Tapencarium (RZL-012) for Flank Fat Reduction: A Proof-of-Concept Study.

Background: RZL-012 is a novel cytolytic drug that has shown promise in reducing localized fat deposits in a single treatment session. Objectives: To assess the safety and efficacy of injecting RZL-012 to the flanks. Methods: A double-blind, placebo-controlled, proof of concept study randomized 12 patients to receive RZL-012 injections in 1 flank and placebo injections in the contralateral flank. After 12 weeks of follow-up, patients could receive RZL-012 in the placebo-treated flank and undergo follow-up for 12 weeks in the open-label phase. Results: At 12 weeks, Investigator Global Aesthetic Improvement Scale assessments showed improvement for 90.9% of RZL-012-treated flanks and 0% of placebo-treated flanks (P < .0001), 81.8% of patients were satisfied with the RZL-012-treated flanks, and 9.1% were satisfied with the placebo-treated flanks (P = .0019). Volume reduction measured on 3-dimensional images was a mean 37.27 mL, which was significantly greater than placebo (P = .0052). The product was well tolerated, with no clinically significant trends in laboratory values, electrocardiograms, or vital signs. Pharmacokinetic analyses demonstrated that RZL-012 is quickly absorbed, reaches maximum concentration in approximately 1.67 h, and has a half-life of 9.1 h. The mean maximal concentration of RZL-012 found in the blood was <1 µg/mL. Conclusions: RZL-012 is a promising option for injectable fat reduction of the flanks in a single treatment session. The drug was well tolerated in this small patient population, with no concerning safety signals, and it had indications of efficacy. Further research is needed in large Phase 2 studies with robust efficacy measurements to confirm these early findings.

The Emerging Role of Injectable Weight Loss Medications in Plastic Surgery: A Systematic Review.

Obesity is a multifactorial disease that represents a substantial global health concern. As of 2016, the World Health Organization (WHO) estimated that over 650 million adults were obese, and more than 1.9 billion were overweight. Surgical interventions or lifestyle changes are typically suggested to patients who experience comorbidities as a result of their weight; however, more recently, antidiabetic medications have been proposed, specifically sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs). This is the first systematic review to evaluate the safety, efficacy, and future role of SGLT-2 inhibitors and GLP-1RAs for weight loss in the world of aesthetic plastic surgery. Sixteen randomized controlled trials were identified that met the eligibility criteria for this systematic review and comprised data from 10,492 patients. All studies reported a decline in body weight following treatment with SGLT-2 inhibitors or GLP-1RAs, ranging from 1.5 to 5 kg. Although adverse events were reported in a large proportion of patients, primarily gastrointestinal manifestations, the literature reports that these were mild to moderate in severity and tended to subside following treatment adjustment. Future research is warranted to determine the ideal SGLT-2 inhibitor or GLP-1RA for weight loss management, and additional randomized controlled trials (RCTs) are needed to determine the efficacy and tolerability of potential combination therapies with SGLT-2 inhibitors and GLP-1RAs.

Characterization of Tissue Histology for the Injectable Cellulite Treatment Collagenase Clostridium Histolyticum-aaes: Results in Swine.

Background: Cellulite is a common aesthetic condition that affects predominantly females. Collagenase clostridium histolyticum-aaes (CCH-aaes) injections disrupt native collagen structures, resulting in an improvement in cellulite appearance. However, injection-site bruising is a frequently occurring adverse event with CCH-aaes treatment. Objectives: To characterize tissue histology following CCH-aaes injection in Yorkshire pigs. Methods: In an animal study, female swine with 10 defined dosing sites on the ventral-lateral aspect received 1 or 2 CCH-aaes (0.07 mg/0.3 mL) or placebo subcutaneous injections at a single site at designated time points before tissue sampling. Results: Injection with CCH-aaes was associated with lysis of mature, collagen-rich septa in the subcutaneous layer at and adjacent to the injection site as early as Day 1. On Day 4, an increase in inflammatory cells and a decrease in hemorrhage (vs Day 2) were observed, with inflammation and hemorrhage decreased by Day 8. By Day 21, deposition of new collagen and reorganization of fat lobules were observed. Observations with repeat CCH-aaes treatment were comparable with 1 course of CCH-aaes treatment. Conclusions: In this animal study, targeted enzymatic subcision of collagenous bands and remodeling of subcutaneous tissue were observed following CCH-aaes injection.

