A Multicenter, Randomized, Evaluator-Blinded Study to Examine the Safety and Effectiveness of Hyaluronic Acid Filler in the Correction of Infraorbital Hollows.

BACKGROUND: Hyaluronic acid injections are increasingly used for correction of infraorbital hollows (IOHs). OBJECTIVES: Examination of effectiveness (IOH correction) and safety of Restylane® EyelightTM hyaluronic acid (HAEYE, Galderma, Uppsala, Sweden) injections. METHODS: Subjects with moderate/severe IOHs, assessed using the Galderma infraorbital hollows scale (GIHS), were randomized to HAEYE injections (via needle/cannula) (Day 1+optional Month-1 touch up) or no-treatment control. Primary endpoint was blinded evaluator-reported Month-3 response, defined as ≥1-point GIHS improvement from baseline (both sides, concurrently). Other endpoints examined investigator-reported aesthetic improvement (GAIS), subject-reported satisfaction (FACE-Q™ satisfaction with outcome; satisfaction questionnaire), and adverse events. RESULTS: Overall, 333 subjects were randomized. Month 3 GIHS responder rate was significantly higher with HA-EYE (87.4%) versus control (17.7%; p<0.001), and comparable between HA-EYE-needle and HA-EYE-cannula groups (p=0.967). HAEYE GAIS responder rate was 87.5-97.7% (Months 3-12). Mean FACE-Q Rasch-transformed scores were 64.3-73.5 (HAEYE) versus 14.1-16.2 (control) through Month 12. Subjects reported looking younger (≥71%) and less tired (≥79%) with reduced under-eye shadows (≥76%) and recovered within 3-5 hours, post-treatment. Efficacy was maintained through Month 12 (63.5% GIHS responders) and through Month 18, after Month-12 retreatment (80.3% GIHS responders; 99.4% GAIS responders; FACE-Q scores: 72.5-72.8). Forty subjects (12.7%) reported typically mild adverse events (4.9% HAEYE-needle; 20.9% HAEYE-cannula). CONCLUSION: HAEYE treatment was effective in correcting moderate/severe IOHs at the primary endpoint (Month 3). Efficacy was sustained through Month 12 after first treatment for 63.5% and through Month 18 for 80.3% (after one retreatment) with needle or cannula administration. Safety outcomes were reassuring.

Long-Term Efficacy and Tolerability of a Daily Serum for Rejuvenation and Prejuvenation of Facial Skin.

Onjectives: To evaluate the long-term efficacy and tolerance of an anti-aging daily serum (AADS) when used twice-daily over 12 weeks by women with moderate skin fatigue and overall photodamage. The treatment targeted rejuvenation and prejuvenation of the facial skin. Method: This was an institutional review board (IRB)-approved, randomized, single-center, double-blinded, vehicle-controlled (VC) study involving healthy subjects. Seventy female subjects were recruited aged 30 to 60 years old, Fitzpatrick skin types I to VI, with moderate overall photodamage, facial skin dullness, and skin firmness. Subjects underwent a 1-week washout period with a skincare regimen consisting of a cleanser, moisturizer, and sunscreen. Subjects were randomized to apply the AADS or VC to their face including upper eyelid, twice-daily for 12 weeks. Long-term efficacy and tolerance, self-assessment questionnaire, and VISIA® clinical photography were performed at baseline, weeks 4, 8, and 12.  Results: Statistically significant improvements in live, clinically graded efficacy parameters were demonstrated at post-baseline timepoints. Facial skin firmness, radiance, and roughness showed the most significant improvements at week 12. Analysis between treatments, in both live and photo-graded parameters, demonstrated merit of the AADS. VISIA® analysis further substantiated the efficacy of the AADS vs the VC. The AADS was well tolerated by clinical scoring and rating by subjects.  Conclusion: The AADS is effective in improving skin fatigue and overall photodamage after 12 weeks of twice-daily application compared with the VC. The AADS is a possible skincare solution for patients seeking a serum with skin rejuvenation and prejuvenation benefits. Citation: Reid L, Palm MD, Kononov T, et al. Long-term efficacy and tolerability of a daily serum for rejuvenation and prejuvenation of facial skin. J Drugs Dermatol. 2023;22(9):917-924. doi:10.36849/JDD.7393.

