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Background Artificial intelligence (AI) platforms are increasingly being utilized in various healthcare applications. There are few platforms that provide quantifiable assessments of dermatologic or aesthetic conditions by employing industry established scales. Objectives The authors sought to report the results of a pilot study that evaluated the utilization and functionality of an AI engine to measure and monitor rhytids (fine lines). For this study, glabellar frown lines were employed as the clinical model. Methods Seventy-one patients were enrolled and monitored remotely employing current high-quality mobile phone cameras over a 14-day period. The patients were prompted to take photographs employing this platform at preset intervals, and these photographs were then rated by the AI platform and qualified raters experienced in the field of facial aesthetics. Results The AI platform had concordance with 2 qualified raters of 46% to 68%, and the inter-rater concordance between 2 rates ranged from 44% to 66%. The intra-rater concordance for the raters was between 57% and 84%, whereas the AI platform had a 100% concordance with itself. The participant and investigator satisfaction ratings of the platform were high on multiple dimensions of the platform. Conclusions This AI platform evaluated photos on a comparable level of accuracy as the qualified raters, and it evaluated more consistently than the qualified raters. This platform may have high utility in clinical research and development, including the management of clinical trials, and efficient management of patient care at the clinical practices.

Background Cellulite is an aesthetic condition affecting the appearance of skin in certain body regions and is associated with body dissatisfaction, psychosocial stress, and decreased quality of life. Previous studies established the safety and feasibility of a novel, minimally invasive device to identify and release septa responsible for cellulite depressions: targeted verifiable subcision (TVS). Objectives The objective of this single-arm, open-label, multicenter study was to evaluate the safety and efficacy of TVS for reducing the appearance of moderate to severe cellulite in adult women. Methods Adult women aged 21 to 55 years and a BMI Results Seventy-four female participants with a mean BMI of 24.8 ± 2.7 and age of 41.4 ± 7.4 years received this single procedure. The mean improvement in Cellulite Severity Scale (N = 68) was 1.5 ± 0.9 (P Conclusions TVS for selectively identifying and verifiably releasing septa responsible for cellulite depressions is an effective and safe means to improve the appearance of moderate to severe cellulite in adult women. Level of Evidence: 2

Many signs of aging manifest in the neck region, including platysmal bands, excess skin, horizontal neck lines and decreasing contour of the neck. While the clinical signs of an aged neck are well-known, data determining the underlying aging process are limited.To decode aging of the neck.This prospective study investigated elasticity and firmness of skin, muscle activity and skin displacement upon muscular contraction in the neck in 77 young-, middle- and old-age individuals. Objective outcome measures, including 3-dimensional imaging, cutometry and surface electromyography, were utilized for all assessments.Mean firmness of skin decreased significantly from young to old individuals (0.37 ± 0.13 mm, 0.30 ± 0.12 mm and 0.26 ± 0.12 mm in young, middle and old subjects, respectively; p lt; 0.001). Gross elasticity decreased significantly from 75.1 ± 13.0% in young subjects, to 64.53 ± 15.7% in middle-aged subjects and 55.79 ± 13.0% in old subjects (p lt; 0.001). The mean y-axis skin displacement increased from 2.48 ± 4.33 mm in young subjects, to 3.11 ± 4.49 mm in middle-aged subjects and 3.61 ± 5.38 mm in old subjects (p = 0.006). The mean signal-to-noise ratio decreased significantly from 16.74 ± 5.77 µV in young subjects, to 14.41 ± 4.86 µV in middle-aged subjects and to 12.23 ± 5.99 µV in old subjects (p lt; 0.001).This study provides insights into the interplay between skin elasticity, muscular activity and the reflected movement of the skin of the neck. Appreciation of these age-related changes lays the fundament for aesthetic treatments in this delicate region.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Despite various aesthetic trends, the ideal lip proportion and lip volume remains elusive. Thus, the aim of this study was to investigate the aesthetic perception of various lip shapes to identify the most attractive lips.Fifty-nine White study participants with a mean age of 32.73 ± 9.4 years were asked to assess lips of various proportions and of various volumes. Gaze assessment and aesthetic rating of the same set of modified lip images were performed.The results revealed that the lip proportion that was rated to be most attractive was the 1:1.6 ratio (upper-to-lower lip, 4.21 of a possible 5). This lip proportion, however, was not the first one to be viewed on initial image display (1.20 sec) and had the shortest duration of a stable eye fixation within the 6-second image display interval (2.18 of 6 seconds). The lip volume that received the highest aesthetic rating was the 100 percent volume (original lip size), with 4.56 of a possible 5. This lip volume, however, had the third longest interval between initial image exposure and the first stable eye fixation (0.81 second) and had the shortest duration of stable eye fixations during the 6 seconds of image display (2.22 of 6 seconds).The results presented could be potentially reflective of the internal cognitive processes during the involuntary and voluntary assessment of lip attractiveness.

Nonsurgical rhinoplasty procedures using soft tissue fillers have gained popularity. With the increasing frequency of such procedures, the incidence of intra-arterial injection of soft tissue filler material and subsequent ischemia has also risen. This article analyzes the topographic anatomy of the dorsal nasal artery in the nasal soft tissue to potentially enhance patient safety in nonsurgical rhinoplasty procedures. The dorsal nasal artery shows a variable topographic course, especially in relationship to the procerus muscle. By understanding the topographic courses of the dorsal nasal artery, aesthetic practitioners may be able to perform nonsurgical rhinoplasty procedures with increased safety and efficacy.

Background Neuromodulators have proven efficacy in reducing facial rhytides and have also been reported to improve jawline contour and the appearance of platysmal bands. Lifting effects of the tail of the eyebrow are expected outcomes when targeting the lateral periorbital region, underscoring the versatility of neuromodulator treatments. Objectives The aim of this study was to analyze the clinical effectiveness of a novel neuromodulator-based injection algorithm with regards to its ability to reposition the middle and lower facial soft tissues. Methods Seventy-five study participants (8 males, 67 females) with a mean [standard deviation] age of 37.5 [8.5] years were injected with neuromodulators in the subdermal plane of the mandibular soft tissues following a standardized algorithm. Live rating of clinical appearance was performed, as well as volume change and skin vector displacement measured by 3-dimensional imaging at baseline, Day 14, and Day 30. Results Three-dimensional volume analysis revealed an increase in midfacial volume by 0.46 mL, and a decrease of the lower facial volume by 0.30 mL compared with baseline. Additionally, an improvement of midfacial fullness (by 0.13) and jawline contour (by 0.44) was reported on clinical rating scales at Day 30 compared with baseline. Conclusions Facial soft tissues can be repositioned during the 30-day follow-up period following a neuromodulator treatment; this was reflected through an increase in midfacial volume as well as through a decrease in lower facial volume. The novel injection algorithm presented can provide a safe and effective option for patients desiring improvement of midfacial fullness and jawline contour with neuromodulator treatment alone. Level of Evidence: 4

