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Background Management of skin and soft-tissue defects of the fingertips is functionally and aesthetically important, but controversial, especially when bones are exposed. Recent advances in wound healing technology allow the use of cells or biological dermis. The authors studied the clinical efficacy of tissue-engineered dermis grafts and artificial dermis grafts versus immediate reconstructive procedures, such as the reverse digital artery island flap, in treating bone-exposed fingertip defects. Methods One hundred eighty-two patients with bone-exposed fingertip defects treated with tissue-engineered dermis grafts (n = 71), artificial dermis grafts (n = 23), or reverse digital artery island flaps (n = 88) were included in this retrospective cohort study. Surgical time, duration of hospitalization, total cost, success rate, healing time, sensory recovery, range of motion, scar quality, and patient satisfaction were compared. Results No tissue-engineered or artificial dermis graft exhibited graft rejection or failure, whereas there was one partial loss and one total loss after reverse digital artery island flap surgery. Tissue-engineered dermis grafts were superior in scar quality, and artificial dermis grafts had shorter surgical times and lower surgical costs; both groups demonstrated superior results in postoperative range of motion and sensory recovery in two-point discrimination tests and shorter hospitalization, compared with the reverse digital artery island flap group. The reverse digital artery island flap had shorter complete closure time and less postoperative tingling sensation. There were no differences in overall patient satisfaction among the groups. Conclusions Tissue-engineered and artificial dermis grafts may be promising alternatives for fingertip reconstruction. In particular, tissue-engineered dermis grafts may deliver superior functional results, including recovery of sensory discomfort and aesthetic results in terms of scar quality over artificial dermis grafts. Clinical question/level of evidence Therapeutic, III. more...

Background Surgical-site infection following complicated septorhinoplasty may result in serious complications. Therefore, efforts to prevent surgical-site infections after complicated septorhinoplasty are important. The purpose of this study was to analyze the microbiological profile of preoperative nasal swab cultures and to evaluate the effect of antibiotic prophylaxis and topical antibiotic decolonization according to the antibiotic sensitivity results of surgical-site infections in complicated septorhinoplasty. Methods This 10-year cohort study included the data on 437 consecutive patients who underwent complicated septorhinoplasty. The patients were categorized into three cohorts based on the time of preoperative nasal swab culture collection. Patients in cohort 1 did not undergo nasal swab cultures and received empirical antibiotics. Patients in cohort 2 underwent only one preoperative nasal swab culture and received microorganism-sensitive antibiotics. Patients in cohort 3 underwent repeated nasal swab cultures. The antibiotics were changed when microorganisms resistant to the empirical antibiotics were isolated. Microbiological data and the rates of surgical-site infection and inflammation were compared among the three cohorts. Results Methicillin-sensitive Staphylococcus aureus was the most commonly isolated microorganism. In cohort 1, two (5 percent) and two (5 percent) patients experienced surgical-site infections and inflammation, respectively. In cohort 2, two (3 percent) and three (4 percent) patients experienced surgical-site infections and inflammation, respectively. In cohort 3, one (0.3 percent) and one (0.3 percent) patient experienced surgical-site infection and inflammation, respectively. Conclusion The present study demonstrated that preoperative screening using repeated nasal swab cultures, followed by appropriate antibiotic prophylaxis and topical antibiotic decolonization, may reduce surgical-site infection in complicated septorhinoplasty. Clinical question/level of evidence Therapeutic, III. more...

Summary Background In a previous study, our group demonstrated that cultured autologous fibroblast-seeded artificial dermis was superior to artificial dermis for covering defects after surgical excision of basal cell carcinoma (BCC) in terms of scar quality. However, utilizing cultured cells for clinical purposes requires Food and Drug Administration–approved facilities and techniques and a lengthy culture period. The purpose of this retrospective study was to compare the effects of tissue-engineered dermis containing stromal vascular fraction (SVF) cells with artificial dermis on scar quality after surgical excision of BCC on the nose. Methods Between April 2010 and February 2018, patients who were treated with tissue-engineered or artificial dermis grafts and those with a follow-up period of greater than a year were included in this study. The Patient and Observer Scar Assessment Scales (POSAS) were compared between two groups according to the location of the graft, which was classified based on nasal subunits: the upper two-thirds zone; the lower one-third zone, except for the ala; and the alar zone. Results A tissue-engineered dermis composed of SVF cells and an artificial dermis were applied to 30 and 47 patients, respectively. In upper two-thirds and lower one-third zones, except for the ala, no statistically significant differences were found in any parameters. In the alar zone, statistically significant differences were detected in 10 of 21 POSAS parameters. Conclusion To cover nasal defects, the tissue-engineered dermis graft may be superior to the artificial dermis graft regarding scar quality at the ala. However, there were no significant differences in other zones. more...

Late-onset inflammation is a rare complication that may occur several months to years after undergoing an uneventful rhinoplasty using alloplastic implants and an uneventful postoperative course. Studies to determine the pathophysiological mechanisms of late-onset inflammation related to implants used in rhinoplasty are limited. The purpose of the study was to analyze differences between non-healthy capsules (NHC) with late-onset inflammation and healthy capsules (HC) without inflammation as controls to determine the possible cause of the inflammation. Between April 2009 and May 2018, 39 patients who underwent rhinoplasty with alloplastic implants underwent histological studies. Twenty-one patients in the NHC group showed late-onset inflammation, while 18 patients in the HC group did not display late-onset inflammation. Capsules around the alloplastic implants were harvested, and histological studies using hematoxylin and eosin, Masson’s trichrome, colloidal iron, and CD31 staining were performed and compared between the NHC and HC groups. In hematoxylin and eosin and Masson’s trichrome staining, edematous granulation tissues, inflammatory cellular contents, and a disorganized collagen layer were increased in the NHC group compared to the HC group. The colloidal iron staining revealed mucin deposition in the NHC group. CD31-positive cells were observed lining the capsule in both groups; however, the lining cells were damaged in the NHC group. Granulation tissues, inflammatory reaction, collagen degeneration, mucin deposition, and endothelial lining cell damage were greater in the NHC group compared to the HC group. Damaged capsules may play a crucial role in late-onset inflammation. 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 . more...

