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BACKGROUND:Temozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ. METHODS:Using patient derived brain tumor initiating cells (BTICs) and orthotopic xenografts as models of newly diagnosed and recurrent high-grade glioma, we assessed the effects of TMZ, ABT-888, and the combination of TMZ and ABT-888 on the viability of BTICs and survival of tumor-bearing mice. We also studied DNA damage repair, checkpoint protein phosphorylation, and DNA replication in mismatch repair (MMR) deficient cells treated with TMZ and TMZ plus ABT-888. RESULTS:Cells and xenografts derived from newly diagnosed MGMT methylated high-grade gliomas were sensitive to TMZ while those derived from unmethylated and recurrent gliomas were typically resistant. ABT-888 had no effect on the viability of BTICs or tumor bearing mice, but co-treatment with TMZ restored sensitivity in resistant cells and xenografts from newly diagnosed unmethylated gliomas and recurrent gliomas with MSH6 mutations. In contrast, the addition of ABT-888 to TMZ had little sensitizing effect on cells and xenografts derived from newly diagnosed methylated gliomas. In a model of acquired TMZ resistance mediated by loss of MMR gene MSH6, re-sensitization to TMZ by ABT-888 was accompanied by persistent DNA strand breaks, re-engagement of checkpoint kinase signaling, and interruption of DNA synthesis. CONCLUSION:In laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ.

The article discusses the intersection of digital technology and dermatology, specifically focusing on the use of artificial intelligence (AI) in diagnosing and treating skin conditions. AI algorithms can analyze diverse medical data to improve diagnostic accuracy and decision-making, while digital tools like smartphone apps and telemedicine platforms powered by AI enhance access to dermatological care. The article also explores the potential of the Metaverse, a virtual universe, in improving communication and training opportunities in dermatology. However, challenges such as data quality, bias, privacy concerns, and regulatory issues need to be addressed for the responsible and effective use of AI in dermatology. [Extracted from the article]

Background: Temozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ. Methods: Using patient derived brain tumor initiating cells (BTICs) and orthotopic xenografts as models of newly diagnosed and recurrent high-grade glioma, we assessed the effects of TMZ, ABT-888, and the combination of TMZ and ABT-888 on the viability of BTICs and survival of tumor-bearing mice. We also studied DNA damage repair, checkpoint protein phosphorylation, and DNA replication in mismatch repair (MMR) deficient cells treated with TMZ and TMZ plus ABT-888. Results: Cells and xenografts derived from newly diagnosed MGMT methylated high-grade gliomas were sensitive to TMZ while those derived from unmethylated and recurrent gliomas were typically resistant. ABT-888 had no effect on the viability of BTICs or tumor bearing mice, but co-treatment with TMZ restored sensitivity in resistant cells and xenografts from newly diagnosed unmethylated gliomas and recurrent gliomas with MSH6 mutations. In contrast, the addition of ABT-888 to TMZ had little sensitizing effect on cells and xenografts derived from newly diagnosed methylated gliomas. In a model of acquired TMZ resistance mediated by loss of MMR gene MSH6, re-sensitization to TMZ by ABT-888 was accompanied by persistent DNA strand breaks, re-engagement of checkpoint kinase signaling, and interruption of DNA synthesis. Conclusion: In laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ. [ABSTRACT FROM AUTHOR]

Presents several articles on care of aging skin presented during the 'Pearls from the International Master Course on Ageing Skin' conference in Paris, France. Cooperation on the study of the mechanism of action and therapeutic applications of the LPG technique; Optimal survival conditions for fatty tissue; Skin cooling processes used by dermatologists.

Summary: Human immunodeficiency virus associated facial lipoatrophy is becoming epidemic and is a distressing sign for patients. Non permanent fillers provide only temporary results and cannot be the solution for severe cases. Lipodystrophy makes the lipofilling difficult to perform with a fibrous low quality fat difficult to harvest. We propose another solution using porous polyethylene implants (Medpor®). Eight patients underwent submalar augmentation through an upper gingivobuccal sulcus incision that allows a subperiosteal dissection. The implants are carved to provide the desired augmentation. Overall, eight patients had good or very good aesthetic postoperative outcomes as determined by the patient and the surgeon. No complications occurred and results remain natural. Porous polyethylene implants (Medpor®) is our treatment of choice for mild to severe facial lipoatrophy. Besides these implants could be removed easily later if needed. [Copyright &y& Elsevier]

