofacial FD is radical resection and reconstruction. To achieve of structural, aesthetic, and functional goals, we use three-dimensionally designed calvarial bone graft for reconstruction of zygomatic defect after radical resection of FD. The authors used a rapid-prototyping model for simulation surgery for radical resection and immediate reconstruction. Donor site was selected from parietal bone reflect shape, contour, and size of defect. Then radical resection of lesion and immediate reconstruction was performed as planned. Outcomes were assessed using clinical photographs and computed tomography scans. Successful reconstruction after radical resection was achieved by three-dimensional calvarial bone graft without complications. After a 12-month follow-up, sufficient bone thickness and symmetric soft tissue contour was well-maintained. By considering three-dimensional configuration of zygomaticomaxillary complex, the authors achieved satisfactory structural, aesthetic and functional outcomes without complications.

Background/Aims: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. Methods: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson’s trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). Results: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFβ in vitro. Conclusions: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.

The columellar strut graft is one of the most commonly used invisible grafts in tip plasty techniques for nasal tip projection. However, the columellar strut graft induces cephalic rotation of the dome with nasal tip projection. This is an effective change in Western people with a long nose; however, this change should be avoided in Asians who have a relatively short nose and visible nostrils. We designed a more convenient and effective technique using a rein-shaped columellar strut graft that can prevent cephalic rotation of the dome. A total of 32 patients underwent surgery with a rein-shaped columellar strut graft with a septal cartilage. The projection and location of the nasal tip, nasal length, and nasolabial angle were measured after taking a photograph of the lateral view, and the preoperative and postoperative results were compared. There were statistically significant differences between the preoperative and postoperative values of the nasal tip projection ratio and nasal tip location ratio. There were no revision surgeries and no direct complications associated with the use of the columellar strut graft. We performed tip plasty with a modified columellar strut graft—the rein-shaped columellar strut graft. In most cases of using this method, the tip projection was increased and the cephalic rotation of the tip was prevented. This surgical procedure can also be used for lengthening (rotating caudally) of the nose in some cases, as well as for the purpose of preventing the cephalic rotation of the tip. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background and objective Polynucleotide (PN) provides a structural scaffold to induce anti-inflammatory and enhanced wound healing properties, and this study aimed to assess the efficacy of PN administration in the prevention of post-operative scars after conventional open total thyroidectomy. Study design materials and methods Forty-two patients with thyroid carcinoma who underwent total thyroidectomy were randomly assigned to the study (PN administration) or control (normal saline) group. All patients underwent a single session of combined ablative and non-ablative fractional laser. The Vancouver Scar Scale (VSS), global photographic assessment, and objective scar were assessed using three-dimensional (3D) camera at baseline and at 2, 4, 8, and 16 weeks after surgery. Results Patients who underwent PN injection demonstrated better surgical scar quality outcome. Participants in the PN administration group had lower VSS scores than the control group (2.09 ± 0.47 vs. 4.01 ± 0.55, respectively) and lower scar height (0.23 ± 0.03 vs. 0.29 ± 0.03, respectively), as measured using 3D imaging. Furthermore, in the PN injected group, the degree of erythema, and pigmentation of the scar were less prominent. No patient developed hypertrophic scar or keloids on the surgical site. No other adverse events, including post-inflammatory hyperpigmentation, scarring, or infection, were observed. Conclusion Adjuvant administration of PN along with conventional fractional laser treatment led to more favorable effect in wound healing and post-operative scar prevention after thyroidectomy. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