IMPORTANCE: In previous studies, this group has reported that cultured human fibroblasts suspended in hyaluronic acid (HA) filler might have potential use as a long-lasting injectable soft-tissue filler. However, the data were insufficient to determine the long-term outcomes. OBJECTIVE: To evaluate the long-term outcomes of cultured human fibroblasts suspended in HA filler used for soft-tissue augmentation. DESIGN, SETTING, AND PARTICIPANTS: A long-term case series study was performed. Between January 2010 and December 2013, a total of 38 patients were treated with fibroblast-HA filler mixture to augment nasal dorsa, nasolabial folds, and cheek depressions. Of these 38 patients, patients with follow-up period of greater than 3 years were included in this study. A total of 22 patients met the inclusion criteria. MAIN OUTCOMES AND MEASURES: Subjective assessment was performed to evaluate degree and time of resorption, improvement, satisfaction, softness of injection sites, and willingness to recommend this treatment to others. Objective assessment was carried out with patients' photographs. Safety and tolerability were also evaluated for this treatment. RESULTS: Of the 22 patients included in this study, 19 were women; mean (SD) patient age was 43 (15) years. All 22 patients experienced improvement following the treatment. Twenty (91%) patients were satisfied with the treatment. Nineteen patients (86%) considered that the injection site was as soft as it was before treatment. Patients’ mean (SD) grading of improvement, satisfaction, and softness were 4.50 (0.51) (95% CI, 4.27-4.73), 4.14 (0.71) (95% CI, 3.82-4.45), and 4.82 (0.50) (95% CI, 4.59-5.00) at the last visit, respectively. Objective assessment demonstrated postoperative improvement in all patients: a rating of “much improved” was given to 7 patients (32%) by investigator 1; 8 patients (36%) by investigator 2; and 12 patients (55%) the injecting physician. This treatment was well tolerated; no adverse event was recorded for any patient. CONCLUSIONS AND RELEVANCE: Injection of cultured human fibroblasts suspended in HA filler might be successful for long-term soft-tissue augmentation. To our knowledge, this study represents the longest follow-up study of soft-tissue augmentation with a fibroblast-HA filler mixture to date. LEVEL OF EVIDENCE: 4. more...

There are no studies about the treatment of nasal bone fractures in patients with dorsal augmentations using silicone implants. We aimed to describe the characteristics of nasal bone fracture in patients who underwent rhinoplasty and compare the difference between closed reduction and conservative treatment of nasal bone fractures in patients with a history of rhinoplasty. Between January 2013 and June 2018, a total of 463 patients were admitted to our center for nasal bone fracture; 17 patients with nasal bone fractures who underwent rhinoplasty were included, of which, five underwent closed reduction in the nasal bone and 12 underwent conservative treatment. Three of 12 patients who were initially treated conservatively underwent a secondary rhinoplasty for esthetic improvements. All patients were classified according to fracture site and the presence of a nasal septal fracture—in accordance with the modified Murray classification—and were analyzed for the correlation between fracture type and disease course. The nasal bone fracture types per computed tomography findings were unilateral (n = 13), bilateral (n = 4), septal (n = 1), and M-type (n = 1). No significant differences in fracture site (P > 0.05) and the presence of a nasal septal fracture (P > 0.05) were found between the groups. Fracture type did not significantly differ among patients who underwent closed reduction, conservative treatment without secondary rhinoplasty, and secondary rhinoplasty (P > 0.05). Despite risking traumatic capsular rupture, implant removal is seldom required and closed reduction is recommended if visible deviations are present; otherwise, only conservative treatment is recommended. 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. more...

Objective: The purpose of this study was to investigate the risk factors for major amputation in patients hospitalized with diabetic foot ulcers involving the hindfoot. Approach: Between January 2003 and October 2017, a total of 1,657 diabetic patients were admitted to the diabetic wound center of Korea University Guro Hospital, for the management of foot ulcers. Among the admitted patients, 117 diabetic patients with hindfoot ulcers were included in this study. One hundred and four patients (89%) healed without major amputation, while 13 patients (11%) healed with major amputation. Data related to 88 potential risk factors, including demographics, ulcer condition, vascularity, bioburden, neurology, and serology, were collected from patients in these two groups for comparison. Results: Among the 88 potential risk factors, 15 showed statistically significant differences between the two groups. In univariate analysis of 88 potential risk factors, nine showed statistically significant differences. In stepwise multiple logistic regression analysis, three of the nine risk factors remained statistically significant. Multivariate-adjusted odds ratios for pulmonary disorders, erythrocyte sedimentation rate (ESR) levels, and total iron-binding capacity (TIBC) levels were 38.525, 1.047, and 0.976, respectively. Innovation: Compared with forefoot and midfoot ulcers, diabetic foot ulcers involving the hindfoot are at increased risk of major amputation because infection may spread proximal to the ankle. However, large-scale cohort studies that specifically discuss the outcomes and characteristics of diabetic hindfoot ulcers are not widely available. Conclusion: Risk factors for major amputation in patients hospitalized with diabetic hindfoot ulcers include pulmonary disorders, high levels of ESR, and decreased TIBC levels. more...

