Effects of a Catechol-Functionalized Hyaluronic Acid Patch Combined with Human Adipose-Derived Stem Cells in Diabetic Wound Healing.

INTRODUCTION: Chronic inflammation and impaired neovascularization play critical roles in delayed wound healing in diabetic patients. To overcome the limitations of current diabetic wound (DBW) management interventions, we investigated the effects of a catechol-functionalized hyaluronic acid (HA-CA) patch combined with adipose-derived mesenchymal stem cells (ADSCs) in DBW mouse models. METHODS: Diabetes in mice (C57BL/6, male) was induced by streptozotocin (50 mg/kg, >250 mg/dL). Mice were divided into four groups: control (DBW) group, ADSCs group, HA-CA group, and HA-CA + ADSCs group (n = 10 per group). Fluorescently labeled ADSCs (5 × 105 cells/100 µL) were transplanted into healthy tissues at the wound boundary or deposited at the HA-CA patch at the wound site. The wound area was visually examined. Collagen content, granulation tissue thickness and vascularity, cell apoptosis, and re-epithelialization were assessed. Angiogenesis was evaluated by immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. RESULTS: DBW size was significantly smaller in the HA-CA + ADSCs group (8% ± 2%) compared with the control (16% ± 5%, p < 0.01) and ADSCs (24% ± 17%, p < 0.05) groups. In mice treated with HA-CA + ADSCs, the epidermis was regenerated, and skin thickness was restored. CD31 and von Willebrand factor-positive vessels were detected in mice treated with HA-CA + ADSCs. The mRNA and protein levels of VEGF, IGF-1, FGF-2, ANG-1, PIK, and AKT in the HA-CA + ADSCs group were the highest among all groups, although the Spred1 and ERK expression levels remained unchanged. CONCLUSIONS: The combination of HA-CA and ADSCs provided synergistic wound healing effects by maximizing paracrine signaling and angiogenesis via the PI3K/AKT pathway. Therefore, ADSC-loaded HA-CA might represent a novel strategy for the treatment of DBW.

Lymph Node to Vein Anastomosis (LNVA) for lower extremity lymphedema.

The microsurgical options for lower limb lymphedema is a challenge. In search to improve the overall result, we hypothesized it would be beneficial to add the functioning lymph nodes to vein anastomosis (LNVA) in addition to lymphovenous anastomosis (LVA). This is a retrospective study of 160 unilateral stage II & III lower extremity lymphedema comparing the outcome between the LNVA + LVA group and the LVA only group from May 2013 to June 2018. MRI was used to identify the functioning lymph nodes. Patient outcome, including lower extremity circumference, body weight, bio impedance test, and other data were analyzed to evaluate whether lymph nodes to vein anastomosis (LNVA) improved outcome. The LNVA + LVA group showed significantly better results for circumference reduction rate, body weight reduction rate, and extracellular fluid reduction rate of the affected limb as compared to the LVA only group for both stage II and III lymphedema. The MRI imaging revealed that 9 cases had no identifiable lymph nodes of the affected limb and 54 cases with a nonfunctioning lymph node upon exploration despite positive imaging. Correlation showed the lymph node size needed to be at least 8 mm in the MRI to be functional. The LNVA + LVA approach for lymphedema has the benefit of better reduction as compared to LVA alone in the lower limb as well as the suprapubic region. Preoperative MRI will help to identify the functioning lymph node by increasing the overall probability of positive outcome.

Changing the Paradigm: Lymphovenous Anastomosis in Advanced Stage Lower Extremity Lymphedema.