Quantifying the degree of dorsal hand atrophy is a challenging endeavor, but often necessary, in both the clinical and the research setting. The aim of this investigation was to create and consecutively validate a 5-point photonumeric scale for assessment of dorsal hand atrophy.A medical team created a novel 5-point photonumeric scale. Twelve international raters were involved in the digital validation, while five raters performed a live validation.For the digital validation of the Croma Hand Atrophy Assessment Scale, a total of 72 subjects (58 females, 14 males) with a mean age of 43.0 ± 14.4 years [18-73 years] were assessed. For the live validation, 88 subjects (73 females, 15 males) with a mean age of 45.0 ± 14.1 years [20-73 years] were rated. The results revealed almost perfect intra-rater (ICC: 0.90 [95% CI: 0.88-0.92]) and inter-rater agreements (ICC: 0.85 [95% CI: 0.81-0.89] and 0.86 [95% CI:0.82-0.89]) in the digital validation and substantial intra-rater (ICC: 0.79 [95% CI: 0.75-0.82]) and inter-rater agreements (ICC: 0.75 [95% CI: 0.68-0.81] and ICC: 0.67 [95% CI: 0.54-0.77]) in the live validation.The created scale to assess dorsal hand atrophy has been shown to provide substantial-to-almost perfect agreement in the digital and live validation cycles and reached comparable intra-rater and inter-rater agreement to already published and validated scales. It is expected that the created scale will help physicians and researchers in the assessment of hand atrophy in the clinical and research setting in the future.

After studying this article, the participant should be able to: 1. Recognize facial muscle contraction direction and muscle morphology based on skin surface movements and facial rhytides. 2. Classify different muscle contraction patterns and target respectively with the recommended dosage and injection technique. 3. Apply the presented injection techniques to the patients' individual anatomy with greater precision and without affecting adjacent muscles or causing other adverse events.Facial muscular anatomy has recently gained increased attention, with new investigative methodologies and new injection techniques arising on the market. These recent advancements have increased our understanding about the functional anatomy of facial muscles and have changed the way health care professionals see and understand their interplay during various facial expressions and in determining facial shape. This new anatomical understanding of facial muscles and their interaction has resulted in superior neuromodulator treatment outcomes with fewer side effects and with increased precision. The latter is of greatest importance, as all facial muscles act as a unit and connect with each other. It is therefore paramount to target during neuromodulator treatments only the muscle responsible for the aesthetic effect desired and not other adjacent muscles, which can have different or even antagonistic effects. Conventional anatomy was previously limited to two-dimensional explanations of muscle locations without incorporating their detailed action or their three-dimensional location of extent. The "new" anatomy incorporates those novel concepts and, once understood, will help health care providers to understand better and to "read" the underlying muscular anatomy based on the wrinkle status and based on the change in skin surface landmarks based on the actions of the underlying musculature. The following article summarizes tips and tricks, pearls and pitfalls, and dos and don'ts during facial neuromodulator injections along with a guide toward adverse event management and patient outcome assessment with special focus on the underlying anatomy.

Background Precise injection technique is vital for avoiding suboptimal eyebrow position when treating glabellar lines with botulinum toxin type A. Objectives The aim of this study was to evaluate the impact of glabellar injection technique on eyebrow position in patients treated with DaxibotulinumtoxinA for Injection (DAXI). Methods This retrospective post hoc analysis involved 60 adults who received a single treatment with DAXI 40 U to the glabella and had standardized facial photography. Median vertical and horizontal displacement of the brows (at rest) at baseline and 2 weeks after glabellar injection were measured. Brow position outcomes were evaluated by an oculoplastic surgeon and expert anatomist. Investigators were interviewed to ascertain individual injection techniques. Results Precise injection location and depth, and median resting brow position following treatment varied between investigators. Positive brow outcomes were achieved with deep DAXI injections into the medial corrugator, superficial lateral corrugator injections placed between the midpupil and lateral limbus, and deep midline procerus injections. Glabellar injection technique that more precisely targeted the corrugator muscles resulted in longer glabellar line treatment duration compared to a less targeted technique. Medial corrugator injections above the medial brow; lateral corrugator injections administered deeply or more medially, toward the medial third of the brow; and procerus injections superior to the inferomedial brow tended to be associated with suboptimal outcomes that were more apparent during dynamic expression. Conclusions Aesthetically pleasing brow outcomes and greater duration of efficacy can be achieved with an injection pattern that precisely treats the anatomic location of the corrugator supercilii and procerus muscles, avoiding the frontalis. Level of Evidence: 4

One-third of U.S. adults are bothered by excessive sweating and 5% suffer from hyperhidrosis, both of which negatively affect quality-of-life (QoL). A single-use disposable patch using the novel targeted alkali thermolysis (TAT) technology is being developed to address this condition.Assess the efficacy and safety of the TAT patch for the treatment of excessive sweating using a randomized, double-blind, sham-controlled study design.Adults with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 ( n = 16) were treated with an active or sham patch for up to 3 minutes (as established in a previous unpublished feasibility study) and evaluated weekly for 6 weeks post-treatment. The primary effectiveness measure was improved HDSS at Week-4.The study met its objective. For the primary efficacy measure, 83% of TAT-treated subjects reported HDSS scores of 1 or 2 at Week-4 versus 0% of sham-treated subjects ( p = .0032). Furthermore, 67% of TAT-treated subjects had a 2-point improvement in HDSS scores versus 0% of sham-treated subjects ( p = .0123). Quality-of-life improvement correlated with HDSS. The TAT patch seemed to be well-tolerated; one transient moderate adverse event that resolved without sequelae was reported.The TAT patch successfully demonstrated efficacy and was well-tolerated.

Background Safety and efficacy endpoints for the single-arm, multicenter, open-label pivotal study, CONtrolled Focal Fibrous Band Release Method (CONFFIRM) [NCT04743635] assessing targeted verifiable subcision (TVS) for the treatment of cellulite were met at 3 months postprocedure and have been published. Final, 12-month data describing durability of treatment effect and safety are presented here for the first time. Objectives The authors sought to evaluate safety and efficacy out to 12 months of initial treatment for a single TVS procedure performed employing the Avéli device (Revelle Aesthetics, Inc.; Mountain View, CA) to treat cellulite on the buttock and thigh areas of adult females. Methods Effectiveness was determined by 3 independent physicians employing the Cellulite Severity Scale and Global Aesthetic Improvement Scale to assess improvement of baseline photographs when compared with 3-, 6- and 12-month posttreatment photographs. Blinded participant-reported outcomes and safety evaluations were also performed at all postprocedure time points. Results Clinically significant improvement in primary endpoint Cellulite Severity Scale scores were sustained out to 1 year, improving by 1.50 (P < .0001) at 3 months, 1.54 points at 6 months, and 1.48 points at 12 months. Adverse events were mild and mostly resolved by the 12-month visit. Conclusions A single TVS treatment has durable efficacy and safety in reducing cellulite on the buttocks and thighs of women with moderate to severe cellulite out to 12 months posttreatment. Level of Evidence: 2

