Evaluating the Safety and Efficacy of a Topical Formulation Containing Epidermal Growth Factor, Tranexamic Acid, Vitamin C, Arbutin, Niacinamide and Other Ingredients as Hydroquinone 4% Alternatives to Improve Hyperpigmentation: A Prospective, Randomized, Controlled Split Face Study.

Hyperpigmentation is a common concern of patients in aesthetic practice. There are various treatment options, but topical depigmenting agents such as hydroquinone (HQ) are usually a first-line option. Given HQ's side effects and potential controversy over its long-term use from prior animal studies, there is a consumer demand for non-HQ topical formulations that provide similar efficacy, but with a reduced adverse reaction profile to HQ. There is increasing evidence to support the use of selective growth factors, tranexamic acid, niacinamide, arbutin, and Vitamin C in improving hyperpigmentation. This study sought to determine whether a non-HQ topical formulation, composed of the aforementioned ingredients, could provide similar or improved efficacy to topical HQ, but with a reduced adverse reaction profile. This single-center, prospective, randomized, controlled split face study investigated the safety and efficacy of a proprietary product SKNB19 compared with hydroquinone 4% (HQ4%) in treating hyperpigmentation. Eighteen adult subjects with facial pigmentation were randomly assigned to have one side of their face treated with SKNB19 twice a day (morning and night application) and the other treated with HQ4% applied nightly. Patients used a 5-point scale to self-assess their overall appearance, and a 4-point scale to assess redness, irritation, and tolerability to the skin-brightening creams. A Wilcoxon signed-rank test was used to test whether there was a statistical difference between the two treatments. Three-dimensional imaging was performed before treatment was administered and again 1 month following treatment initiation using a Canfield Vectra 3D imaging system. Five independent reviewers comprising two dermatologists, two facial plastic surgeons, and one oculoplastic surgeon graded and performed a qualitative comparative assessment of each side of the face using the before and after images. A Wilcoxon signed-rank test was used to test whether there was a statistical difference in overall appearance between SKNB19- and HQ4%-treated sides. SKNB19-treated hyperpigmentation had a statistically significant improvement in the overall appearance of hyperpigmentation and was shown to be 28.5% better than HQ4%-treated skin in the patient self-assessment and 27% better than HQ4%-treated skin in the independent reviewer assessment. On pair-wise comparison, the independent reviewer assessment also showed that 88.2% of the SKNB19-treated sides appeared equal or better than the HQ4%-treated sides. One patient dropped out of the study because of severe intolerance to HQ4%. No patients experienced intolerance to SKNB19, and all were able to continue its use without adverse effects. SKNB19-treated hyperpigmentation also had a statistically significant reduction in irritation when compared with HQ4%-treated hyperpigmentation. Patients reported a reduction in redness when using SKNB19 as opposed to HQ4%, but these figures did not reach statistical significance. This study supports that SKNB19, a recently developed non-HQ proprietary product, is safe and effective in improving hyperpigmentation. SKNB19 significantly improved the appearance of hyperpigmentation when compared with HQ4% in both patient self-assessment and independent reviewer assessment. SKNB19 exhibited a lower adverse reaction profile and was significantly better tolerated than HQ4%. SKNB19 should be considered as a safe and effective non-HQ alternative for the management of hyperpigmentation.

Measured gain in projection with the extended columellar strut-tip graft in endonasal rhinoplasty.