BACKGROUND: Traditionally, lymphovenous anastomosis is not routinely performed in patients with advanced stage lymphedema because of difficulty with identifying functioning lymphatics. This study presents the use of duplex ultrasound and magnetic resonance lymphangiography to identify functional lymphatics and reports the clinical outcome of lymphovenous anastomosis in advanced stage lower extremity lymphedema patients. METHODS: This was a retrospective study of 42 patients (50 lower limbs) with advanced lymphedema (late stage 2 or 3) that underwent functional lymphovenous anastomoses. Functional lymphatic vessels were identified preoperatively using magnetic resonance lymphangiography and duplex ultrasound. RESULTS: An average of 4.64 lymphovenous anastomoses were performed per limb using the lymphatics located in the deep fat underneath the superficial fascia. The average diameter of lymphatic vessels was 0.61 mm (range, 0.35 to 1 mm). The average limb volume was reduced 14.0 percent postoperatively, followed by 15.2 percent after 3 months, and 15.5 percent after 6 months and 1 year (p < 0.001). For patients with unilateral lymphedema, 32.4 percent had less than 10 percent volume excess compared to the contralateral side postoperatively, whereas 20.5 percent had more than 20 percent volume excess. The incidence of cellulitis decreased from 0.84 per year to 0.07 per year after surgery (p < 0.001). CONCLUSION: This study shows that functioning lymphatic vessels can be identified preoperatively using ultrasound and magnetic resonance lymphangiography; thus, lymphovenous anastomoses can effectively reduce the volume of the limb and improve subjective symptoms in patients with advanced stage lymphedema of the lower extremity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Therapeutic Effects against Tissue Necrosis of Remote Ischemic Preconditioning Combined with Human Adipose-Derived Stem Cells in Random-Pattern Skin Flap Rat Models.

INTRODUCTION: Remote ischemic preconditioning (rIPC) is a preventive strategy against ischemia-reperfusion injury. To reduce ischemia-reperfusion injury of random-pattern skin flaps, we investigated the therapeutic effects of rIPC combined with human adipose-derived stem cells (hADSCs) in a rat model. MATERIAL AND METHODS: In total, 24 female Sprague Dawley rats were divided into four groups (n = 6 each): control (skin flap only), rIPC, hADSCs, and rIPC + hADSCs. rIPC was performed in the hind limb of the rats over three cycles of 5 min of occlusion and 5 min of reperfusion, using a tourniquet. A rectangular (3 × 9 cm) dorsal skin flap was used. hADSCs (5 × 105 cells/100 µL) labeled with fluorescent dye were transplanted into the normal subcutaneous tissue at the skin flap boundary. After 14 days, the therapeutic effects of rIPC and hADSCs were evaluated via analysis of the necrotic flap area, histopathologic assessment, and immunohistochemistry (von Willebrand Factor (vWF) and CD31). RESULTS: The necrotic area of the skin flap significantly decreased in the rIPC + hADSCs group (32.75 ± 1.43%) compared with the control (40.60 ± 3.27%, P < 0.01) and rIPC groups (38.84 ± 0.77%, P < 0.05). Dye-labeled hADSCs migrated to the skin flap from the injection site. In the rIPC + hADSCs group, the epithelial tissue and skin appendage had regenerated, and the smooth muscle and subcutaneous fat layers were preserved. Many more vWF- and CD31-positive vessels were observed in the rIPC + hADSCs group compared with the other groups. CONCLUSIONS: The rIPC + hADSCs treatment appeared to reduce skin flap necrosis and activated neovascularization in rats. Therefore, it may be a good strategy for clinical treatment of ischemia-reperfusion injury.

The molecular pathogenesis of Trichilemmal carcinoma.

BACKGROUND: Trichilemmal carcinoma (TC) is an extremely rare hair follicle tumor. We aimed to explore the genetic abnormalities involved in TC to gain insight into its molecular pathogenesis. METHODS: Data from patients diagnosed with TC within a 12-year period were retrospectively reviewed. Genomic DNA isolated from a formalin-fixed paraffin-embedded (FFPE) tumor tissue block was sequenced and explored for a panel of cancer genes. RESULTS: DNA was extracted from the FFPE tissue of four patients (50% female; mean age, 51.5 years) diagnosed with TC for analysis. The tumor was located in the head and neck of three patients and in the shoulder of one patient. TP53 mutations (p.Arg213*, p.Arg249Trp, and p.Arg248Gln) were found in three patients. Fusions previously identified in melanoma were detected in two patients (TACC3-FGFR3 and ROS1-GOPC fusions). Other mutations found included NF1-truncating mutation (Arg1362*), NRAS mutation (p.Gln61Lys), TOP1 amplification, and PTEN deletion. Overall, genetic changes found in TC resemble that of other skin cancers, suggesting similar pathogenesis. All patients with TP53 mutations had aggressive clinical course, two who died (OS 93 and 36 months), and one who experienced recurrent relapse. CONCLUSIONS: We reported the genomic variations found in TC, which may give insight into the molecular pathogenesis. Overall, genetic changes found in TC resembled that of other skin cancers, suggesting similar pathogenesis. TP53 mutations was were identified in patients who had an aggressive clinical course. Genetic alterations identified may further suggest the potential treatment options of TC.

