Lisa Donofrio

HIGH LEVEL EXPRESSION OF FMS PROTO-ONCOGENE mRNA IS OBSERVED IN CLINICALLY AGGRESSIVE HUMAN ENDOMETRIAL ADENOCARCINOMAS

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.

Structural Autologous Lipoaugmentation: A Pan‐Facial Technique

Background. Structural collapse is a hallmark of the aging face. Autologous fat transplantation is the ideal way to correct the atrophy that accompanies senescence. Objective. To set guidelines for optimizing the results from autologous fat transfer in accordance with the scientific literature. Methods. Structural augmentation is a specific technique for the harvesting and transplantation of viable adipocytes. It involves the cardinal principles of atraumatic harvesting and multilayer blunt pan‐facial infiltration of fat. Results. Staged adipocytes transfers using banked, frozen fat is an ideal way to keep patient downtime to a minimum. The use of blunt transfer cannulas has extended the application of fat transfer into the pan‐facial arena and improved the overall results.

Randomized sham-controlled trial to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting.

Background: High-intensity focused ultrasound presents a noninvasive approach to body sculpting for nonobese patients. The purpose of this study was to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for sculpting of the abdomen and flanks. Methods: Adults (aged 18 to 65 years) with subcutaneous abdominal fat greater than or equal to 2.5 cm thick who met screening criteria were randomized to receive high-intensity focused ultrasound treatment of the anterior abdomen and flanks at energy levels (a total of three passes each) of 47 J/cm2 (141 J/cm2 total), 59 J/cm2 (177 J/cm2), or 0 J/cm2 (no energy applied, sham control). The primary endpoint was change from baseline waist circumference at the iliac crest level at posttreatment week 12. Subjective aesthetic assessments included the Global Aesthetic Improvement Scale and a patient satisfaction questionnaire. Safety assessments included adverse events, laboratory values, and physical examinations. Results: For the primary endpoint, in the intent-to-treat population, statistical significance versus sham was achieved for the 59-J/cm2 (–2.44; p = 0.01) but not the 47-J/cm2 treatment group (–2.06 cm; p = 0.13). In a per-protocol population, statistical significance versus sham was achieved for both the 59-J/cm2 (–2.52 cm; p = 0.002) and the 47-J/cm2 treatment groups (–2.10 cm; p = 0.04). Investigator subjective measures of global aesthetic improvement and patient satisfaction also favored each active treatment versus sham. Adverse events included mild to moderate discomfort, bruising, and edema. Laboratory values and physical examinations were unremarkable. Conclusions: Treatment with this high-intensity focused ultrasound device reduced waist circumference and was generally well tolerated for noninvasive body sculpting. Reduction in waist circumference was statistically significant with both active treatments (per protocol). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. Figure. No caption available.

Multicenter, Randomized, Phase III Study of a Single Dose of IncobotulinumtoxinA, Free from Complexing Proteins, in the Treatment of Glabellar Frown Lines

BACKGROUND Botulinum toxin type A is a proven, effective aesthetic treatment for glabellar frown lines. IncobotulinumtoxinA (NT 201, Xeomin/Xeomeen/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a 150‐kDa botulinum toxin type A free of complexing proteins. OBJECTIVE To assess the efficacy and safety of incobotulinumtoxinA in a randomized, double‐blind, placebo‐controlled, Phase III study in patients with moderate to severe glabellar frown lines. MATERIALS AND METHODS Two hundred seventy‐six patients were randomized 2:1 to receive a single injection of 20 U of incobotulinumtoxinA or placebo, respectively. Efficacy was assessed at day 30 using a Food and Drug Administration–mandated composite endpoint; a responder was defined as a patient with a 2‐point or greater improvement in glabellar frown lines on a 4‐point scale as assessed by investigator and patient. Safety was assessed periodically through Day 120. RESULTS Treatment with a single dose of incobotulinumtoxinA was significantly superior to placebo in the treatment of glabellar frown lines at Day 30 using the composite endpoint (p < .001), with investigators and patients assessing glabellar frown lines as significantly more improved after incobotulinumtoxinA injection than with placebo (p < .001). IncobotulinumtoxinA was well tolerated. CONCLUSION A single dose of 20 U of incobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar frown lines using new Food and Drug Administration efficacy variables.

