Randomized, Controlled, Multicentered, Double-Blind Investigation of Injectable Poly-L-Lactic Acid for Improving Skin Quality.

BACKGROUND: Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss. OBJECTIVE: To evaluate the effect of repeated PLLA injections on skin quality. METHODS: Forty healthy women were enrolled in this randomized, controlled, double-blind, multicenter study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections, into both sides of the face. Follow-up visits were at 6, 9, and 12 after the last treatment. Assessments included biophysical measuring instruments, live ratings, patient questionnaires, and rating of standardized pictures by a blinded evaluator. RESULTS: At the 12-month follow-up, there was a statistically significant increase of skin elasticity and hydration in PLLA-treated subjects and a decrease in transepidermal water loss in both groups. Pigmentation, erythema, and pore size were significantly decreased, whereas radiance and smoothness were significantly increased at 12 months per blinded investigator rating in this group. No treatment-related adverse events occurred. CONCLUSION: Repeated PLLA treatments may improve skin quality in a time-dependent manner.

An Advanced, Physician-Strength Retinol Peel Improves Signs of Aging and Acne Across a Range of Skin Types Including Melasma and Skin of Color

Background: Facial chemical peels are highly sought after by patients with photodamage, acne, and melasma. An advanced, physician-strength superficial peel, containing 3% retinol with other firming and volumizing ingredients was developed to exfoliate, improve the appearance of fine lines and wrinkles, and plump and firm skin, while promoting a bright, even complexion. Objective: A clinical study was conducted to evaluate the tolerability, safety, and efficacy of the 3% retinol peel with a supportive homecare regimen across a range of peel candidates, females aged 18-65 years, with photodamage, acne, hyperpigmentation or melasma, and skin of color, over a series of 2-4 peels. Method: The 3% retinol peel formulation was administered under physician direction in 6-week intervals. Subjects with photodamaged skin, acne, hyperpigmentation/melasma, or skin of color (Fitzpatrick skin types IV-VI) received 2-4 peels along with a supportive homecare regimen. Dermatologist grading, self-assessment, and digital photography documented tolerability and efficacy parameters. Results: 24 subjects participated in the study with a total of 78 peels administered (Photodamage group, n=14 [with an Acne subgroup, n=5]; Melasma group, n=5; Skin of Color, n=5). The 3% retinol peel along with the homecare regimen was well tolerated under physician direction in all skin types and conditions assessed. Obvious peeling was noticeable in many subjects 3 days post-peel and resolved by day 7. In the photodamaged group, dermatologist clinical grading of fine lines, wrinkles, pore size, laxity, mottled pigmentation, lack of clarity/radiance, and overall photodamage was significantly improved (P<0.05). Benefits were observed in all groups and supported by self-assessment. Digital photography demonstrated tolerability in the days immediately post-peel, along with benefits to photodamage. Conclusion: The 3% retinol superficial peel was well tolerated and an efficacious cosmetic treatment under physician supervision in subjects of all skin types to firm skin, improve fine lines and wrinkles, and promote a bright, even complexion. J Drugs Dermatol. 2019;18(9):918-923.

A prospective, randomized, double-blinded, split-face pilot study comparing Q-switched 1064-nm Nd:YAG versus 532-nm Nd:YAG laser for the treatment of solar lentigines.

Treating photoaging with laser technologies has increased in popularity due to their efficacy, minimal downtime, and side effects. New Q-Switched (QS) Nd:YAG lasers' frequency doubled with 532 nm wavelength can both target epidermal chromophores as well as stimulate collagen production. The objective of this study was to compare single-pulsed 1064-nm Nd:YAG with dual-pulsed 532-nm/1064-nm QS laser for reducing solar lentigines. Ten subjects with solar lentigines were enrolled in this prospective, randomized, double-blind, split-face study. Subjects received six laser treatments (half-face dual, half single) at 2-week intervals. Blinded investigator and subject assessments were conducted 1 month posttreatment to evaluate global skin improvement, safety, and patient satisfaction. Blinded investigator assessments showed statistically significant improvement in the dual-treated side. Patient satisfaction was also statistically significantly increased in the dual-treated side. In conclusion, dual laser treatment can result in superior and safe global improvement of photoaging.