Synergistic Effect of Adipose-Derived Stem Cells and Fat Graft on Wrinkles in Aged Mice.

BACKGROUND: The authors investigated the synergistic effects of adipose-derived stem cells and fat graft on skin wrinkles in a nude mouse model of chronologic aging. METHODS: After 50 weeks of chronologic aging, 44 female BALB/c nude mice were classified into four groups: (1) negative control, (2) mice injected subcutaneously with fat on the back skin (0.5 cm), (3) mice injected with adipose-derived stem cells (1 × 10 cells in 0.5 cm Hanks balanced salt solution), and (4) mice injected with both fat (0.5 cm) and adipose-derived stem cells (1 × 10 cells in 0.5 cm Hanks balanced salt solution). The degree of wrinkling was evaluated using replica analysis, and skin biopsies were performed after 4 weeks. The dermal thickness and density of collagen were determined. Type I procollagen and matrix metalloproteinase levels were determined using real-time polymerase chain reaction and Western blot analysis. Tropoelastin, fibrillin-1, and CD31 levels were evaluated using immunohistochemistry. RESULTS: Based on the total wrinkle area, there was significant wrinkle reduction in the fat-treated and adipose-derived stem cell with fat-treated groups. Type I procollagen mRNA and collagen levels were significantly higher in the adipose-derived stem cell with fat-treated group than in the adipose-derived stem cell-treated and the fat-treated groups. In addition, the adipose-derived stem cells with fat graft group exhibited significantly higher CD31 expression level than the adipose-derived stem cell-treated and the fat-treated groups. CONCLUSION: Both adipose-derived stem cells and fat graft have a wrinkle-reducing effect and synergistically affect collagen synthesis and neovascularization.

Comparison of the efficacy and safety of povidone-iodine foam dressing (Betafoam), hydrocellular foam dressing (Allevyn), and petrolatum gauze for split-thickness skin graft donor site dressing.

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.

Palmar Ulnar Artery Perforator Free Flap for Fingertip Reconstruction: Anatomical and Clinical Study.

BACKGROUND: Fingertips are a common site for hand injuries. The ideal substitute for fingertip pulp is tissue that matches texturally with minimal donor site morbidity. We described anatomical findings from cadaveric studies and the reliability of the palmar ulnar artery perforator (PUAP) free flap techniques for the reconstruction of fingertips injuries. METHODS: The cadaveric study involving 8 hands was conducted to illuminate the anatomy of the hypothenar region. We investigated the emerging point of perforators, diameter of the artery at the origin, and the length of the pedicle. Forty-four patients with fingertip injuries underwent fingertip reconstruction using PUAP free flaps. Data on the baseline patient demographics, hospital courses, and flap sizes were obtained retrospectively. The 6-month postoperative sensory capacity was determined using a 2-point discrimination test. RESULTS: The cadaveric study found that the PUAP pedicles arose from the superficial palmar arch, the mean length of pedicles, and the diameter and location of perforators were also analyzed. The PUAP flap sizes varied from 2.0 × 2.3 cm to 2.5 × 3.5 cm, and the mean operative time was 124 min. In all cases, we performed neurorrhaphy for fingertip sensory restoration. All donor sites were closed primarily, and the 2-point discrimination test result was 5.7 ± 0.87 mm 6 months after surgery. CONCLUSIONS: We confirmed the anatomical consistency of the PUAP. Among the numerous reconstruction options available for fingertip injuries, the PUAP free flap is a useful fingertip reconstruction option.

The originating pattern of deep inferior epigastric artery: anatomical study and surgical considerations.