Ultraviolet (UV) irradiation affects neuronal structures of the skin and accelerates skin aging. Cytokine cascades in keratinocytes after UV irradiation may result in a paracrine inhibitory effect on nerve cells. The purpose of the present study was to determine the direct effect of cytokines induced by UV radiation on nerve cells in terms of neuronal senescence. Our group performed a preliminary study to determine cytokines induced in UV-irradiated keratinocytes. Among 40 cytokines studied, granulocyte-macrophage colony-stimulating factor (GM-CSF) was increased 4-fold in inflammation antibody array. The GM-CSF was added to cultured human neuroblastoma cells. To evaluate the effect of cellular senescence, the authors performed real-time polymerase chain reaction (RT-PCR), western blot, immunocytochemical, and phase-contrast microscopic evaluations. Expression levels of matrix metallopeptidase-9 (MMP-9), nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1), inducible nitric oxide synthase (iNOS), and interleukin β1 (IL-β1) were assessed by RT-PCR. Expression levels of AAP and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) related to formation of beta-amyloid were evaluated by western blot analysis. Expression levels of MMP-9, NF-κB1, iNOS, and IL-β1 after treatment with GM-CSF were significantly higher than those in the control group. Enhanced expression of AAP and BACE1 was also observed in the treatment group. Thus, GM-CSF might have a provocative effect on nerve cells in terms of neuronal senescence. more...

BACKGROUND In the diabetic foot, the skin may crack and develop fissures, potentially increasing vulnerability to ulceration and infection. Therefore, maintaining adequate skin hydration may be crucial for diabetic wound healing. However, no clinical study has addressed this issue. This study aimed to determine and compare the effect of the skin hydration level on diabetic wound healing with that of the tissue oxygenation level, which is recognized as the most reliable parameter in predicting diabetic wound healing. METHODS This retrospective study included 263 diabetic patients with forefoot ulcers. Skin hydration and transcutaneous oxygen pressure data collected before and after percutaneous transluminal angioplasty were analyzed. Skin hydration and tissue oxygenation were graded as poor, moderate, or acceptable. Wound healing outcomes were graded as healed without amputation, minor amputation, or major amputation. Wound healing outcomes were compared using four parameters: skin hydration at baseline, transcutaneous oxygen pressure at baseline, post-percutaneous transluminal angioplasty skin hydration, and post-percutaneous transluminal angioplasty transcutaneous oxygen pressure. RESULTS Each of the four parameters exhibited statistically significant correlations with wound healing outcomes. In the concurrent analysis of both skin hydration and transcutaneous oxygen pressure, skin hydration was a dominant parameter (p = 0.0018) at baseline, whereas transcutaneous oxygen pressure was a dominant parameter (p < 0.0001) following percutaneous transluminal angioplasty. CONCLUSIONS Skin hydration level might be a useful predictor for diabetic wound healing. In particular, the skin hydration level before recanalization was found to be superior to transcutaneous oxygen pressure in predicting wound healing. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III. more...

Background and Objectives Beneficial effects of human adipose-derived stromal vascular fraction (SVF) cell injection on microcirculation have been recently reported in in vitro and in vivo studies. However, no clinical studies have reported its effect in diabetic patients who commonly experience compromised tissue perfusion, regardless of the status of intravascular blood flow. The present piloting study was designed to clinically examine the possibility of SVF cell injection to accelerate microcirculation, particularly in ischemic diabetic feet. Methods Ten diabetic feet were included to receive subcutaneous injection of SVF cells around wounds. Transcutaneous partial oxygen pressure (TcPO2) and cutaneous microvascular blood flow were measured before and every four weeks after cell injection until the 12th week visit. Results TcPO2 values increased from 31.3±7.4 before injection to 46.4±8.2 mmHg at 12 weeks after SVF injection (1.5-fold, p more...

Background:The objective of this study was to illustrate a novel technique for lifting of the aging upper lip with nasal tip plasty in Asians. With this procedure, a shortening of the philtrum, an increase of the vermilion, and a natural and nicer mouth can be obtained, with increase of the tip of t more...

Aging is a biologic process characterized by time-dependent functional declines that are influenced by oxidative stress-induced inflammatory reactions. In particular, ultraviolet (UV) irradiation plays a key role in cellular senescence in photo-aged skin. However, the cellular senescence of epidermal keratinocytes and dermal fibroblasts by UV irradiation may differ depending on the exposure time and dosage of UV irradiation. Therefore, the purpose of the study was to evaluate and compare the effects of UV irradiation on cellular senescence in human epidermal keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). After cell viability test, 200 mJ/cm2 UV irradiation was used in this study. To evaluate the reactive oxygen species and reactive nitrogen species production, the levels of glutathione (GSH) and nitrite (NO2) were measured. We also performed reverse transcription-polymerase chain reaction, Western blot analysis, and senescence-associated beta-galactosidase assay. An overall decrease in GSH and an increase in NO2 were observed in the HaCaT and HDF cells. However, the time-line and dose-dependent effects varied. Higher expressions of tumor necrosis factor-α, inducible nitric oxide synthase, and interleukin-1β than that of the control group were observed in both cells. The HDF cells showed high levels of matrix metallopeptidase 9 and neutral endopeptidase protein but low levels of SIRT1 and procollagen I. The expression of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) was increased in the HaCaT cells, but not in the HDF cells. The NF-κB peaked at 1 hour after UV irradiation in the HaCaT cells. The “turning-on” signal was faster in the irradiated HaCaT cells. more...