Introduction: The integration of artificial intelligence (AI) into cosmetic medicine promises to revolutionize the field by enhancing diagnosis, treatment planning, and patient care., Objective: This manuscript explores the current adoption and perceptions of AI among professionals in the realm of cosmetic dermatology and plastic surgery, utilizing insights from the IMCAS Congress 2024 attendees., Methods: A survey employing a digital questionnaire with 14 questions was distributed among attendees of the IMCAS Congress 2024 to evaluate their familiarity with AI, usage in clinical practice, perceived advantages, and concerns regarding data privacy and security., Results: The survey revealed that a majority of respondents are familiar with AI's potential in cosmetic medicine, yet there is a notable discrepancy between awareness and actual application in practice. Concerns over data privacy and a pronounced need for further training were also highlighted., Conclusion: Despite recognizing AI's benefits in cosmetic medicine, significant barriers such as data privacy concerns and the need for more comprehensive training resources must be addressed. Enhancing education on AI-applications and developing strategies to mitigate privacy risks are imperative for leveraging AI's full potential in improving patient care and outcome in cosmetic medicine., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Hyaluronic acid-based dermal fillers are the cornerstones of wrinkle correction and facial contour redefinition., Objective: To assess the efficacy and safety of EST LF compared with RES L for the treatment of nasolabial folds (NLFs)., Materials and Methods: In this prospective, split-face, randomized, investigator and subject-blinded trial, 45 subjects with moderate-to-severe symmetrical NLFs were randomized to EST LF on one side of the face and RES L on the other side and were followed up for 9 months. The primary end point was change in WSRS score from the baseline to Month 1 (M1). Secondary end points included changes in WSRS score at other time points, aesthetic improvement, wrinkle volume quantification, adverse events, and local tolerance., Results: The efficacy difference between EST LF and RES L at M1 was in favor of EST LF (-0.16, CI, -0.28 to -0.03]), demonstrating its noninferiority. Considering other time points, significant differences were observed at 3 and 6 months for EST LF , assessed with WSRS, GAIS, or NLF volume quantification. Both treatments were well tolerated., Conclusion: EST LF is effective and well tolerated for the treatment of NLFs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery, Inc.)

Alluzience (abobotulinumtoxinA RTU; Ipsen, Paris, France and Galderma SA, Lausanne, Switzerland) is the first ready-to-use (RTU) botulinum toxin type A liquid solution approved for the treatment of glabellar lines in Europe. In this article, the authors provide consensus recommendations on the aesthetic usage of abobotulinumtoxinA RTU. Members of the International Board on Alluzience convened to develop consensus on the treatment of glabellar lines as well as other facial wrinkles based on their own extensive experience. Consensus recommendations were developed to provide practical guidelines for injection of abobotulinumtoxinA RTU. General guidance on proper assessment, treatment planning, and patient education is provided, as well as specific injection guidelines per indication. Indications covered include glabellar lines, crow's feet, horizontal forehead lines, lateral eyebrow lift, lower eyelid wrinkles, bunny lines, drooping nasal tip, perioral wrinkles, drooping mouth corners, masseter hypertrophy, hollow cheek lines, dimpled chin, and platysmal bands. These guidelines provide a practical framework to support routine injection of facial muscles with Alluzience., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society.)

Background: Despite the absence of Phase III clinical trial data to support their use, 3.4% of all neurotoxin treatments performed internationally for esthetic purposes in 2020 were performed in patients 65 years of age and older., Objectives: To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of moderate to severe glabellar lines in the subset of Phase III clinical trial participants who were 65 years of age and older., Methods: Post hoc analyses were performed on all patients who had been treated with a single dose of 20 U prabotulinumtoxinA in the three 150-day, placebo-controlled Phase III glabellar line clinical studies. Patients were grouped by age: ≥65 years (n = 70) versus <65 years (n = 667). The endpoints of primary interest were the proportion of responders with a ≥1-point improvement from baseline at maximum frown on the 4-point Glabellar Line Scale and treatment-related adverse events., Results: For the efficacy endpoint of primary interest, responder rates among patients 65 years of age and older were numerically less than those of patients less than 65 years by an absolute mean difference of just -2.7% across all visits; none of the differences at any visit were statistically significant. The most common treatment-related adverse event was headache, occurring in 5.7% of those 65 years of age and older and in 9.7% of those less than 65 years., Conclusions: 20 U prabotulinumtoxinA administered for the treatment of glabellar lines was efficacious in patients 65 years of age and older; it was also well tolerated by this cohort., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Wound healing is a process that involves multiple physiological steps, and despite the availability of various wound treatment methods, their effectiveness is still limited due to several factors, including cost, efficiency, patient-specific requirements, and side effects. In recent years, nanovesicles called exosomes have gained increasing attention as a potential wound care solution due to their unique cargo components which enable cell-to-cell communication and regulate various biological processes. Umbilical cord blood plasma (UCBP) exosomes have shown promise in triggering beneficial signaling pathways that aid in cell proliferation and wound healing. However, there is still very limited information about the wound-healing effect of UCBP exosomes in the literature., Objectives: The primary objective of this study was to investigate the "hybrosome" technology generated with calf UCBP-derived exosome-liposome combination., Methods: The authors developed hybrosome technology by fusing cord blood exosome membranes with liposomes. Nanovesicle characterization, cell proliferation assay, wound-healing scratch assay, immunohistochemistry analysis, anti-inflammation assay, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and cellular uptake studies were performed using the novel hybrid exosomes., Results: Experimental results showed that hybrosome increases cell proliferation and migration by 40% to 50%, depending on the dose, and induces an anti-inflammatory effect on different cell lines as well as increased wound healing-related gene expression levels in dermal cells in vitro. All in all, this research widens the scope of wound-healing therapeutics to the novel hybrosome technology., Conclusions: UCBP-based applications have the potential for wound treatments and are promising in the development of novel therapies. This study shows that hybrosomes have outstanding abilities in wound healing using in vitro approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society.)

