Clinical Trial of Alpha and Beta Defensin Skin Care Regimen for Improvement of Periocular Wrinkles.

BACKGROUND: Defensins recruit leucine-rich repeat-containing G protein-coupled receptor 6 positive (Lgr6+) stem cells which ultimately regenerate new basal stem cells, healthy keratinocytes, and nascent hair follicles. Thus, defensins are an exciting, novel therapy for the reversal of skin aging. METHODS: This is a multicenter, prospective, open-label clinical trial. Twenty healthy subjects, aged 45-80, with Fitzpatrick skin types II-IV were enrolled in the study. A skin care regimen containing alpha-defensin 5 and beta-defensin 3 were applied to the face twice daily for 12 weeks. This skin care regimen contains a greater percentage of defensins than that already studied.7 All participants underwent imaging at baseline, day 30, day 60, and day 90. Primary endpoints included investigator scoring on the Fitzpatrick-Goldman wrinkle scale and percent improvement in periorbital wrinkles, laxity, pigmentation, erythema, texture, and radiance. Secondary endpoints were investigator Global Aesthetic Improvement Score (GAIS), subject GAIS, and investigator assessment of tolerability. A final subject questionnaire was completed on day 90.  Results: Based on the Fitzpatrick-Goldman wrinkle scale, a statistically significant improvement was noted in both wrinkling and elastosis from baseline to day 90. 30% of subjects were rated as much improved and 50% of subjects were rated as improved on the physician GAIS at the 90 day follow up. Improvements were noted in all aspects of skin quality including wrinkles, laxity, dyschromia, erythema, texture, and radiance.  Conclusion: The enhanced formula containing increased concentrations of alpha-defensin 5 and beta-defensin 3 is a safe and efficacious topical therapy for the treatment of periorbital rhytids. CITATION: Hartman N, Loyal J, Taub A, et al. Clinical trial of alpha and beta defensin skin care regimen for improvement of periocular wrinkles. J Drugs Dermatol. 2023;22(9):874-880. doi:10.36849/JDD.7184.

Global Expert Opinion on Cryolipolysis Treatment Recommendations and Considerations: A Modified Delphi Study.

Background: Cryolipolysis is an increasingly popular nonsurgical fat-reduction procedure. Published treatment guidance and adverse event (AE) management protocols are limited. Objective: A modified Delphi study aimed to establish global expert consensus on the use of CoolSculpting (Allergan Aesthetics, an AbbVie Company, Irvine, CA), a noninvasive cryolipolysis treatment system. Methods: A literature search informed survey topics for an 11-expert Delphi panel. Panelists completed an online 39-question survey. An interim panel discussion, with open-ended questions and yes/no voting, informed a second survey containing 61 statements, for which panelists rated agreement using a 5-point Likert scale. Topics included treatment outcome and responder definitions, patient evaluation and selection, treatment protocols, patient satisfaction, and AEs. Results: Panelists achieved consensus on 38 final guidelines and recommendations. They reached moderate to complete consensus on 4 statements on defining responders (ie, patients with a range of visible improvement) and 6 statements on patient factors contributing to treatment outcomes (eg, how well the applicator conforms to patient body region). Panelists defined minimum numbers of treatment cycles to achieve visible clinical outcomes for 12 body regions, with moderate to complete consensus on 31 statements. They achieved a strong to complete consensus on 7 statements about patient satisfaction (eg, importance of patient expectations, visible improvement, and before-and-after photographs). Panelists defined management strategies for AEs, with moderate to complete consensus on 15 statements. Conclusions: A modified Delphi process yielded multiple guideline recommendations for cryolipolysis, providing a needed resource for the broad range of clinicians who perform this noninvasive fat-reduction procedure.