A Randomized, Multicenter, Evaluator-blind Study to Evaluate the Safety and Effectiveness of VYC-12L Treatment for Skin Quality Improvements.

BACKGROUND: Skin quality may be assessed by degrees of skin smoothness, fine lines, and hydration. VYC-12L is a recently developed hyaluronic acid filler to improve skin quality. OBJECTIVE: This was a randomized, evaluator-blind study assessing safety and effectiveness of intradermal VYC-12L treatment for improving cheek skin smoothness, fine lines, and hydration. METHODS: Participants (≥22 years) with moderate-to-severe investigator-assessed Allergan Cheek Smoothness Scale (ACSS) scores were randomized in 2:1 ratio to receive VYC-12L or control (no treatment with optional treatment). Effectiveness was assessed 1 month after last injection (initial or touch-up) by a responder rate (≥1-grade improvement from baseline on both cheeks) using investigator-rated ACSS and Allergan Fine Lines Scale (AFLS), and tissue dielectric constant probe-measured skin hydration. Safety was evaluated throughout. RESULTS: Participants (VYC-12L, n = 131; control, n = 71) were 86.1% female with a median age of 58.0 years. At month 1, ACSS and AFLS responder rates were statistically significantly higher in the VYC-12L group (57.9%, 58.3%, respectively) than in the untreated controls (4.5%, 5.4%, respectively; p < .001). VYC-12L ACSS and AFLS responder rates remained consistent throughout the 6-month follow-up. Six participants reported treatment-related adverse events; none led to study discontinuation. CONCLUSION: VYC-12L is an effective, well-tolerated treatment for lasting improvement of cheek skin smoothness, fine lines, and hydration.

Cellulite: Current Treatments, New Technology, and Clinical Management.

BACKGROUND: Cellulite is a well-known concern for many women; however, treatment can prove challenging because of the complexities of cellulite etiology, the various factors contributing to its appearance, and the multitude of therapies and procedures available. OBJECTIVE: To discuss current cellulite treatment options and effective clinical management. METHODS: A roundtable meeting was convened to discuss and share views on current cellulite treatment options, new technologies, and clinical management. The participants' views helped guide a narrative review on this topic. RESULTS: Advanced interventions for cellulite treatment-such as physical and acoustic subcision, radiofrequency, and injectable biostimulators-are gradually being established, with accumulating evidence showing efficacy, patient satisfaction, and potentially long-lasting outcomes. Cellulite severity rating scales are necessary for assessing treatment outcomes, but these can be complex to use in clinical practice, and the majority do not include patient or clinician perspectives. CONCLUSION: With the advent of new treatments and technologies, cosmetic surgeons and dermatologists will need to tailor their approach to each patient's needs and manage patient expectations because multimodal methods are likely to be required to address the various factors underlying cellulite appearance.

Two-Step Skincare Regimen Addressing Aging in Three Unique Geographic Locations: A Prospective, Multi-Center, Open-Label Study.

BACKGROUND: Extrinsic factors including solar radiation and air pollution significantly impact facial skin aging. The efficacy and tolerability of a 2-step skincare regimen consisting of a vitamin C antioxidant serum (VCAS) and a 100% mineral tinted sunscreen moisturizer (TSM) were evaluated in women with hyperpigmented and photodamaged facial skin exposed to beach, mountain, and river-traversed basin city stressors. METHODS: This was an institutional review board (IRB)-approved, multi-center, prospective, open-label study involving healthy subjects. Thirty-six females aged 35 to 60 years with Fitzpatrick Skin Types I to V and exhibiting moderate to severe hyperpigmentation and moderate photodamage were recruited. The VCAS was applied to the global face twice-daily (morning and evening), and the TSM was applied in the morning with at least 2 reapplications during daily activity for 12 weeks. Clinical grading with a validated scale, standardized photography, and a self-assessment questionnaire were performed at baseline and weeks 4, 8, and 12. RESULTS: Statistically significant improvements were shown in clinically graded efficacy parameters at weeks 4, 8, and 12. Subjects showed an average improvement of 11.7%, 14.9%, and 19.1% in overall photodamage and an average improvement of 19.5%, 23.4%, and 24.5% in clarity/brightness at weeks 4, 8, and 12, respectively. Forehead lines and cheek lines demonstrated clinically significant improvement from baseline to week 12. Both products were well-tolerated and well-perceived by subjects. CONCLUSION: The 2-step skincare regimen was well-tolerated and effective in improving extrinsic signs of facial aging induced by solar radiation and air pollution stressors after 12 weeks of use. J Drugs Dermatol. 2023;22(1):16-22. doi:10.36849/JDD.7154.