Background: Despite a growing interest among men in cosmetic procedures such as botulinum toxin, comparator clinical trial data in this population are limited., Objectives: The authors sought to compare the efficacy and safety of prabotulinumtoxinA and onabotulinumtoxinA for the treatment of males with moderate to severe glabellar lines., Methods: Post-hoc analyses were performed on the subpopulation of male patients treated with either a single dose of 20 U prabotulinumtoxinA (n = 25) or 20 U onabotulinumtoxinA (n = 31) in the EVB-003 Phase III glabellar line clinical study. One key efficacy endpoint was the proportion of responders with a ≥1-point improvement from baseline at maximum frown on the 4-point Glabellar Line Scale., Results: Compared with onabotulinumtoxinA-treated males, the percentages of responders who had a ≥1-point improvement on the Glabellar Line Scale at maximum frown were higher at all postbaseline time points for prabotulinumtoxinA-treated males (P > 0.05 at all visits) by an absolute overall mean difference of 10.1% across all visits. Similar trends were observed for efficacy endpoints based on global aesthetic improvement and subject satisfaction. PrabotulinumtoxinA-treated males had a higher incidence of treatment-related headache and eyelid ptosis., Conclusions: The percentages of patients who met the definition of a responder were higher at almost all time points examined for prabotulinumtoxinA-treated males. Despite the high level of consistency across all measures, differences between the 2 treatment groups did not reach statistical significance. Further study is warranted to establish if these post-hoc analyses observations are reproducible in a larger male patient population., (© 2022 The Aesthetic Society.)

Background: AbobotulinumtoxinA (aboBoNT-A) solution is a new ready-to-use formulation developed to reduce preparation time and improve reproducibility of injections., Objective: To further evaluate treatment of moderate-to-severe glabellar lines (GLs) using pooled data from 2 Phase III studies., Methods: Following double-blind treatment with 50 U aboBoNT-A solution (n = 251) or placebo (n = 123), GL severity was assessed by investigators (ILA) and subjects (SSA). Other assessments included subject-reported time to onset, subject satisfaction, FACE-Q, and adverse events., Results: One month after aboBoNT-A solution treatment, 88% had none-or-mild GLs at maximum frown and 93% had ≥1-grade improvement in ILA (similar for SSA), 24% to 27% remaining improved at Month 6. Glabellar lines responder rates remained higher than placebo throughout Month 6 ( p < .001). Almost two-thirds of subjects reported onset within 3 days, nearly a quarter reporting effect by Day 1. Subject satisfaction with GL appearance, and FACE-Q satisfaction with facial appearance overall and psychological well-being were also improved over placebo throughout Month 6, p < .05. Treatment-related adverse events were nonserious and mild or moderate., Conclusion: Pooled analysis confirmed a duration of effect on GLs of up to 6 months for aboBoNT-A solution, with onset starting within 24 hours, high subject satisfaction, and improved psychological well-being. The treatment was well tolerated., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery, Inc.)

Background: Nonsurgical rhinoplasty is a procedure that is gaining popularity in aesthetic clinics particularly because of its minimally invasive nature compared with surgery. It is recognized that there are ethnic variations in nose injection techniques and planned aesthetic outcomes., Objectives: The objective of this study was to explore experts' views about the ethnic differences in the anatomical features of the nose and procedure-related considerations in nonsurgical rhinoplasty., Methods: Using a priori set topics and questions, 4 expert aesthetic physicians, from 4 different ethnic backgrounds and working in 4 different regions, were asked to describe the essential elements to be considered when planning a nonsurgical rhinoplasty, including product choice, injection technique, safety measures, and any practical hints to facilitate achieving the desired outcome., Results: All invited experts responded to the full set of questions. There were similarities between the treating physicians in some of the technical steps. Nevertheless, there were several differences identified regarding baseline anatomy and patient expectations that could be attributed to ethnicity. Patients' and physicians' expectations regarding a successful nonsurgical rhinoplasty can vary depending on their ethnic backgrounds. Therefore, with the current global ethnic and cultural diversities, in addition to the knowledge of the nasal anatomy and safe injection techniques, it is imperative that aesthetic practitioners have full awareness and a good understanding of these ethnic variations., Conclusions: Nonsurgical rhinoplasty is a highly demanded aesthetic procedure. Patients' ethnic differences need to be carefully taken into consideration when discussing, planning, and performing nasal fillers injection., (© 2022 The Aesthetic Society.)

Background: A ready-to-use liquid formulation of abobotulinumtoxinA (aboBoNT-A solution) has been developed., Objectives: The aim of this study was to assess the long-term efficacy and safety of aboBoNT-A solution for the treatment of glabellar lines., Methods: This was a multicenter, multinational, Phase III study (NCT02493946), with randomized double-blind placebo-controlled (DBPC; 2:1 aboBoNT-A solution 50 U/placebo) and open-label (4 cycles aboBoNT-A solution) periods; additional patients were recruited into the open-label period. Patients were 18 to 65 years old, BoNT-naïve, and dissatisfied/very dissatisfied with moderate/severe glabellar lines at maximum frown. Investigator's live assessment (primary endpoint)/subject's self-assessment of glabellar line severity at maximum frown, patient satisfaction with glabellar line appearance, and FACE-Q patient-reported scales (facial appearance overall, psychological well-being, aging) were assessed. Adverse events were monitored. Analyses were performed on DBPC and long-term analysis (LTA; all patients receiving ≥1 aboBoNT-A solution injection) populations., Results: Responder rates for the investigator's live assessment, the subject's self-assessment, and patient satisfaction were consistent at Day 29 postinjection across repeat LTA cycles (82.2%-87.8%, 62.8%-80.6%, and 72.2%-87.8%, respectively), with statistically significantly higher responder rates vs placebo (DBPC cycle: 81.6% vs 0.8%, 68.1% vs 2.3%, and 83.1% vs 5.7%, respectively; all P < 0.0001). Consistent improvements on FACE-Q scales occurred with repeat cycles (DBPC cycle: aboBoNT-A solution vs placebo, P < 0.0001). No new or unexpected adverse events, or neutralizing antibodies, were observed., Conclusions: These results support the long-term efficacy and safety of aboBoNT-A solution, and its superiority over placebo, for treatment of glabellar lines in adults., (© 2021 The Aesthetic Society.)