The selection of materials for orbital wall reconstruction has been a matter of debate. This study aimed to evaluate the effectiveness of an acellular allogenic dermal matrix (ADM) as an orbital wall reconstruction material and to compare the results of orbital wall reconstruction with the ADM to those of reconstruction with the more widely used absorbable mesh plate and porous polyethylene. We retrospectively reviewed the clinical charts and computed tomography images of 73 patients who underwent orbital reconstruction at 1 institution between March 2013 and February 2014. In the ADM group, the mean defect size of 29 patients was 2.89 cm. After orbital wall reconstruction with ADM, patients with preoperative enophthalmos (7 patients), limited range of eyeball movement (6 patients), and diplopia (12 patients) showed improvements. In the comparative study, the 3 groups showed no significant differences with respect to age distribution (P = 0.522), defect size (P = 0.455), and preoperative findings such as enophthalmos (P = 0.811), diplopia (P = 0.357), and limited range of eyeball movement (P = 0.795). All the preoperative symptoms improved in every group, and in the ADM group, no complication was observed during the postoperative follow-up. ADM is a biocompatible material that combines the flexibility and rigidity required to support the orbital soft tissue. Therefore, it could be an excellent alternative material for orbital wall reconstruction.

INTRODUCTION The nose is the most protruding central part of the face, and nasal bone fractures are the most common of facial bone fractures, leading up to 39%. Despite its high frequency, not many studies handled the etiology of nasal bone fractures, leading to the necessity of a recent demographic study. MATERIALS AND METHODS A total of 1111 patients diagnosed with nasal bone fracture from 2013 to 2018 at our institute were evaluated. A retrospective review of the various demographic and etiologic characteristics was done. RESULTS Numerous factors associated with nasal bone fractures were analyzed. Male patients were 3.3 times greater than the number of female patients, and twenties were the most common age range. Violence was the overall most common cause of injury, while slip down was the most common cause for females. Upon monthly distribution, the highest incidence of nasal bone fractures occurred in September, followed by March and December. The authors further divided the patients by time zone of the fractures, and male patients were most commonly injured from midnight to 3 AM, while female patients were 6 PM to 9 PM. CONCLUSION Our findings represent a recent urban data of various etiologic factors of nasal bone fracture. The concept of school violence has been widely used since 1990s, and our data reflects that violence of the youth is a serious issue of the society. The mechanism of injury differed among sexes and age groups, and such discrepancies will aid physicians to better understand facial bone fracture patients and educate them in the future.

Recent advances in keloid management favor the administration of combination therapy over monotherapy.The authors evaluated the safety and efficacy of combination therapy to treat keloids using fractional lasers, cryotherapy, and intralesional corticosteroids.The authors performed a retrospective study involving 35 Korean patients. Each patient underwent treatment using the 1,550 nm nonablative fractional erbium-glass laser, followed by the 10,600 nm ablative fractional carbon dioxide laser. Laser treatment was immediately followed by the administration of superficial cryotherapy and intralesional triamcinolone injection. Therapeutic efficacy was assessed using the Vancouver Scar Scale (VSS) score and the 7-point patient self-assessment score.The mean total and subcategory VSS scores showed statistically significant improvements. The height and pliability scores showed the most significant and quickest responses to the combination therapy. The patients reported remarkable improvement in itching, pain, and limitations of motion after a single combination therapy session. Twenty patients were followed up for 1 year after the discontinuation of the combination treatment, and the recurrence was observed only in one patient. No significant adverse effects were observed throughout the follow-up period.Combination keloid therapy using fractional lasers, superficial cryotherapy, and intralesional triamcinolone injection is safe and more effective than individual monotherapies.

Postoperative adhesion is a natural phenomenon that occurs in damaged tissue cells. Several anti-adhesion agents are currently used, but there is no leading-edge product with excellent adhesion-preventive effects. The purpose of this study was to develop ideal anti-adhesive agents using human-derived acellular dermal matrix (ADM). We developed 5 new biocompatible thermosensitive anti-adhesion barriers (AABs) using micronized human-derived ADM, hyaluronic acid, and temperature-sensitive and biocompatible synthesized polymers. The biocompatibility, anti-adhesion effect, and biodegradability of these AABs were compared with those of commercial thermosensitive anti-adhesion agents. No cytotoxic effects were observed in vitro and in vivo. Animal testing of adhesion resistance confirmed that the adhesion area, strength, and grade of AAB03 were statistically superior to those of the control group. Factors related to adhesion formation, such as lymphocytes, macrophages, microvessels, and collagen fiber density, were observed using specific staining methods; the results confirmed that AAB03 group exhibited significantly lower macrophage counts, microvessel density, and collagen fiber density than the control groups. Furthermore, AAB03 was completely absorbed by 6 weeks. Thus, AAB03 has the potential to be used as a high-performance anti-adhesion agent.