Microvascular free flap transfer has become a prevailing surgery with a failure rate of5%. However, pedicle thrombosis occurs more frequently than indicated by the failure rate. This difference is due to the successful salvage of failing flaps. During exploration, thrombi are often encountered at anastomotic sites, whereas these causes could not explain vascular compromise in other patients. Thus, we hypothesized that thrombogenic processes might occur at remote sites, specifically within microvessels of the transferred flap. This study retrospectively evaluated 323 patients who underwent microvascular free flap transfer between March 2012 and October 2016 at Korea University Guro Hospital. All patients requiring emergency exploration within 7 days after surgery were retrospectively reviewed. Of patients, 15 required explorative surgery for suspected circulatory compromise. Eight were diagnosed with thrombosis at the perianastomotic site and salvaged in accordance with our protocol. There was no detectable thrombosis at the anastomotic site in seven patients, including one patient in whom thrombosis resolved with topical papaverine application and heparinization. The remaining six patients were diagnosed with intra-flap microthrombosis without discernable thrombosis at the anastomotic site. All patients were treated following our urokinase administration protocol and salvaged without complications. Possible external causes should first be evaluated when salvaging free flaps; in the absence of such evidence, urokinase administration may be utilized as a last resort. This study is the first report describing the effectiveness of pharmacological thrombolysis in resolving intra-flap microthrombosis. Furthermore, a safe and efficient urokinase administration protocol is suggested for perianastomotic thrombosis and intra-flap microthrombosis. more...

Background aims A previous study demonstrated that human umbilical cord blood–derived mesenchymal stromal cells (hUCB-MSCs) have superior wound-healing activity compared with fibroblasts in vitro . However, wound healing in vivo is a complex process that involves multiple factors. The purpose of this study was to compare the effects of hUCB-MSCs and fibroblasts on diabetic wound healing in vivo . This study especially focused on collagen synthesis and angiogenesis, which are considered to be the important factors affecting diabetic wound healing. Methods Porous polyethylene discs were loaded with either fibroblasts or hUCB-MSCs, and a third group, which served as a control, was not loaded with cells. The discs were then implanted in the back of diabetic mice. During the first and the second week after implantation, the discs were harvested, and collagen level and microvascular density were compared. Results In terms of collagen synthesis, the hUCB-MSC group showed the highest collagen level (117.7 ± 8.9 ng/mL), followed by the fibroblast group (83.2 ± 5.2 ng/mL) and the no-cell group (60.0 ± 4.7 ng/mL) in the second week after implantation. In terms of angiogenesis, the microvascular density in the hUCB-MSC group was 56.8 ± 16.4, which was much higher than that in the fibroblast group (14.3 ± 4.0) and the no-cell group (5.7 ± 2.1) in the second week after implantation. Conclusions These results demonstrate that hUCB-MSCs are superior to fibroblasts in terms of their effect on diabetic wound healing in vivo . more...

A new polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam; Genewell, Seoul, Korea) was recently developed based on the hypothesis that its physical properties, including improved moisture-retention capacity and antimicrobial activity, are at least as good as those achieved with the current foam dressings that contain silver, but also associated with reduced cost and cytotoxicity to host cells. The purpose of this in vitro study was to evaluate the efficacy of Betafoam by comparing its physical properties, antimicrobial activity, and cytotoxicity with those of 3 silver foam dressings (Allevyn-Ag [SmithNephew, Hull, United Kingdom]; Mepilex-Ag [Mölnlycke Health Care, Gothenburg, Sweden]; and PolyMem-Ag [Ferris MFG Corp, Burr Ridge, Illinois]) used worldwide.This study measured each dressing's pore size, fluid absorption time, fluid absorption capacity, fluid retention capacity, antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, and cytotoxicity to mouse fibroblasts.Betafoam had the smallest pore size, the fastest fluid absorption time, greatest fluid absorption, and best retention capacities among the tested foam dressings. Antimicrobial activity was not significantly different among the dressings. However, Betafoam also demonstrated the lowest cytotoxicity to the fibroblasts.Betafoam may result not only in desirable rapid regulation of exudation but also antimicrobial activity with minimal cytotoxicity to host cells that are key requirements for wound healing. more...

Background Capsular contracture is an incurable complication after silicone-based implant surgery. Myofibroblast is the predominant cell in the contracted capsule. We hypothesized that human adipose derive stromal cells (hASCs) together with fibroblast may show a similar phenotypic characteristics of myofibroblast after the treatment of inflammatory cytokines in vitro. Materials and methods Interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) were treated in the culture of hASCs and HDFs. Lyn peptide inhibitor was applied as an inhibitor. The changes of cell surface markers (CD105, CD73, CD34, CD45, CD31, CD325 and CD146) were assessed. The expression of various cytokines related to wound contraction were tested such as TGF-β, α-SMA, HGF, FGF, ENT-1, and TSP-1. Myo-D, α-SMA, and glial fibrillary acidic protein (GFAP) were evaluated by blotting and immunocytochemical staining. The collagen-gel contraction assay was performed for the functional contraction of myofibroblastic phenotype. Results The expression of α-SMA, Myo-D and GFAP after the treatment of IL-3/GM-CSF showed similar results in hASCs and HDFs. Enhanced expression of TGF- β was observed in HDFs and the increase of ENT-1 and TSP-1 was significant in hASCs. Collagen-gel with HDFs contracted significantly within 24 h after the treatment of IL-3/GM-CSF, and the contraction was inhibited by Lyn peptide inhibitor. But in hASCs, the gel-contraction was not significant. Conclusion IL-3/ GM-CSF effected on the myofibroblastic differentiation of hASCs as well as it did on HDFs. But hASCs did not show the phenotypic gel-contraction within 24 h. more...