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction.

BACKGROUND: Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. OBJECTIVES: The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction. METHODS: Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment. RESULTS: The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs). CONCLUSIONS: A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.

Real-World Experience With Collagenase Clostridium Histolyticum-aaes for Buttock and Thigh Cellulite: Focus on Administration and Safety Profile.

Background: Collagenase clostridium histolyticum-aaes (CCH-aaes) is approved for the treatment of moderate-to-severe buttock cellulite in adult women. Objectives: To report on real-world experience with CCH-aaes in the treatment of buttock and thigh cellulite. Methods: Retrospective analysis of medical records from a single treatment center. Results: The population comprised 28 consecutively treated women; mean age was 40.5 years (range, 23-56 years) and mean body mass index was 25.9 kg/m2 (range, 19.6-41.0 kg/m2). Treatment areas were buttocks only (78.6% of patients), thighs only (10.7%), or both buttocks and thighs (10.7%). Most patients (89.3%) were treated in 2 areas (buttocks or thighs) at each visit; however, 3 patients were treated in 4 areas. At each session, the CCH-aaes dose was 0.07 mg per dimple (0.3 mL of 0.23 mg/mL for buttock cellulite; 1.5 mL of 0.046 mg/mL for thigh cellulite). The mean number of treatment sessions was 2.6 (range, 1-4) for buttock cellulite and 2.5 (range 1-3) for thigh cellulite. The mean number of dimples treated was 11.5 (range, 3-17) per buttock, 11.0 (range, 1-14) per thigh, and 23.4 (range, 8-32) overall per treatment session. Injection site-related adverse events of special interest were experienced by all 28 patients: bruising (100%), edema (96.4%), tenderness (85.7%), nodules (39.3%), pruritus (32.1%), and hyperpigmentation indicative of hemosiderin staining (7.1%). Mean duration of injection-site bruising was 8.8 days (range, 2-15 days). Conclusions: CCH-aaes is an effective, well-tolerated, minimally invasive treatment option for buttock and thigh cellulite in women.

Cellulite Pathophysiology and Psychosocial Implications.

BACKGROUND: Cellulite is a highly prevalent aesthetic condition in postpubertal women. OBJECTIVE: The objective of this article was to describe the latest data on the pathophysiology of cellulite and to highlight the psychosocial aspects that should be considered when treating cellulite. METHODS: A roundtable meeting was convened to discuss and share views on the latest data on the pathophysiology and psychosocial aspects of cellulite. The participants' experience helped guide a narrative review on this topic. RESULTS: The pathophysiology of cellulite primarily involves fibrous septal changes. Strategies targeting the fibrous septa have shown the most consistent efficacy, while showing inconsistent or short-term results when targeting the other components of cellulite, such as decreased dermal thickness, vascular alterations, and inflammation. Female sex, increased age, and high body mass index contribute to cellulite pathophysiology. CONCLUSION: Patients seeking treatment for cellulite are willing to endure numerous treatments, high cost, temporary and/or delayed results, and invasive procedures with potential adverse effects. Psychological discomfort has been reported among patients with cellulite, and understanding their behaviors and psychological characteristics can help clinicians provide better care to these patients seeking treatment.

Cellulite: Clinical Challenges and Future Perspectives.

BACKGROUND: Existing cellulite interventions pose various clinical challenges related mostly to ecchymosis and recovery time. OBJECTIVE: To discuss the current treatment options for minimizing recovery time, efficacy of these options, and investigations into possible future approaches. METHODS: A roundtable meeting was convened to discuss and share views on the clinical challenges seen in the present practice of cellulite treatments along with future approaches and mitigation strategies. The participants' views helped guide a narrative review on this topic. RESULTS: Cosmetic clinicians have a range of new interventions to choose from for cellulite improvement, each with different benefits and safety aspects. Bruising is a typical side effect that is seen with treatments targeting the fibrous septa, such as subcision and injectable treatments, and in some cases may produce long-lasting hyperpigmentation from postinflammatory hyperpigmentation or hemosiderin staining. Various strategies that could potentially mitigate bruising and other adverse effects of cellulite treatment are under clinical investigation, including, but not limited to, different injection techniques and dilutions, compression garments, cold packs, arnica gel, pulsed dye laser treatment, intralesional epinephrine, and tranexamic acid. CONCLUSION: Clinical challenges including varying treatment outcomes and certain treatment sequelae remain, and further research is needed to prevent side effects and improve treatment outcomes.