The treatment of gynecomastia depends on multiple factors, and the best modality is controversial. In this study, we aimed to determine the best management approach by comparing outcomes of two groups of patients with gynecomastia who received subcutaneous mastectomy combined with liposuction and liposuction only. We conducted a retrospective analysis of 64 patients who underwent surgery for gynecomastia. We divided the patients into two groups: group A, patients who underwent liposuction only; and group B, patients who underwent liposuction and subcutaneous mastectomy. The serial photographs of all patients were clinically evaluated with respect to size, shape, scarring, and overall outcome by three plastic surgeons, and patient satisfaction was surveyed with regard to palpable lumps, size, shape, scarring, and overall outcome. Of the 64 subjects, 16 received liposuction only, and 48 received the combination procedure. A total of 125 breasts were involved. The doctors’ scores for size and overall outcome were significantly better in the combination group, whereas scarring was better in the liposuction-only group. Similarly, patient satisfaction regarding size was significantly higher in the combination group, and satisfaction regarding scarring was significantly higher in the liposuction-only group. The scores for scarring in the combination treatment group were acceptable. Our study shows that combination treatment with liposuction and subcutaneous mastectomy results in satisfactory outcomes, including the extent of scarring. We conclude that this combination treatment should be recommended as the standard surgical treatment for gynecomastia and can provide excellent results in cases where glandular tissue needs to be removed. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Red ginseng is well known for its angiogenic effects and its effect of increasing expression of vascular endothelial growth factors (VEGFs), but little experimental evidence has been published. In this study, we examined the effect of red ginseng using an ischemic flap model. Twenty male Sprague-Dawley rats were divided into two groups of 10. One group drank red ginseng solution from 7 days prior to surgery to 7 days after, whereas the other group drank distilled water. We created a local flap on the back of each rat. We analyzed the surviving area of the flap for 10 days after surgery and measured the blood flow of the flap. Ten days after the operation, CD31-positive vessels and VEGF expression were examined by immunohistochemistry. The percentages of surviving areas of the flap were 76 ± 3% for the experimental group and 39 ± 5% for the control group (P = 0.0002). Blood flow in the experimental group increased for 10 days after the surgery. The number of newly generated capillaries in the experimental group was 14.0 ± 3.5, which was significantly higher than 5.7 ± 1.9 in the control group. The expression of VEGF in the experimental group was significantly higher than in the control group (p = 0.0003). Administration of red ginseng extract increases the survival of ischemic flaps via angiogenesis and elevated blood flow. Further clinical studies are warranted to apply the effect shown in this current investigation to various ischemic conditions.

The effects of platelet-rich plasma (PRP) on improvement of bone regeneration have been widely investigated. However, use of a proper scaffold is also important to the delivery of bioactive materials. The aim of this study was to analyze the effects of PRP with acellular dermal matrix (ADM) as a bone substitute in a cranial defect model. Twenty-nine New Zealand white rabbits were randomly divided into four groups including control, PRP, ADM, and PRP with ADM. A 15 × 15-mm2 bony defect was carefully created in the cranium. The experimental materials were applied in each group. After 16 weeks, the volume and surface area of new bone were measured using three-dimensional computed tomography and digital photography, and the new bone was analyzed histologically. The PRP with ADM group exhibited a statistically significant increase in volume and surface area of newly formed bone compared with the other groups (p