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 investigators rating on the FWS, and 2‐point or more responders at maximum frown on Day 30 according to the patients 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.

Safety and Tolerability of High-Intensity Focused Ultrasonography for Noninvasive Body Sculpting: 24-Week Data From a Randomized, Sham-Controlled Study

BACKGROUND High-intensity focused ultrasonography (HIFU) is a nonsurgical, noninvasive method for body sculpting in nonobese patients. The technique ablates subcutaneous adipose tissue by causing molecular vibrations that increase tissue temperature and induce rapid cell necrosis. OBJECTIVES The authors evaluate the long-term safety of a HIFU device for sculpting the abdomen and flanks. METHODS Adults with subcutaneous abdominal fat ≥2.5 cm in thickness who met screening criteria were randomized to receive HIFU treatment of the anterior abdomen and flanks at 1 of 3 energy levels (3 passes per patient): 47 J/cm(2) (141 J/cm(2) total), 59 J/cm(2) (177 J/cm(2) total), or 0 J/cm(2) (no energy applied; sham control). Safety was assessed for 24 weeks and included laboratory testing, physical examinations, and documentation of adverse events. RESULTS Adverse events (AE) included mild to moderate discomfort, ecchymosis, and edema, all of which were transient. There were no reports of scarring or burns and no clinically meaningful changes in lipid panel findings, inflammatory markers, or renal or hepatic function. Physical examination results were unremarkable. CONCLUSIONS This HIFU device exhibited an AE profile similar to that of sham treatment. There were no significant changes from baseline in laboratory values, including lipid levels.

Improvement in nasolabial folds with a hyaluronic acid filler using a cohesive polydensified matrix technology: results from an 18-month open-label extension trial.

BACKGROUND Repeat treatments of nonpermanent dermal fillers are used in the long‐term treatment of wrinkles and folds and to volumize. OBJECTIVE To determine the safety and effectiveness of a nonanimal‐sourced hyaluronic acid (HA) (which uses a cohesive polydensified matrix (CPM) technology [CPMHA]) for the treatment of nasolabial folds (NLFs) during an 18‐month open‐label extension trial. METHODS AND MATERIALS Ninety‐five of 118 subjects continued with this optional open‐label extension of a split‐face, double‐blind trial. All subjects received CPMHA in both NLFs at 24 weeks after treatment in this study and were assessed at weeks 32, 48, 72, and 96. Touch‐ups were allowed for optimal correction. Safety was assessed according to reported adverse events (AEs) and serum antibody measurement. RESULTS At all four post‐week 24 time points, the severity of the NLFs showed a decrease from baseline on the Wrinkle Severity Rating Scale. The effects persisted in the majority (˜80%) of subjects without repeat treatment for at least one interval of 48 weeks. The study filler was well tolerated, with only one related AE (injection site bruising) reported. Little potential for immunogenic reactions was identified. CONCLUSION This CPMHA is a well‐tolerated and effective treatment for at least 48 weeks in the majority of subjects for the correction of moderate to severe NLFs with repeat injections given over an 18‐month period. This study was sponsored by Merz Pharmaceuticals, LLC. B. Hardas, M. Kaur, S. Grundy, and E. Pappert are employees of Merz. The authors were compensated for their work as investigators.