Duplex mode ultrasound imaging can detect the course of the main vascular structures in the face, which are known to be subject to variation. Once duplex mapping has been performed, measures can be taken to prevent injection into an artery, thereby avoiding skin necrosis or, worse, vision loss. For this reason, in particular, we predict that in the coming years sonography will become standard equipment in the offices of cosmetic doctors. We discuss the basics of vascular imaging by Doppler ultrasound, both in normal and pathologic situations. Starting from the 7 basic positions for the ultrasound probe, all facial arteries relevant in cosmetic medicine can be found., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Interest in Doppler ultrasound (DUS) analysis of the face has grown in cosmetic medicine, in particular for injectable fillers. When dealing with complications, DUS has the advantage of easily visualizing the filler and identifying the problem in relation to the patient's anatomy. When working with hyaluronic acid filler, ultrasound-guided injections with hyaluronidase can precisely target the problem. In addition, DUS can be used to study the anatomy of a patient, specifically to prevent intravascular injections. We predict that in a few years' time DUS will become standard equipment in the offices of cosmetic doctors. We discuss the basics of ultrasound imaging of different tissues with the concomitant terminology. With the use of 7 basic DUS probe positions, key anatomic reference points can be easily found. From these, all relevant anatomic structures in the face can be observed and analyzed. With some practice, physicians will ultimately be able to acquire a complete 3-dimensional mental image of a patient's face., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

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., (© 2020 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Background: While the temporal lifting technique has gained increasing attention, there is a dearth of objective and reliable evidence of its effects., Aim: The objective of the present study is to analyze the ability of the temporal lifting technique to reduce the midfacial volume by soft tissue repositioning and to achieve an improved pan-facial appearance by targeting exclusively the subdermal plane of the posterior and superior temple with soft tissue fillers., Methods: A total of 12 patients (1 male and 11 females) with a mean age of 36.75 ± 6.6 years and a mean body mass index of 23.04 ± 1.3 kg/m 2 were included in this prospective clinical single-center interventional study. Injection-related outcome was evaluated utilizing 3D skin vector displacement and surface volume analyses and scoring based on five different evaluators., Results: Three months after the treatment, the global esthetic improvement scale rating showed an improved outcome (3.08) when evaluated by the independent observers, very improved outcome when evaluated by the treating physician (4.33), and exceptional improvement when rated by the patient (4.83). Temporal volume improved by 0.36 (P < .001), lower cheek fullness by 0.47 (P < .001), and jawline contouring by 0.51 (P < .001). No major adverse events were reported during the 3-month observational period., Conclusion: Objective outcome measures have provided evidence that by augmenting the posterior superior temple the volume of the middle face can be reduced and the contour of the jawline can be accentuated; this is due to the underlying fascial anatomy and the resulting soft tissue re-position., (© 2020 Wiley Periodicals LLC.)

Background: The FACE-Q patient-reported outcome assesses patient experiences/outcomes with aesthetic facial procedure. A recent trial of abobotulinumtoxinA (ASI, liquid formulation) was the first to our knowledge to assess satisfaction with FACE-Q after glabellar line (GL) injection., Objectives: The authors sought to evaluate patient satisfaction with ASI for GL treatment employing 3 FACE-Q scales: facial appearance, psychological well-being, and aging appearance., Methods: This was a Phase 3, randomized, double-blind, placebo-controlled trial (NCT02353871) of ASI 50 units in adults with moderate-to-severe GL with 6-month follow-up., Results: Significantly greater least squares mean changes from baseline were associated with ASI treatment (N = 125) vs placebo (N = 59) for satisfaction with facial appearance at all visits until day 148 (5 months; P < 0.0001-0.0037), psychological well-being at all visits (P < 0.0001-0.0279), and aging appearance at all visits except day 148 (P < 0.0001-0.0409). Significant differences (ASI vs placebo) were observed at all visits for individual items: "how rested your face looks" (P < 0.0001-0.0415), "I feel okay about myself" (P = 0.0011-0.0399), and "I feel attractive" (P < 0.0001-0.0102). Maximal least squares mean (standard error) changes in aging appearance score were -1.4 (0.3; ASI) and -0.3 (0.4; placebo). Investigators' live assessment of GL at maximum frown significantly correlated with improvements in FACE-Q facial appearance and psychological scales (all patients: r = -0.41 and r = -0.36 [both P < 0.0001], respectively)., Conclusions: Significant improvements in patient satisfaction with aging, facial appearance, and, importantly, psychological well-being were demonstrated with ASI employing FACE-Q scales up to 5 to 6 months post-injection. Results support a long duration of efficacy with ASI and use of FACE-Q in future trials and clinical practice., (© 2019 The American Society for Aesthetic Plastic Surgery, Inc.)