Although platelet-rich plasma (PRP) is widely used to enhance bone graft survival, the effect of PRP itself on bone regeneration is unclear. Because activated PRP releases many growth factors in a bolus, there are controversies regarding the effect of activation of the PRP on bone regeneration. Thus, we studied the effect of activated versus nonactivated PRP on bone regeneration and compared the effect with that of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a critical-sized cranial defect model. Forty New Zealand white rabbits were randomly divided into 4 groups. Defect sizing 15 × 15 mm(2) was created on the cranium of each rabbit, and then a collagen sponge soaked with normal saline, rhBMP-2, nonactivated PRP, or PRP activated with CaCl2 solution was immediately placed on the defect. After 16 weeks, using three-dimensional computed tomography and digital photography, the volume and new bone surface area were measured. The newly created bone was histologically analyzed. The experimental groups showed a significantly increased volume and surface area of new bone compared with the control group (P < 0.05), but no significant differences were found among the experimental groups. Histologic examination in the experimental groups showed newly created bone that had emerged in the center as well as the margin of the defect. Overall, these results indicate that PRP enhanced bony regeneration regardless of activation with an effect that was comparable to that of rhBMP-2. Thus, PRP has therapeutic effects on bone regeneration and may replace rhBMP-2, which is costly.

Recently, thymic stromal lymphopoietin (TSLP), which is well studied in allergic diseases, has been reported in fibrotic diseases, including idiopathic pulmonary fibrosis and atopic dermatitis fibrosis. However, the role of TSLP in keloid is obscure. In this study, we assessed the expression of TSLP in keloid tissue and investigated the possible role of TSLP in keloid pathogenesis. We observed that TSLP expression was increased in keloid tissue compared to normal tissue. Furthermore, TSLP treatment induced increased collagen I and collagen III expression in fibroblasts via transforming growth factor-β; however, there was higher expression in keloid fibroblasts compared to normal fibroblasts. Stromal cell-derived factor-1α, which was recently reported to enhance wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area, increased after TSLP treatment in fibroblasts and was primarily expressed in α-smooth muscle action-positive myofibroblasts in keloid tissue. Furthermore, fibrocytes expressing CXCR4, a stromal cell-derived factor-1α receptor, were significantly increased in keloid tissue compared to normal tissue. Finally, intradermal TSLP injection on BALB/c mice increased stromal cell-derived factor-1α expression and CXCR4 + fibrocytes infiltration. Our data suggest that TSLP is a potent inducer of collagen and transforming growth factor-β production in keloid fibroblasts. In addition, it might activate the CXCR4/stromal cell-derived factor-1 axis to increase fibrocyte infiltration into the keloid tissue.

Background Although various techniques of mandibular angle ostectomy have been devised to correct overly prominent bony contours, none have incorporated methods to delineate the surgical line with precision. Herein, the authors describe one means of marking an ostectomy line more easily, using a specially designed oscillating-blade saw. Methods Between July 2013 and June 2014, a total of 75 patients underwent quantitative mandibular angle ostectomy using a custom oscillating-blade saw equipped with a scalable guide. Corticectomy, also done routinely to improve frontal appearance, called for a reciprocating saw only. Aesthetic outcomes gauged subjectively by the questionnaire about satisfaction and symmetry after postoperative 6 months. Results Satisfaction score was 4.9 and symmetric score was 4.7. No major complications, such as persistent nerve injury or fracture, were encountered. Conclusions Use of an oscillating-blade saw equipped with a scalable guide facilitated quantitative mandibular angle ostectomy, enabling precise, and reproducible surgery with satisfactory outcomes with less complications.