Safety and Efficacy of Renuvion Helium Plasma to Improve the Appearance of Loose Skin in the Neck and Submental Region.

BACKGROUND: Minimally invasive procedures that deliver thermal energy to subcutaneous tissue offer a solution when deciding between excisional and noninvasive options to address face and neck aging-related changes. A minimally invasive helium plasma device, Renuvion, was first utilized for subdermal tissue heating to reduce skin laxity under an FDA general clearance for cutting, coagulation, and ablation of soft tissue. OBJECTIVES: The purpose of this study was to demonstrate the safety and effectiveness of the helium plasma device for improving the appearance of loose skin in the neck and submental region. METHODS: Patients undergoing the procedure with the helium plasma device in the neck and submentum were studied. They were seen for 6 months following the procedure. The primary effectiveness endpoint for improvement in lax skin in the treatment area was determined by 2 of 3 blinded photographic reviewers. The primary safety endpoint was the level of pain after treatment. RESULTS: The primary effectiveness endpoint was met; 82.5% demonstrated improvement at Day 180. The primary safety endpoint was met; 96.9% of patients experienced no pain to moderate pain to Day 7. There were no serious adverse events reported related to the study device or procedure. CONCLUSIONS: The data demonstrate benefit to patients by improvement of the appearance of lax skin in the neck and submental region. Outcomes resulted in US Food and Drug Administration 510(k) clearance in July 2022, expanding indications for the device to include subcutaneous dermatological and aesthetic procedures to improve the appearance of loose skin in the neck and submental region.

Injection Adipocytolysis for Body and Jawline Contouring: Real-World Experience and Treatment Considerations.

BACKGROUND: The role of ATX-101 in submental fat reduction has been well documented; however, its applicability across multiple anatomic areas is to be explored. OBJECTIVES: The authors sought to describe the experience with ATX-101 subcutaneous injections for body and jawline contouring and evaluate its safety. METHODS: This single-arm, single-center observational study included 201 patients who underwent injection adipocytolysis with ATX-101 (area-adjusted dose of 2 mg/cm2) in the jowl, abdomen (upper/lower), thigh (inner/outer/banana roll), arm, anterior periaxillary fat, back (lower/upper/nape/lipoma), knee (anterior/medial), chest, and/or neck. The number of treatment sessions, treatment volumes, doses, injections required for each anatomic area, and associated adverse events were recorded. RESULTS: The mean number of treatment sessions conducted was 1.8. Multiple sessions were common for the jowl (mean: 2.0 and mean volume administered varied significantly between persons receiving 1 or multiple sessions [P = 0.005]). The mean volume and mean number of injections per session were highest in the chest (84.7 mL and 423.5, respectively) and lowest in the jowl (0.8 mL and 4.6, respectively). The chest (0.2 mL) and nape (0.2 mL) received the highest mean ATX-101 dose per injection site per session, whereas the inner thigh (0.11 mL) and upper back (0.11 mL) received the least. Adverse events observed were localized to the injection site. All patients experienced edema after each session, whereas numbness, tenderness, bruising, and paresis were experienced by 99.6%, 94.2%, 33.1%, and 2.6% of patients, respectively. Alopecia was not observed. CONCLUSIONS: ATX-101 was well tolerated for body and jawline contouring.

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.

A Multicenter, Randomized, Double-Blind, Split-Body Clinical Trial Evaluating the Efficacy and Outcomes of a Topical Product Pre and Post Aesthetic Surgical Body Procedures.