Nonanimal Sourced Hyaluronic Acid–Based Dermal Filler Using a Cohesive Polydensified Matrix Technology is Superior to Bovine Collagen in the Correction of Moderate to Severe Nasolabial Folds: Results from a 6‐Month, Randomized, Blinded, Controlled, Multicenter Study

BACKGROUND Dermal fillers are used to augment wrinkles and folds, and a variety of hyaluronic acid (HA)‐based products are available. The non‐animal‐sourced HA studied was cross‐linked using a two‐step process and employing cohesive polydensified matrix (CPM) technology. This HA gel (CPMHA) has variable density and viscosity zones for adaptation in the dermis. OBJECTIVE To compare the safety and effectiveness of CPMHA with that of bovine collagen (COL) in the correction of moderate to severe nasolabial folds (NLFs) in a split‐face study. METHODS AND MATERIALS One hundred eighteen subjects were randomized to receive CPMHA and COL on contralateral sides of the face. NLF severity was measured using the Wrinkle Severity Rating Scale (WSRS). The initial treatment was evaluated after 2 weeks, and an optional touch‐up to optimal cosmetic correction was permitted if needed. Subjects returned every 2 weeks (up to 24 weeks) for evaluation. Safety was assessed using spontaneous adverse event (AE) reporting. RESULTS CPMHA resulted in a significantly greater reduction in the mean change of WSRS than COL at weeks 8 (p=.009), 12 (p<.001), 16 (p<.001), and 24 (p<.001). There were no significant differences between the two groups in the proportion of AEs considered related to the injection site procedure. Most AEs were mild to moderate in severity and resolved within 7 days. CONCLUSION CPMHA was well tolerated and first demonstrated to be noninferior and then superior in terms of effectiveness to COL over 24 weeks for the treatment of NLF, including the primary end point at week 12. Merz Pharmaceuticals, LLC funded this Food and Drug Administration clinical trial. Bhushan Hardas, Mandeep Kaur, Starr Grundy, and Eric Pappert are employees of Merz Pharmaceuticals.

A randomized, evaluator-blinded, controlled study of the effectiveness and safety of small gel particle hyaluronic acid for lip augmentation.

OBJECTIVES To assess the effectiveness and safety of small gel particle hyaluronic acid (SGP‐HA) for lip augmentation. METHODS Adults (n = 180; aged 18–65) scoring 1 (very thin) to 2 (thin) on the 5‐point validated Medicis Lip Fullness Scale (MLFS) for the upper or lower lip were randomized (3:1) to SGP‐HA (≤1.5 mL/lip) or no treatment. Co‐primary effectiveness end points were blinded‐evaluator MLFS score for upper or lower lip at week 8. Secondary end points (MLFS score, independent photographic review, Global Aesthetic Improvement Scale [GAIS], safety assessments) were measured throughout the study. RESULTS Statistically significantly more MLFS responders (≥1 grades of MLFS improvement at week 8) received SGP‐HA (93% combined upper and lower lip responders [95% upper lip; 94% lower lip]) than no treatment (29% combined; p < .001). SGP‐HA improved self‐assessed combined lip GAIS (97% week 8; 74% week 24) significantly more than no treatment (0% throughout; p < .001). The SGP‐HA group reported anticipated swelling (58%) and bruising (44%), 88% mild or 11% moderate severity, without unanticipated device adverse events. CONCLUSIONS SGP‐HA is highly effective and well tolerated for lip augmentation. Statistically significant improvement was evident based on the MLFS at 8 weeks, with visible results reported in the majority of participants 6 months after treatment.

Development and Validation of a Photonumeric Scale for Evaluation of Volume Deficit of the Temple.

BACKGROUND A validated scale is needed for objective and reproducible comparisons of temple appearance before and after aesthetic treatment in practice and clinical studies. OBJECTIVE To describe the development and validation of the 5-point photonumeric Allergan Temple Hollowing Scale. METHODS The scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each grade. The clinical significance of a 1-point score difference was evaluated in a review of image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 298) completed during 2 sessions occurring 3 weeks apart. RESULTS A score difference of ≥1 point was shown to reflect a clinically significant difference (mean [95% confidence interval] absolute score difference, 1.1 [0.94–1.26] for clinically different image pairs and 0.67 [0.51–0.83] for not clinically different pairs). Intrarater agreement between the 2 validation sessions was almost perfect (mean weighted kappa = 0.86). Interrater agreement was almost perfect during the second session (0.81, primary endpoint). CONCLUSION The Allergan Temple Hollowing Scale is a validated and reliable scale for physician rating of temple volume deficit.