Cellular Senescence in Human Skin Aging: Leveraging Senotherapeutics.

BACKGROUND: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health. SUMMARY: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures. KEY MESSAGES: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging.

Immunogenicity of Botulinum Toxin A: Insights.

BACKGROUND: Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse. OBJECTIVE: This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses. MATERIALS AND METHODS: The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it. RESULTS: The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses. CONCLUSION: Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes.

Embracing Spectrum: Celebrating LGBTQIA+ Journeys in Aesthetic Medicine: A Kaleidoscope of Identity.

PURPOSE: This synaptic systemised review critically examines the provision of aesthetic medical care to LGBTQIA+ (lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and more) individuals, assessing both the clinical practices and the educational frameworks that guide interactions with LGBTQIA+ patients in aesthetic settings. METHODS: Following PRISMA-S guidelines, a comprehensive review was conducted, initially identifying 159 potentially relevant articles. Upon stringent full-text review, 33 studies met the inclusion criteria and were subject to an in-depth thematic analysis. The scope encompassed qualitative studies, quantitative analyses, and a cross section of interdisciplinary research, predominantly from Western settings. RESULTS: The analysis distilled four principal themes: the imperative of identity affirmation in aesthetic interventions, substantial barriers to inclusive and empathetic care, the critical need for patient empowerment, and the existing deficiencies within medical education regarding LGBTQIA+ care. These themes highlight a complex interplay between the clinical aspirations of LGBTQIA+ individuals and the current capacity of aesthetic medicine to cater to this diversity. CONCLUSIONS: There is a pressing need for a paradigmatic shift towards more inclusive, competent, and sensitive aesthetic medical care for LGBTQIA+ patients. It underscores the necessity of reform in medical education and advocates for policy changes that promote a more equitable healthcare environment. This research serves as a call to action, emphasizing the ethical imperative to integrate comprehensive LGBTQIA+ care competencies into aesthetic medicine curricula and practice. LEVEL OF EVIDENCE IV: 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.

Exosomes Exposed: Overview Systematic Review on Evidence Versus Expectation in Aesthetic and Regenerative Medicine.

INTRODUCTION: Exosomes, diminutive extracellular vesicles, are integral to intercellular communication, harbouring potential for applications in regenerative medicine and aesthetic interventions. The field, however, grapples with the complexities of harmonising exosome characterisation protocols and safeguarding therapeutic integrity. METHODOLOGY: In this scholarly overview, systematic adherence to the Cochrane Collaboration and Preferred Reporting Items for Overviews of Reviews guidelines was observed, scrutinising the congruence of exosome-related therapies with the Minimal Information for Studies of Extracellular Vesicles standards delineated by the International Society for Extracellular Vesicles, alongside criteria set forth by the International Society for Cell Therapy and the International Society for Stem Cell Research. A meticulous search strategy spanning databases such as PubMed, Scopus, Web of Science, EMBASE, and Cochrane database was employed to encapsulate studies pertinent to the isolation, characterisation, and functional assessment of exosomes. RESULTS: The initial search yielded 225 articles, of which 17 systematic reviews were selected based on predefined criteria, encompassing 556 primary studies. Notwithstanding the acknowledged therapeutic promise of exosome modalities, the synthesis illuminated a prevalent deficiency in adherence to established reporting and experimental benchmarks, notably in exosome source characterisation and bioactive constituent delineation. A critical appraisal employing the AMSTAR-2 tool underscored a pervasive shortfall in methodological rigour. CONCLUSION: This review accentuates the imperative for stringent methodological standardisation within exosome research to fortify the validity and reproducibility of empirical findings. Amidst the burgeoning therapeutic optimism, the discipline must rectify methodological disparities and comply with regulatory mandates, ensuring the ethically sound and scientifically robust advancement of exosome-based therapeutic modalities. LEVEL OF EVIDENCE IV: 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 .

Integrating Psychological Insights into Aesthetic Medicine: A Cross-Generational Analysis of Patient Archetypes (IMPACT Study).