A randomized, single-blind, study evaluating a 755-nm picosecond pulsed Alexandrite laser vs. a non-ablative 1927-nm fractionated thulium laser for the treatment of facial photopigmentation and aging.

Background: Laser toning is one of the most popular strategies to treat facial photopigmentation and aging. Several laser modalities, including fractional non-ablative, Q-switched (QS) lasers and new generation picosecond lasers have been used for this indication. However, there is paucity of head to head comparisons of older generation of lasers with new ones. Objective: To compare a 755 nm picosecond pulsed alexandrite laser with a non-ablative 1927 nm fractionated thulium laser for the treatment of facial photopigmentation and aging through a randomized, single-blind study. Materials and methods: 20 subjects (skin types I-IV) were randomized to receive either four 755-nm picosecond alexandrite laser treatments, spaced 3 weeks apart, or two dual wavelength thulium fiber fractionated 1550/1927 nm laser treatments, spaced 6 weeks apart. Follow-up assessment visits occurred 4 and 12 weeks after the last study treatment. Results: At the 4- and 12-week follow-up, both groups showed significant improvement of photoaging, pigmentation, skin quality according to the investigator and subjects assessments. When comparing the two groups, subjects in 755 nm group had statistically significant greater improvement in investigator assessments of photoaging/skin quality and subject satisfaction than those in the 1927 nm group. Conclusion: Both the non-ablative 1927 and 755 nm picosecond laser can improve facial photopigmentation, but the latter can yield superior results with less pain and side effects according to patient and investigator assessments.

Brightening and Improvement of Facial Skin Quality in Healthy Female Subjects With Moderate Hyperpigmentation or Dark Spots and Moderate Facial Aging

Objective: To evaluate the safety and efficacy of ISDINCEUTICS Melaclear® serum (Barcelona, Spain) on skin brightness, skin quality, and signs of facial aging. Design: This was a single-center, observational, open label, prospective clinical study. Ten healthy females (ages 30-70) with moderate signs of facial aging and moderate photodamage (hyperpigmentation and/or sun spots) were enrolled. Treatment consisted of topical twice-daily application of Melaclear serum, morning and evening, to the face and neck for 12 weeks. Efficacy assessments were conducted at weeks 4, 8, and 12. Standardized photographs, expert investigator grading, tolerability assessments, and subjects reported outcome measures were performed at all visits. Adverse events (AEs) were monitored throughout. Visual assessments of the face and neck included grading for radiance, smoothness, pigmentation, erythema, pore size, skin clarity, skin brightness, skin tone, luminosity, skin complexion, photodamage, hyperpigmentation, wrinkle severity, pigment via the modified Melasma Area and Severity Index (MASI), and overall global aesthetic improvement (GAIS). Safety and tolerability assessments included an evaluation of face and neck for stinging/burning by the subject and dryness, scaling, edema, and erythema by the treating investigator at all study visits. Results: All enrolled subjects completed the study. At the 8 and 12-week follow up visit, there was a statistically significant improvement in the investigator GAIS (1.1 and 1.3, respectively) for the face from baseline. MASI scores were all statistically significantly reduced in the face from week 8 onward relative to baseline. In addition, all skin quality parameters assessed in the face significantly improved from baseline to week 12. Subject global aesthetic improvement scale scores (SGAIS) were also significantly improved at week twelve from baseline (1.8 change) as were skin quality assessments. The average rating for patient satisfaction was 2, or "satisfied" with the overall treatment effectiveness from week 4 onwards. For the neck none of the investigator or subject assessments improved significantly at any time point. No adverse events, tolerability events, or unexpected side effects were observed or reported for any of the subjects. Conclusion: Twice a day treatment of women with moderate facial photoaging and hyperpigmentation with Melaclear serum can significantly improve skin quality, reduce the severity and intensity of hyperpigmentation, and improve signs of photodamage within 12 weeks without any side effects. J Drugs Dermatol. 2018;17(12):1310-1315.

Single-Center, Double-Blind, Randomized, Placebo-Controlled, Study of the Efficacy and Safety of a Cream Formulation for Improving Facial Wrinkles and Skin Quality.

