Patient-reported outcomes after incobotulinumtoxinA treatment for upper facial wrinkles.

BACKGROUND: Botulinum toxins are used for facial rejuvenation. OBJECTIVE: To investigate the efficacy, patient satisfaction, and skin physiology after incobotulinumtoxinA treatment of the upper face. MATERIALS AND METHODS: Thirty women aged 35 to 55 were enrolled in this single-center prospective 16-week study. Patients and an investigator blinded to visit number assessed wrinkle severity after incobotulinumtoxinA treatment of glabellar, periorbital, and forehead lines using Validated Assessment Scales at Days 0 (baseline), 2, 7, 14, 28, and 112. Responder rates (for each region) and mean wrinkle scores (whole upper face) were calculated. Treatment satisfaction was self-assessed by questionnaire. Transepidermal water loss (TEWL), stratum corneum hydration, and skin pH were measured to assess skin barrier function. RESULTS: Wrinkle severity decreased rapidly after treatment. Responder rates generally peaked at Days 7 to 14. At 112 days, mean scores remained significantly lower than baseline (p < .05). Patients were significantly more satisfied with their appearance after treatment; most felt "younger" and "more attractive" (p < .05). Transepidermal water loss decreased significantly throughout (p < .05), and stratum corneum hydration increased. No treatment-related adverse events occurred. CONCLUSION: IncobotulinumtoxinA rapidly improved wrinkle severity, and improvements were maintained for up to 112 days. Increased stratum corneum hydration and reduced TEWL may improve skin quality. IncobotulinumtoxinA was well tolerated and improved patients' self-perception.

The Facial Adipose System: Its Role in Facial Aging and Approaches to Volume Restoration.

BACKGROUND: Volume loss in facial adipose tissue plays a critical role in the aesthetics of facial aging. Furthermore, the facial adipose system is a complex network of distinct compartments, and a detailed understanding of these compartments is essential for optimal facial volume restoration. OBJECTIVE: To review the facial adipose system, age-related changes, and the role of volume restoration products for facial rejuvenation. METHODS: Publications including deceased donors' dissection studies and more recent studies using computed tomography were reviewed to provide an up-to-date understanding of the facial adipose system anatomy and age-related changes. Current volume restoration treatment options including hyaluronic acid, calcium hydroxylapatite, and poly-L-lactic acid are discussed. RESULTS: Facial aging is associated with volume loss in superficial and deep adipose compartments, including those of the forehead, cheek, lip, chin, and jowl areas. Volume restoration products can be used to address the age-related changes of the facial adipose compartments. CONCLUSION: Understanding the complex network of facial adipose compartments and their age-related changes allows for the optimal use of injectable volume restoration products for facial rejuvenation that can be customized to the anatomical needs of each patient.

Comparison of Validated Assessment Scales and 3D digital fringe projection method to assess lifetime development of wrinkles in men.

BACKGROUND: The assessment of wrinkle severity is an important evaluation criterion to determine the efficacy of aesthetic treatments. Aim of the present study was to compare Validated Assessment Scales (VAS) and 3D fringe projection (PRIMOS(®) ) for the evaluation of facial wrinkles in men and to determine standard values for each level of the VAS. METHODS: 150 male subjects (20 to 70 years) were selected following strict criteria. Wrinkle severity at periorbital, glabella and forehead lines was evaluated using the 3D fringe projection and 5-point photonumeric VAS. The results of both methods were matched by determining quantitative values for each level of the clinical rating scale. RESULTS: High average correlation with age was found for VAS, Wd, maxWd, lWd, Wv, aWa and pWa. With a Wd of 60 to 70µm crow's feet and forehead lines are pronounced first, whereas glabella lines develop in subject's mid-forties, by an Wd of 180µm. Wrinkle severity increases at all locations every 10 years of age by one level of the VAS. This increase corresponds to an increase of Wd about 100 µm at glabella and forehead lines, and about 50 µm at crow's feet. CONCLUSION: The presented reference values for the Validated Assessment Scale are an important step towards an optimized assessment of skin aging and aesthetic dermatological treatments. The data helps to combine the precession of a biophysical measurement with the practical relevance of a clinical rating.

Quantification of age-related facial wrinkles in men and women using a three-dimensional fringe projection method and validated assessment scales.

BACKGROUND: Whereas the molecular mechanisms of skin aging are well understood, little information is available concerning the clinical onset and lifetime development of facial wrinkles. OBJECTIVES: To perform the first systematic evaluation of the lifetime development of facial wrinkles and sex-specific differences using three-dimensional (3D) imaging and clinical rating. METHODS: 200 men and women aged 20 to 70 were selected. Wrinkle severity of periorbital, glabellar, and forehead lines was evaluated using 3D imaging and validated assessment scales. RESULTS: Wrinkle severity was greater at all assessed locations with older age. In men, wrinkles manifested earlier and were more severe than in women. In women, periorbital lines were the first visible wrinkles, in contrast to the forehead lines in men. In both sexes, glabellar lines did not clinically manifest before the age of 40. CONCLUSION: The results of the present study confirm a progressive increase of crow's feet and forehead and glabellar lines in men and women. Although the development of facial wrinkles happens earlier and is more severe in men, perimenopause seems to particularly affect development in women. Clinical ratings and 3D measurements are suitable methods to assess facial wrinkle severity in men and women.