Background The number of soft-tissue filler injections performed in the United States is constantly increasing and reflects the high demand for enhanced facial and body attractiveness. The objective of the present study was to measure the viscoelastic properties of soft-tissue fillers when subjected to different testing frequencies. The range of tested frequencies represents clinically different facial areas with more [lips (high frequency)] or less [zygomatic arch (low frequency)] soft-tissue movement. Methods A total of 35 randomly selected hyaluronic acid-based dermal filler products were tested in an independent laboratory for their values of G', G″, tan δ, and G* at angular frequencies between 0.1 and 100 radian/second. Results The results of the objective analyses revealed that the viscoelastic properties of all tested products changed between 0.1 and 100 radian/second angular frequency. Changes in G' ranged from 48.5 to 3116 percent, representing an increase in their initial elastic modulus, whereas changes in G″ ranged from -53.3 percent (i.e., decrease in G″) to 7741 percent (i.e., increase in G″), indicating both an increase and a decrease in their fluidity, respectively. Conclusions The increase in G' would indicate the transition from a "softer" to a "harder" filler, and the observed decrease in G″ would indicate an increase in the filler's "fluidity." Changes in the frequency of applied shear forces such as those occurring in the medial versus the lateral face will influence the aesthetic outcome of soft-tissue filler injections.

Background 2D baseline and follow-up clinical images are potentially subject to inconsistency due to alteration of imaging parameters. However, no study to date has attempted to quantify the magnitude by which such images can be influenced. Objective The objective of the present study is to identify the magnitude by which images can be influenced by changing the imaging light angle. Methods This study is based on the evaluation of 2D frontal images of the face and included a total of 51 subjects of which n = 14 were males and n = 37 were females. Faces were photographed at 0°, 30°, and 60° light angle under identical and standardized conditions. Images were randomized and rated by 27 blinded raters for age, facial attractiveness, body mass index (BMI), temporal hollowing, lower cheek fullness, nasolabial sulcus severity, and jawline contour. Results Facial attractiveness decreased, facial unattractiveness increased and the evaluated BMI (based on facial assessment) increased statistically significantly at 60°. The assessment of regional facial scores, i.e., temporal hollowing, lower cheek fullness, and jawline contour, showed no statistically meaningful changes both at 30° and at 60° light angle. Conclusion The results indicate that there might be an observed blind range in light angle (0°–30°) which does not influence facial assessment. Increasing the light angle past the threshold value to 60° might result in a statistically significant impact on facial perception which should be accounted for when documenting and/or presenting facial 2D images. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Background The most severe complications following soft tissue filler injections result from the intraarterial administration of the filler product. Although hyaluronic acid–based filler can be trans-arterially dissolved with hyaluronidase, no information is available on calcium hydroxylapatite (CaHA)-based fillers. Objective The authors sought to test whether CaHA-based fillers can be trans-arterially dissolved by sodium thiosulfate (STS) when evaluated in cadaveric and in vitro models. Methods Human cadaveric facial arterial segments were each filled with 0.2 cc of commercially available CaHA product and submerged for 24 hours in 4 different STS-containing solutions: 10 cc STS (300 mg/cc) (pure, 1:1 dilution, 1:2 dilution), 0.9% saline and 10 cc STS (300 mg/cc), and 300 IU (bovine) hyaluronidase in a 1:1 ratio. Results Intraarterial CaHA was detected in human facial artery segments after 24 hours independent of the STS concentration employed. Submerging the arterial segments in STS (300 mg/cc) and 300 IU (bovine) hyaluronidase (1:1 ratio) also did not dissolve the intraarterial CaHA product. Gray scale analyses did show, however, that increasing concentrations of STS resulted in increased disintegration of CaHA in an in vitro experimental setting. Conclusions The results of this study indicate that STS is limited in its potential to dissolve intraarterial CaHA of cadaveric human facial arteries, despite the fact that it appears effective when in direct contact with the CaHA. Adverse events caused by intraarterial administration of CaHA-based fillers still lack a suitable antidote.

Background ATX-101 (deoxycholic acid) significantly reduced submental fat (SMF) severity in two 24-week Phase 3 studies (REFINE-1 and REFINE-2). Objectives The aim of this study was to evaluate the durability of effect and long-term safety of ATX-101. Methods REFINE study patients who maintained ≥1-grade improvement on the Clinician-Reported SMF Rating Scale (CR-1 responders) 12 weeks after their last REFINE treatment were eligible for enrollment in this multicenter, double-blind, nontreatment, long-term, follow-up study (NCT02163902). The primary endpoint was CR-1 response at Years 1, 2, and 3. Patient-reported satisfaction, psychological impact, and adverse events were monitored. Results In total, 224 patients (ATX-101, n = 113; placebo, n = 111) were enrolled. Maintenance of CR-1 response was significantly better in the ATX-101 group than in the placebo group at Year 1 (86.4% vs 56.8%; P Conclusions Improvements in submental contour achieved with ATX-101 are maintained for 3 years in most patients. No new safety signals emerged. Level of Evidence: 2

Biophysical modeling of development started with Alan Turing. His two-morphogen reaction-diffusion model was a radical but powerful simplification. Despite its apparent limitations, the model captured real developmental processes that only recently have been validated at the molecular level in many systems. The precision and robustness of reaction-diffusion patterning, despite boundary condition-dependence, remain active areas of investigation in developmental biology.

Background Most injection techniques utilizing hyaluronic acid-based soft tissue fillers have predictable outcomes at the location injected. However, the temporal region has been identified to have aesthetic effects beyond the temple. Aims To identify and quantify the panfacial aesthetic effects of three different temporal injection techniques. Patients/methods The medical records of nine female and five male Caucasian patients with a mean age of 50.9 ± 11.9 years were retrospectively reviewed for the effects of these techniques: supraperiosteal, interfascial, and subdermal. Panfacial effects were evaluated by the semiquantitative assessment of aesthetic scores for the temple volume, the temporal crest visibility, the lateral orbital rim visibility, the position of the eyebrows, the severity of lateral canthal lines, the midfacial volume, and the contour of the jawline. Results The supraperiosteal injection technique had the greatest influence on improving the temporal volume (25.0%), the temporal crest (33.3%), and the lateral orbital rim visibility (31.0%) scales but had no effects in other facial regions. The interfascial injection technique revealed good effects on improving temporal hollowing (23.3%) but had an even greater effect on the crow's feet (26.8%) and on the position of the eyebrow (33.3%). The subdermal injection technique had its greatest effects in the lower face by improving the contour of the jawline (26.8%) followed by the improvement of the lower cheek fullness scale (14.3%). Conclusion Future injection algorithms could utilize all three injection techniques together as one multi-layer injection approach with a tailored proportion of each technique based on the aesthetic needs of the patient.