Background: Skin preconditioning prior to and following procedures, has previously been demonstrated to hasten and optimize healing, and decrease the symptoms and signs associated with invasive surgery. These trials involved the use of multiple topical products. In an effort to control costs and to increase patient compliance, a single surgical product was developed, with actives aimed at decreasing swelling, bruising, induration, and internal fibrous banding. Objectives: This multi-center trial was designed to measure the efficacy of this single product in these mentioned parameters. Methods: A double-blind, randomized, split body, clinical study was undertaken in 29 patients involving 38 surgical procedures. Assessments included photography, biopsies, ultrasound imaging, and blinded investigator and participant assessments. Results: Differentiated results between test comparator sides became apparent at postop day 10-14 (as previously observed). Thus, blinded investigator and participant assessment scores demonstrated statistical significance exclusive to the test product side at postop day 10-14 for ecchymoses and then extending to skin discoloration, edema, induration and subcutaneous fibrous banding, at weeks 3, 4, 6, and 12. Ultrasound evaluation confirmed the earlier dissolution of fibrous banding on the test side in the subcutaneous tissue at the 3-6-week postop period. In addition, biopsies assessing the pre-conditioned period prior to surgery confirmed that the topical test product stimulated a remodeled extracellular matrix without comparative changes on the opposite side. Conclusions: A single peri-surgical product designed for the use with invasive surgery produced significant differences in ecchymosis, skin discoloration, edema, induration and ongoing resolution of fibrous banding over many weeks. This study validation provides an additional adjunct to surgical procedures.

Safety of Helium-based Plasma Technology for Coagulation of Soft Tissue: A Retrospective Review.

Background: The subdermal application of energy using a helium-based plasma radiofrequency (RF) device has been shown to improve skin laxity. Helium-based plasma RF technology (Renuvion; Apyx Medical, Clearwater, FL) utilizes RF to ionize helium into an electrically conductive plasma capable of coagulating and contracting soft tissue with high precision and minimal thermal spread. This study provides information on the early use of the new generation of electrosurgical generator (APYX-RS3) containing a feature that allows for quantification of the amount of energy delivered to tissue during treatments. Objectives: To collate procedure details, treatment settings, and safety data in patients treated with a helium-based plasma device for soft tissue coagulation. Methods: A retrospective review was conducted of patients aged ≥ 18 years who underwent treatment with a helium-based plasma RF device (Renuvion) for soft tissue coagulation. Demographic data, procedure details, and adverse events were collected. Results: Chart review identified 47 patients with an average age of 45 years and an average BMI of 25.8 kg/m2. The amount of energy (J) delivered per treatment area was greatest for abdomen, buttocks, and thighs, with an average of 13.7 kJ, 13.5 kJ, and 10.6 kJ, respectively. No serious, unexpected, or device-related AEs were reported. Conclusions: The use of the generator that quantifies the energy (joules) being applied during the procedure allows the provider to understand and optimize their energy usage. While further research is needed to establish the safety and efficacy of the device for skin tightening, this study provides important information regarding energy application.

Evaluating a Topical Adjunctive Post Submental ATX-101 (Deoxycholic Acid) Injections for Improved Recovery: A Single-Center, Double-Blind, Randomized Controlled Pilot Study.

BACKGROUND: Optimizing postprocedural recovery and outcomes for patients is the aim for all physicians. TransFORM Body Treatment with TriHex Technology (TFB) is a topical product that aids in the elimination of fat particles created during procedures and the reduction of associated inflammation, thus speeding up postprocedure recovery time. OBJECTIVES: Evaluation of postprocedural symptoms, signs, and healing following submental deoxycholic acid (DCA) injections in combination with TFB. METHODS: Participants received 2 treatments of submental DCA injections. Posttreatment 1, every participant received TFB to apply twice daily to the submental area. Follow-up visits included weeks 1, 2, and 4. After week 4, participants discontinued TFB for 30 days before the second treatment. At the second treatment visit, participants were randomized to receive either TFB or a bland moisturizer to apply twice daily with the same follow-up visits as posttreatment 1. Induration measurements, submental fullness grading, and standardized photography were captured at every visit. At all follow-up visits and before treatment 2, investigator assessments and participant assessments were completed. RESULTS: Posttreatment 2, investigator assessments of edema and induration decreased in participants using TFB at weeks 1 and 2 compared with the bland moisturizer. Induration measurements objectively showed a statistically significant reduction at week 2 (posttreatment 2) in participants using TFB compared with the bland moisturizer. Furthermore, participants reported less tenderness and soreness in the TFB group over the bland moisturizer. CONCLUSIONS: Investigator assessments, participant query, and objective induration analyses have demonstrated that the use of TFB post DCA injections may reduce induration, edema, and discomfort associated with this procedure.