Background: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum., Objectives: The authors sought to investigate the efficacy and safety of prabotulinumtoxinA compared to onabotulinumtoxinA and placebo for the treatment of glabellar lines., Methods: This was a 150-day, multicenter, double-blind, controlled, single-dose Phase III study. Adult patients (n = 540) with moderate to severe glabellar lines at maximum frown as assessed by the investigator on the validated 4-point Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), who also felt that their glabellar lines had an important psychological impact, were enrolled. Patients were randomized 5:5:1 to receive a single treatment (0.1 mL injected into each of 5 glabellar sites) of 20 U prabotulinumtoxinA (n = 245), 20 U onabotulinumtoxinA (n = 246), or placebo (n = 49). The primary efficacy endpoint was the proportion of responders (patients with a Glabellar Line Scale score of 0 or 1 at maximum frown by investigator assessment) on day 30., Results: Responder rates for the primary efficacy endpoint were 87.2%, 82.8%, and 4.2% in the prabotulinumtoxinA, onabotulinumtoxinA, and placebo groups, respectively. The absolute difference between prabotulinumtoxinA and onabotulinumtoxinA groups was 4.4% (95% confidence interval [-1.9, 10.8]). Given that the lower bound of the 95% confidence interval for the difference was less than -10.0%, noninferiority of prabotulinumtoxinA vs onabotulinumtoxinA was concluded. Five patients (3 prabotulinumtoxinA, 1.2%; 1 onabotulinumtoxinA, 0.4%; 1 placebo, 2.0%) experienced serious adverse events, none of which were study drug related., Conclusions: A single treatment of 20 U prabotulinumtoxinA was safe and effective and noninferior to 20 U onabotulinumtoxinA for the treatment of moderate to severe glabellar lines., (© 2019 The Aesthetic Society.)

Background: Safety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection., Objectives: The authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown., Methods: The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator's live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action., Results: Responder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile., Conclusions: ASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA., (© 2019 The Aesthetic Society.)

Background: There are no guidelines regarding post-treatment surveillance specific to skull base chordomas., Objective: To determine an optimal imaging surveillance schedule to detect both local and distant metastatic skull base chordoma recurrences., Methods: A retrospective review of 91 patients who underwent treatment for skull base chordoma between 1993 and 2017 was conducted. Time to and location of local and distant recurrence(s) were cataloged. Existing chordoma surveillance recommendations (National Comprehensive Cancer Network [NCCN], London and South East Sarcoma Network [LSESN], European Society for Medical Oncology [ESMO], Chordoma Global Consensus Group [CGCG]) were applied to our cohort to compare the number of recurrent patients and months of undiagnosed tumor growth between surveillances. These findings were used to inform the creation of a revised imaging surveillance protocol (MD Anderson Cancer Center Chordoma Imaging Protocol [MDACC-CIP]), presented here., Results: Thirty-four patients with 79 local/systemic recurrences met inclusion criteria. Mean age at diagnosis and follow-up time were 45 yr and 79 mo, respectively. The MDACC-CIP imaging protocol significantly reduced the time to diagnosis of recurrence compared with the LSESN and CGCG/ESMO imaging protocols for surveillance of local disease with a cumulative/average of 576/16.9 (LSESN), 336/9.8 (CGCG), and 170/5.0 (MDACC-CIP) months of undetected growth, respectively. The NCCN and MDACC-CIP guidelines for distant metastatic surveillance identified a cumulative/average of 65/6.5 and 51/5.1 mo of undetected growth, respectively, and were not significantly different., Conclusion: The MDACC-CIP for skull base chordoma accounts for recurrence trends unique to this disease, including a higher rate of leptomeningeal spread than sacrococcygeal primaries, resulting in improved sensitivity and prompt diagnosis.

Background: Our understanding of the aging changes involving the cranium and its impact on the overlying soft tissues is limited., Objectives: This study was designed to look at the changes that occur in the cranium with aging and to propose an additional mechanism for loss of support for overlying soft tissues., Methods: One hundred and fifty-seven white individuals (10 males and 10 females in each decade: 20-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years, 70-79 years, 80-89 years, and 8 males and 9 females aged 90-98 years) were investigated. Computed tomographic (CT) multiplanar scans with standardized measurements of cranial thickness were performed for the frontal bone, nasion, vertex, pterion, lambda, calvarial and midfacial height, and sagittal and transverse diameter., Results: Increasing age correlated with a decrease in sagittal diameter in both males (rp = -0.201) and females (rp = -0.055) but with an increase in transverse diameter in both males (rp = 0.233) and females (rp = 0.207). Frontal bone thickness decreased in males -1.57mm/-18.14%, whereas it increased slightly in females +0.26mm/+3.04%. At the pterion, bone thickness increased significantly in both genders. Calvarial volume decreased with increased age in both males and females: -70.2 ml/-5.35% and -61.4 ml/-5.10%, respectively., Conclusions: The lateral expansion of the skull may favor a skeletonized appearance of the face in elderly individuals. The computed volume of the calvaria decreased with advancing age in both genders, providing an additional element in the multifactorial model for facial soft-tissue laxity.