Objective The aim of the study was to identify the effectiveness of the combination of tissue stabilized guided subcision, microfocused ultrasound, and minimally invasive calcium hydroxylapatite injections in various sequences for treating skin surface irregularities of the buttocks and thighs. Material and methods 61 females (body mass index: 22.6 p 2.4 kg/ms, age: 37.2 p 6.8 years) were enrolled in this randomized interventional prospective study. Treatment arms included a variable combination and sequence of three treatment modalities: (1) Tissue-stabilized guided subcision, (2) microfocused ultrasound, and (3) calcium hydroxylapatite injections. Six months after the final intervention skin laxity and skin dimpling severity scores were assessed by the study participants, the treating physicians and by eleven blinded independent board-certified experts. Results No adverse events were observed during the study that required intervention outside the standard of care treatment protocol. The combination of three treatment modalities was shown to provide greater improvement in skin laxity 1.88 (95% CI, 0.66n5.37) and skin dimpling 1.31 (95% CI, 0.61n2.81) scores as compared to any combination of two modalities. The combination of concomitant microfocused ultrasound and calcium hydroxylapatite injections followed three months later by tissue stabilized guided subcision yielded the greatest improvement in skin laxity 2.23 (95% CI, 0.51n9.82) and skin dimpling 1.79 (95% CI, 0.67n4.78) at 9-month follow-up. Conclusion This study provides evidence for the effectiveness of combination therapies for the improvement of skin surface irregularities on the buttocks and thighs. J Drugs Dermatol. 2020;19(11): 1030-1038. doi:10.36849/JDD.2020.5117.

Background Operative procedures to enhance the aesthetic appearance of the feet are associated with risks. Minimally invasive procedures to volumize the dorsum of the foot are to this point not described. The present study investigates the safety and efficacy of such procedures in a retrospective clinical, anatomical, and ultrasound-based study. Methods A total of 106 feet from 53 female patients (mean age, 64.1 ± 8.3 years) were investigated retrospectively after the injection of a commercially available calcium hydroxylapatite product using a single-entry proximal-to-distal fanning injection technique. Anatomical dissections in 20 fresh, nonembalmed feet from 10 human body donors (mean age, 83.1 ± 8.8 years) were dissected, and 20 feet from 10 healthy volunteers (mean age, 26.5 ± 6.2 years) were examined by ultrasound imaging to help guide conclusions. Results Aesthetic outcome after 3 months was graded by the patients as 4, connoting good improvement (range, 3 to 5). No allergic reactions or other types of adverse events were documented. The layered anatomy of the dorsum of the foot was confirmed by anatomical dissections and ultrasound imaging as follows: skin, dorsal superficial fatty layer, dorsal superficial fascia, dorsal intermediate fatty layer, superficial lamina of the dorsal deep fascia, dorsal deep fatty layer, and deep lamina of the dorsal deep fascia. Conclusions Minimally invasive injections of soft-tissue filler in the dorsum of the foot can provide an alternate solution to enhance the aesthetic appearance of feet. The present study provides support for the safety and efficacy of volumizing procedures using a 22-gauge, 50-mm, blunt-tip cannula. Clinical question/level of evidence Therapeutic, IV.

Background Pre-injection aspiration procedures could increase safety during soft tissue filler injections. However, various influencing factors have been detected in vitro that could result in false negative aspiration results. Objective A case series was retrospectively investigated to identify factors contributing to positive blood aspiration procedures in vivo. Methods This study evaluated 213 clinical cases positive for blood aspiration documented in an Asian population: 208 females (43.8 ± 7.2 years old) and 5 males (46.8 ± 7.8 years old) during soft tissue filler injections. Injection location, layer (depth) of injection, product injected, size of utilized needle (gauge), length of needle (inch), priming of needle (yes/no), injection angle (degree), and time until blood was visible in the needle hub (seconds) were evaluated. Results The most frequent location where a positive aspiration was observed was the pyriform fossa (n = 56; 26.3%), the most frequent plane was the supra-periosteal plane (n = 195; 91.5%), and the most frequent needle utilized was a 27G needle (n = 125; 58.7%). Statistically significantly more positive cases were identified when the needle was primed compared with an unprimed needle (P Conclusions Pre-injection aspiration could be a valuable tool to prevent accidental intravascular injection of soft tissue filler. The results of the present investigation show that aspiration can be performed with an acceptable aspiration time, that is, less than 2 seconds, if a suitable product/needle combination is chosen. Level of Evidence: 4

Objective The most promising facial region for inducing pan-facial effects is the temporal region. The temple displays signs of facial aging itself which include temporal volume loss and increased visibility of the temporal crest, the temporal vasculature, the lateral orbital rim, and the upper zygomatic arch. The objective of this article is to provide a detailed review of temple anatomy pertaining to routinely performed temporal injection techniques, their expected esthetic outcomes as well as the intendant advantages, disadvantages, and procedure pearls. Materials and methods This narrative review is based on the clinical experience of the authors treating the temporal region for esthetic purposes. The postulated outcome of each technique was observed during the routine clinical practice of the authors. Results The temporal region is based on a bony platform consisting of the parietal, frontal, sphenoid, and temporal bones. The overlying soft tissues are arranged in layers which contain the temporal neurovascular structures. The temporal soft tissues consist of 10 parallel layers which vary in their thickness depending on age-related influences. Six different techniques will be addressed, which include subdermal and interfascial techniques for volumizing, low and high supraperiosteal techniques for volumizing, and supraauricular and temporal lifting techniques. Conclusion This narrative provides a detailed anatomic overview of the temporal region and describes each commonly performed injection technique with respect to anatomy, esthetic outcome, as well as potential pearls and pitfalls. It is hoped that the description contained herein may guide esthetic practitioners toward safer and more natural outcomes when treating the face.

Background Lips are considered a key element of facial attractiveness due to their central position in the face and their elemental role in verbal and nonverbal communication. Objectives The authors sought to provide clinically relevant information on the 3-dimensional pathway of the superior and inferior labial arteries within the lips to increase safety during labial soft tissue filler injections. Methods The study enrolled 41 healthy volunteers with a mean age of 26.17 ± 9.6 years and a mean body mass index of 23.09 ± 2.3 kg/m2. Ultrasound imaging was performed at 6 different locations. The position of the labial arteries within the lips, depth of the arteries, cranio-caudal location of each artery in relation to the vermilion border, and diameter of the superior/inferior labial arteries were recorded. Results The most frequent location of both the superior and inferior labial arteries was the submucosal plane (58.5%) followed by intramuscular (36.2%) and subcutaneous (5.3%) planes. The depth of the superior labial artery in the upper lip was 5.6 ± 0.13 mm, whereas the depth of the inferior labial artery in the lower lip was 5.2 ± 0.14 mm. Both arteries were more frequently located within the red lip: upper lip (83% vs 18.7%) and lower lip (86.2% vs 13.8%). In the midline, the artery coursed within the red lip in all investigated volunteers. Conclusions Clinically, results of this study favor a superficial injection plane for lip volumization procedures. A perpendicular approach to the lip (coming from the cutaneous lip) might increase safety because the artery is located most frequently within the red lip.