To improve healing of pressure ulcer wounds, it is important to optimize the conditions of the area surrounding the wound. Negative pressure wound therapy (NPWT) promotes wound healing, however, the removal of NPWT can cause pain or focal bleeding, delaying wound healing or causing infection. In this study, we reviewed the efficacy of the lipidocolloid non-adherent dressing (Urgotul&reg, ) as a wound contact layer. A total of 38 patients from the same facility who applied NPWT from April 2016 to October 2019 were included and divided into two groups, NPWT with the lipidocolloid non-adherent dressing (group 1, experimental group, 19 patients) and NPWT only (group 2, control group, 19 patients). The condition of the wound was examined prior to NPWT application, at one week, and again at three weeks after application. No significant differences were found between groups for general characteristics, bacterial culture or photo analysis. However, when comparing groups based on the time of examination, there was a significant reduction of the wound size in group 1 (p = 0.001) but not in group 2 (p = 0.082). Therefore, the current study finds that using the lipidocolloid non-adherent dressing as a wound contact layer in NPWT stimulates healing by shrinking the size of the pressure ulcer wound.

Purpose Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. Materials and methods Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. Results Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. Conclusion These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Background Although previous studies have focused on determining prognostic and causative variables associated with fistula-related complications after head and neck reconstructive surgery, only a few studies have addressed preventive measures. Noting that pooled saliva complicates wound healing and precipitates fistula-related complications, we devised a continuous suction system to remove saliva during early postoperative recovery. Methods A continuous suction system was implemented in 20 patients after head and neck reconstructive surgery between January 2012 and October 2017. This group was compared to a control group of 16 patients at the same institution. The system was placed orally when the lesion was on the anterior side of the retromolar trigone area, and when glossectomy or resection of the mouth floor was performed. When the orohypopharynx and/or larynx were eradicated, the irrigation system was placed in the pharyngeal area. Results The mean follow-up period was 9.2±2.4 months. The Hemovac system was applied for an average of 7.5 days. On average, 6.5 days were needed for the net drain output to fall below 10 mL. Complications were analyzed according to their causes and rates. A fistula occurred in two cases in the suction group. Compared to the control group, a significant difference was noted in the surgical site infection rate (P Conclusions Clinical observations showed reduced saliva pooling and a reduction in the infection rate. This resulted in improved wound healing through the application of a continuous suction system.

Background Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed. Methods The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-β), and Western blotting with Wnt-3 and β-catenin. Increases in the levels of TGF-β, Wnt, and β-catenin were detected after irradiation. Results All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects. Conclusions This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing.

Objective The purpose of this study is to evaluate the long-term results of flap volume change, swallowing capacity, speech intelligibility, and differences between vertical rectus musculocutaneous (VRAM) and anterolateral musculocutaneous (ALT) free flaps in total tongue reconstruction. Patients and methods We retrospectively analyzed the medical records of 31 patients who underwent total tongue reconstruction with VRAM (24 cases) and ALT flap (7 cases). The mean age of patients was 52.09 ± 2.25 years. The tumor types were as follows: squamous cell carcinoma (28 cases), adenoid cystic carcinoma (2 cases), and metastatic cancer (1 case). The flap volume was determined based on clinical and imaging examinations. Swallowing and speech function were analyzed using seven-point rating scales. Results All flaps survived eventually after surgery; however, 1 patient underwent VRAM flap experienced partial flap necrosis, wound dehiscence in 4 patients underwent VRAM flap, and infection in 3 patients (VRAM; 2 patients, ALT; 1 patient). The mean follow-up period was 3.97 ± 0.54 years. The volume of the flaps remained relatively constant over time. The swallowing capacity positively correlated with the flap volume (P 0.05). Conclusion The preservation of flap volume was important to achieve superior swallowing capacity; however, it was insufficient to promote the speech outcome. The functional outcomes did not differ depending on the type of flap. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.