IMPORTANCE: The extended columellar strut-tip graft was designed to improve nasal tip projection and tip definition in patients undergoing rhinoplasty. OBJECTIVE: To determine whether the extended columellar tip graft leads to a true and measurable increase in nasal tip projection or simply gives the illusion of an increase in projection. DESIGN: Retrospective case review. The mean time of follow-up photographs was 32 months after surgery (range, 8 months to 10 years). PARTICIPANTS: The study population comprised 15 patients who underwent primary or revision rhinoplasty during the last 10 years. INTERVENTION: Primary or revision rhinoplasty. MAIN OUTCOME MEASURE: The outcome measure was the long-term gain in nasal tip projection. Preoperative and postoperative images were cropped and sized equally for accurate comparison. All measurements were made from the alar-facial crease to the tip defining point. RESULTS: In all 15 patients, an increase in tip projection was obtained. The mean increase in projection was 19% compared with the preoperative projection. After applying a paired t test for analysis, there was a statistically significant increase in nasal projection (P < .05). CONCLUSIONS AND RELEVANCE: The extended columellar strut-tip graft effectively corrected poor nasal tip projection. The effect is maintained years later. The extended columellar strut-tip graft is an excellent choice in endonasal rhinoplasty to improve poor tip projection and definition. LEVEL OF EVIDENCE: 4.

Subjective and objective improvement in breathing after rhinoplasty.

OBJECTIVE: To determine whether rhinoplasty improves subjective and objective nasal patency. DESIGN: Retrospective study including subjective breathing scores and acoustic rhinometry before and 6 to 9 months after septorhinoplasty among a cohort of 31 patients. We used a paired t test to analyze the difference between preoperative and postoperative values. SETTING: Academic medical center. PATIENTS: Patients undergoing septorhinoplasty with potassium titanyl phosphate laser turbinate reduction at a single institution. RESULTS: The mean subjective breathing scores improved significantly, with an overall improvement of 38%. The overall mean volume increased and the overall resistance decreased, but the changes were significant only on the right side. The minimal cross-sectional area (MCA) did not change, but the distance of the MCA of the nasal cavity moved anteriorly by 0.23 cm on the left side. The patients were stratified into subsets based on other procedures undergone, including spreader grafts and alar batten grafts, and on the absence of osteotomies. These groups had similar results. In patients with severe obstruction, all measured values improved more than any other subgroup, including the MCA, which improved significantly by an average of 55%. Patients with normal preoperative MCA values did not experience any significant changes except for an anterior shift in MCA. CONCLUSIONS: Septorhinoplasty increases nasal volume, decreases nasal resistance, and advances the MCA anteriorly. These changes coexist with subjective improvements in nasal patency, which suggests that this new anatomic configuration creates a positive outcome on nasal airflow. Spreader grafts do not increase the MCA significantly. Patients with preoperative severe obstruction have the best overall improvement, whether measured subjectively or objectively.

Antidepressants and bleeding risk after face-lift surgery.

OBJECTIVE: To determine the rate of post-face-lift hematoma among users of serotonin reuptake inhibitors (SSRIs) vs non-SSRI users. Selective serotonin reuptake inhibitors have come under recent scrutiny because of possible bleeding risks. However, cessation of SSRIs carries inherent risks. METHODS: The medical charts for 250 consecutive patients who underwent a modified deep-plane face-lift and 13 patients who underwent neck-lift from January 2010 to May 2011 were reviewed for the incidence of postoperative hematoma. Patients' medical records were examined for medical comorbidities, coagulopathy, and medication list, with particular attention to any usage of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs). RESULTS: Twenty-two percent of patients were taking SSRIs or SNRIs. We observed a total hematoma (major + minor) rate of 1.95% for non-SSRI/SNRI users vs 1.72% for SSRI/SNRI users. The minor hematoma rate was 1.95% among nonusers vs 0% for users. The major hematoma rate was 0% among nonusers vs 1.72% for users. CONCLUSIONS: Usage of SSRIs was more common in this large series of face-lift patients than in the general population. In these patients, SSRIs in the perioperative period are found to be safe and did not seem to adversely affect outcome. We found no evidence to support discontinuing SSRIs perioperatively.

Facial flap complications.

Knowledge of fundamental concepts can help decrease the chance of complications in plastic surgery. Local flap reconstruction for facial defects has many pitfalls. This article describes common complications in local flap reconstruction of the face and describes strategies that prevent problems.

Intraoperative suction-assisted evaluation of the nasal valve in rhinoplasty.