Background Cosmetic treatment of the forehead using neuromodulators is challenging. To avoid adverse events, the underlying anatomy has to be understood and thoughtfully targeted. Clinical observations indicate that eyebrow ptosis can be avoided if neuromodulators are injected in the upper forehead, despite the frontalis muscle being the primary elevator. Methods Twenty-seven healthy volunteers (11 men and 16 women) with a mean age of 37.5 ± 13.7 years (range, 22 to 73 years) and of diverse ethnicity (14 Caucasians, four African Americans, three Asians, and six of Middle Eastern descent) were enrolled. Skin displacement vector analyses were conducted on maximal frontalis muscle contraction to calculate magnitude and direction of forehead skin movement. Results In 100 percent of investigated volunteers, a bidirectional movement of the forehead skin was observed: the skin of the lower forehead moved cranially, whereas the skin of the upper forehead moved caudally. Both movements converged at a horizontal forehead line termed the line of convergence, or C-line. The position of the C-line relative to the total height of the forehead was 60.9 ± 10.2 percent in men and 60.6 ± 9.6 percent in women (p = 0.941). Independent of sex, the C-line was located at the second horizontal forehead line when counting from superior to inferior (men, n = 2; women, n = 2). No difference across ethnicities was detected. Conclusions The identification of the C-line may potentially guide practitioners toward more predictable outcomes for forehead neuromodulator injections. Injections above the C-line could mitigate the risk of neuromodulator-induced brow ptosis.

Epithelial bending is a fundamental process that shapes organs during development. Previously known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Here we report a different mechanism that occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement: cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards. Movement is achieved by active cell-on-cell migration: outer cells migrate with apical, centripetally polarised leading edge protrusions but remain attached to the basal lamina, depressing more central neighbours to “telescope” the epithelium downwards into underlying mesenchyme. Inhibiting protrusion formation by Arp2/3 protein blocks invagination. FGF and Hedgehog morphogen signals are required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by a morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes., Mechanisms that regulate epithelial bending mainly link to cell shape changes, for example, the formation of wedge shaped cells. Here, the authors identify a different cell behaviour in the salivary glands and teeth where initial invagination arises by a coordinated vertical cell movement.

Limited dilute lidocaine infiltration facilitates a comfortable procedure and a rapid recovery process following a novel intervention for reduction of cellulite. Infiltration of dilute lidocaine has many other practical applications in dermatologic surgery.This article describes a safe, effective technique for local infiltration of limited volume dilute lidocaine anesthesia in a cellulite reduction procedure.The limited dilute lidocaine technique was utilized in studies of a novel device designed to reduce the appearance of cellulite by focal release of fibrous septa in a minimally invasive procedure. No sedation was used. A small (27- to 30-gauge) needle was used to deliver anesthesia to the entry sites. Then, a 20-gauge spinal needle was tunneled under the skin in the superficial plane to manually deliver anesthetic along the advancement pathway of the device and marked cellulite targets.During the initial studies, the mean delivered anesthesia volume was 357.2 ml (range, 250-525 ml) or 18.7 mg/kg (range, 11.1-28.4 mg/kg). The mean anesthesia time was 16 min (range, 8-32 min). The mean number of cellulite depressions treated was 19.8 (range, 11-34). Adverse events were closely monitored, and there were no signs of toxicity in any study patients. There were very low levels of discomfort; all patients reported the procedure was tolerable. This technique facilitates a time-efficient procedure and minimizes weeping of excess fluid during recovery.When administered with care and skill, the limited dilute anesthesia technique is a safe, effective approach for local anesthesia with many practical applications in dermatologic surgery.

Background The understanding of functional facial anatomy and the interplay between facial structures is crucial for safe and effective minimally invasive and cosmetic surgical procedures. Aim In this experimental study, we investigate the hypothesis that smiling can alter the blood flow in the angular/facial vein. Materials and methods Twenty-six observations from 15 healthy volunteers (6 men, 9 women) with a mean age of 50.53 ± 13.27 (range: 24-66) were obtained. Doppler ultrasound imaging of the infraorbital segment of the angular vein (cranial to the zygomaticus major muscle) was performed and the venous flow was measured in a smiling and a resting, nonsmiling facial position. Results A statistically significant change in venous blood flow was detected upon smiling: a reduction in flow from 6.12 ± 3.0 cm/s to 0.52 ± 1.3 cm/s (P = .001). After three seconds, 80.8% of the observations had a blood flow of 0.0 cm/s. Increasing age was significantly correlated with a persistent blood flow during smiling (rp = .469; P = .016). No differences between gender and sides of the face were observed. Conclusion The results of this experimental study reveal that smiling can significantly reduce the venous flow in the angular/facial vein. Contraction of the zygomaticus major muscle compresses the vein against the underlying maxilla. Both minimally invasive and surgical procedures that alter the SMAS, the periocular musculature or the deep midfacial fat compartments might affect angular/facial venous flow.

BACKGROUND: Injections of biostimulator agents are increasing in popularity as an alternative to surgical or energy-based skin tightening procedures. The present study was designed to develop a formula that helps to guide health care providers injecting biostimulators into the correct plane to enhance effectiveness and longevity by targeting precisely the superficial fascial system. METHODS: 150 Caucasian individuals (75 males and 75 females) were investigated with a balanced distribution of age (n=30 per decade: 20–29, 30–39, 40–49, 50–59, and 60–69 years) and body mass index (n=50 per group: BMI≤24.9kg/m2, BMI between 25.0 and 29.9kg/m2 BMI≥30kg/m2). The distance between skin surface and the superficial fascia was measured via ultrasound in the buccal region, premasseteric region, the lateral neck, posterior arm, abdomen, buttocks, anterior thigh, medial thigh, and posterior thigh. RESULTS: Mean thickness of the superficial fatty layer is variable between the different locations investigated with smallest values for the lateral neck of 3.71mm ± 0.55 [range, 2.00–5.00mm] and greatest values for the gluteal region with 20.52mm±10.07 [range, 6.10–38.40mm]. A formula was developed to estimate the thickness of the superficial fatty layer based on the targeted region, age, gender, and body mass index of the patient: Thickness of superficial fatty layer (mm): Region constant + (XX* BMI) - (YY*Age). CONCLUSIONS: Injections of biostimulators deeper than the calculated values might result in reduced efficacy as the superficial fascial system is not targeted and the effected collagen neogenesis does not affect the skin surface. J Drugs Dermatol. 2020;19(1):36-44. doi:10.36849/JDD.2020.4619