PURPOSE: Studies focusing on the originating patterns of the deep inferior epigastric artery (DIEA) have not been conducted. Here, we analyzed the vascular anatomy of the DIEA with computed tomographic angiography (CTA) to provide assistance during proximal pedicle dissection of a DIEA-based flap. METHODS: We conducted a retrospective study on patients who had undergone breast reconstruction with the transverse rectus abdominis musculocutaneous flap and the deep inferior epigastric perforator flap from March 2006 to October 2016. Preoperative three-dimensional computed tomographic angiograms of the abdominal wall (hemi-abdominal walls) were employed in this study, and three independent surgeons reviewed all CTA images. The originating angles and the distance from the originating point to the DIEA turning point were analyzed. Moreover, we assessed the relationship between the measured values and patients' characteristics, such as abdominal surgery history. RESULTS: CTA data of 184 patients and 368 hemiabdomens were reviewed and analyzed. Most of the DIEAs originated from the external iliac artery in the medial direction, proceeded caudally, and curved in a cephalic direction. The average descending length was 11.29 mm. As the DIEA origin angle decreased (toward the caudal direction), the distance of the initial descent increased (r = 0.382, p < 0.01). In addition, the descending length was significantly larger (p < 0.01) in the operation group (12.22 mm) than in the non-operation group (9.86 mm). CONCLUSIONS: Surgeons should consider DIEA-originating patterns to ensure safe pedicle dissection during flap elevation.

A new all-purpose bilateral cleft lip repair: Bilateral cheiloplasty suitable for most conditions.

BACKGROUND: Only experienced surgeons can produce satisfactory results with most of the current surgical methods for bilateral cleft lip repair. The existing methods require not only preoperative orthodontic maneuvers but also accurate measurements for surgical design. We describe an easy-to-design and simple-to-execute general purpose surgical technique to repair most bilateral cleft lips. METHODS: A retrospective review was performed for the patients who underwent bilateral cleft lip repair using our novel method between 2003 and 2016. The authors collected data from medical records, and the aesthetic results were judged using the aesthetic result categories by three independent surgeons; indirect anthropometry was applied to patients over 9 years of age. In addition, we investigated the complications, the reoperation rate, and the reasons for reoperation. RESULTS: Bilateral cleft lip surgery was performed in 146 cases between 2003 and 2016. Seventy-eight patients had bilateral complete cleft lips, 47 patients had bilateral incomplete cleft lips, and 21 patients had bilateral complete and incomplete cleft lips (asymmetric patients). There were no acute complications requiring re-surgery, such as wound dehiscence, hematoma, and infection. According to aesthetic classification, 74 patients (51%) were classified into category I and 72 patients (49%) into category II; no patients were classified into categories III and IV. Seventy patients (48%) underwent secondary lip operations. In anthropometry, the measurements were observed to be symmetrical; left and right measurement data were not significantly different. The main purposes of the revision were excision of widened philtral scars (42 cases) and correction of lateral vermilion bulging (28 cases). CONCLUSIONS: We have found our novel technique to be simple and capable of providing consistent, reproducible, and reliable results.

Atypical Growing Pattern of Superficial Temporal Artery Pseudoaneurysm.

Superficial temporal artery pseudoaneurysm is rare and usually caused by trauma. Pseudoaneurysms have been reported to occur most frequently from 2 to 6 weeks after trauma and they range from 1 to 3 cm in diameter. The authors present a case of a patient with an atypical delayed rapid growing pseudoaneurysm, who had undergone neurosurgery after head trauma 20 years ago.A 72-year-old woman underwent craniotomy and extradural hemorrhage removal through a left temporoparietal incision caused by head trauma after a traffic accident 20 years prior. The mass of less than 1 cm in diameter was incidentally found by magnetic resonance imaging 8 years ago. However, the patient had no symptoms and the pseudoaneurysm was not considered a significant finding. Several weeks ago, the patient recognized a palpable mass by chance. She observed it without any medical evaluation and treatment. However, the size of the mass suddenly increased without the patient undergoing trauma. It presented as a soft, pulsating round mass of about 3 cm in diameter. Under general anesthesia, the mass was removed without problems. It was a round-shaped mass of 2.2 cm × 2.4 cm in diameter. The transverse cross-section evidenced it was filled with blood clots. The biopsy revealed a dilated vascular wall with an organized thrombus and neovascularization, which are characteristic for a thrombosed pseudoaneurysm.Thus, given that a pseudoaneurysm can grow at any time, medical doctors should strongly consider surgical removal as opposed to simple observation.