BACKGROUND: Aesthetic medicine has evolved significantly, accommodating diverse demographics and motivations influenced by societal shifts and technological advancements. The IMPACT (integrative multigenerational psychological analysis for cosmetic treatment) study refines patient archetypes, integrating psychological theories to tailor treatments, especially for younger demographics and LGBTQIA + communities. METHODS: This cross-sectional study utilized a comprehensive, validated survey with a Cronbach's alpha of 0.89 and a Content Validity Index (CVI) of 0.92, distributed across a globally diverse, generationally stratified sample. Techniques like regression analysis, ANOVA, Bayesian modelling, and factor analysis were employed to analyse the data, focusing on developing nuanced patient archetypes. RESULTS: Among 5645 participants, 5340 complete responses highlighted significant generational differences in aesthetic preferences. Millennials showed a strong preference for non-invasive procedures (ß = 0.65, p < 0.001). ANOVA results confirmed significant variances across generations [F (3, 5118) = 157.6, p < 0.001], with post-hoc analyses delineating specific inter-group differences. Bayesian modelling provided insights into the probability of non-invasive preferences among younger cohorts at over 92% certainty. Factor analysis revealed key dimensions such as 'Generational Influence' and 'Technological Adoption,' which helped in defining archetypes including Dynamic Self-Identity, Digital Native, Stability Seeker, Classic Conservatism, and Holistic Health, collectively explaining up to 78% of the variance in responses. CONCLUSION: The IMPACT study underscores the influence of generational identity and digital exposure on aesthetic preferences, advocating for personalized, archetype-based treatment approaches. This aligns with enhancing patient satisfaction and treatment outcomes, promoting an adaptive aesthetic medicine practice that meets the evolving needs of modern patients. LEVEL OF EVIDENCE IV: 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 .

Regenerative Aesthetics: A Genuine Frontier or Just a Facet of Regenerative Medicine: A Systematic Review.

BACKGROUND: Regenerative aesthetics claims to enhance cosmetic outcomes through advanced biological interventions like Stem cell and Exosome therapy, Polydeoxyribonucleotide (PDRN), Photobiomodulation, bioactive peptides and treatment for cellular senescence yet lacks substantial scientific and regulatory validation. OBJECTIVE: To evaluate the scientific and clinical foundations of regenerative medicine techniques in non-surgical aesthetics and assess the legitimacy of regenerative aesthetics as a medical specialty. METHODS: A systematic review was conducted according to PRISMA guidelines, searching databases including PubMed, Scopus, and Web of Science for studies published in the last ten years. We included 19 studies, comprising 14 randomized controlled trials (RCTs) and 5 prospective studies, focusing on interventions that purportedly use regenerative medicine principles in aesthetic applications. RESULTS: The review highlights a prevalent gap in molecular and clinical evidence supporting the efficacy and safety of regenerative aesthetics. Despite the robust design of the included RCTs and prospective studies, there remains a significant lack of consistent, high-quality evidence proving the effectiveness of these interventions. Issues such as inadequate reporting, unclear molecular mechanisms, and absence of long-term safety data were common. CONCLUSION: The field of regenerative aesthetics lacks the necessary scientific rigour and regulatory compliance to be recognized as a legitimate medical specialty. This review underscores the need for stringent scientific validation and regulatory oversight to ensure patient safety and treatment efficacy before these techniques can be recommended for clinical use. LEVEL OF EVIDENCE II: 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 .

Generational Exploration on Aesthetic Medicine Products: Influence of Social Media, Reviews, and Brand Identity-GEMS Bond Survey.

INTRODUCTION: The study investigates the impact of social media reviews and brand identity on consumer preferences in the non-surgical aesthetics products across different generations. It highlights the evolving landscape of aesthetic medicine and surgery, driven by technological advancements and a cultural shift towards individual well-being. The research aims to explore the interplay between generational preferences, the influence of social media, and the role of brand identity in shaping consumer decisions. METHODS: A cross-sectional study design was employed, with a sample size of > 5000 participants stratified across various generational cohorts. The study utilized an online questionnaire to capture both quantitative and qualitative insights into consumer behaviour, with statistical analysis performed to identify patterns and relationships. RESULTS: Analysis of 5850 responses revealed distinct generational preferences and behaviours. Social media engagement varied significantly across generations, with younger cohorts placing a higher emphasis on online reviews. The study also found that brand identity's influence is diminishing in decision-making processes, with consumers increasingly relying on peer reviews and social media content. CONCLUSION: The findings highlight a pivotal shift in the non-surgical aesthetics consumer market, emphasizing the growing importance of social media and peer reviews over traditional brand identities. Importantly, the study underscores the critical need for integrating patient safety and evidence-based practice within marketing strategies. As consumer preferences evolve towards valuing transparency and authenticity, non-surgical aesthetics providers must prioritize these elements, ensuring that their services are not only appealing but also grounded in safety and scientific validity. LEVEL OF EVIDENCE IV: "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 ."

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. The aim of this review was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses were based on the number of cases with data available. A total of 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Strokelike features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (P < .001). The 3 most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intraarterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (P > .05). Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

Integrative Assessment for Optimizing Aesthetic Outcomes When Treating Glabellar Lines With Botulinum Toxin Type A: An Appreciation of the Role of the Frontalis.