BACKGROUND ATX-101 (deoxycholic acid injection) is approved for reduction of moderate or severe submental fat (SMF). OBJECTIVE To evaluate the efficacy and safety of ATX-101 in subjects with mild or extreme SMF. PATIENTS AND METHODS Adults with mild or extreme SMF (based on clinician assessment) were randomized to receive ≤6 treatments with ATX-101 or placebo. Efficacy end points, evaluated at 12 weeks after last treatment, included percentage of subjects who achieved ≥1-grade improvement in SMF from baseline based on both clinician and patient assessment (composite CR-1/PR-1 response) as well as multiple subject-reported outcomes. Safety end points included change in skin laxity and incidence of adverse events. RESULTS Overall, 61.3% of ATX-101-treated subjects versus 6.7% of placebo-treated subjects with mild SMF and 89.3% versus 13.3% of subjects, respectively, with extreme SMF achieved a composite CR-1/PR-1 response (p < .001 for both). ATX-101-treated subjects also reported higher levels of satisfaction and greater reductions in the psychological impact of SMF versus placebo-treated subjects regardless of baseline SMF severity. Skin laxity was unchanged or improved in most of the subjects. Adverse events were mainly mild/moderate, transient, and associated with the injection site. CONCLUSION ATX-101 was efficacious and well tolerated for reduction of mild or extreme SMF.

Background Nonsurgical skin-tightening procedures are increasing in popularity, as patients seek aesthetic interventions that are safe with minimal downtime. Objective This study was designed to provide precise data on the depth of the superficial fascia-the structure of action-of the face and neck. Methods One hundred fifty Caucasian individuals (75 men and 75 women) were investigated with a balanced distribution of age (n = 30 per decade: 20-29, 30-39, 40-49, 50-59, and 60-69 years) and body mass index (BMI) (n = 50 per group: BMI ≤ 24.9 kg/m, BMI between 25.0 and 29.9 kg/m, and BMI ≥ 30 kg/m). The distance between skin surface and the superficial fascia was measured through ultrasound in the buccal region, premasseteric region, and lateral neck. Results The mean distance between skin surface and superficial fascia was for the buccal region 4.82 ± 0.9 mm, range (2.60-6.90); for the premasseteric region 4.25 ± 0.6 mm, range (2.60-5.80); and for the lateral neck 3.71 ± 0.5 mm, range (2.0-5.0). The depth of the superficial fascia increased with increasing BMI, whereas it decreased with advanced age. Conclusion Knowing the precise depth of the superficial fascia for nonsurgical skin-tightening procedures will guide practitioners toward safer and more effective outcomes.

The objective of this investigation was to create and to examine the reproducibility and validity of 5-point photonumeric assessment scales that allow objective assessment of chin retrusion and jawline sagging using a digital and a live validation.Two new 5-point photonumeric scales created to assess chin projection and jawline sagging were validated by 12 experts in a digital validation and by 5 experts in a live validation setting. Intra-rater agreement and inter-rater agreement were assessed.For the digital validation, an almost perfect intra-rater (Kappa: 0.89 [95% CI: 0.86-0.91]) and almost perfect inter-rater agreement in both sessions (Kappa: 0.80 [95% CI: 0.74-0.86] and 0.80 [95% CI: 0.74-0.86]) was achieved for the Croma Chin Projection Assessment Scale, while intra-rater agreement (Kappa: 0.88 [95% CI: 0.85-0.91]) was almost perfect for the Croma Jawline Sagging Assessment Scale and inter-rater agreement being substantial in the first session (Kappa: 0.76 [95% CI: 0.71-0.81]) and almost perfect in the second session (Kappa: 0.81 [95%CI: 0.76-0.85]). For the live validation, intra-rater agreement was almost perfect for the Croma Chin Projection Assessment Scale (Kappa: 0.82 [95%CI: 0.74-0.90]) and the Croma Jawline Sagging Assessment Scale (Kappa: 0.83 [95%CI: 0.77-0.89]), while inter-rater agreement was substantial in both sessions for both scales.The created chin and jawline photonumeric grading scales are valid and reliable tools for assessing chin projection and jawline sagging. The scales will be of value for standardized chin evaluation and quantifying outcomes in clinical research and daily practice.

Background One of the early signs of aging is loss of jawline contour. Not all cases require surgical intervention and soft-tissue augmentation with injectable fillers may restore the profile and youthful appearance of the jawline. Objective To demonstrate the effectiveness and safety of calcium hydroxylapatite with lidocaine [CaHA (+); Radiesser (+)] to improve the contour of jawline after deep (subdermal and/or supraperiosteal) injection. Methods Healthy eligible patients with moderate or severe ratings on the Merz Jawline Assessment Scale (MJAS) were randomized 2:1 to treatment with CaHA (+) or to control. Patients in the control group remained untreated until week 12, then received delayed treatment. Touch-ups were allowed in both groups, and re-treatment was allowed in the treatment group only. Effectiveness was evaluated on the MJAS, patient and investigator Global Aesthetic Improvement Scales, and FACE-Qt questionnaires. Adverse events were recorded over a 60-week period. Results Treatment response rate (g1-point MJAS improvement) was 93/123 (75.6%) for the treatment group and 5/57 (8.8%) for the control/delayed-treatment group at week 12. The difference between response rates was statistically significant (Pl0.0001), showing superiority of treatment over control. Satisfaction with aesthetic improvement was reported by patients and treating investigators throughout the study. A total of 76/113 (67.3%) patients who responded to treatment 12 weeks after initial injection also demonstrated persistent improvement 48 weeks after initial treatment. The study demonstrated a favorable safety profile, with no reported unexpected adverse events. Conclusions CaHA (+) is a safe and effective treatment for improving the contour of the jawline. J Drugs Dermatol. 2021;20(11): 1231-1238. doi:10.36849/JDD.6442.

The objective of this investigation was to create and validate 5-point photonumeric scales for the assessment of dynamic crow's feet, static crow's feet, and infraorbital hollows.Three novel 5-point photonumeric scales were created by a medical team. A total of 12 raters from all over the world performed a digital validation, and a total of 5 raters a live validation of the created scale.The statistical analysis revealed almost perfect intra-rater and inter-rater reliability in the digital validation of the scales for the assessment of static and dynamic crow's feet as well as infraorbital hollows. In the live validation, both crow's feet scales showed almost perfect intra-rater reliability, while the Croma Infraorbital Hollow Assessment Scale showed substantial intra-rater reliability. Inter-rater reliability was substantial for all three scales in the live validation. All three scales, the Croma Dynamic Crow's Feet Assessment Scale, Croma Static Crow's Feet Assessment Scale, and Croma Infraorbital Hollow Assessment Scale, were validated digitally and in a live setting.The created scales to assess infraorbital hollowing, dynamic and static crow's feet have been shown to provide substantial to almost perfect agreement in the digital and live validation and can thus be considered as helpful tools in the clinical and research setting. While technical methods and appliances to assess the degrees of severity of age-dependent features are advancing, validated scales are of great importance due to their ease of use and, as shown by the validations, reliability, and reproducibility.