Real-world effectiveness and safety of collagenase clostridium histolyticum-aaes injections for the treatment of thigh cellulite in women: An open-label study interim analysis.

BACKGROUND: Collagenase clostridium histolyticum-aaes (CCH-aaes) is approved in the United States for moderate-to-severe cellulite in the buttocks of adult women. AIM: Interim analysis to evaluate efficacy/safety of CCH-aaes in the treatment of thigh cellulite. METHODS: Data were analyzed from a phase 3, open-label study (REAL). Women with mild-to-moderate cellulite on both thighs (Clinician Reported Photonumeric Cellulite Severity Scale score, 2 or 3) received ≤0.84 mg (volume, 18 ml) of CCH-aaes subcutaneously, in up to 12 dimples per posterolateral thigh, in up to 3 treatment sessions (Days 1, 22, and 43). Follow-up was on Day 90 (interim cutoff). A subset of women participated in the concurrent study (PIXELS), which included high-definition photography and 3D-image scanning of treatment areas. RESULTS: Twenty-two women (44 thighs) were included in the interim analysis (mean age, 42.3 years; thighs with mild cellulite, 68.2%). Investigators reported high percentages of responders (score of "improved" or better on Investigator Global Aesthetic Improvement Scale) at Day 90 for either thigh (86.4%; primary endpoint) or both thighs (72.7%). Patient-reported bother due to cellulite was reduced at Day 90; mean change was 15.3 points (85.5% reduction) in BODY-Q Appraisal of Cellulite Scale total score (possible range, 11-44). In PIXELS analysis, Day 90 3D-image scans showed improvement from baseline in skin roughness in some of the treated thigh areas. The most commonly reported adverse events were injection-site bruising and pain (95.5% and 50.0% of patients, respectively). CONCLUSIONS: CCH-aaes treatment of mild-to-moderate thigh cellulite was effective and generally well tolerated, with markedly reduced cellulite-related bother.

Spot Reduction of Localized Fat Deposits on the Lateral Thighs by Simultaneous Emission of Synchronized Radiofrequency and High-Intensity Focused Electromagnetic Energy: Magnetic Resonance Multicenter Study.

BACKGROUND: Unwanted lateral fat most prominently affects the female population and may cause self-esteem issues. OBJECTIVE: To investigate the effectiveness and safety of synchronized high-intensity focused electromagnetic (HIFEM) + radiofrequency (RF) for the treatment of lateral thigh adipose tissue. MATERIALS AND METHODS: Ninety-three subjects (21-70 year old) received 4, 30-minute HIFEM + RF treatments of the lateral thighs. Magnetic resonance imaging (MRI) of the treated area was obtained at baseline, 1, 3, and 6 months post-treatment to document the changes in fat layer thickness. Furthermore, digital photographs, circumference measurements of the lateral thighs, subjects' satisfaction questionnaires, and therapy safety and comfort were documented. RESULTS: Magnetic resonance imaging revealed a significant reduction of fat tissue in the saddlebag region peaking at 3 months (-18 ± 5.5 mm; N = 51). The thigh circumference measured at 3 predefined levels decreased on average by 2.3 cm, with the greatest change at the level of 10 cm below the infragluteal fold (-3.5 cm, 3-month follow-up). Results were maintained at 6 months. No adverse events were recorded. The therapy was found comfortable with a high satisfaction rate. CONCLUSION: High-intensity focused electromagnetic + RF treatment to the lateral thigh area demonstrated effectiveness in long-term fat thickness reduction by MRI imaging. Secondary endpoint showed simultaneous effectiveness and safety.