The Classification and Prognosis of Periocular Complications Related to Blindness following Cosmetic Filler Injection.

Common side effects during hyaluronic acid filler injections are typically mild and reversible, but several reports of blindness have received attention. The present study focused on orbital symptoms combined with blindness, aiming to classify affected patients and predict their disease course and prognosis. From September of 2012 to August of 2015, nine patients with vision loss after filler injection were retrospectively reviewed. Ptosis, ophthalmoplegia, and enophthalmos were recorded over a 6-month follow-up, and patients were classified into four types according to periocular symptom manifestation. Two patients were categorized as type I (blindness without ptosis or ophthalmoplegia), two patients as type II (blindness and ptosis without ophthalmoplegia), two patients as type III (blindness and ophthalmoplegia without ptosis), and three patients as type IV (blindness with ptosis and ophthalmoplegia). The present study includes previously unpublished information about orbital symptom manifestations and prognosis combined with blindness caused by retinal artery occlusion after cosmetic filler injection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Cartilage suspension using a poly (lactic-co-glycolic) acid system.

BACKGROUND: This study aims to determine whether a bar-like implant made of poly lactic-co-glycolic acid (PLGA) could be used for cartilage suspension and whether the implant would be suitable for rhinoplasty. METHODS: Three types of in vivo animal experiments were performed. First, the ear cartilage was incised in a full-thickness pattern, and the PLGA system was placed between the upper and lower cartilage to offer support to the tissue. Second, after the ear cartilage was forcibly bent, an implant was placed in the cartilage. For these rabbits, the outer aspect of the ear cartilage was assessed at 2, 4, 8, 10, and 12 weeks postoperatively. In addition, tissue samples were collected for histological evaluation 12 weeks after surgery. Third, the bar-like nasal implant was used for nasal septal suspension. We obtained micro-computed tomography (CT) images and evaluated the inflammatory reaction at 12 weeks postoperatively. RESULTS: The results of both the ear suspension and bending retention tests revealed that the characteristic shapes of the cartilage were well preserved at 12 weeks postoperatively. Moreover, no abnormal inflammatory reaction was present in any site in the experimental group. We successfully implanted the bar-like nasal implant in the rabbit's septum, and no complications occurred. Furthermore, the physical examination and the micro-CT images did not reveal any nasal obstruction or inflammation. CONCLUSIONS: We confirmed that an implant made of PLGA can be maintained in the cartilage tissue and believe that this can be applied in rhinoplasty as an alternative to autologous cartilage.

Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior epigastric island skin flap survivability in ischaemia-reperfusion injury rat model.

BACKGROUND: Ischaemia-reperfusion injury (IRI) results in oxidative damage and a profound inflammatory reaction, leading to cell death. GV 1001 is a telomerase-based 16-mer peptide vaccine developed against cancer. However, it has also been reported to possess antioxidant and anti-inflammatory properties. The aim of this study was to determine if GV 1001 can reduce the negative effects caused by IRI in a rat skin flap model owing to its anti-oxidant and anti-inflammatory properties. MATERIALS AND METHODS: In order to evaluate the effect of GV 1001, 5 × 5 cm2 inferior epigastric artery based island skin flaps were dissected in 39 8-week-old Sprague-Dawley rats weighing 220-270 g. The rats were divided into three groups: (I) non-ischaemic group; (II) IRI with saline; and (III) IRI with 10 mg GV 1001 treatment. Drugs were administered intra-muscularly directly before and after ischaemia. Flap survival area, neutrophil infiltration, cytokine levels (interleukin [IL]-1, IL-6, and tumour necrosis factor-α), malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. Flap survivability was analysed at 7 days after surgery. RESULTS: Flap survival area was significantly larger in group III than in group II. Cytokine release level was also significantly lower in group III. Neutrophil infiltration grade, MDA level, and SOD activity slightly decreased in Group III; however, the changes were not statistically significant. CONCLUSION: These results imply that GV 1001 exerts a protective effect against IRI through antioxidant effects, reducing reactive oxygen species, and suppressing the inflammatory cascade.