BackgroundThe tear trough is one of the most challenging facial regions for soft-tissue filler injections. A thorough understanding of the underlying facial, muscular, and vascular anatomy is crucial to perform safe and effective tear trough injectable treatments.ObjectivesThe authors sought to evaluate the location and function of the angular vein in the tear trough in 3 different facial expressions: repose, smiling, and max. orbicularis oculi contraction.MethodsTwenty study participants with a mean age of 48.3 years and mean BMI of 24.5 kg/m2 were investigated via functional ultrasound imaging. The diameter of the angular vein and the velocity and direction of venous blood flow were analyzed in repose, smiling, and during max. orbicularis oculi contraction.ResultsThe angular vein was identified in 100% of the cases to travel inside the orbicularis oculi muscle (intra-muscular course) within the tear trough, whereas the angular artery was not identified in this location. The distance between the angular vein and the inferior orbital rim was (lateral to medial): 4.6 mm, 4.5 mm, 3.9 mm, and 3.8 mm. The caudally directed blood flow was in repose 10.2 cm/s and was 7.3 cm/s at max. orbicularis oculi muscle contraction; however, no blood flow was detectable during smiling.ConclusionsThe diameter and the venous blood flow of the angular vein varied between the 3 tested facial expressions. Based on these anatomical findings, the deep injection approach to the tear trough is recommended due to the intramuscular course of the angular vein.

Background Current options for the reduction of acne scarring (eg, ablative laser resurfacing) are associated with considerable side effects and limitations in terms of patient population. Percutaneous collagen induction via microneedling poses an alternative treatment method due to its low rates of reported adverse events and side effects. Objective To assess the safety and effectiveness of microneedling treatments in reducing acne scars. Methods A total of 22 patients (18 females and 4 males) with a mean age of 38 ± 7.6 years were assessed regarding the appearance of facial acne scarring. Acne scars were assessed via the Acne Scar Assessment Scale (ASAS) and the Goodman and Baron acne scar grading scale before and after two/three treatments. Additionally, the post-interventional development of side reactions, adverse events, and patient-reported outcomes (eg, pain/discomfort, skin redness) was reported. Results Compared to baseline, the mean ASAS value was improved statistically significantly on average by 1.41 and 1.46 after the second treatment as assessed by the independent raters and the patients, respectively. In patients who received a total of three treatments, a statistically significant mean improvement in ASAS value of 1.35 and 1.66 compared to baseline was assessed by the independent raters and patients, respectively. No unexpected adverse events were reported. The severity and rate of side reactions decreased over the course of this study. Conclusion Microneedling treatments can pose a safe and effective option in the reduction of acne scarring. In this study, microneedling helped achieving a significant reduction of acne scars while showing high patient safety.

Amyotrophic lateral sclerosis and frontotemporal dementia are overlapping diseases in which MRI reveals brain structural changes in advance of symptom onset. Recapitulating these changes in preclinical models would help to improve our understanding of the molecular causes underlying regionally selective brain atrophy in early disease. We therefore investigated the translational potential of the TDP-43Q331K knock-in mouse model of amyotrophic lateral sclerosis-frontotemporal dementia using MRI. We performed in vivo MRI of TDP-43Q331K knock-in mice. Regions of significant volume change were chosen for post-mortem brain tissue analyses. Ex vivo computed tomography was performed to investigate skull shape. Parvalbumin neuron density was quantified in post-mortem amyotrophic lateral sclerosis frontal cortex. Adult mutants demonstrated parenchymal volume reductions affecting the frontal lobe and entorhinal cortex in a manner reminiscent of amyotrophic lateral sclerosis-frontotemporal dementia. Subcortical, cerebellar and brain stem regions were also affected in line with observations in pre-symptomatic carriers of mutations in C9orf72, the commonest genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Volume loss was also observed in the dentate gyrus of the hippocampus, along with ventricular enlargement. Immunohistochemistry revealed reduced parvalbumin interneurons as a potential cellular correlate of MRI changes in mutant mice. By contrast, microglia was in a disease activated state even in the absence of brain volume loss. A reduction in immature neurons was found in the dentate gyrus, indicative of impaired adult neurogenesis, while a paucity of parvalbumin interneurons in P14 mutant mice suggests that TDP-43Q331K disrupts neurodevelopment. Computerized tomography imaging showed altered skull morphology in mutants, further suggesting a role for TDP-43Q331K in development. Finally, analysis of human post-mortem brains confirmed a paucity of parvalbumin interneurons in the prefrontal cortex in sporadic amyotrophic lateral sclerosis and amyotrophic lateral sclerosis linked to C9orf72 mutations. Regional brain MRI changes seen in human amyotrophic lateral sclerosis-frontotemporal dementia are recapitulated in TDP-43Q331K knock-in mice. By marrying in vivo imaging with targeted histology, we can unravel cellular and molecular processes underlying selective brain vulnerability in human disease. As well as helping to understand the earliest causes of disease, our MRI and histological markers will be valuable in assessing the efficacy of putative therapeutics in TDP-43Q331K knock-in mice., Graphical Abstract Graphical Abstract

Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/β-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of β-catenin in mouse molar epithelium, we found that loss of Wnt/β-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active β-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/β-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.

Background Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening. Objectives The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice. Methods Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program. Results The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors. Conclusions The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as “how-to” guidance based on the experience of expert injectors who have successfully treated the face and body. Level of Evidence: 4

Background Injectable soft tissue fillers are used on a global scale for a variety of aesthetic indications. Despite their widespread use, there is a dearth of information regarding needle deformation following injection procedures. Repeated injections with the same needle could lead to progressive needle tip deformation, potentially resulting in decreased precision and increased patient discomfort. Objectives The objective of this study was to quantify the magnitude of needle tip deformation utilizing scanning electron microscopy (SEM) image analysis. Methods An observational study was performed evaluating 4 differently sized needles following soft tissue filler injections for 5 different aesthetic indications (zygomatic arch, infraorbital, midcheek, nasolabial sulcus, and perioral) in patients aged 36 to 64 years. Following treatment, each needle was visualized and imaged through SEM, and the percentage of deformation in relation to the total amount of needle tip surface was calculated. Results The factor most influencing needle tip damage was revealed to be the number of injection passes, ie, dermal transitions. Per injection procedure, an increase in needle tip damage of 4.7% occurred. Touching the bone deformed the needle tip by 9.6% and an increase in needle size resulted in 0.13% more damage. Conclusions To the authors’ knowledge, this is the first SEM investigation to provide objective evidence for the deformation of needle tips after repeated facial soft tissue filler injections. These data may help improve patient safety and comfort during these minimally invasive procedures. Level of Evidence: 3