Multicenter evaluation of a topical hyaluronic acid serum.

BACKGROUND: A new hyaluronic acid (HA) formulation was developed based on high molecular weight (MW) compounds used on the surface of the skin while using peptides to stimulate the high MW HA production by fibroblasts and keratinocytes from within the skin layers. Detailed science has been submitted to this journal in a previous publication. This multicenter study aims to validate the science by demonstrating the safety and efficacy of the product in the clinical realm. OBJECTIVES: This study evaluated the efficacy and safety of a topical HA serum in facial skin. METHODS: An open-label clinical study was undertaken over 4 months from November 2021 to March 2022. Participants applied the topical serum twice daily and were provided a gentle cleanser and an SPF 30+ to use in the morning. Follow-up visits were conducted at weeks 2, 4, and 8. At every visit, participants were measured for hydration post 15 minutes of cleansing the skin and post 15 minutes of product application for cumulative skin hydration sensor measurements. Additional procedures included participant assessments and satisfaction, investigator assessments, biopsies, and photography. RESULTS: At each follow-up visit, there was an increase in hydration measurements compared to baseline, in both immediate scores and cumulative long-term scores. At weeks 4 and 8, there was a statistically significant increase in hydration compared to baseline and the prior visit. Participants' assessments progressively increased over 2-, 4-, and 8-week intervals with significantly favorable ratings in all measured parameters. Similarly, investigator assessment grades were statistically significant (p < 0.0001) for decreased fine lines/wrinkling, crepiness, texture, erythema, and dryness, and increased (p < 0.0001) for moisture/hydration. Histology revealed increased CD44 staining in 6 of the 7 participants biopsied, denoting increased HA stimulation. In all of the participant biopsies, H&E staining demonstrated improvement in solar elastosis. Photography revealed remarkable improvement in erythema, tone, and texture. CONCLUSIONS: The study results demonstrated that the formulation produced significant improvements in immediate and long-term hydration effects on the skin as measured by the skin hydration sensor, 'wearifi' technology, comparison of before and after biopsies, and participant and investigator assessments. This high MW HA formulation produced excellent clinical improvement in skin health and hydration.

Safety, Pharmacodynamic Response, and Treatment Satisfaction With OnabotulinumtoxinA 40 U, 60 U, and 80 U in Subjects With Moderate to Severe Dynamic Glabellar Lines.

BACKGROUND: OnabotulinumtoxinA 20 U reduces glabellar line (GL) severity at maximum frown for approximately 3 to 4 months. Small studies have suggested that >20-U doses may increase the efficacy and duration of response for GLs. OBJECTIVES: The aim of this study was to evaluate safety, pharmacodynamic response, and treatment satisfaction with onabotulinumtoxinA doses ≥20 U for GLs. METHODS: This 48-week, double-blind study compared 40, 60, and 80 U onabotulinumtoxinA vs 20 U and placebo in women with moderate or severe dynamic GLs on the Allergan Facial Wrinkle Scale. The following parameters were evaluated: the percentage of subjects with investigator-assessed ≥1-grade Facial Wrinkle Scale improvement from baseline at maximum frown (responders) at Week 24; the estimated median duration of response; the proportion of mostly/very satisfied responders on the Facial Line Satisfaction Questionnaire follow-up Items 1 to 5; and treatment-emergent adverse events. RESULTS: The modified intent-to-treat population (N = 226) had a mean age of 48.0 years, with similar baseline GL severity between treatment groups. Week 24 responder rates were 0% for placebo and 16.0%, 32.0%, 30.6%, and 38.5% for onabotulinumtoxinA 20, 40, 60, and 80 U, with significant (P < 0.05) differences for 40 and 80 U vs 20 U. Median duration of response was longer with all higher doses vs 20 U (≥24.0 vs 19.7 weeks; P < 0.05 vs 20 U at Week 24). Facial Line Satisfaction Questionnaire results indicated high subject satisfaction. The incidence and severity of treatment-emergent adverse events did not exhibit a dose-response effect. CONCLUSIONS: GL treatment with onabotulinumtoxinA doses >20 U demonstrated longer duration of response and higher patient-reported satisfaction vs the on-label 20-U dose with no apparent impact on safety variables.

Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer.

Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with aGC or without aGC adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease-free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22 to 2.49; log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23 to 2.57; log-rank P = .001) but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as a negative predictor for aGC efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance.

Designing topical hyaluronic acid technology-Size does matter .

INTRODUCTION: Hyaluronic acid (HA) plays an important role in cellular and extracellular matrix (ECM) homeostasis. Recent studies demonstrate that low molecular weight (MW) HA has pro-inflammatory characteristics while high MW HA is considered anti-inflammatory and regenerative. In formulating a topical HA product, the possibility of creating a focused high MW HA technology was posed, combining external surface high MW HA constituents with active agents promoting fibroblast production of high MW in the depths of the dermis. METHODS: Human dermal fibroblasts and keratinocytes were treated with various agents, and RNA sequencing (RNA-seq) was conducted to identify genes involved in HA synthesis. HA production by fibroblasts was assessed by collecting the culture supernatant, concentrating the protein, and conducting polyacrylamide gel electrophoresis (PAGE). The gel was stained with Stains-All to identify bands relative to known HA products of different MWs. Subsequently, the supernatants were treated with hyaluronidase to confirm the bands corresponded to HA. RESULTS: The RNA-seq results revealed a variety of agents upregulated HA-related genes. However, a potent upregulation of HA synthesis gene was observed by hexapeptide-11 in the keratinocytes and a newly identified proprietary octapeptide in the fibroblasts. PAGE demonstrated not only robust production of HA by octapeptide, but significantly, the HA produced was ~2 Mega Daltons in size. Octapeptide was the most potent stimulator among the tested agents. CONCLUSION: Comprehensive in vitro testing identified a group of active agents that stimulated high MW HA production. This novel approach to HA topical application with exclusively high MW HA production should maximize hydration capacity while encouraging regenerative activity within the ECM. Multi-center trials are underway.

Safety and Effectiveness of Hyaluronic Acid Filler, VYC-20L, via Cannula for Cheek Augmentation: A Randomized, Single-Blind, Controlled Study.

BACKGROUND: Using cannulas to deliver facial fillers may reduce adverse events (AEs) compared with needle injection. OBJECTIVE: To evaluate the safety and effectiveness of VYC-20L (20 mg/mL hyaluronic acid gel with lidocaine) via cannula for midface age-related volume deficit. MATERIALS AND METHODS: This multicenter, evaluator-blind, randomized, within-subject, controlled study enrolled adults with moderate to severe Mid-Face Volume Deficit Scale (MFVDS) scores. VYC-20L was administered in one cheek via cannula (with optional needle use in the zygomaticomalar region) and in the other cheek via needle. The primary effectiveness end point was the mean (95% confidence interval [CI]) paired difference between treatments in MFVDS score change from baseline to Month 1; an upper CI limit of less than 0.5 determined noninferiority. Injection-site responses (ISRs), procedural pain, and AEs were assessed. RESULTS: Of 60 randomized and treated subjects, the mean change in MFVDS score from baseline to Month 1 was -1.8 with cannulas and -1.9 with needles, providing a mean (95% CI) paired difference of 0.1 (-0.05 to 0.25). Most ISRs were mild/moderate and resolved within 2 weeks. Procedural pain was minimal, and no serious AEs were reported. CONCLUSION: VYC-20L for cheek augmentation was safe and effective using a cannula and noninferior to needle injection.

A Randomized, Comparator-Controlled Study of HARC for Cheek Augmentation and Correction of Midface Contour Deficiencies.