Bone regeneration is a complex process influenced by various physiological factors. Platelet-rich plasma (PRP) contains many growth factors and has shown osteogenic effects. The PRP is usually activated before use. However, the authors showed that nonactivated PRP (nPRP) and activated PRP have comparable osteogenic effects in the previous study. Generally, a scaffold has been needed for the application of PRP in the cranial defect model. In this study, the authors aimed to compare the performance of scaffold free platelet-rich fibrin (PRF) to nPRP as an adjuvant for bone regeneration.Twenty-four New Zealand White rabbits were randomly allocated into 3 groups: control, nPRP, and PRF. A 15 × 15 mm defect was created on each rabbit's cranium. Acellular collagen sponges (Gelfoam) were placed on the defects of the control group, Gelfoam with nPRP was used for the nPRP group, and PRF membrane was directly applied for the PRF group. nPRP and PRF were obtained from each subject's peripheral blood. Sixteen weeks later, the volume of regenerated bone was measured using 3-dimensional computed tomography. The surface area was measured via autopsy, and the samples were then obtained for histological analysis.Bone regeneration in the experimental groups was significantly greater than that in the control group. There were no significant differences in the area of regeneration or histological characteristics between the nPRP and PRF groups.In the calvarial defect of the rabbits, the use of PRF and scaffolded PRP showed comparable bone regeneration effects, which suggested that PRF might be a therapeutic alternative for bone grafts.

Prominent ear is the most common external ear deformity. To comprehensively treat prominent ear deformity, adequate comprehension of its pathophysiology is crucial. In this article, we analyze cases of prominent ear and suggest a simple classification system and treatment algorithm according to pathophysiology. We retrospectively reviewed a total of 205 Northeast Asian patients’ clinical data who underwent an operation for prominent ear deformity. Follow-up assessments were conducted 3, 6, and 12 months after surgery. Prominent ear deformities were classified by diagnostic checkpoints. Class I (simple prominent ear) includes prominent ear that developed with the absence of the antihelix without conchal hypertrophy. Class II (mixed-type prominent ear) is defined as having not only a flat antihelix, but also conchal excess. Class III (conchal-type prominent ear) has an enlarged conchal bowl with a well-developed antihelix. Among the three types of prominent ear, class I was most frequent (162 patients, 81.6%). Class II was observed in 28 patients (13.6%) and class III in 10 patients (4.8%). We used the scaphomastoid suture method for correction of antihelical effacement, the anterior approach conchal resection for correction of conchal hypertrophy, and Bauer’s squid incision for lobule prominence. The complication rate was 9.2% including early hematoma, hypersensitivity, and suture extrusion. Unfavorable results occurred in 4% including partial recurrence, overcorrection, and undercorrection. To reduce unfavorable results and avoid recurrence, we propose the use of a classification and treatment algorithm in preoperative evaluation of prominent ear. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants. Higher Wnt3a and β-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of β-catenin and mRNA expression of type-I and -III collagen were significantly decreased following treatment with dE1-k35/sLRP6E1E2 in HDFs and KFs. The expression of LRP6, β-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-β1 were decreased in Wnt3a- or TGF-β1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both β-catenin and Smad 2/3 complex. The expression levels of type-I and -III collagen, fibronectin, and elastin were also significantly reduced in keloid tissue explants after treatment with dE1-k35/sLRP6E1E2. These results indicate that Wnt decoy receptor-expressing Ad can degrade extracellular matrix in HDFs, KFs, and primary keloid tissue explants, and thus it may be beneficial for treatment of keloids.