Current treatment guidelines for biofilm-associated infections (BAI) recommend repeated sharp/surgical debridement followed by treatment with antimicrobial agents until the wound becomes self-sustaining in terms of a positive wound-healing trajectory. However, complete removal of a biofilm is unlikely, and biofilms reform rapidly. We have treated BAI in patients with chronic diabetic ulcers using a meshed skin graft combined with negative pressure wound therapy (NPWT) immediately after surgical debridement, rather than waiting until the development of clean and healthy granulation tissue; the purpose of this exploratory study was to report the clinical results of this treatment strategy. This retrospective study included 75 patients with chronic diabetic ulcers who were treated for BAI by using surgical debridement, simultaneous meshed skin grafts, and NPWT. Healing time along with the percentage of complete wound closure within 12 weeks were evaluated; bacteria isolated from the wounds and their relation to the wound healing rate were investigated. All 75 wounds healed successfully, and the mean time for complete wound healing was 3.5 ± 1.8 weeks. In particular, 76% of wounds healed uneventfully without graft loss. A mean of 3.3 bacterial colonies/wound were isolated; however, no significant difference in wound healing was observed between the monomicrobial and polymicrobial groups. This exploratory study suggests that surgical debridement and simultaneous meshed skin grafts combined with NPWT may be successfully used to combat BAI in patients with chronic diabetic ulcers. We look forward to larger pivotal studies to confirm or refute these initially promising findings. more...

BACKGROUND Hyperpigmentation following ultraviolet irradiation has cosmetic concerns. Botulinum toxin type A can favorably affect skin pigmentation. However, the mechanism of skin pigmentation is unclear. METHODS In vitro, human epidermal melanocytes were co-cultured with human keratinocytes. After cells were treated with botulinum toxin type A, cell morphology, proliferation, and dendricity were analyzed, and immunofluorescence, tyrosinase activity, and melanin contents were determined. To evaluate the effect of botulinum toxin type A on ultraviolet B-irradiated mouse skin, ultraviolet B alone was applied to one side of the back of each mouse as a control, whereas ultraviolet B plus injection of botulinum toxin type A was applied to the contralateral side. Skin pigmentation, histology, and the number of dihydroxyphenylalanine-positive melanocytes were evaluated. The L* colorimeter value was measured. Enzyme-linked immunosorbent assay determinations of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 were performed. RESULTS Immunohistochemical staining revealed botulinum toxin type A in the cytoplasm of melanocytes and in the positive control. In vitro, melanocyte dendricity and melanin contents were decreased slightly but significantly (p < 0.05) after botulinum toxin type A treatment. In vivo, botulinum toxin type A suppressed skin pigmentation. The number of dihydroxyphenylalanine-positive melanocytes was also significantly lower than in the control side. Tyrosinase activity and melanin content were also significantly reduced (p < 0.05). Botulinum toxin type A also significantly reduced the amounts of basic fibroblast growth factor, interleukin-1 alpha, and prostaglandin E2 (all p < 0.05). CONCLUSION Botulinum toxin type A can suppress epidermal melanogenesis through both direct and indirect mechanisms. more...

To demonstrate the efficacy of a highly hydrophilic polyurethane foam dressing in the treatment of diabetic ulcers.Diabetic foot ulcers often pose a difficult treatment problem. Polyurethane foam dressings have been used worldwide to accelerate wound healing, but only a few clinical studies demonstrate the effect of foam dressing on the healing of diabetic ulcers.Medical records of 1342 patients with diabetic ulcers who were admitted and treated at the authors' institution were reviewed. A total of 208 patients met the study's inclusion criteria. Of these 208 patients, 137 were treated with a highly hydrophilic polyurethane foam dressing, and 71 were treated with saline gauze (control group). Except for the application of polyurethane foam dressing, the treatment method was identical for patients in both groups. The wound healing outcomes of the 2 groups were compared.Complete wound healing occurred in 87 patients (63.5%) in the polyurethane foam dressing group and in 28 patients (39.4%) in the control group within 12 weeks (P.05, X test). The mean percentage of wound area reduction in both groups was statistically significant (P.05, Mann-Whitney U test). The mean time required for complete closure in patients who achieved complete healing within 12 weeks was 6.2 (SD, 3.4) weeks and 7.3 (SD, 2.6) weeks in the polyurethane foam dressing and control groups, respectively (P.05, Mann-Whitney U test).These results indicate that the highly hydrophilic polyurethane foam dressing may provide an effective treatment strategy for diabetic foot ulcers. more...

The present study was undertaken to determine whether a more aesthetically acceptable nostril shape could be created by manipulating the dilator naris muscles. Patients who had round or horizontally shaped nostrils were treated by resecting the dilator naris muscle to attenuate the dilating and lateral pulling effect of the muscles. The resected muscle segments were inserted into the nasal tip area to project the nasal tip. Manipulating the dilator muscle shaped the nostril more vertically and enhanced nasal tip augmentation. The ratio of the short axis to the long axis of the nostril was improved significantly. The interaxial angle became more acute. The patient satisfaction score was also increased. A more aesthetically pleasing nostril shape can be produced by resecting and grafting the dilator naris muscle segments. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV. more...

Dermal fillers are generally accepted as safe and well-tolerable cosmetic tools. However, adverse reactions have been reported in the literature. Here, we present a case of atypical facial filler granuloma and compare its histologic features with those of the classic paraffinoma. more...

Negative-pressure wound therapy (NPWT) has become a common wound care treatment modality for a variety of wounds. Several previous studies have reported that NPWT increases blood flow in the wound bed. However, NPWT might decrease tissue oxygenation in the wound bed because the foam sponge of NPWT compresses the wound bed under the influence of the applied negative pressure. Adequate tissue oxygenation is an essential consideration during diabetic foot management, and the foot is more sensitive to ischemia than any other region. Furthermore, the issue as to whether NPWT reduces or increases tissue oxygenation in diabetic feet has never been correctly addressed. The aim of this study was to evaluate the influence of NPWT on tissue oxygenation in diabetic feet.Transcutaneous partial oxygen pressures (TcPO2) were measured to determine tissue oxygenation levels beneath NPWT dressings on 21 feet of 21 diabetic foot ulcer patients.A TcPO2 sensor was fixed at the tarsometatarsal area of contralateral unwounded feet. A suction pressure of -125 mm Hg was applied until TcPO2 reached a steady state. The TcPO2 values for diabetic feet were measured before, during, and after NPWT.The TcPO2 levels decreased significantly after applying NPWT in all patients. Mean TcPO2 values before, during, and after therapy were 44.6 (SD, 15.2), 6.0 (SD, 7.1), and 40.3 (SD, 16.4) mm Hg (P.01), respectively.These results show that NPWT significantly reduces tissue oxygenation levels in diabetic feet. more...