BACKGROUND: HARC is a soft and flexible hyaluronic acid filler containing lidocaine, manufactured using XpresHAn® technology, restoring natural-looking volume and soft contours. OBJECTIVES: To evaluate safety and effectiveness of HARC for cheek augmentation and correction of midface contour deficiencies compared to a control product HAJV (hereafter referred to as Control). Primary objective was to demonstrate non-inferiority of HARC compared to the Control, by blinded evaluation of change from baseline in midface fullness 12 weeks after last injection, using a 4 grade midface volume scale (MMVS). MATERIALS AND METHODS: Subjects over the age of 21 with loss of fullness in the midface area (MMVS score 2, 3, or 4) were randomized 2:1 to treatment with HARC(n=142) or Control (n=68). Optional touch-up was allowed after 4 weeks. Study assessments included MMVS, aesthetic improvement, subject satisfaction, and safety. Subjects were followed for 48 weeks. RESULTS: Overall, most subjects were female (89%) and mean age was 53 years (range 24-80). Total mean volume injected was 4.3 mL for HARC and 4.9 mL for Control. Primary objective was met; mean change from baseline in MMVS score at week 12: -1.4 (HARC), -1.3 (Control), 95% CI: -0.22, 0.06. HARC effectiveness was supported by a high degree of aesthetic improvement and subject satisfaction throughout 48 weeks. Related adverse events were generally mild and transient. CONCLUSIONS:  HARC was well tolerated and non-inferior to Control for correction of midface fullness at 12 weeks after last injection. Aesthetic improvement and subject satisfaction were high and lasted through week 48.  J Drugs Dermatol. 2021;20(9):949-956. doi:10.36849/JDD.6191.

A Randomized Study on PLLA Using Higher Dilution Volume and Immediate Use Following Reconstitution.

BACKGROUND: The reconstitution volume of a PLLA-containing injectable device has gradually increased in clinical practice, often in combination with adding lidocaine to the solution. OBJECTIVE: This study, SCRIPT (Sculptra Contemporary Reconstitution & Injection Procedure Trial) evaluated PLLA for correction of nasolabial folds after changes in reconstitution and injection procedures. Primary endpoint for effectiveness was change from baseline of nasolabial folds, assessed by blinded evaluation using a validated wrinkle assessment scale (WAS), at week 48. METHODS: Subjects were treated to optimal correction of nasolabial folds at a single treatment regimen consisting of ≤4 injection sessions, with PLLA reconstituted with 8 mL or 5 mL sterile water for injection (SWFI), randomized 2:1. The 8 mL product included an additional 1 mL 2%-lidocaine and was injected immediately following reconstitution. Assessments included wrinkle severity, aesthetic improvement and safety. RESULTS: A total of 80 subjects were included in the study. Most subjects were female (95%), mean age was 51.5 years. Primary endpoint was met and subjects from both study groups demonstrated high WAS responder rates (≥1-grade improvement from baseline) at week 24 (≥75%) and week 48 (≥67%). Aesthetic improvement was high (≥86%) throughout the study. Adverse events related to study product or injection procedure were mostly mild and transient. CONCLUSION: PLLA reconstituted with 8 mL SWFI demonstrated a comparable treatment effect to that of the reference group in reducing wrinkle severity of nasolabial folds. Safety was not compromised using a higher reconstitution volume including lidocaine, injected immediately after reconstitution.

A Randomized, Controlled, Evaluator-Blinded, Multi-Center Study of Hyaluronic Acid Filler Effectiveness and Safety in Lip Fullness Augmentation.

BACKGROUND: HARK was recently approved in the US for lip augmentation and correction of upper perioral rhytids. OBJECTIVE: To demonstrate noninferiority of HARK versus a control (HAJV) in lip fullness augmentation at Week 8 after last injection (blinded evaluation). Secondary objectives were to evaluate the effectiveness and safety of HARK in lip fullness augmentation and correction of upper perioral rhytids. METHODS AND MATERIALS: Treatment with HARK or control (randomized 2:1) was administered on Day 1 in this 48-week, evaluator-blinded study with optional touch-up at Week 4. Primary endpoint was change from baseline to Week 8 in lip fullness. Secondary endpoints included lip fullness, wrinkle severity, aesthetic improvement, subject satisfaction, adverse events, and local tolerability (subject diary entries). RESULTS: The primary objective was met; HARK was noninferior to control in lip fullness augmentation at Week 8. Lip fullness and wrinkle severity improvement persisted at Week 48, and was accompanied by high aesthetic improvement and subject satisfaction scores. The mean volume of HARK injected was approximately 20% lower than control. Treatment-related adverse events and local tolerability symptoms were predominantly mild and transient. CONCLUSION: HARK was noninferior to control in lip fullness augmentation at Week 8, well-tolerated, and effective throughout this 48-week study.

