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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]

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.)