Hyperpigmentation, mainly following UV-irradiation, can cause major cosmetic concerns. Human adipose tissue-derived stem cells (ASCs) have been reported to serve as whitening agents through a paracrine effect. However, there have been few reports on the direct effects of ASCs on skin pigmentation following UVB-irradiation.To evaluate the effect of ASCs on UVB-irradiated mouse skin, UVB-irradiation alone was applied to one side of the backs of mice (melanin-processing hairless mouse, HRM-2) as a control, and UVB-irradiation plus injection of ASCs was applied to the contralateral side. Skin pigmentation and histology were evaluated and the number of DOPA-positive melanocytes in the mouse skin was counted. The absolute value of ΔL* via a colorimeter was measured to evaluate the degree of skin pigmentation. The effects of ASCs on the melanogenic activities of mouse skin were examined by measuring the tyrosinase activity and the melanin contents in the epidermis of the mouse skin.Skin pigmentation was suppressed in the ASC-injected side. Moreover, the change in skin thickness following UVB irradiation was reduced in the ASC-injected side. The number of DOPA-positive melanocytes in the ASC-injected side (139 ± 18 cells/mmCollectively, these results suggest that ASCs injected subcutaneously into the backs of mice can attenuate tanning following UVB-irradiation, through suppression of tyrosinase activity. more...

Although therapies with human amnion/chorion are used to ameliorate acute and chronic wounds, it is unclear which component of the amnion/chorion tissue promotes wound healing. To characterize the comparative effects of amnion and chorion in wound healing, we used human adipose-derived stromal cells to assess cell viability, migration, and gel contraction after treatment with amnion membrane extract (AME) or chorion membrane extract (CME). We then correlated the possible effectors via AME and CME protein profiling, and compared them by enzyme-linked immunosorbent assay (ELISA), western blotting, and immunocytochemistry. Cell viability was significantly increased with 50 and 100 μg/mL AME treatment, but with CME treatment, a significant increase was only observed with 100 μg/mL. With CME treatment, cell migration was 2.22-fold greater than the control, and collagen gels showed 20% greater contraction. Compared to control, the expression levels of α-smooth muscle actin (SMA) and smooth muscle protein 22-alpha (SM22α) increased both with AME and CME treatments, whereas calponin expression decreased. Protein profiling revealed significantly higher tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-8, exotoxin, and adiponectin levels in CME than in AME, and ELISA revealed 8-fold higher adiponectin levels in cells treated with CME than those treated with AME. Immunocytochemistry revealed that α-SMA, SM22α, and calponin were significantly higher in CME- than AME-treated cells; however, adiponectin treatment did not enhance α-SMA, SM22α, or calponin expression. In conclusion, amnion and chorion membrane extracts exerted differential effects on proliferation and contraction of human adipose-derived stromal cells. Amnion extract was superior at inducing cell proliferation and migration, whereas CME was superior at inducing cell contraction. more...

Numerous studies have demonstrated the various medicinal properties of Panax ginseng, including angiogenic, immuno-stimulating, antimicrobial, and anti-inflammatory activities, which can be helpful in chronic wound healing. However, a direct role for P. ginseng in chronic wound healing has not been demonstrated. The present study was designed to evaluate the effects of P. ginseng extract on diabetic fibroblasts in vitro. Human diabetic fibroblasts were cultured in the presence of Ginsenoside Rb1 (G-Rb1), the active component in P. ginseng (10 ng/mL), and untreated diabetic fibroblasts were used as controls. Cell proliferation, collagen synthesis, the production of various growth factors (basic fibroblast growth factor [bFGF]; vascular endothelial growth factor [VEGF]; and transforming growth factor-β1 [TGF-β1]), and the synthesis of matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were compared using enzyme-linked immunosorbent assay and immunofluorescence staining. Compared with the control group, G-Rb1-treated fibroblasts showed significantly (P more...

Porous high-density polyethylene implants (Medpor®) have been extensively used for septal extension grafts in Asian rhinoplasty. However, studies on the long-term complications associated with Medpor® have not been reported. Therefore, the purpose of this study was to evaluate the long-term complications of septal extension grafts using Medpor® and present a reconstructive strategy for destructed septal L-struts. We conducted a 12-year retrospective medical chart review of 428 patients who visited our center for septorhinoplasty. Among 428 patients, 43 patients had Medpor® for septal extension grafts previously applied at other clinics. The quadrangular cartilage was devoid or destructed in the area where Medpor® was previously applied. Therefore, all patients underwent secondary septorhinoplasty using autogenous cartilage grafts. Patient outcome was assessed to evaluate satisfaction, hardness of nasal tip, functional nasal obstruction symptom evaluation (NOSE) scores, and pain scores. Anthropometric analyses were carried out with patients’ photographs. Postoperative complications were also evaluated. After septal L-strut reconstruction, 87% of patients were satisfied with their aesthetic results. Hardness of nasal tip, NOSE scores, and pain scores also improved after reconstruction. Anthropometric analyses demonstrated that increased nasal length and decreased columellar–labial angle were achieved in patients with short nose deformities. No postoperative complications related to the reconstruction were recorded for any patient. The devastated destruction of nasal support lines was found after the use of Medpor® for septorhinoplasty. Therefore, the use of Medpor® should be reduced. Autogenous cartilage grafts are the last resort for reconstruction of destructed septal L-struts. 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 . more...