Despite the perception that treatment of glabellar lines with botulinum toxin A is straightforward, the reality is that the glabellar region contains a number of interrelated muscles. To avoid adverse outcomes, practitioners need to appreciate how treatment of 1 facial muscle group influences the relative dominance of others. In particular, practitioners need to understand the independent role of the frontalis in eyebrow outcomes and the potential for negative outcomes if the lower frontalis is unintentionally weakened by botulinum toxin A treatment. In addition, practitioners must recognize how inter-individual variation in the depth, shape, and muscle fiber orientation among the upper facial muscles can affect outcomes. For optimal results, treatment of the glabellar complex requires a systematic and individualized approach based on anatomical principles of opposing muscle actions rather than a one-size-fits-all approach. This review provides the anatomical justification for the importance of an integrated assessment of the upper facial muscles and eyebrow position prior to glabellar treatment. In addition, a systematic and broad evaluation system is provided that can be employed by practitioners to more comprehensively assess the glabellar region in order to optimize outcomes and avoid negatively impacting resting brow position and dynamic brow movement.

The Efficacy and Duration of Onabotulinum Toxin A in Improving Upper Facial Expression Lines With 64-Unit Dose Optimization: A Systematic Review and Meta-Analysis With Trial Sequential Analysis of the Randomized Controlled Trials.

BACKGROUND: Onabotulinumtoxin A (Onabot A) was the first treatment to be approved for aesthetic indications, namely glabellar lines (GLs), crow's feet lines (CFLs), and forehead lines (FHLs), with a cumulative dose of 64 U. OBJECTIVES: The aim of this study was to conduct a meta-analysis to combine the available data for approved doses for GLs, CFLs, and FHLs to explore the effect and duration of simultaneous treatment with Onabot A. METHODS: PubMed/MEDLINE, Embase, and other national clinical trial registries were searched for randomized controlled trials from January 2010 to July 2022. The meta-analysis, trial sequential analysis, and investigator-assessed time to return to nonresponder status in GLs, CFLs, and FHLs following Onabot A were plotted to elicit a cumulative dose-adjusted response curve based on Kaplan-Meier analysis with a log-rank test. RESULTS: Fourteen randomized controlled trials were eligible for quantitative analysis. A total of 8369 subjects were recruited across the trials. The meta-analysis results show that Onabot A is very effective in reducing moderate to severe GLs, CFLs, and FHLs. The cumulative Z-curve for GLs, CFLs, and FHLs also exceeds the required information size (RIS). Kaplan-Meier analysis with a log-rank test demonstrated that simultaneous treatment of GLs, CFLs, and FHLs requires 182 days (95% CI = 179, 215 days) (P < 0.00002) to return to nonresponder status. CONCLUSIONS: Treatment of the upper facial expression lines with Onabot A is effective, and the approved cumulative dose of 64 U gives longer-lasting effects.

Retrospective review of delayed adverse events secondary to treatment with a smooth, cohesive 20-mg/mL hyaluronic acid filler in 4500 patients.

BACKGROUND: Recent publications have suggested an increased risk of delayed adverse events (DAEs) with a smooth, cohesive 20-mg/mL hyaluronic acid filler, Juvéderm Voluma (HA-V). OBJECTIVE: To examine the occurrence of HA-V DAEs and identify patterns and characteristics. METHODS: Charts from patients who received HA-V between February 1, 2009, and February 28, 2018 from 2 clinics were analyzed. RESULTS: In 4500 patients who received 9324 treatments with HA-V, 44 DAEs were identified, for a combined incidence of 0.98% per patient, 0.47% per treatment, and 0.23% per syringe. Patients with DAEs received a slightly larger cumulative amount of HA-V than those who did not. Delayed swelling and nodule formation were the most common reactions and occurred a median of 4 months after treatment, with an increase in frequency between October and January. About a third were preceded by an identifiable immunologic stimulus. DAEs were transient and resolved without incident. LIMITATIONS: The retrospective nature made it difficult to capture time to resolution or remember potential triggers. CONCLUSION: In this large, long-term, retrospective review, HA-V DAEs occurred at a rate of 0.98% per patient. Although the exact cause has yet to be elucidated, we hypothesize that an increase in fragmentation during the HA-V degradation process may trigger an inflammatory response after an immunologic trigger.

Update on Avoiding and Treating Blindness From Fillers: A Recent Review of the World Literature.