Ultrasound Evaluation of a Single Treatment With a Temperature Controlled Multi-Frequency Monopolar Radio Frequency Device for the Improvement of Localized Adiposity on the Abdomen and Flanks

BACKGROUND AND OBJECTIVES: Energy modalities used for fat reduction include cryotherapy, focused and unfocused ultrasound, radiofrequency, and laser. Two devices have been proven to reduce fat layer thickness using ultrasound as measurement after a single treatment. We hypothesized that a novel, high frequency monopolar radiofrequency device could increase the fat temperature enough to reduce its thickness as measured by ultrasound, without excessively increasing the temperature of the skin, leading to a safe, tolerable, and clinically relevant reduction of fat. STUDY DESIGN/MATERIALS AND METHODS: A high frequency monopolar radiofrequency platform was used to treat twelve patients on the abdomen or flanks (truSculpt® 3D, Cutera, Brisbane, CA). Each patient received one treatment session, consisting of 15-minute increments for four areas (60 minutes total). Each area (approximately 144 cm2) was treated with a gliding handpiece technique to a skin temperature of 44-45˚C, correlating to in vivo measurements of the subcutaneous layer of >45˚C. Patients were evaluated at eight- and twelve-weeks following treatment. Clinical efficacy was measured using 360˚ positioned clinical photography. Fat layer reduction was measured with ultrasound. Safety was assessed by the treating physician; patient comfort was assessed during treatment via a 10-point pain scale. RESULTS: All patients responded to treatment. Ultrasound measurements indicated mean fat layer reduction of 4.6 mm, which correlated with a 24% reduction in fat layer thickness at 12 weeks. A significant improvement was noted between the 8-week and the 12-week follow up. A high level of inter-patient consistency was achieved with most patients (10/12= 83%) having an average fat thickness reduction of >20%. No adverse events were observed, and pain scores during the treatment session ranged from 2 to 4 out of 10. CONCLUSION: High frequency monopolar radiofrequency device produced consistent and statistically significant fat thickness reduction from a single 60-minute treatment session, with minimal discomfort and no demonstrated side effects. Results are comparable to other hypo- and hyper-thermic fat treatment technologies. KEY WORDS: fat reduction, radiofrequency, monopolar RF, fat thickness reduction, body sculpting J Drugs Dermatol. 2020;19(1):28-34. doi:10.36849/JDD.2020.4568

The Treatment of Acne Scars, a 30-Year Journey.

Over the past 30 years, the treatment of acne scars has undergone changes that have been significantly influenced by the concurrent development of new devices. The advent of fractional resurfacing lasers was a watershed moment for acne scarring therapy. The author recounts a career history of considerations of acne scarring treatments as well as the literature supporting the experiences causing changes in practice. Fractional ablative and nonablative lasers, sublative radiofrequency, picosecond lasers, microneedling with and without radiofrequency and fillers are the bulk of the treatments covered, along with a discussion of combination therapy. A practical algorithm for acne scarring for selection of treatment modalities is presented.

Stem Cells in Dermatology and Anti-aging Care of the Skin.

Multipotent stem cells have paved the way for new applications and deeper understanding in regenerative medicine and the pathophysiology of aging. During skin aging, cumulative photodamage, exhaustion of endogenous stem cell populations, mechanical stress, and increased fibrosis lead to skin with decreased epidermal thickness and compromised dermal integrity. Specific stem cells in the hair follicle create new keratinocytes after activation by defensin peptides, released by neutrophils during wounding. Studies pertaining to defensin peptides' efficacy on skin aging have been published, highlighting their potential as a new therapy for skin rejuvenation.

Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation.