Background The anterolateral thigh (ALT) flap has become a predominant option in the field of reconstruction. However, some difficulties in harvesting flap exist due to the anatomical variability of the perforators. Reports have provided solutions for unreliable perforators. Although numerous cases that showed successful conversion to tensor fasciae latae (TFL) flap or anteromedial thigh (AMT) flap have been reported in the literature, none fully addresses the reliability of the perforators that have been described to date. Therefore, we conducted a systematic literature review to compare the reliability of the TFL flap with that of the AMT flap when an ALT flap perforator is not suitable. Methods A systematic review of the MEDLINE, PubMed, and Cochrane Library electronic databases was performed to compare the characteristics of TFL and AMT flap perforators. Results A total of 13 articles were included for review. The mean number of TFL perforators varied from 1.41 to 3.17 per thigh. The mean number of AMT perforators was between 0.59 and 1.3 per thigh. The cumulative assessment of the clinical and anatomical studies showed 456 perforators in 180 TFL flaps (mean, 2.53) and 145 perforators in 162 AMT flaps (mean, 0.90). The mean pedicle length of the TFL and AMT flaps ranged from 7.0 to 9.59 cm and from 7.4 to 11.0 cm, respectively. The mean perforator diameter was similar in both flaps. Conclusion Currently available literature suggests that the TFL flap may be a more reliable alternative when adequate perforators are not found for ALT flap harvest. more...

Salivary duct carcinoma is a rare malignant tumor that resembles high-grade breast ductal carcinoma. It was first described by Kleinsasser et al. [1] in 1968, and is characterized by aggressive behavior, early metastasis, local recurrence, and a high mortality rate. It most commonly occurs in the parotid gland. Previously reported cases of salivary duct carcinomas involved only the superficial lobe of the parotid gland or both the superficial and deep lobes [2]. This study reports an unusual case of salivary duct carcinoma confined to the deep lobe of the parotid gland. A 59-year-old man presented with a long history of a painless lump on the left preauricular area that had gradually enlarged over the previous year. He denied pain, numbness, and facial weakness. Physical examination showed a well-defined 4×3-cm mass in the left parotid region. The mass was firm, non-compressible, and non-tender on palpation. His left facial nerve function was intact (House-Brackmann grade I). Neither cervical lymphadenopathy nor abnormalities within the oral cavity were found. Fine needle aspiration, which is not diagnostic, was not performed. Computed tomography (CT) (Fig. 1) revealed a 2.5×3.2×4.1-cm, well-enhanced, huge, lobulated, and predominantly solid tumor in the superficial lobe of the left parotid gland. The preoperative laboratory data, including electrocardiography, urinalysis, and a chest radiograph, were unremarkable. A benign tumor, such as pleomorphic adenoma, was strongly suspected, and the patient was therefore taken to the operating room with the intention of performing a left superficial parotidectomy. During the operation, the branches of the facial nerve were preserved via a modified Blair incision. Subsequently, tumor involvement in the deep parotid lobe was identified (Fig. 2). Malignancy was identified in the frozen section of a sample taken from the mass located on the deep lobe. The excision of the superficial part of the parotid gland was completed, the branches of the facial nerve were subsequently elevated, and the deep lobe of the parotid gland was resected. The lesion was classified as cT2NxM0. Fig. 1 Computed tomography scan showing a solid mass in the left parotid gland. Fig. 2 Intraoperative photograph showing the mass located on the deep lobe of the parotid gland. The forceps are shown retracting the superficial lobe. The gross specimen showed a roughly ovoid, nodular, gray-white mass with an irregular border (Fig. 3). The histology report indicated that the tumor was an invasive ductal lesion with cribriform patterns and comedonecrosis (Fig. 4). The resected superfical lobe showed a normal parotid architecture and no tumor. The final diagnosis was salivary duct carcinoma of the deep lobe of the left parotid gland. One of the surgical margins was focally positive for malignancy. No perineural invasion or lymphovascular involvement was found. Control chest CT and positron emission tomography (PET)-CT were negative. Since postoperative CT and magnetic resonance imaging revealed no definitive evidence of perineural spread or metastatic lymphadenopathy, elective neck dissection was not performed. The patient received postoperative chemoradiation therapy with 60 Gy administered in 30 fractions and biweekly cisplatin monotherapy. Following temporary facial nerve paralysis (House-Brackmann grade IV), the patient recovered fully functional left facial movement (House-Brackmann grade I) five months after the operation. He has received regular follow-up for one year with no signs of recurrence or metastasis. Fig. 3 Gross specimen of the deep lobe of the parotid gland. Fig. 4 Histological features (H&E, ×200) of salivary duct carcinoma, showing a cribriform pattern. Salivary duct carcinoma represents more...

Background The global prevalence of myelomeningocele has been reported to be 0.8–1 per 1,000 live births. Early closure of the defect is considered to be the standard of care. Various surgical methods have been reported, such as primary skin closure, local skin flaps, musculocutaneous flaps, and skin grafts. The aim of this study was to describe the clinical characteristics of myelomeningocele defects and present the surgical outcomes of recent cases of myelomeningocele at our institution. Methods Patients who underwent surgical closure of myelomeningocele at our institution from January 2004 to December 2013 were included in this study. A retrospective chart review of their medical records was performed, and comorbidities, defect size, location, surgical procedures, complications, and the final results were analyzed. Results A total of 14 patients underwent surgical closure for myelomeningocele defects. Twelve cases were closed with direct skin repair, while two cases required local skin flaps to cover the skin defects. Three cases of infection occurred, requiring incision and either drainage or removal of allogenic materials. One case of partial flap necrosis occurred, requiring secondary revision using a rotational flap and a full-thickness skin graft. Despite these complications, all wounds eventually healed completely. Conclusions Most myelomeningocele defects can be managed by direct skin repair alone. In cases of large defects, in which direct repair is not possible, local flaps may be used to cover the defect. Complications such as wound dehiscence and partial flap necrosis occurred in this study; however, all such complications were successfully managed with simple ancillary procedures. more...