A Multicenter Noncomparative Clinical Study on Midface Rejuvenation Using a Nonabsorbable Polypropylene Mesh: Evaluation of Efficacy and Safety.

BACKGROUND: Facial rejuvenation can be achieved using a variety of techniques. Since minimally invasive procedures for face lifting have become popular because of their convenience and short operating time, numerous minimally invasive surgical procedures have been developed. In this study, a nonabsorbable polypropylene mesh is introduced as a new face lifting instrument, with the nasolabial fold as the main target area. In this paper, we report the efficacy and safety of a polypropylene mesh in midface rejuvenation. METHODS: Thirty-three subjects with moderate-to-severe nasolabial folds were enrolled from two medical institutions for a noncomparative single-sample study. A mesh was inserted above the superficial muscular aponeurotic system layer, reaching the nasolabial folds through a temporal scalp incision. After 3 weeks, the temporal end of the mesh was pulled to provide a lifting effect. Then, the mesh was fixed to the deep temporal fascia using nonabsorbable sutures. To evaluate efficacy, we compared the scores on the Wrinkle Severity Rating Scale and a visual analog scale for patient satisfaction between the baseline and 7 weeks postoperatively. In addition, we evaluated safety based on the incidence of adverse events. RESULTS: The treatment was deemed effective at improving wrinkles in 23 of 28 cases, and patient satisfaction improved significantly during the study period. There were seven cases of skin or subcutaneous tissue complications, including edema and erythema, but there were no suspected serious adverse events. CONCLUSIONS: Face lifting using a nonabsorbable mesh can improve nasolabial folds without serious adverse effects. Thus, this technique is safe and effective for midface rejuvenation.

Effect of Low-Level Laser Therapy on Human Adipose-Derived Stem Cells: In Vitro and In Vivo Studies.

BACKGROUND: Low-level laser therapy (LLLT) continues to receive much attention in many clinical fields. Also, LLLT has been used to enhance the proliferation of various cell lines, including stem cells. This study investigated the effect of LLLT on human adipose-derived stem cells (ADSCs) through in vitro and in vivo studies. METHODS: Low-level laser irradiation of cultured ADSCs was performed using a 830 nm Ga-Al-As (gallium-aluminum-arsenide) laser. Then, proliferation of ADSCs was quantified by a cell counting kit-8. In the in vivo study, irradiated ADSCs or non-irradiated ADSCs were transplanted, and then, low-level laser irradiation of each rat was performed as per the protocol. Cell viability was quantified by immunofluorescent staining using the human mitochondria antibody. RESULTS: In the in vitro study, the laser-irradiated groups showed an increase in absorbance compared to the control group. Also, in the in vivo study, there was a significant increase in the number of human ADSCs in the laser-irradiated groups compared to the control group (p < 0.001). CONCLUSIONS: Our study showed that LLLT could enhance the proliferation and viability of ADSCs. The ADSCs enhanced by LLLT could be applied in various clinical fields. With the use of LLLT, the proliferation and viability of various cells can be enhanced, besides ADSCs. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

A phase III, randomized, double-blind, matched-pairs, active-controlled clinical trial and preclinical animal study to compare the durability, efficacy and safety between polynucleotide filler and hyaluronic acid filler in the correction of crow's feet: a new concept of regenerative filler.

The Rejuran® is a new filler product made from purified polynucleotides. Here we present data from an animal study and a clinical trial to examine the durability, efficacy and safety of the Rejuran® on crow's feet. For the animal study, 25 mice were divided into three groups: Group 1 received phosphate buffered saline (PBS); Group 2 were treated with Yvoire®; and Group 3 were treated with Rejuran®. The durability and efficacy of each treatment were assessed by microscopy and staining. In the clinical trial, 72 patients were randomized to receive Rejuran® treatment for crow's feet on one side and Yvoire-Hydro® on the contralateral side, at a ratio of 1:1. Repeated treatments were performed every two weeks for a total of three times, over a total of 12 weeks' observation. All injections and observations of efficacy and safety were performed by the same two investigators. In the animal study, the Rejuran® group showed similar durability and inflammatory response to the Yvoire® group. Upon efficacy assessment, the Rejuran® group showed the greatest elasticity and collagen composition, and a significant difference in skin surface roughness and wrinkle depth. In the clinical trial, the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups, and in safety outcomes there were no unexpected adverse effects. Our data suggest that the Rejuran®, as a new regenerative filler, can be useful to reduce wrinkles, by showing evidence for its efficacy and safety.