High-mobility group box protein-1 (HMGB-1) plays a central role in the inflammatory network, and uncontrolled chronic inflammation can lead to excessive scarring. The aim of this study was to evaluate the anti-inflammatory effects of polydeoxyribonucleotide (PDRN) on scar formation. Sprague-Dawley rats (n = 30) underwent dorsal excision of the skin, followed by skin repair. PDRN (8 mg/kg) was administered via intraperitoneal injection for three (PDRN-3 group, n = 8) or seven (PDRN-7 group, n = 8) days, and HMGB-1 was administered via intradermal injection in addition to PDRN treatment for three days (PDRN-3+HMGB-1 group; n = 6). The scar-reducing effects of PDRN were evaluated in the internal scar area and by inflammatory cell counts using histology and immunohistochemistry. Western blot, immunohistochemistry and immunofluorescence assays were performed to observe changes in type I and type III collagen and the expression of HMGB-1 and CD45. Treatment with PDRN significantly reduced the scar area, inflammatory cell infiltration and the number of CD45-positive cells. In addition, the increased expression of HMGB-1 observed in the sham group was significantly reduced after treatment with PDRN. Rats administered HMGB-1 in addition to PDRN exhibited scar areas with inflammatory cell infiltration similar to the sham group, and the collagen synthesis effects of PDRN were reversed. In summary, PDRN exerts anti-inflammatory and collagen synthesis effects via HMGB-1 suppression, preventing scar formation. Thus, we believe that the anti-inflammatory and collagen synthesis effects of PDRN resulted in faster wound healing and decreased scar formation.

Asian noses are relatively small and flat compared to Caucasians; therefore, rhinoplasty procedures often focus on dorsal augmentation and tip projection rather than reduction in the nasal framework. Various autologous and alloplastic implant materials have been used for dorsal augmentation. Recently, human acellular dermal matrices have been introduced as an implant material for dorsal augmentation, camouflaging autologous implants without an additional donor site. Here, we introduce a cross-linked human acellular dermal matrix as an implant material in augmentation rhinoplasty and share the clinical experiences. Eighteen patients who underwent augmentation rhinoplasty using acellular dermal matrix from April 2014 to November 2015 were reviewed retrospectively. Clinical outcomes and complications were assessed at the outpatient clinic during the follow-up period ranging from 8 to 38 months. Contour changes were assessed through comparison of preoperative and postoperative photographs by two independent plastic surgeons. Patient satisfaction was assessed at the outpatient clinic by six questions regarding aesthetic and functional aspects. Postoperative photographs demonstrated the height of the nasal dorsum did not decrease over time except two patients whose ADM was grafted into a subperiosteal pocket. Others who underwent supraperiosteal implantation showed acceptable maintenance of dorsal height. No major complication was reported. Overall, patient satisfaction scored 81.02 out of 100. Cross-linked human ADM has advantages of both autogenous and alloplastic materials. The surgical results remain stable without complications. Therefore, it is a suitable alternative implant material for dorsal augmentation in rhinoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Micronized cross-linked human acellular dermal matrices (ADMs) contain the extracellular components necessary for cell integration and tissue remodeling, and have high tensile strength and durability. We hypothesized that such material could serve as a scaffold to enhance the survival of adipocytes in grafted fat. Nude mice (n = 15) were randomly assigned to three groups, each receiving different subcutaneous injections into two dorsal paravertebral areas: fat and saline (control), fat and micronized ADM (E1), and fat and diluted micronized ADM (E2). Digital photographs were taken at 2-week intervals, and the grafted fat volumes and weights were examined after 10 weeks. A histological analysis of the grafted fat was performed, and the expression of vascular endothelial growth factor (VEGF) was examined. The grafted fat volumes decreased over time in all groups; however, at 10 weeks, the grafted fat was better preserved in both experimental groups, with significantly greater weights than in the group C (both, p

Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it’s pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of keloid. Therefore, we generated mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On keloid tissues, mortalin expression was higher than adjacent normal tissues and it’s protein expressions were activated keloid fibroblasts (KFs). After primary keloid spheroid were transduced with dE1-RGD/GFP/shMot for knockdown of mortalin, expression of type I, III collagen, fibronectin, and elastin was significantly reduced and transforming growth factor-β1, epidermal growth factor receptor (EGFR), Extracellular Signal-Regulated Kinases 1 and 2 (Erk 1/2), and Smad 2/3 complex protein expression were decreased. In addition, increased TUNEL activities and cytochrome C were observed. Further, for examine of mortalin and p53 interaction, we performed immunofluorescence analysis. Knockdown of mortalin relocated p53 to the cell nucleus in primary keloid spheroids by dE1-RGD/GFP/shMot transduction. These results support the utility of knockdown of mortalin to induce apoptosis and reduce ECMs expression in keloid spheroid, which may be highly beneficial in treating keloids.

Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-&kappa, B, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-&beta, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-&beta, treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.

Background Perineal defects are commonly encountered during the treatment of conditions such as malignancy, infectious disease, and trauma. Covering large defects in the perineal area is challenging due to its complicated anatomy and the need for functional preservation. Methods Fourteen patients who underwent reconstructive surgery with multiple perforator flaps for defects >100 cm2 in the perineal area were included in this retrospective cohort study. Characteristics of the perforator flap operation and postoperative outcomes were reviewed. Results Reconstruction was performed using 2 perforator flaps for 13 patients and 3 perforator flaps for 1 patient. Internal pudendal artery perforator flaps were mainly used for covering the defects. The average defect size was 176.3±61.8 cm2 and the average size of each flap was 95.7±31.9 cm2. Six patients had minor complications, such as wound dehiscence and partial necrosis of the flap margin, which were corrected with simple revision procedures. Conclusions Multiple perforator flaps can be used to achieve successful reconstructions of large perineal defects that are difficult to reconstruct with other coverage methods.

Reconstruction after total maxillectomy with extensive orbital floor defects poses a significant challenge for the reconstruction. The aim of this study is to present the outcomes of orbital floor reconstruction using tensor fascia lata slings after total maxillectomy and to compare these results to orbital floor reconstruction using alloplastic implants.This was a retrospective analysis of 19 consecutive patients who underwent tumor resection with orbital floor removal for malignancies. Reconstructions were performed using either tensor fascia lata slings (Group A) or alloplastic implants (Group B). The early and late postoperative outcomes such as wound infection, plate exposure, ectropion, diplopia, and enophthalmos, were analyzed and compared between the two groups.Patients in group A had significantly less wound complication than in group B (p 0.05). In group A, there were no early or late wound complications after the operation. However, in group B, five patients had infection, the plate was exposed in eight of fourteen patients, and three patients had enophthalmos. Eight patients in group B underwent reoperation to correct their complications.Reconstruction of the orbital floor with a tensor fascia lata sling offers reliable support to the globe and prevents the ophthalmic complications associated with loss of orbital support.

The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids.Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry.The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids.These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.

Purpose The combination of acellular dermal matrix (ADM) and split-thickness skin graft (STSG) has been widely adopted to overcome functional and cosmetic limitations of conventional STSG. In this study, we evaluated the efficacy of this combination using 2 types of ADM: cadaveric acellular dermal matrix (CDM) and bovine acellular dermal matrix (BDM). Methods We recruited 72 patients undergoing autologous STSG to cover radial forearm free flap donor sites. They were included in 1 of 3 therapeutic groups: group 1, STSG using CDM (n = 29); group 2, STSG using BDM (n = 20); and group 3, STSG only (n = 23). Functional skin values for skin elasticity, humidification, transepidermal water loss, and color were determined. Values were compared between graft sites and adjacent normal (control) skin, and between grafted areas of each group. Results All skin defects were successfully reconstructed without graft loss. Groups 1 and 2 demonstrated better elasticity than did group 3, based on the analysis using the ratio of grafted area to control. Grafted areas in all 3 groups exhibited less moisture than did control normal skin. There was less transepidermal water loss in group 1 than in group 3, which implied that CDM application had better barrier capacity against water evaporation. Graft sites of groups 1 and 3 exhibited darker and redder color compared with control areas. Conclusions Composite forearm defects were successfully restored and exhibited acceptable quality after treatment with an ADM plus STSG. Applying either CDM or BDM under a STSG was a suitable procedure, as verified by objective measurements. Elasticity was well preserved in CDM and BDM groups. However, both ADMs revealed functional impairment of humidification. Type of study/level of evidence Therapeutic IV.