INTRODUCTION: Several therapeutic modalities from topicals to chemical peels and energy-based devices are available to improve skin quality and reduce the appearance of wrinkles in the face and neck area. OBJECTIVE: The objective of this single-center, double blinded, placebo-controlled study was to evaluate the safety and efficacy of Nimni Cream by Hydropeptide® on skin quality and wrinkles. METHODS: 20 patients were randomized in a 3:1 ratio to use either Nimni Cream by Hydropeptide or placebo starting with twice a week application and increasing to daily for 8 weeks. Patient and investigator assessments were conducted on week 4 and 8. RESULTS: At week 8, blinded and treating investigator assessments showed a statistically significant improvement in global aesthetic improvement scale assessments in the active group for the face, but not the neck area. There was also a trend towards improvement in Fitzpatrick Wrinkle Scale scores in the active, but not placebo group, at both time-points, for the face and neck, but the results were not statistically significant. The majority of patients were satisfied with the results and no adverse effects were reported. CONCLUSION: Nimni Cream by Hydropeptide is safe and effective for improving skin quality in the face and can be considered a satisfactory therapeutic option adjuvant to aesthetic procedures. J Drugs Dermatol. 2018;17(6):664-669.

Prospective, pilot evaluation of the performance of nanofractional radiofrequency for improvement of skin texture via skin resurfacing.

BACKGROUND: The latest generation of radiofrequency, nanofractional radiofrequency, allows the heat energy to be delivered through the use of pins or needles as electrodes, facilitating increased efficacy and reduced pain, downtime, and side effects. OBJECTIVE: The objective of this prospective pilot clinical study was to evaluate the efficacy of nanofractional radiofrequency in skin resurfacing. METHODS AND MATERIALS: Seventeen subjects were enrolled in the study, and each received three nanofractional radiofrequency (160-pin tip) treatments in the facial area at 3-week intervals. Follow-up visits were scheduled at 1 and 2 months after the final treatment. Clinical photography, patient, and investigator assessments were conducted during the treatment visits and follow-up. RESULTS: All subjects completed the study. At the 1- and 2-month follow-up, there was a moderate to significant improvement (2.6 and 3.5, respectively, P = .01) according to the investigator global esthetic improvement scale rating. Most subjects reported that they were satisfied or very satisfied with the outcome and level of comfort. CONCLUSION: Nanofractional radiofrequency is a safe and effective strategy for improving texture, tone, and skin laxity with high patient satisfaction and tolerable safety profile.

Efficacy and safety of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults: A pooled analysis of two phase 2 clinical trials.

BACKGROUND AND PURPOSE: There is a need for new treatment options for moderate-to-severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, has recently been approved for this indication. METHODS: A pooled analysis of a phase 2a (NCT01548404) and a phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2 weeks (q2w) in adults with moderate-to-severe AD. RESULTS: Dupilumab significantly improved clinical outcomes in both analyses at week 12. Itch was significantly improved in the pooled analysis as measured by peak pruritus Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p < .0001 vs. placebo at week 12); similar results were shown for the q2w dose. Dupilumab had an acceptable safety profile. CONCLUSIONS: Consistent with previous studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at week 12, including improvements in itch and sleep loss. IMPLICATIONS FOR PRACTICE: Subcutaneous dupilumab is an effective new treatment option for adults with moderate-to-severe AD.

Characterization of total and active matrix metalloproteinases-1, -3, and -13 synthesized and secreted by anterior cruciate ligament fibroblasts in three-dimensional collagen gels.

Anterior cruciate ligament (ACL) injury and subsequent reconstructive surgery is increasing with an estimated 200,000 reconstructions performed yearly in the United States. Current treatment requires reconstruction with autograft or allograft tissue with inherent disadvantages. The development of tissue-engineered ligament replacements or scaffolds may provide an alternative treatment method minimizing these issues. The study of ligament fibroblast catabolic and anabolic responses to mechanical and biologic stimuli in three-dimensional (3D) cell culture systems is critical to the development of such therapies. A 3D cell culture system was used to measure the total content and active forms of matrix metalloproteinases (MMPs)-1, -3, and -13 to assess the potential role of the mechanical environment in regulation of matrix turnover by ligament fibroblasts. The production, retention, and secretion of MMPs by ACL fibroblasts in 3D culture were measured over a 14-day period. The total MMP content and MMP activity were determined. The level of all MMPs studied increased over 7-10 days and then reached a steady state or decreased slightly in both the collagen gels and the media. This system will now permit the study of externally applied cyclic and static strains, strain deprivation, and the potential combined role of the cytoskeleton and MMPs in matrix turnover in ligaments.

Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation.

Activation of myeloid cells by orthopedic particulate debris is a key event in the pathogenesis of periprosthetic osteolysis and implant loosening after total joint replacement (TJR). Several lines of evidence implicate NACHT, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome-mediated production of interleukin 1 beta (IL-1ß) in the pathogenesis of clinical disorders ascribable to foreign particulate materials, including asbestos, silica, and urate crystals. Recent reports indicate that orthopedic polymer products and metallic particulates and ions may activate the same pathway. Here, we investigated the contribution of the NALP3 inflammasome to the pathogenesis of peri-implant osteolysis. Pharmaceutical and genetic perturbations of caspase-1 and inflammasome components were used to assess the role of the NALP3 inflammasome in IL-1ß production and osteoclast formation by human monocytes and mouse macrophages in response to polymethylmethacrylate (PMMA) particle phagocytosis. The role of caspase-1 in a mouse calvarial model of particle-mediated osteolysis was assessed using µCT. Phagocytosis of PMMA particles induces caspase-1 dependent release of IL-1ß from human monocytes and mouse macrophages. Importantly, using macrophages from mice deficient in components of the NALP3 inflammasome, we show PMMA-induced IL-1ß production is strictly dependent on these components. Mice lacking caspase-1, the sole effector of the NALP3 inflammasome, show reduced orthopedic wear particle-induced calvarial osteolysis compared to wild-type controls. Absence of NALP3 inflammasome components fails to alter osteoclast formation in vitro. Our findings identify the NALP3 inflammasome as a critical mediator of orthopedic wear-induced osteolysis and as a viable therapeutic target for the treatment of periprosthetic osteolysis.

Activation of MKK3/6, SAPK, and ATF-2/c-jun in ACL fibroblasts grown in 3 dimension collagen gels in response to application of cyclic strain.

Signal transduction pathways involved in response to cyclic tensile strain and strain deprivation in anterior cruciate ligament (ACL) fibroblasts grown in 3D collagen gels were investigated. Application of cyclic tensile strain resulted in significant activation (phosphorylation) of MKK3/6, SAPK and their downstream target transcription factors, ATF-2 and c-jun, while strain deprivation resulted in a decrease in these kinases and transcription factors. These data suggest that ACL fibroblasts cultured in 3D collagen gels respond to the mechanical environment and provide a useful system for determination of the molecular mechanisms involved in the regulation of proliferation and matrix turnover by mechanical load.

Troponin T expression in trout red muscle correlates with muscle activation.

Red or aerobic muscle from the anterior of rainbow trout Oncorhynchus mykiss activates (generates force) more quickly than that from the posterior. TnT is a component of the troponin complex that modulates muscle activation once Ca(2+) is bound. Since trout express at least two forms of TnT in their red muscle (S1 and S2), the differential expression of these two forms was predicted to explain variations in contractile properties. TnT isoforms from trout muscle were identified through hydroxy-apatite chromatography of purified myofibrillar proteins followed by SDS-PAGE. Western blots employing a mammalian anti-troponin T monoclonal antibody were used to identify TnT isoforms. The relative expression of the two isoforms of TnT was then examined at seven longitudinal positions from each of three fish using SDS-PAGE and densitometry on the silver-stained TnT bands. A significant shift in expression was detected from anterior to posterior in all three fish with TnT S1 becoming more dominant in the posterior red muscle. As predicted, a shift in TnT expression was associated with the decrease in activation rate along the length of the fish. This study was then extended to include a different species of salmonid, brook trout Salvelinus fontinalis, to explore the generality of TnT modulation of muscle activation. Muscle contractile properties were determined from anterior and posterior muscle, and relative expression of S1 and S2 was determined. Unlike rainbow trout, there is no consistent longitudinal pattern of muscle activation in brook trout: some fish have kinetically faster muscle in the anterior, some in the posterior. Similarly, there is no consistent pattern of TnT expression. Individual analysis of muscle activation and TnT expression in brook trout provides insight into the role of TnT in modulating muscle activation in slow fish muscle.