Effects of polydeoxyribonucleotide in the treatment of pressure ulcers.

This study aimed to examine the positive effects of polydeoxyribonucleotide (PDRN) on the wound-healing process in pressure ulcers. In this randomized controlled trial, the effects of PDRN were compared over time between an experimental group (n=11) and a control group (n=12). The former was administered the same dose of PDRN intramuscularly (1 ampule, 3 mL, 5.625 mg, for 5 days) for 2 weeks and perilesionally (1 ampule, 3 mL, 5.625 mg, twice a week) for 4 weeks. The primary endpoint for determining efficacy was wound healing in the pressure ulcers, which was reflected by the wound surface area determined using VISITRAK Digital (Smith & Nephew, Largo, FL). The secondary endpoint was the pressure ulcer scale for healing score, determined using pressure ulcer scale for healing (PUSH Tool 3.0 developed by the National Pressure Ulcer Advisory Panel). After the 4-week treatment period, PDRN therapy was found to significantly reduce the wound size and PUSH score, without adverse effect during the treatment. The findings indicate that PDRN can positively modify the wound healing process in pressure ulcers, and its use could improve the clinical outcomes of patients and lower the need for additional therapies or hospital stay.

Safety and efficacy of ulthera in the rejuvenation of aging lower eyelids: a pivotal clinical trial.

BACKGROUND: The changes in the periorbital region are among the most prominent features of the aging process in the lower eyelids. Intense focused ultrasound (IFUS), known as the Ulthera System, was designed to correct this process. The current study assessed the safety and efficacy of the Ulthera System. METHODS: This study enrolled seven adult patients who presented from March 2011 to May 2012 for correction of lower eyelid aging by Ulthera. The subjects were treated using Ulthera 1.5 and 3.0 mm probes. The 1.5 mm probe is used to tighten of loose eyelid skin and the deep dermis, whereas the 3.0 mm probe is used to tighten the orbicularis oculi muscle and the orbital septum. The patients were evaluated for allergic reactions and other side effects. The subjects' satisfaction with clinical photographs and the degree of pain were evaluated. Moreover, orbital computed tomography (CT) and ophthalmologic examinations were performed. The study used CT both as a research tool and as a clinical score system for evaluating aging lower eyelids and performed statistical analysis. RESULTS: Based on the CT images, the difference between the pre- and postoperative distances from the baseline (line between the most inferior point of the supraorbital rim and the most superior point of the infraorbital rim) to the most protruding point of the orbital septum was 0.51 ± 0.23 for the right eye (p < 0.001) and 0.54 ± 0.17 for the left eye (p < 0.001). The subjective score for patient satisfaction was 3.85 ± 0.69. The objective satisfaction scores reported by two blinded researchers were respectively 3.45 ± 1.69 and 3.25 ± 1.43. During the study period, no adverse events and no suspected serious adverse reactions were noted. CONCLUSIONS: Tightening of infraorbital laxity and skin can be achieved using the Ulthera System. Patients showed a minimal pain level during treatment, and topical analgesic cream was able to manage pain during the procedure.

Medial epicanthoplasty using the "inside-out" technique.

The epicanthal fold, a skin remnant covering the medial canthal region, is especially common in Asians. Although numerous surgical techniques for the treatment of the epicanthal fold have been developed, the results.in terms of scars and a natural look remain controversial. In this regard, the authors have developed a new method for medial epicanthoplasty. From January 2005 to December 2011, medial epicanthoplasty was performed on 1132 patients using a technique in which the skin flap inside of the medial epicanthal fold is moved outward (the "Inside-Out" technique). Preoperative and postoperative (2 months) interepicanthal distance was measured. Satisfactory results were achieved in the majority of cases. While nine patients complained of visible scarring after the operation, the scar formation spontaneously resolved within 6 months. This new "Inside-Out" technique for the treatment of the epicanthal fold is easy, simple, and delivers good aesthetic results.