BACKGROUND/OBJECTIVES: Anti-aging strategies utilizing stem cells are in the forefront. Alpha and beta defensins are natural immune peptides that have been shown to activate an LGR6-positive stem cell locus in the hair follicle, identified as the source of most new epidermal cells during acute wound healing. We investigated the ability of biomimetic alpha and beta defensin molecules, supplemented with supportive cosmetic ingredients, formulated into three skin care products, at improving the structure and function of aging skin. METHODS: A participant- and investigator -blinded, placebo-controlled, multi-center trial was performed in outpatient settings. Forty-four healthy female subjects, aged 41-71 years, skin types I-V, completed the study with 2/3 receiving full formula and 1/3 receiving the placebo formula. A skin care regimen of 3 products (serum, cream, and mask) containing alpha-defensin 5 and beta-defensin 3, and other cosmetic ingredients, was applied to the face, post-auricular, and neck skin two times per day for 12 weeks in those receiving full formula, whereas the placebo group received the identically packaged regimen without the active ingredients. Methods of evaluation included histopathology and immunohistochemistry (7 subjects), clinical evaluation of pores, superficial and deep wrinkles based on Griffiths scale, and high-resolution photography (all subjects). In addition, a subset of 15 patients were evaluated with the QuantifiCare system (3-dimensional imaging and skin care scores for evenness, pores, oiliness) and Cortex measurements (high-resolution skin ultrasound, TEWL, elasticity, color, and hydration). Data points for evaluation included baseline, 6 weeks, and 12 weeks. All patients used the same sunscreen and cleanser, which was provided to them. RESULTS: The full formula regimen caused a significantly (P equals 0.027) increased thickness of the epidermis as seen in histology, not seen in the placebo group, with no signs of inflammation. No excessive cell proliferation was detected in either group as measured by Ki67-immunohistochemistry. Reduction in visible pores, superficial wrinkles, oiliness, pigmentation, and improvement of skin evenness, were statistically significant. A trend for improvement was also observed in skin elasticity, TEWL, and hydration; these did not achieve statistical significance. Ultrasound and histopathology demonstrated increases in dermal thickness in individual patients, without statistical significance. Comprehensive improvement in all 5 parameters, including visible pores, hyperpigmentation, superficial and deep wrinkles, and epidermal thickness, was statistically significant when the subset of participants assigned for histology in full formula group was compared with the placebo group participants. CONCLUSIONS: A 3-product skin care regimen containing alpha and beta defensins globally improves the visual appearance and structure of aging skin without irritation, dryness, or inflammation. Specifically, this regimen increases epidermal thickness, reduces appearance of pores, reduces wrinkles, and reduces melanin. This skin care regimen stimulates rejuvenation without evidence of increase of a marker of carcinogenic stimulation. This data is consistent with the hypothesis that a defensin-containing skin care regimen activates the body's own dormant stem cells to generate healthy new epidermal cells.

J Drugs Dermatol. 2018;17(4):426-441.

Longitudinal associations between self-regulation and the academic and behavioral adjustment of young children born preterm.

Much of the research to date about the structure of self-regulation in early childhood has been conducted with low medical risk samples, with the general conclusion that self-regulation can be separated into overlapping executive function and effortful control factors that differentially predict child outcomes. We examined the factor structure of 36-month self-regulation among children born prematurely (n = 168) and the extent to which self-regulation predicted maternal ratings of children's socioemotional and academic competence when they were six years of age. Statistical analyses revealed a single self-regulation factor for this high neonatal risk sample, and this self-regulation factor mediated associations between early sociodemographic risk and mothers' ratings of academic competence and externalizing problems. Our findings suggest that early intervention research with children born preterm should focus on promoting supportive early environments, particularly parental sensitivity to infant cues.

Advancing the Care of Post-Acne Scarring: Expert Insights Into New Treatment Options.

Most patients with acne have some degree of facial scarring even after their acne resolves, extending the period of psychosocial distress. Unfortunately, management of acne scars remains challenging. Many treatments for post-acne scarring including chemical peels, skin needling, laser resurfacing, surgical repair, subcision lifting, and punch elevation lifting, are limited by moderate and unpredictable results, significant morbidity, and substantial patient investments in time and money. The most recent addition to the armamentarium is tissue augmentation with soft tissue fillers, including a recently approved polymethylmethacrylate-collagen filler. Matching individual patient needs to the appropriate treatment is crucial. While many patients with acne scars have unrealistic expectations about treatment outcomes, open, honest, and realistic dialogue regarding their treatment options and concerns can facilitate realistic expectations. This article is based on a consensus discussion by the authors, who all have experience managing post-acne scarring, as well as the content of a series of live CME-accredited symposia in connection with major dermatology meetings.

J Drugs Dermatol. 2016;15(5):518-525.

Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies present in HA5 promotes restoration of endogenous epidermal HA while delivering instant smoothing effects.

New Methods for the Clinical Enhancement of Photodynamic Therapy.

The prolonged incubation time of Photodynamic Therapy (PDT) as well as the need for two treatments to achieve high efficacy have motivated physicians to experiment with treatment parameters and PDT enhancements in order to maximize results and practicality. This review explores recent published strategies including occlusion, temperature elevation, pretreatment with topical 5-FU, and microneedle or laser-assisted reduction of the stratum corneum barrier. All of these innovations improve efficacy, reduce the need for multiple treatments or both, although there are concomitant increases in post-procedure side effects.

A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint.

BACKGROUND: A prospective, randomized, double-blind, multicenter, Phase III trial of incobotulinumtoxinA using new Food and Drug Administration endpoints. OBJECTIVE: To investigate the efficacy and safety of a single dose of incobotulinumtoxinA for the treatment of glabellar frown lines. MATERIALS AND METHODS: Two hundred seventy-one subjects with moderate to severe glabellar frown lines at maximum frown-as assessed by an investigator according to the facial wrinkle scale (FWS)-were randomized 2:1 to receive one treatment of 20 U of incobotulinumtoxinA or placebo, respectively, and assessed over 120 days. The primary efficacy variable was a composite endpoint consisting of patients who were 2-point or more responders at maximum frown on Day 30 according to the investigator's rating on the FWS, and 2-point or more responders at maximum frown on Day 30 according to the patient's assessment on a 4-point scale. Safety analyses were performed throughout the study. RESULTS: IncobotulinumtoxinA was statistically significantly more efficacious than placebo using a new rigorous composite endpoint (p < .0001). CONCLUSION: A single dose of 20 U of incobotulinumtoxinA is superior to placebo in the treatment of glabellar frown lines at Day 30 and is well-tolerated.

Cheek augmentation improves feelings of facial attractiveness.

OBJECTIVE: Aesthetic fillers aim to rejuvenate the aging face, but the true end goal is to help patients feel better about their appearance. Cheek augmentation seems to elicit immediate recognition of an improved appearance. This study aims to quantify that impression. METHODS: 10 women aged 40 to 60 years were not preselected but were the first 10 women willing to undergo the study who fit the inclusion and exclusion criteria. Prior to receiving the filler, participants were asked to rate on a visual analog scale (VAS) from 1 to 6 how they felt about their appearance. Each woman received 1.0 cc of hyaluronic acid filler (Perlane, Medicis Corporation, Phoenix, AZ) into each cheek. Two weeks later they returned for photos and to complete the same VAS scale. RESULTS: Seven of ten women felt 0.5 to 2 points better about their appearance as measured by their VAS responses. CONCLUSION: Cheek augmentation improves how a woman feels about her attractiveness.

Facial tightening with an advanced 4-MHz monopolar radiofrequency device.

BACKGROUND: Over the past 10 years, radiofrequency (RF) technology has been utilized for nonablative treatments for the treatment of rhytides and skin laxity. This manuscript reviews the scientific background of collagen synthesis in vivo and in response to RF energy as well as a clinical study of 17 patients receiving a series of facial treatments with a 4-MHz monopolar RF (Pellevé, Ellman International, Inc, Oceanside, NY). Clinical methods, results, and a review of the literature for RF aesthetic treatments of the face are presented. METHODS: Seventeen patients were treated in one site with 6 total treatments scheduled as follows: 1 session was performed every 15 days for 2 consecutive sessions, 1 session every month for 2 consecutive sessions, and 1 session every 2 months for 2 consecutive sessions. Both the treating physician and the patients via live viewing and comparison with baseline photographs performed assessment of results. Results are reported as averages across the 17 patients. RESULTS: Two weeks after the first treatment, patients noted an overall average of 25% to 30% improvement. Just before the last or sixth treatment, there was an average of 50% improvement noted by the physician, with patients ranking an average self-improvement of 48%. The treating physician rated average improvement of 46% compared with baseline, whereas the patients ranked average improvement of 30% compared with baseline at 1 year after treatment was initiated (6 months after the final treatment). Patients find this treatment to be very well tolerated, with minimal to no discomfort and no downtime or significant side effects. CONCLUSIONS: The Pellevé 4-MHz monopolar RF device is effective, safe, and very well tolerated for treating laxity, texture, and wrinkles of the skin without complication or discomfort. Evidence in the literature supports the scientific mechanism of action of acute collagen modification and continued neocollagenesis observed with the system. In this cohort, patients maintain approximately 50% improvement on average at 6 months and a 30% to 50% improvement 1 year after beginning the treatments, 6 months after completion.