Background: In most countries, approved botulinum toxin type A formulations require reconstitution before injection., Objectives: To evaluate the efficacy and safety of a ready-to-use liquid formulation of abobotulinumtoxinA (abobotulinumtoxinA solution for injection, ASI) in subjects with moderate to severe glabellar lines (GL)., Methods: In this Phase II, double-blind, placebo-controlled, randomized study, 176 female subjects (aged 30 to 60 years) were randomized into five treatment groups: ASI 20, 50, or 75 U, reconstituted abobotulinumtoxinA (aboBoNT-A) 50 U, and placebo. GL severity was assessed at maximum frown using a 4-point grading scale. Responders were subjects with severity grade of moderate [2] or severe [3] at baseline improving to none [0] or mild [1], evaluated at each time-point by Investigator's Live Assessment (ILA) or Subject's Self-Assessment (SSA). Safety profiles were also determined., Results: Baseline characteristics were similar across groups. Responder rates on Day 29 by ILA were significantly greater for ASI 20, 50, and 75 U versus placebo (88.9%, 91.4%, and 87.9% vs. 0%, respectively; P < 0.0001). Similar results were observed by SSA. A greater proportion of responders was observed in ASI groups vs placebo from Day 8 to 113 for ILA and SSA (P < 0.001). AboBoNT-A responder rate on Day 29 for ILA was 77.1% (P < 0.1006 vs ASI 50 U); with comparable results by SSA. The ASI safety profile was comparable to that of aboBoNT-A., Conclusions: Ready-to-use liquid formulation of abobotulinumtoxinA was shown to be efficacious, with comparable results to reconstituted abobotulinumtoxinA, and to have a favorable safety profile in subjects with severe to moderate GL., (© 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com)

Background: Hyaluronic acid (HA) filler injection is an increasingly popular aesthetic procedure., Objective: To compare the effectiveness and safety of two HA fillers (HAED and HAPER) for the treatment of severe nasolabial folds (NLFs)., Materials and Methods: This was an evaluator-blinded and subject-blinded split-face study. At baseline, HAED or HAPER was randomly assigned to the left or right NLF. The follow-up period was 12 months. Effectiveness was assessed using the wrinkle severity rating scale (WSRS) and subject preference. Safety was assessed by adverse events and local tolerability symptoms recorded by subjects during 3 weeks after the treatment., Results: At 6 months, HAED was noninferior to HAPER (assessed by mean change from baseline in WSRS score). There was a significant difference in mean WSRS score change from baseline in favor of HAED at 3 to 12 months, and a majority of subjects preferred HAED over HAPER at 12 months. However, the overall responder rate was similar between products, and it remained high throughout the study. At 12 months, approximately 80% of subjects were still responders. Both products were well tolerated and associated with a few treatment-related adverse events., Conclusion: To conclude, HAED was at least as effective and well tolerated for the treatment of severe NLFs as HAPER.

Introduction: The shape and contour of the chin and neck play an important role in facial esthetics. As such, excess fat within the submental area (double chin) can negatively affect facial esthetics and body image. Common treatments for submental contouring include invasive procedures such as surgical rejuvenation and targeted liposuction. Energy devices (lasers, radiofrequency, and ultrasound) may be used to improve submental skin laxity while cryolipolysis was recently cleared in the United States for use in the submental area. However, ATX-101 (deoxycholic acid injection) is the only injectable drug approved in the United States and Canada for reduction of submental fat., Areas Covered: The efficacy and safety of ATX-101 have been extensively evaluated in a global clinical development program including multiple Phase I/II studies and four large Phase III trials. Available data from ATX-101 trials are reviewed. Expert commentary: Injectables have been well established for facial rejuvenation. Extending injectable treatment into the chin and neck is a major advance for nonsurgical cosmetic correction. Overall, the evidence supports ATX-101 as a safe and effective, minimally invasive treatment alternative for reduction of submental fat that will provide a major tool for the esthetic physician.

Background: Emervel consists of a range of 5 hyaluronic acid (HA) fillers (Touch, Classic, Lips, Deep, and Volume), with a fixed HA concentration (20 mg/mL), and various degrees of cross-linking and calibration., Objectives: To describe the current use of Emervel fillers in France., Methods: Prospective multicenter, cross-sectional, real-practice, descriptive survey, including 1,822 patients injected with Emervel fillers for face rejuvenation by 58 French physicians between September 2010 and July 2011. The injection modalities were left to the respective physician's discretion., Results: The physicians were dermatologists (52.3%), surgeons (43.8%), or general practitioners (14.1%). Nasolabial folds (NLF) with a mean severity 2.4 were mainly injected with Emervel Deep (51.0%) and Emervel Classic (36.0%) (mean volume: 1.0 mL), and primarily with the linear retrograde (LR) technique (89.3%). Marionette lines (ML), with a mean severity 2.6 were mainly injected with Emervel Deep (52.5%) and Emervel Classic (34.6%) (mean volume: 0.8 mL), and mainly with the LR technique (79.5%). More than 90% of patients had scores of 0 or 1 for erythema, bruising, edema, and pain. No serious adverse events were reported up to 15 months after the injection., Conclusion: These data could contribute to upcoming international consensus on optimal injection modalities of the Emervel range of HA fillers.