OBJECTIVE: To introduce and analyze suction-assisted analysis of nasal valve strength in functional septorhinoplasty. This is a novel method for helping the surgeon analyze the integrity of a patient's airway during surgery. METHODS: In this prospective study, 20 patients who underwent functional septorhinoplasty were analyzed. Negative pressure using suction tubing was placed at the nasal sill, and measurements of the amount of maximal depression of the nasal valve were performed in the operating room immediately before incision and immediately after closure of the incisions. RESULTS: All 20 patients had an immediate decrease in the deviation of the weakest point of the valve, with a mean change of 2.14 mm. The change on both sides was statistically significant (paired t test, P < .001). This novel method helped the surgeons decide which grafts provided the most immediate structural benefit. CONCLUSIONS: Structure-based septorhinoplasty can immediately improve the strength of the nasal valve. Suction-assisted analysis of the nasal valve can be a useful "real-time" tool for determining which maneuvers improve the strength of the nasal valve.

A novel mouse model of cutaneous radiation injury.

BACKGROUND: Radiation therapy is a cornerstone of oncologic treatment. Skin tolerance is often the limiting factor in radiotherapy. To study these issues and create modalities for intervention, the authors developed a novel murine model of cutaneous radiation injury. METHODS: The dorsal skin was isolated using a low-pressure clamp and irradiated. Mice were followed for 8 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy specimens were taken and examined histologically. Tensiometry was performed and Young's modulus calculated. RESULTS: High-dose radiation isolated to dorsal skin causes progressive changes in skin perfusion, resulting in dermal thickening, fibrosis, persistent alopecia, and sometimes ulceration. There is increased dermal Smad3 expression, and decreased elasticity and bursting strength. CONCLUSIONS: This model of cutaneous radiation injury delivers reproducible localized effects, mimicking the injury pattern seen in human subjects. This technique can be used to study radiation-induced injury to evaluate preventative and therapeutic strategies for these clinical issues.

Anatomic considerations in the aging face.

A thorough knowledge of the anatomy of the aging face is essential to a safe and effective operation. Over time, the face undergoes changes in skin and subcutaneous tissues evidenced by rhytides and thinning. There are also changes in the tone and character of facial muscles. Changes in fat structures in the face cause aesthetic changes that can be addressed surgically. Knowledge of the anatomy of the face and neck will aid in understanding the changes that occur with aging and will allow for a more complete strategy in rejuvenating the aging face.

Effects of various submucous resection techniques of septal cartilage on nasal tip projection.

BACKGROUND: There is little research which determines whether septoplasty affects nasal projection. OBJECTIVES: To assess the effect of various septoplasty (submucous resection, SMR) techniques on nasal tip projection in a fresh cadaver model. METHODS: The nasal tip projection was measured on 6 fresh cadaver heads and compared postoperatively after a sequence of submucous septoplasty maneuvers. Five different septoplasty techniques were performed in the same sequence on each cadaver. After each technique, measurements were performed. RESULTS: Removal of a central square piece of quadrangular cartilage resulted in a loss of projection in 3 in 6 (50%) heads, with average loss of 7.76%. Removal of additional cartilage along the bony cartilaginous junction resulted in no loss of projection. Removing more septum along the floor resulted caused a change loss in nasal projection in 1 in 6 (17%) cadavers. Removing the remaining septum, except for the L-strut resulted in a loss of projection in 2 in 6 (33%) heads with an average percent change in tip projection of 9.08%. Swinging door technique resulted in a loss of projection in 1 cadaver (17%), with loss of 6.25%. All 6 cadavers experienced loss of nasal projection. When all maneuvers were taken in total, there was a statically significant average decrease in projection of 8.93% (range, 5.00-13.04%, p = 0.008). CONCLUSION: Primary septoplasty carries a risk of nasal tip projection, with certain maneuvers carrying higher risk.

Regulators and mediators of radiation-induced fibrosis: Gene expression profiles and a rationale for Smad3 inhibition.