A randomized, blinded, bilateral intraindividual, vehicle-controlled trial of the use of photodynamic therapy with 5-aminolevulinic acid and blue light for the treatment of actinic keratoses of the upper extremities.

BACKGROUND/OBJECTIVE: Actinic keratoses (AKs) on the upper extremities are difficult to treat. This study compares the efficacy and tolerability of photodynamic therapy (PDT) using 20% 5-aminolevulinic acid solution (ALA) and blue light versus ALA vehicle and blue light for the treatment of AKs of the dorsal hand and forearm. METHODS: Subjects were treated twice at an eight-week interval by ALA with blue light on one hand and forearm and with ALA vehicle and blue light on the contralateral hand and forearm. ALA incubation time was two hours under occlusion. Efficacy and tolerability were compared. RESULTS: The mean lesion count reductions (58.4 ± 22.2% and 24.8 ± s20.6% four weeks after the second treatment for the ALA and vehicle-treated sides, respectively) differed significantly (P=0.0004). Eleven of 15 subjects (73%) in the ALA-treated side achieved at least 50 percent reduction in lesion count compared to only two subjects (13%) in the vehicle-treated side four weeks after the second treatment. The difference was significant (P=0.0143). Photodamage grade reduction was also significant (P=0.0309) after the second treatment. Subject satisfaction was moderate to very satisfied (86.7%) on the ALA-treated side. Transient adverse events were significantly greater on the ALA-treated side for erythema (P=0.0011), edema (P=0.0199) and stinging and burning (P=0.0016) 48 hours after the first treatment. CONCLUSIONS: Two sessions of PDT using ALA with blue light is a moderately effective, well-tolerated treatment of actinic keratoses of the dorsal hand and forearm.

Treatment of Acne Scars of Skin Types II to V by Sublative Fractional Bipolar Radiofrequency and Bipolar Radiofrequency Combined with Diode Laser.

OBJECTIVE: This study evaluated the safety and efficacy of sublative fractional bipolar radiofrequency and bipolar radio frequency combined with diode laser for the treatment of both superficial and deep acne scars in patients with skin types II to V. DESIGN: Prospective, single-center study. Subjects received up to five treatments with sublative fractional bipolar radiofrequency and bipolar radiofrequency combined with diode laser. Treatments were directed to at least two facial (forehead, perioral, cheeks) and/or neck areas with acne scars at four-week intervals. Treatment parameters on each subject were based on skin type and on skin responses to test spots on the target area just before treatment. SETTING: Physician office. PARTICIPANTS: Subjects (n=20, aged 40.7±10.5 years [mean ± SD], skin types II-V) with acne scars and without acne lesions enrolled in this prospective study. MEASUREMENTS: RESULTS were evaluated just before each treatment and at four and 12 weeks after the final treatment using the Goodman Scar Scale, a quantitative method of evaluating scars that attempts to reduce grading subjectivity, as well as by patient satisfaction. RESULTS: Acne scars improved significantly one month after three treatments and improvement persisted for at least 12 weeks after the fifth treatment. Improvement was not affected by skin type. Adverse effects were limited to transient erythema and edema. CONCLUSION: The combination of diode laser and bipolar radiofrequency energy device in addition to fractionated sublative radiofrequency is a safe and statistically significantly effective combined modality for the treatment of both superficial and deep acne scars in patients with skin types II to V with minimal downtime and no significant side effects.