BACKGROUND: Sudden loss of vision secondary to filler treatments is a rare but catastrophic complication. OBJECTIVES: The aim of this study was to update the published cases of blindness after filler injection that have occurred since we published our review of 98 cases in 2015, and to discuss prevention and management strategies. METHODS: A literature review was performed to identify all cases of visual complications caused by filler injection identified between January 2015 and September 2018. RESULTS: Forty-eight new published cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nasal region (56.3%), glabella (27.1%), forehead (18.8%), and nasolabial fold (14.6%). Hyaluronic acid filler was the cause of this complication in 81.3% of cases. Vision loss, pain, ophthalmoplegia, and ptosis were the most common reported symptoms. Skin changes were seen in 43.8% of cases and central nervous system complications were seen in 18.8% of cases. Ten cases (20.8%) experienced complete recovery of vision, whereas 8 cases (16.7%) reported only partial recovery. Management strategies varied greatly and there were no treatments that were shown to be consistently successful. CONCLUSIONS: Although the risk of blindness from fillers is rare, practitioners who inject filler should have a thorough knowledge of this complication including prevention and management strategies.

Appreciation of the Vascular Anatomy of Aesthetic Forehead Reflation.

BACKGROUND: Worldwide, the brow is the most common facial site to receive aesthetic treatment. However, the forehead above the brows has been comparatively less well studied with respect to both neuromodulators and fillers. Age-related remodeling of the forehead with loss of facial bone has been demonstrated on detailed radiographic studies. Concurrent loss of facial fat deposits also adds to the volume depletion. The resulting shallow scalloped depressions in the central 2/3 of the forehead give a tired and aged appearance as do the deep etched horizontal forehead lines which are often associated. Temporal hollowing may be an important associated feature. METHODS: Combination treatment of the upper face with neuromodulators to elevate the brows and diluted hyaluronic acid (HA) fillers to smooth the medial glabellar complex and reflate the forehead and temple has recently become a desired and popular treatment. Several techniques have been described in the literature. All these techniques are designed to allow forehead reflation with reduction of the possibility of vascular compromise. CONCLUSION: Avoidance of the supratrochlear and supraorbital vasculature with cosmetic filler injections is possible by insertion of needle or cannula into the subgaleal space above their transition from preperiosteal to subcutaneous level. Using this technique we have so far not seen any vascular compromise and we present this technique in the interest of patient safety.

The Facial Platysma and Its Underappreciated Role in Lower Face Dynamics and Contour.

BACKGROUND: The platysma is a superficial muscle involved in important features of the aging neck. Vertical bands, horizontal lines, and loss of lower face contour are effectively treated with botulinum toxin A (BoNT-A). However, its pars facialis, mandibularis, and modiolaris have been underappreciated. OBJECTIVE: To demonstrate the role of BoNT-A treatment of the upper platysma and its impact on lower face dynamics and contour. MATERIAL AND METHODS: Retrospective analysis of cases treated by an injection pattern encompassing the facial platysma components, aiming to block the lower face as a whole complex. It consisted of 2 intramuscular injections into the mentalis muscle and 2 horizontal lines of BoNT-A injections superficially performed above and below the mandible (total dose, 16 onabotulinumtoxinA U/side). Photographs were taken at rest and during motion (frontal and oblique views), before and after treatment. RESULTS: A total of 161 patients have been treated in the last 2 years with the following results: frontal and lateral enhancement of lower facial contour, relaxation of high horizontal lines located just below the lateral mandibular border, and lower deep vertical smile lines present lateral to the oral commissures and melomental folds. CONCLUSION: The upper platysma muscle plays a relevant role in the functional anatomy of the lower face that can be modulated safely with neuromodulators.

Cryolipolysis for Reduction of Arm Fat: Safety and Efficacy of a Prototype CoolCup Applicator With Flat Contour.

BACKGROUND: Cryolipolysis of the arms has been shown to be an effective but somewhat time-consuming process. OBJECTIVE: The study evaluated safety and efficacy of a contoured cup cryolipolysis applicator for reduction of arm fat. The prototype was designed to maximize tissue contact with the cooling surface to improve comfort, while reducing treatment time by 25 minutes. MATERIALS AND METHODS: Both arms were treated using a prototype device that delivered treatment in 35 minutes at -11°C. Photographic and ultrasound documentation was captured at baseline and 12 weeks post-treatment. Efficacy was assessed by photo review and measurement of fat reduction in ultrasound images. Immediately after 1, 4, and 12 weeks post-treatment, clinical assessments were performed to evaluate treatment areas and sensory alterations. RESULTS: Thirty women were enrolled and completed treatments to both arms. Ultrasound measurements found mean fat layer reduction of 3.2 mm with an SD of 2.7 mm. Blinded independent photo review found 85.2% correct identification of baseline photographs by at least 2/3 of reviewers. There were no unanticipated adverse device effects. Four study subjects experienced numbness in the treatment area beyond the 12-week visit that subsequently resolved without intervention. CONCLUSION: These data suggest that the CoolCup prototype applicator provides rapid, safe, and effective arm treatment.