OBJECTIVE: Radiotherapy, an essential modality in cancer treatment, frequently induces fibrotic processes in the skin, including accumulation of extracellular matrix. Transforming growth factor-ß is essential in regulating extracellular matrix gene expression and is dependent on Smad3, an intracellular mediator/transcription factor. Our study characterized the genetic expression involved in extracellular matrix accumulation during radiation-induced fibrosis. We performed Smad3 gene silencing in an attempt to abrogate the effects of radiation. STUDY DESIGN: Laboratory research. SETTING: University laboratory. SUBJECTS AND METHODS: C57 murine dermal fibroblasts were irradiated with 20 Gy RNA isolated (0, 6, 12, 24, 48, 72 hours postirradiation) and mRNA analyzed (reverse transcriptase polymerase chain reaction) for known regulators (Smad3, interleukin-13 [IL-13]), tumor necrosis factor-α [TNF-α]) and mediators of fibrosis (collagen 1A1 [Col1A1]), TGF-ß, matrix metalloprotease-1 and -2 (MMP-1, MMP-2), and tissue inhibitor of metalloprotease-1 (TIMP-1). Smad3 gene expression was silenced using siRNA in an effort to restore an unirradiated gene profile. RESULTS: Following irradiation, there was a steady increase in mRNA expression of Smad3, IL-13, TGF-ß, Col1A1, MMP-2, TIMP-1, with peak at 12 to 24 hours and subsequent decline by 72 hours. TNF-α expression remained elevated throughout. MMP-1 showed minimal expression initially, which decreased to negligible by 72 hours. Inhibition of Smad3 significantly decreased expression of Col1A1, TGF-ß, MMP-2, and TIMP-1. IL-13 and TNF-α expression was not affected by Smad3 silencing. CONCLUSION: We have characterized the early-phase mRNA expression profiles of the major mediators of radiation-induced fibrosis. Smad3 siRNA effectively abrogated the elevation of Col1A1, TGF-ß, TIMP-1, and MMP-2. IL-13 and TNF-α were unaffected by Smad3 silencing and appear to be minor regulators in fibrosis. These findings suggest a therapeutic rationale for Smad3 silencing in vivo.

Inhibition of Smad3 expression in radiation-induced fibrosis using a novel method for topical transcutaneous gene therapy.

OBJECTIVE: To attempt to mitigate the effects of irradiation on murine skin after high-dose radiation using a novel transcutaneous topical delivery system to locally inhibit gene expression with small interfering RNA (siRNA) against Smad3. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Twenty-five wild-type C57 mice. INTERVENTION: In an isolated skin irradiation model, the dorsal skin of C57 wild-type mice was irradiated (45 Gy). Just before irradiation, Smad3 and nonsense siRNA were applied to 2 separate dorsal skin areas and then reapplied weekly. Skin was harvested after 1 and 4 weeks. Smad3 expression were assessed by immunohistochemistry, and collagen deposition and architecture was examined using picrosirius red collagen staining. MAIN OUTCOME MEASURES: Epidermal thickness was measured semiquantitatively at 4 weeks. Radiation-induced fibrosis was measured quantitatively via tensiometry. The Young modulus, a measure of cutaneous rigidity inversely related to elasticity, was determined, with normal irradiated skin serving as a control specimen. RESULTS: Murine skin treated with topical Smad3 siRNA demonstrated effective Smad3 inhibition at 1 week and persistent suppression at 4 weeks. Collagen deposition and epidermal thickness were significantly decreased in skin treated with Smad3 siRNA compared with control irradiated skin. Tensiometry demonstrated decreased tension in Smad3 siRNA-treated skin, with a Young modulus of 9.29 MPa (nonirradiated normal skin, 7.78 MPa) compared with nonsense (control) siRNA-treated skin (14.68 MPa). CONCLUSIONS: Smad3 expression can be effectively silenced in vivo using a novel topical delivery system. Moreover, cutaneous Smad3 inhibition mitigates radiation-induced changes in tissue elasticity, restoring a near-normal phenotype.

Current concepts in the management of the aging forehead in facial plastic surgery.