Introduction: A monocentre double-blind two parallel group clinical study was conducted to assess whether a new skincare regimen containing retinol, adenosine and hyaluronic acid, applied after the injection of botulinum toxin A to the glabellar area, provided a beneficial effect., Material and Methods: Standardised photographs acquired using LifeViz cameras and zoomed pictures of the glabella and of the crow's feet areas were analysed with automatic well-defined procedures. Perceived efficacy and tolerance were also analysed by comparison between the two groups., Results: A beneficial effect versus placebo-treated group was proven in the group having topically applied the new skincare regimen for 2 months following botulinum toxin A injection with no touch up after 1 month. 3D image analysis showed more rapid results on D10 and enhanced efficacy on M2. Moreover, a beneficial effect independent of injection was measured in the crow's feet area, and analysis of the self-evaluation questionnaire showed enhanced efficacy perceived by the volunteers., Conclusion: A specially developed skincare regimen applied immediately after botulinum toxin A injection completes the beneficial effect of the injection on the glabellar area and offers clinical benefits in fine lines, wrinkles and smoothness on the whole face.

Background: Hyaluronic acid (HA) fillers are frequently used for the correction of facial soft tissue defects., Aim: To compare the efficacy and safety of a novel HA filler, HA(E) (Emervel Deep), with those of HA(P) (Restylane Perlane) in the treatment of severe nasolabial folds (NLF)., Patients/methods: A split-face, randomized and evaluator-blinded comparison study. Subjects were randomized to receive injection of HA(E) or HA(P) on their left or right NLF. Efficacy was evaluated based on the change in Wrinkle Severity Rating Scale (WSRS) from baseline. Local tolerability was assessed based on subject diary during the first 3 weeks after injection. Adverse events were also evaluated., Results: At both weeks 12 and 24, the mean improvement in WSRS from baseline was significantly greater for HA(E) than for HA(P) (1.58±0.89 vs. 1.33±0.82 at week 24; P=0.002). Similar volume of both products was injected at baseline and touch-up. Both fillers were well tolerated, with similar worst score distribution and mean score for erythema, edema/swelling, bruising, and pruritus. Significantly less severe pain/tenderness was reported with HA(E) than with HA(P) (P<0.05)., Conclusions: The new HA filler HA(E) provides better efficacy and similar local tolerability compared with HA(P) 6 months after the treatment of severe NLF., (© 2011 Wiley Periodicals, Inc.)

Background: The UltraShape Contour I System (CE 0344; UltraShape Ltd., Yoqneam, Israel) is a noninvasive fat reduction and body contouring system currently approved for use outside the United States that utilizes focused ultrasound to selectively disrupt adipocytes., Objective: To evaluate the clinical safety and efficacy of the Contour I system when the intervals between treatments are shortened., Methods: Twenty-five healthy Caucasian women were selected from the patient population at two clinics in Paris, France, and received three 30- to 90-minute Contour I treatments in the abdominal region at two-week intervals. Safety parameters evaluated included adverse events, local skin reaction, and pain. Efficacy parameters evaluated included treatment area circumference, body weight, and comparison of before and after photos. Untreated thigh areas served as an internal control. Subjects were followed for 84 days after the last treatment (day 112)., Results: No adverse events occurred. The majority of subjects (n = 23; approximately 90%) reported no pain. Mean midline circumference (2 cm below midline) was reduced by 2.47 cm (P < .001) on day 14 after the first Contour I treatment, 3.51 cm (P < .001) on day 56, and 3.58 cm (P < .001) on day 112. Peak midline circumference reduction was 3.12 cm on day 112. Most patients (n = 14; 63%) reported a positive change in body contour. Mean thigh circumference (the control area) was unchanged; the relative change between treated and untreated areas of the abdomen was significantly different at all time points. Circumference and weight reduction were significantly correlated (r = 0.42-0.71) at all time points; mean weight decrease was not statistically significant. Circumference reduction on day 112 positively correlated with patients' subjective satisfaction scores., Conclusions: Our data showed that successive Contour I treatments at two-week intervals were safe and tolerable and also significantly reduced treatment area circumference.

Injection of botulinum toxin type A (BoNTA) is the most common nonsurgical aesthetic procedure undertaken in the United States (U.S.). A new formulation of BoNTA (abobotulinumtoxinA, Dysport™) has recently been approved in the U.S. for the treatment of glabellar lines. This product has been used for facial aesthetics in other parts of the world for more than 15 years, whereas in the U.S. a different formulation (onabotulinumtoxinA, Botox® Cosmetic) has been used for many years. The various formulations of neurotoxins are unique and are not interchangeable nor are doses convertible from one product to another, so it is important that recommendations be developed to assist U.S. clinicians in understanding the differences between the two available formulations of BoNTA, which should ensure successful outcomes with these products. A group of worldwide experts on the aesthetic use of BoNTA convened in February 2009 in New York, NY, to review the use of BoNTA and to develop consensus recommendations for the use of the new formulation, since such guidelines previously had only been published in German. This publication summarizes key discussions from the meeting as well as recommendations and suggestions regarding the use of abobotulinumtoxinA in the areas of the face most commonly treated with BoNTA.

Background: Botulinum toxin type A (BoNT-A) is frequently used to treat crow's feet; the optimal dose for each toxin preparation should be established., Objective: To compare the efficacy and safety of three doses of BoNT-A with placebo to treat crow's feet., Methods: Subjects with moderate to severe crow's feet at maximum smile (mild to severe at rest) were randomized to a single bilateral BoNT-A treatment (15, 30, or 45 U) or placebo. Outcome measures included evaluation of crow's feet by an independent panel from blinded photographs at maximum smile, investigator assessment, and patient satisfaction., Results: Independent panel assessments (Week 4) showed that all BoNT-A doses resulted in significant improvements in crow's feet severity at maximum smile (p<.001); a clear dose-response effect was seen. Improvement over placebo was seen in the 30-U and 45-U groups to Week 12. Investigator assessment showed significant improvement for all doses for 12 weeks at maximum smile and rest (p< or =.01). Patient satisfaction was significantly greater for all doses than for placebo for 16 weeks (all p<.05). All doses were well tolerated. CONCLUSION BoNT-A (15, 30, or 45 U) is an effective and safe treatment for mild to severe crow's feet.