Best Clinical Practices with ATX-101 for Submental Fat Reduction: Patient-related Factors and Physician Considerations.

BACKGROUND: Submental fat can be reduced with ATX-101 (deoxycholic acid injection), a customizable and minimally invasive alternative to liposuction. In the years since its approval, the treatment patterns of ATX-101 have evolved. METHODS: A panel of experienced physicians from the United States gathered to generate best practices for the use of ATX-101 in submental contouring. RESULTS: The expert panel provided their insights on appropriate patient selection, managing patient expectations of ATX-101 treatment outcomes, and adverse events, and guidance on ATX-101 administration for optimal outcomes are presented here. CONCLUSION: These best clinical practices on the use of ATX-101 for the reduction of submental fat should enable physicians to enhance the patient treatment experience and outcomes.

Clinical experience of poly-L-lactic acid injections for body contouring treatment.

INTRODUCTION: Clinical data on body contouring with injectable poly-L-lactic acid are sparsely reported in published literature. This study describes the lead author's clinical experience using injectable poly-L-lactic acid for body contouring in various anatomic locations. METHODS: Twenty consecutive patients undergoing body contouring treatments with poly-L-lactic acid were prospectively followed. All treatments were performed at a single clinic between February 2017 and February 2019. Treatment details such as reconstitution, injection volume and dosage were documented. Treatment response was assessed independently by patients and the treating physician. Adverse events were recorded. RESULTS: Twenty patients (85% women) received injectable poly-L-lactic acid for body contouring treatments such as buttocks volumization, cellulite and skin quality treatment. In most patients (65%), poly-L-lactic acid was administered to correct postsurgical soft tissue deformities. Overall, patients had a mean of 5.1 treatment sessions in a mean of 1.4 anatomic locations. The most commonly treated anatomic locations were buttocks (58% of treatment sessions), thighs (20%) and abdomen (9%). Dosage and injection volume varied between patients depending on anatomic location and desired outcome. Most treatment sessions (86%) resulted in improvement of the treated area. Adverse events included bruising, oedema, numbness and tenderness. Nodule formation was recorded for one patient (5%). CONCLUSION: According to the lead author's clinical experience, poly-L-lactic acid injection is well tolerated and can achieve good aesthetic outcomes when used for body contouring in appropriate patients. Preliminary data suggest that poly-L-lactic acid injection may be a viable nonsurgical technique for correcting postsurgical soft tissue deformities.

Attitudes Toward Submental Fat Among Adults in the United States.

BACKGROUND: Excess submental fat (SMF) can cause submental fullness resulting in negative perceptions of individuals. However, the impact of SMF on perceptions of social traits has not been well studied. OBJECTIVE: To characterize the impact of SMF on external value judgments in adults in the United States. METHODS: Respondents completed an online survey in which they reacted to statements about individuals with varying grades of SMF. Attributes were rated on a scale from 0 to 100 with higher scores for more positive attributes. RESULTS: Similar proportions of respondents (N = 1996) indicated that women and men with double chins were less attractive than those without (91% and 90%, respectively). A double chin was more likely to be noticed on a woman than on a man (78% of respondents). With increasing SMF, individuals were perceived as significantly less likeable, intelligent, happy, active, and easygoing. Those with greater amounts of SMF were rated as significantly less attractive than those with less SMF. For all attributes, male respondents rated all individuals lower than female respondents did. CONCLUSION: Results from this study provide further evidence of negative perceptions of individuals with SMF. Aesthetics of the submental area, especially SMF, likely impact the overall assessment of attractiveness and social attributes.