Chart Review Presenting Safety of Injectable PLLA Used With Alternative Reconstitution Volume for Facial Treatments.

BACKGROUND: Since the approval of Sculptra Aesthetic, the amount of sterile water used to reconstitute the product has gradually increased in clinical practice. A retrospective chart review was conducted to evaluate patient safety associated with a larger reconstitution volume, and to investigate specific parameters for how Sculptra Aesthetic is used in a real-world clinical setting. OBJECTIVE: The primary objective of the study was to evaluate the safety of Sculptra Aesthetic when using a reconstitution volume of 7 to 10 mL, via collection of adverse events related to the product or injection procedure reported in medical records. METHODS: This was a multi-center, retrospective chart review conducted in the US. Medical records for subjects treated in the facial area with Sculptra Aesthetic reconstituted to 7–10 mL were reviewed to obtain information about demographics, treatment data, and adverse events. Each injector completed a questionnaire regarding reconstitution and injection procedures generally used. RESULTS: There were 4483 treatments performed in 1002 subjects; nearly half (48%) had 3 or 4 treatments during the studied period. Subjects most commonly received treatment in the midface/cheek area (97%), temple (94%), and jawline (54%). All injectors indicated adding lidocaine to the solution, resulting in total volumes of 8–10 mL. Adverse events were reported by 3.6% of subjects, all mild in intensity. Nodules were reported by 4 subjects (0.4%). CONCLUSION: The low number of AEs reported in this retrospective chart review suggests that facial aesthetic treatment with PLLA reconstituted to a final volume of 8–10 mL, including anesthetics, is associated with a favorable risk benefit ratio. J Drugs Dermatol. 2021;20(1):18-22. doi:10.36849/JDD.5631.

Magnetic Resonance Imaging Evaluation of Changes in Gluteal Muscles After Treatments With the High-Intensity Focused Electromagnetic Procedure.

BACKGROUND: High-intensity focused electromagnetic (HIFEM) field procedure induces changes in the gluteal muscles and improves the aesthetic appearance of the buttocks. OBJECTIVE: This study aims to objectively assess the hypertrophic response of the gluteal muscles after HIFEM treatments. MATERIALS AND METHODS: Seven subjects (40.00 ± 6.68 years) received 4, 30-minute HIFEM treatments of the buttocks. Magnetic resonance imaging of the pelvic region was obtained at baseline, 1-month, and 3-month follow-up to reconstruct 3D volumes of musculusgluteus maximus, medius, and minimus. Volumetric changes were calculated and statistically analyzed. Standardized photographs, weight measurements, patient satisfaction, treatment comfort, and adverse events were also documented. RESULTS: Volumetric analysis revealed a significant increase (p = .001) in the size of the examined muscles at 1-month (+10.81 ± 1.60%) and 3-month (+13.23 ± 0.91%) follow-up. A more profound hypertrophic effect was seen in the upper buttock region. This translated into a visible buttock lifting, also captured by patient photography. Gluteal adipose tissue was insignificantly affected. Patients were satisfied, and they found the treatments comfortable. No adverse events were observed. CONCLUSION: Simultaneous enhancement of gluteal muscles was documented. This represents the first objective evaluation of the HIFEM-induced structural changes in the gluteal muscles and physiologic documentation of the aesthetic improvement previously reported by other authors.

Developing a Topical Adjunct to Injectable Procedures.