Background: Several clinical scoring systems have been used to evaluate the efficacy of botulinum toxin A in the treatment of hyperkinetic wrinkles. So far very few have been investigated for their reproducibility., Objective: The aim of this study was to investigate the reproducibility of two clinical four-point scales for lateral canthal lines (crow's feet), at rest and at maximum smile., Material and Methods: Based on standardized photographs, a consensus atlas depicting the different severity grades [from 0 (none) to 3 (severe)] was developed. After training based on the atlas, 49 photographs at rest and 48 at maximum smile were graded by the same group of investigators on 2 consecutive days (n=9 on Day 1; n=8 on Day 2). The scores were compared for reproducibility using kappa statistics., Results: Overall, reproducibility was good for both scales. Interobserver reproducibility showed an agreement of 0.6 at rest and 0.58 at maximum smile (unweighted kappa). Intraobserver reproducibility showed an agreement between 0.47 and 0.86 at rest and between 0.62 and 0.81 at maximum smile (unweighted kappa). Using weighted kappa analysis, the agreement ranged between 0.63 and 0.91 at rest and between 0.71 and 0.85 at maximum smile., Conclusion: The clinical scales using scores of 0 to 3 for crow's feet, both at rest and at maximum smile, show a good inter- and intraobserver reproducibility. The use of these scores in clinical trials can be recommended.

Background: Facial lipoatrophy has been observed to occur in a variety of patient populations, with inherited or acquired disease, or even in aging patients as a natural progression of tissue change over time. There is currently no framework from which physicians of all medical specialties can communally discuss the manifestations, diagnoses, and management of facial lipoatrophy., Objective: The aim of this assembly was to derive a definition of facial lipoatrophy capable of being applied to all patient populations and develop an accompanying grading system., Results: The final consensus of the Facial Lipoatrophy Panel encompasses both aging and disease states: "Loss of facial fat due to aging, trauma or disease, manifested by flattening or indentation of normally convex contours." The proposed grading scale includes five gradations (Grades 1-5; 5 being the most severe), and the face is assessed according to three criteria: contour, bony prominence, and visibility of musculature., Conclusion: Categorizing the presentation of facial lipoatrophy is subjective and qualitative, and will need to be validated with objective measures. Furthermore, during the assembly, several topics were exposed that warrant further research, including the physiology of volume loss, age and lipoatrophy, and human immunodeficiency virus and lipoatrophy.

Background: Interest in facial lipoatrophy (LA) has recently intensified; this phenomenon is linked to the rise in the number of people adversely affected by the condition as a side effect of antiretroviral treatment for HIV, combined with the growing number of cosmetic products that claim to be able to correct the appearance of LA. Despite growing awareness of the problem, there is at present no standard and accepted technique with which to assess the severity of LA., Objective: This review explores facial LA, the use of ultrasound in the evaluation of facial LA, its advantages and disadvantages, and will place the technique in the context of other means of assessing regional skin and fat thickness., Method: Review of literature published on PubMed. RESULTS Ultrasound, as with any technique used to assess facial LA, is associated with distinct advantages and disadvantages., Conclusions: Studies that use a number of different techniques to evaluate changes in dermal thickness provide the greatest insight into both perceived and actual changes in facial LA. Further investigation into the use of these techniques is warranted, along with a formal consensus of facial LA grades.

Objective: To investigate the efficacy and safety of 2 injection site patterns (3- and 5-injection patterns [30 and 50 U]) of botulinum toxin A (Dysport; Ipsen Pharma, Ettlingen, Germany), in the treatment of glabellar and central forehead wrinkles., Design: Multicenter, double-blind, placebo-controlled, randomized, 16-week trial., Setting: Twenty-three German dermatologic centers., Patients: Two hundred twenty-one patients with moderate or severe glabellar wrinkles when frowning maximally. Intervention Centers were randomly assigned to the 3-injection site pattern (3 injections of 10 U of botulinum toxin A or placebo) or 5-injection site pattern (5 injections of 10 U of botulinum toxin A or placebo). All centers used 3 sites in the procerus and corrugator muscles; the 2 additional sites were approximately 1-cm cranial from the corrugator sites., Main Outcome Measure: Wrinkle severity was graded by 4 independent experts blinded to the treatment received using digital photographs and a standardized clinical scale (range, 0 [no wrinkles] to 3 [severe wrinkles]). A reduction of at least 1 point between weeks 0 and 4 was considered a therapeutic success (responder)., Result: One hundred ten patients (73 receiving botulinum toxin A vs 37 receiving placebo) received 3 injections; 111 patients (73 receiving botulinum toxin A vs 38 receiving placebo) received 5 injections. After 4 weeks, the proportions of responders were 86.1% vs 18.9% and 86.3% vs 7.9%, respectively (P<.001 for both). No major adverse effects were observed., Conclusions: The 3 central injection sites are essential for the treatment of glabellar wrinkles. The 2 additional injection sites in the forehead region, targeting the frontalis muscle, did not significantly improve efficacy.