PURPOSE OF REVIEW: This article reviews the significant recent literature on the constantly evolving approach to surgical rejuvenation of the forehead and brow. RECENT FINDINGS: Recent literature describes a variety of modifications to traditional endoscopic approaches, particularly regarding new permanent and temporary fixation techniques. There is continued effort to deepen our understanding of upper facial anatomy and its relationship to the aging process. As interest and research in this area continue to grow, improved quantification of surgical results becomes important. SUMMARY: There has been significant development and refinement of endoscopic approaches to foreheadplasty. Nonetheless, debate regarding the durability, quality of results, and complications of endoscopic versus open approaches continues. Ultimately, optimal results may be achieved through a variety of surgical techniques, but require a thorough understanding of the anatomic basis of aging, attention to detail, and adequate brow fixation.

Quantitative comparison between microperforating osteotomies and continuous lateral osteotomies in rhinoplasty.

OBJECTIVE: To determine the difference in nasal bone narrowing between 2 techniques: the low lateral intranasal perforating osteotomy technique and the low lateral continuous osteotomy technique. METHODS: A retrospective analysis of preoperative and postoperative photographs to determine the changes of the dorsal width of the nose (width of plateau of the nose, or dorsal nasal highlight) and the ventral width (junction of the flattened surface of the maxilla and the ascending nasal process of the maxilla). RESULTS: Twenty patients underwent continuous osteotomies, and 40 underwent intranasal perforating osteotomies. The continuous osteotomy technique had a preoperative to postoperative decrease in the ventral width of 7.0% (P < .01). The perforating osteotomy technique had a decrease in the ventral width of 3.6% (P < .001). Neither technique resulted in a statistically significant change in dorsal width (P < .25). There was no significant difference in ventral and dorsal narrowing when comparing continuous osteotomies to perforating. CONCLUSIONS: Both the continuous and perforating osteotomy technique resulted in a decrease in the ventral nasal bone width. No statistical difference was found between continuous and perforating osteotomy techniques in the amount of nasal bone narrowing (P < .25).

Orbicularis suspension flap and its effect on lower eyelid position: a digital image analysis.

OBJECTIVE: To evaluate changes in lower eyelid position using digital image analysis in patients who have undergone an orbicularis suspension flap combined with blepharoplasty. METHODS: A total of 68 patients (136 eyes) underwent a lower eyelid orbicularis oculi suspension flap combined with blepharoplasty. Digital image analysis was used to standardize each patient's preoperative and postoperative photographs for accurate objective comparison. The photographs were analyzed for lower eyelid position. RESULTS: The mean (SD) preoperative standardized distance from the center of the pupil to the lower eyelid margin (MRD2) in all procedures was 5.53 (0.74) mm. The mean (SD) postoperative standardized MRD2 was 5.22 (1.0) mm. There was a statistically significant difference in MRD2 position such that the postoperative MRD2 position decreased or the lower eyelid position was elevated by an average of 0.31 mm in comparison to the preoperative position (P < .001). CONCLUSIONS: A well-performed suspension flap can elevate the lower eyelid position to a more natural and anatomically appropriate position. By resuspending the ptotic orbicularis muscle, the suspension flap also reinforces the underlying attenuated orbital septum. Such cases may not achieve the optimum level of rejuvenation if isolated lower eyelid blepharoplasty is performed.

Biomechanical analysis of anchoring points in rhytidectomy.

OBJECTIVE: To quantify tissue tearing force at various anchoring points on the face. METHODS: This is a prospective anatomic study using 4 fresh cadavers of persons aged 60 to 70 years at the time of death, for a total of 8 sides. Standardized 1-cm distances were measured at the various anchor points, and a single 0 Prolene suture loop was tied at each standardized anchoring point. Steady force was applied perpendicular to the plane of the face with a digital hanging scale. The scale was pulled until the suture ruptured the tissue at the anchoring point. The values at which the tissue ruptured were recorded, averaged, and compared. RESULTS: The average tissue force was 7.01 kg for the root of the zygoma vs 3.44 kg for the temporalis fascia (P < .05). The average tissue force was 5.50 kg for infralobular tissue vs 4.09 kg for tissue of the superficial musculoaponeurotic system located 1 cm anterior to the infralobular tissue (P < .05). The force for the fascia of the sternocleidomastoid was 3.89 kg vs 5.57 kg for the mastoid fascia (P < .05). There was a statistically significant difference between vertical bites of the temporalis fascia at 1.90 kg vs horizontal bites of the temporalis at 5.01 kg (P < .05). CONCLUSION: The tissue tearing force varies by location on the face as well as suture orientation.