To date no precise data are available for extrusion forces related to the G-prime and G-double-prime of fillers in combination with different 27G and 30G needles. Therefore, the objective of this study was to analyze extrusion forces of various product-needle-combinations containing two different 27G and two different 30G needles in combination with fillers of a wide range of elastic moduli starting from 2.0ndash; 166.0 Pa.Four different fillers with the following elastic moduli 1.87, 11.65, 61.80, 165.50 Pa were combined with four different needles: 27Gfrac12;rdquo;, internal diameter: 0.300mu;m; 27Gfrac12;rdquo;, internal diameter: 0.241mu;m; 30Gfrac12;rdquo;, internal diameter: 0.241mu;m and 30Gfrac12;ldquo;, internal diameter: 0.240mu;m. Product-needle-combination were subjected to uni-axial mechanical testing and the respective extrusion force was measured.The results of this study revealed that the G-prime and the G-double-prime of a product are statistically significantly related to their extrusion force, with higher G-prime/G-double-prime products requiring higher extrusion forces. The results additionally revealed that whether the size of the needle was described as 27G or 30G by the respective manufacturer statistically significant differences between the measured extrusion forces were detected.Injectors need to be aware that not every 27G/30G needle has the same extrusion force even though the external diameter is similar (27G or 30G); this might additionally influence the ability to withdraw blood during a pre-injection aspiration manoeuvre. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5237.

Tooth germs undergo a series of dynamic morphologic changes through bud, cap, and bell stages, in which odontogenic epithelium continuously extends into the underlying mesenchyme. During the transition from the bud stage to the cap stage, the base of the bud flattens and then bends into a cap shape whose edges are referred to as “cervical loops.” Although genetic mechanisms for cap formation have been well described, little is understood about the morphogenetic mechanisms. Computer modeling and cell trajectory tracking have suggested that the epithelial bending is driven purely by differential cell proliferation and adhesion in different parts of the tooth germ. Here, we show that, unexpectedly, inhibition of cell proliferation did not prevent bud-to-cap morphogenesis. We quantified cell shapes and actin and myosin distributions in different parts of the tooth epithelium at the critical stages and found that these are consistent with basal relaxation in the forming cervical loops and basal constriction around enamel knot at the center of the cap. Inhibition of focal adhesion kinase, which is required for basal constriction in other systems, arrested the molar explant morphogenesis at the bud stage. Together, these results show that the bud-to-cap transition is largely proliferation independent, and we propose that it is driven by classic actomyosin-driven cell shape–dependent mechanisms. We discuss how these results can be reconciled with the previous models and data.

Cellulite is a common female cosmetic concern for which there are few treatment options with long-term effectiveness data. The aim of this multisite prospective registry study was to collect observational data on the real-life clinical use of a tissue stabilized-guided subcision (TS-GS) system for long-term improvement of cellulite appearance.Fifty-three subjects were enrolled and received a single treatment using the TS-GS system. Physicians treated the subjects according to their standard of care. Global Aesthetic Improvement Scale (GAIS) was completed by the patient and clinician assessing overall aesthetic improvement after 180 days. Treatment parameters, pain scores, quality of life data, and expected treatment effects and adverse events were also recorded throughout the study.The patient and physician GAIS scores at Day 180 revealed an overall improvement in 91% and 96% of patients, respectively. Quality of life and self-confidence scores also improved through 180 days. No serious adverse events were reported. Expected treatment effects were similar to those reported in the pivotal trial supporting FDA clearance.This study demonstrated significant improvement in the appearance of cellulite after a single treatment session in patients with moderate-to-severe cellulite. These results are consistent with the previously published the pivotal study data.

Background The deep intramuscular approach during buttock augmentation with fat grafting has been associated with a significantly increased risk for pulmonary fat embolism. This study was designed to provide guidance for injection into the subcutaneous fat. Methods The authors investigated 150 Caucasian individuals with an equal distribution of men and women (n = 75 each) and a balanced distribution of age (n = 30 per decade: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 to 69 years) and body mass index (n = 50 per group: ≤24.9 kg/m, between 25.0 and 29.9kg/m, and ≥30 kg/m). Ultrasound-based measurements were conducted of the thickness of the total, superficial, and deep gluteal fatty layers. Results An increase in body mass index of 1.0 kg/m corresponded to an increase of 3 mm of the total gluteal subcutaneous fat of men and a 4-mm increase of the total gluteal subcutaneous fat in women. With increasing age, the thickness of the deep fatty layer increased, whereas with increasing body mass index the thickness of the superficial layer primarily increased. Formulas were generated to estimate the total thickness of the gluteal subcutaneous fatty layer for men [total thickness (in millimeters) = -33.56 + (age × 0.078) + (body mass index × 3.042)] and women [total thickness (in millimeters) = -56.997 + (age × 0.1) + (body mass index × 3.86)]. Conclusions Knowing the total thickness of the gluteal subcutaneous fat (i.e., the safe space) allows surgeons to estimate their operating range for cannula motion even if no ultrasound machine is available during buttock augmentation with fat grafting. This can increase safety, potentially reducing the number of adverse events.

BACKGROUND Soft-tissue filler injections for the treatment of facial aging can result in different skin surface effects depending on the targeted facial fat compartment and fascial plane. This work investigates the tissue response of defined amounts of soft-tissue filler material injected into superficial and deep facial fat compartments by means of the calculation of the surface-volume coefficient. METHODS Four fresh frozen cephalic specimens obtained from human donors (three female and one male; mean age, 74.96 ± 22.6 years; mean body mass index, 21.82 ± 6.3 kg/m) were studied. The superficial and deep lateral forehead compartments, deep temporal fat pad, sub-orbicularis oculi fat compartment, and deep medial cheek fat compartment were injected with aliquots of 0.1 cc of contrast-enhanced material and scanned using three-dimensional surface imaging, resulting in a total of 226 injection and scanning procedures. RESULTS The sub-orbicularis oculi fat compartment revealed the highest correlation coefficient (rp = 0.992; p < 0.001) and the highest surface-volume coefficient (0.94). The compartment with the lowest tissue response was the deep medial cheek fat compartment (rp = 0.745; p < 0.001; surface-volume coefficient = 0.29), followed by the deep lateral forehead compartment (rp = 0.814; p < 0.001; surface-volume coefficient = 0.68), superficial lateral forehead compartment (rp = 0.824; p < 0.001; surface-volume coefficient = 0.74), and deep temporal fat pad (rp = 0.947; p < 0.001; overall surface-volume coefficient = 0.64). CONCLUSIONS These results, confirmatory in their nature to current injection strategies, provide evidence for the validity and reliability of the surface-volume coefficient. Injection procedures should be targeted in terms of facial fat compartments and fascial planes for a desired aesthetic outcome, as each fat compartment and fascial plane has unique tissue responses to injected soft-tissue fillers.