Injectable procedures have come to play an enormous part in everyday aesthetic medical practice. Whether its use is directed at volumizing with fillers, decreasing volume using enzymes, skin-tightening using multi-needle approaches, or neuromuscular blockade, the injectable route is the means of delivery in all these cases, making injectable procedures the most common aesthetic procedure performed. As with all procedures, expected and unexpected consequences may follow including bruising, swelling, discomfort, and the possibility of infection. This paper outlines the scientific process and validation of a product designed as an adjunct to injection therapy and the scientific deep dive needed to encompass both symptomatic and adjunctive purposes. On the symptomatic side, bruising, swelling, and pain were considered, while volumetric enhancement, regeneration, and anti-microbial/biofilm effects were desired outcomes from the adjunctive perspective. Utilizing peptides and active agents aimed at reducing excess residual iron and stimulating macrophage absorption of red blood cells, we were able to achieve efficient resolution of bruising. In addition, peptides were included to stimulate collagen, elastin, and hyaluronic acid in synergy with the injectable. Anti-inflammatory, antimicrobial, and antibiofilm agents were added to aid in the safety profile of the injectable. In vivo testing of bruising resolution demonstrated that at day 2/3, participants using the study product (INhance Post-Injection Serum with TriHex Technology®, Alastin Skincare, Inc. Carlsbad, CA) had 73% less bruise color intensity and statistically significant improvement over the bland moisturizer. Overall, 81% of subjects applying the study topical product had less bruising at day 2/3 compared to the bland moisturizer. J Drugs Dermatol. 2020;19(4):398-404. doi:10.36849/JDD.2020.5016.

Efficacy, Patient-Reported Outcomes, and Safety for Millennial Subjects Treated With OnabotulinumtoxinA for Moderate to Severe Horizontal Forehead Lines.

BACKGROUND: Millennials (aged 18-34 years) represent a growing segment of the facial aesthetic market. OBJECTIVE: To evaluate investigator-assessed efficacy, patient-reported outcomes (PROs), and safety for millennials versus subjects aged at least 35 years after onabotulinumtoxinA treatment of forehead lines (FHL) across 2 phase 3 studies. METHODS: Eligible subjects with moderate to severe FHL received onabotulinumtoxinA (FHL: 20 U; glabellar lines: 20 U, with/without 24 U in crow's feet line regions) or placebo. All findings were pooled by the age group. RESULTS: Millennials composed 15% of subjects (176/1,178). Day 30 responder rates of at least 1-grade Facial Wrinkle Scale improvement in FHL severity for millennials versus subjects aged 35 years and older were 100% versus 97.8% at maximum eyebrow elevation and 78.4% versus 83.5% at rest, respectively. Responder rates were significantly greater with onabotulinumtoxinA than placebo (p ≤ .015) for both groups through Day 180. Similar trends were observed for achieving none/mild severity. Both age groups reported high satisfaction rates and improved psychological impacts with onabotulinumtoxinA treatment. No new safety signals were detected. CONCLUSION: OnabotulinumtoxinA treatment was well tolerated, and both age groups experienced significant improvements in FHL severity, high satisfaction, and improved psychological impacts after treatment. Millennials reported numerically greater improvements.

Final Data from the Condition of Submental Fullness and Treatment Outcomes Registry (CONTOUR)

Perceptions of attractiveness can be negatively affected by submental fullness. Patients seeking to improve their submental contour have a variety of treatment options including surgical procedures, energy-based devices, and injectable treatment. The Condition of Submental Fullness and Treatment Outcomes Registry (CONTOUR) was designed to provide insights into the treatment of submental fat (SMF) in clinical practice. CONTOUR was a prospective observational study that enrolled 1029 adults at 91 sites in the United States and Canada. Patients were followed until treatment completion, discontinuation, or 1 year elapsed from enrollment without treatment. Final data from CONTOUR are reported here. Of the 676 patients who underwent treatment, 570 were treated with ATX-101 (deoxycholic acid injection), 77 with energy-based devices, 23 with surgical liposuction, 5 with laser liposuction, and 9 with other treatments. The majority of treated patients were facial aesthetic treatment naive. A markedly greater percentage of patients with mild or moderate SMF at baseline received treatment with ATX-101 or energy-based devices, whereas the majority of patients undergoing liposuction had severe or extreme SMF. Physicians most frequently cited a preference for a noninvasive/minimally invasive procedure as the reason for choosing either ATX-101 or energy-based devices. The majority of patients were at least partially satisfied with results, regardless of the chosen treatment. Data from CONTOUR indicate that cost is the most important factor in a patient's decision to undergo treatment, that choice of treatment method is most influenced by SMF severity and preference for nonsurgical versus surgical intervention, and that the availability of noninvasive/minimally invasive options has made SMF treatment an attractive first procedure for patients who have not undergone previous facial aesthetic treatments. ClinicalTrials.gov identifier: NCT02438813. J Drugs Dermatol. 2019;18(1):40-48.