Diabetic foot ulcers are the main cause of non-traumatic lower extremity amputation. The objective of this study was to evaluate the risk factors for major amputation in diabetic foot patients. Eight hundred and sixty diabetic patients were admitted to the diabetic wound centre of the Korea University Guro Hospital for foot ulcers between January 2010 and December 2013. Among them, 837 patients were successfully monitored until complete healing. Ulcers in 809 patients (96·7%) healed without major amputation and those in 28 patients (3·3%) healed with major amputation. Data of 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology and serology were collected from patients in the two groups and compared. Among the 88 potential risk factors, statistically significant differences between the two groups were observed in 26 risk factors. In the univariate analysis, which was carried out for these 26 risk factors, statistically significant differences were observed in 22 risk factors. In a stepwise multiple logistic analysis, six of the 22 risk factors remained statistically significant. Multivariate-adjusted odds ratios were 11·673 for ulcers penetrating into the bone, 8·683 for dialysis, 6·740 for gastrointestinal (GI) disorders, 6·158 for hind foot ulcers, 0·641 for haemoglobin levels and 1·007 for fasting blood sugar levels. The risk factors for major amputation in diabetic foot patients were bony invasions, dialysis, GI disorders, hind foot locations, low levels of haemoglobin and elevated fasting blood sugar levels. more...

Background Among the various signs and symptoms of orbital fractures, certain clinical findings warrant immediate surgical exploration, including gaze restriction, computed tomographic (CT) evidence of entrapment, and prolonged oculocardiac reflex. Despite proper surgical reconstruction, prolonged complications such as diplopia and gaze restriction can occur. This article evaluated the prognostic factors associated with prolonged complications of orbital fractures with muscle incarceration. Methods The medical records of 37 patients (37 orbits) with an orbital fracture with muscle incarceration from January 2001 to January 2015 were reviewed. The presence of Incarcerated muscle was confirmed via CT, as well as by intraoperative findings. Various factors potentially contributing to complications lasting for over 1 year after the injury were categorized and analyzed, including age, cause of injury, injury-to-operation time, operative time, fracture type, nausea, vomiting and other concomitant symptoms and injuries. Results All patients who presented with extraocular muscle limitations, positive CT findings, and/or a positive forced duction test underwent surgery. Of the 37 patients, 9 (24%) exhibited lasting complications, such as diplopia and gaze restriction. The mean follow-up period was 18.4 months (range, 1–108 months), while that of patients who experienced prolonged complications was 30.1 months (range, 13–36 months). Two factors were significantly associated with prolonged complications: injury-to-operation time and nausea/vomiting. Loss of vision, worsening of motility, and implant complication did not occur. Conclusions Patients who present with gaze limitations, with or without other signs of a blow-out fracture, require a thorough evaluation and emergent surgery. A better prognosis is expected with a shorter injury-to-operation time and lack of nausea and vomiting at the initial presentation. more...

Aims The purpose of this study was to investigate the risk factors for major amputation in patients hospitalized with diabetic forefoot ulcers. Methods Between January 2003 and December 2018, a total of 1792 diabetic patients were admitted to the diabetic wound center for the management of diabetic foot ulcers. Among the patients, 1032 diabetic patients with forefoot ulcers were included in this study. Nine hundred and eighty-three patients (95%) healed without major amputations while 49 patients (5%) healed after major amputations. Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from the patients in these two groups for comparison. Results Among the 88 potential risk factors, 34 showed statistically significant differences between the two groups. In the univariate analysis of 88 risk factors, 33 showed statistically significant differences. In stepwise multiple logistic regression analysis, four of the 33 risk factors remained statistically significant. The multivariate-adjusted odds ratios for gender, magnesium levels, platelet levels, and glycated hemoglobin (HbA1c) levels were 8.216, 2.480, 1.009, and 0.570, respectively. Conclusion Risk factors for major amputation in patients hospitalized with diabetic forefoot ulcers include male gender, increased magnesium, increased platelet levels, and low levels of HbA1c. more...

BACKGROUND: To analyze oncologic outcomes and reconstruction quality in locally advanced stage breast cancer after performing immediate autologous breast reconstruction (IABR). METHODS: From 2007 to 2014, data of patients aged ≤70 years old with stage II–III breast cancer who received total mastectomy (TM) were extracted from medical records. Exclusion criteria were: previous contralateral breast cancer, follow-up loss before adjuvant therapy completion, and artificial reconstruction. Patients were divided into two groups: (I) TM alone, and (II) TM + IABR. Overall survival (OS) and loco-regional recurrence free survival (LRRFS) were calculated. Times of minor revision, abnormal image findings in breast, and change of breast height were observed. RESULTS: Sixty-one of 188 patients received IABR after TM. Stage IIIB–C was the most important prognostic factor for OS (P more...

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTL) is a rare disease presenting with non-specific symptoms, typically originating in the nasal cavity, palate, or midfacial region. Oral cavity is an extremely rare site for this type of lymphoma. In this report, we present a case of palatal perforation and oro-nasal fistula as a manifestation of recurrent ENKTL. Complicated disease entity should be considered when surgeons deal with palatal perforation and oro-nasal fistula. more...