Oculocardiac reflex associated with a large orbital floor fracture.

A 40-year-old man presented with bradycardia, left eye pain, and intermittent nausea 1 day after blunt trauma to the left orbit. Imaging revealed a large orbital floor fracture with significant herniation of orbital contents but no obvious extraocualar muscle entrapment. Oculocardiac reflex was suspected, and the fracture was repaired surgically within 24 hours of presentation. His bradycardia resolved immediately postoperatively. This case is a unique presentation of the oculocardiac reflex in a large orbital floor fracture with significant herniation of orbital contents but without extraocualar muscle entrapment.

Plating in microvascular reconstruction of the mandible: can fixation be too rigid?

OBJECTIVE: Determine long-term loss of mandible height with use of stress-shielding reconstruction plates for free fibula flap mandible reconstruction. DESIGN: Retrospective single-blinded medical record review. SUBJECTS: Seventy patients who had fibula free flap mandible reconstructions performed for 10 years. Patients who underwent radiotherapy were excluded. METHODS: Review of 70 fibula free flap mandible reconstructions performed for the last 10 years in a city hospital revealed 7 patients (10%) who had resections for benign odontogenic diseases. All had a three-dimensional cast model made, on which the reconstruction plate was bent to the desired shape preoperatively. Free fibula height on panoramic x-ray images taken preoperatively and at 2 and 12 months postoperatively. RESULTS: Seven (10%) patients met criteria for the study. Bone height was maintained at 2 months postoperatively, but at 12 months, there was a statistically significant loss of fibular bone height averaging 20% in the anterior, body, and ramus areas (P < 0.05). Despite this, all patients were considered eligible for dental rehabilitation, and 4 of 7 patients have had osseointegrated implants placed. CONCLUSIONS: As opposed to miniplates, increased resorption may have been due to the stress-shielding phenomenon unique to a reconstruction plates. However, this did not seem to affect the ability to place osseointegrated implants.

Treatment of dorsal deviation.

The deviated nasal dorsum is a complex problem with a variety of proposed solutions. Straightening the deviated nose should be focused on maximizing cosmetic outcome while preserving or improving nasal function. Deviations can occur in one or a combination of the nasal thirds. A simple approach to treatment is to develop a strategy for each third of the nose. Tailoring maneuvers to alleviate problems in each specific third helps the surgeon deal with deviations in an effective and straightforward manner.

Flat panel cone beam computed tomography of the sinuses.

OBJECTIVE: This study aims to compare the image quality and potential diagnostic accuracy of paranasal sinus CT scans generated by flat panel cone beam CT at three specific data acquisition times. STUDY DESIGN: Prospective, single blinded analysis. SUBJECTS AND METHODS: Eleven patients without previous radiologic evaluation were selected based on history and findings suspicious for chronic sinusitis. Each patient was scanned at three different acquisition times: 10, 20, and 40 seconds. A panel of neuroradiologists and otolaryngologists, blinded to the scan acquisition time, individually reviewed images and rated overall image quality and visualization of specific anatomic sites. Image noise values were also calculated. Techniques were compared with a Wilcoxon matched-pairs signed ranks test. RESULTS: Compared to the 10-second acquisition time, the 40- and 20-second acquisition time techniques had significantly better image quality (P < 0.05) and image noise (P < 0.05). No difference in image quality and image noise existed between the 20- and 40-second techniques. No difference in visualization of specific anatomic structures existed between any of the time techniques. CONCLUSION: The quality of flat panel CT imaging of the sinuses directly relates to scan time and thus radiation dose.