Eosinophilic globules (syn. hyaline inclusions) and protein crystalloids in the nasal mucosa of rats treated with synthetic amorphous silica, an unspecific chitinase-like-protein-positive background lesion.

In a 13-week inhalation toxicity study with three recovery periods (3, 6, and 12 months), Crl: WI rats were allocated to nine groups, each containing 25 animals per sex. Eight groups were treated daily by inhalation with the test items at concentrations of 0.5, 1.0, 2.5, or 5.0 mg/m3 (SAS 1 groups 2, 3, 4, or 5, respectively; SAS 2 groups 6, 7, 8, or 9, respectively). Controls (group 1) were treated with air only. In nasal cavities, the major lesions consisted of increased eosinophilic globules and chitinase-3-like-protein-positive crystalloids* in the nasal mucosa, mainly in nasal cavity levels 2-4 up to week 26 of recovery without any further injury in olfactory mucosa, mainly in SAS 1-treated animals. Eosinophilic globules in the rodent nasal cavity are common and increase with age; they represent a particular finding of the rodent nasal mucosa. The relevance of chitinase-3-like protein (Ym1 + Ym2) expression in the rodent nasal mucosa is unknown but is normal in control animals. Both findings developed without any indicator for inflammatory processes. The increase of these unspecific background findings is considered an indicator of minor irritative effects. Due to the clear lack of nasal tissue injury or concurrent changes (degeneration, necrosis, inflammatory infiltrate, dysplasia, and/or neoplasia) following repeated inhalation exposure to SAS, it is deemed that the eosinophilic globules (hyaline inclusions) combined with the formation of eosinophilic protein crystalloids in this study represent an adaptive response.

Enhanced study design for acute inhalation studies with hydrophobic surface-treated particles to determine toxicological effects including suffocation.

High concentrations of low-density particles may cause effects in acute inhalation toxicity studies which can be easily underestimated or misinterpreted following strictly the OECD TG 436, i.e., limited parameters as mortality and gross lesions will be evaluated only. Seven particle types (synthetic amorphous silica (SAS) HMDZ-SAS, silica gel, pyrogenic SAS, and precipitated SAS, calcium carbonate, aluminum oxide pyrogenic alumina, organic red pigment) were chosen at the highest technically feasible concentration of approximately 500 mg/m3 for acute inhalation studies with an expanded endpoint setup. Therefore additional parameters and a thorough histopathological evaluation of an extensive set of organs, including the respiratory tract emphasizing the nasal cavities were added. Six Crl:WI rats per study were exposed for four hours from which three animals were sacrificed after 24 hours and three animals after 14 days. HMDZ-SAS caused early death in all animals due to blockage of the nasal passages caused by its hydrophobicity. For all other Si-containing compounds, histology revealed minor inflammatory and reactive lesions in lungs after 24 hours that were still present after 14 days, except in silica gel-treated animals. After 14 days, for pyrogenic SAS, precipitated SAS, and pyrogenic alumina, granulomas formed in the BALT and lung-associated lymph nodes. In contrast, the calcium carbonate induced almost no findings, and the red pigment (also tested for the additional dose of 1000 mg/m3) stuck partially to the nasal mucosa without causing pathological damage and partly entered the lungs without showing any adverse effects. The results of the present study highlight the advantage of improving the rather simple study design of acute inhalation studies by implementing an extended study design.

Current status of surgery in dermatology.

An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein.

Stabilized hyaluronic acid-based gel of non-animal origin for skin rejuvenation: face, hand, and décolletage.

BACKGROUND: Mid-dermal injection of stabilized hyaluronic acid (HA) is well established as a treatment to reduce the effects of skin aging. OBJECTIVE: To assess the efficacy and safety of a stabilized HA-based gel of non-animal origin manufactured using the patented NASHA® technology (Restylane® Vital Light, Q-Med AB, Uppsala, Sweden) administered using a pre-filled micropuncture injector device for rejuvenation of the skin. METHODS: Three treatment sessions 4 weeks apart were performed on one side of the face, the dorsum of one of the hands and one side of the décolletage, leaving the other side untreated. Skin quality was assessed via blinded live evaluation and subject satisfaction by questionnaire. Aesthetic change was evaluated independently by the subject and a blinded evaluator. Subjects were followed up to week 36. RESULTS: Thirty subjects aged 40-65 years were enrolled. Overall skin quality across all three treatment areas was judged to be improved on the treated side in over 80% of subjects throughout the study. Significant aesthetic improvements on the treated sides were observed at all visits, with the exception of the décolletage at week 36. CONCLUSIONS: This was the first study that used a micropuncture injector device for injection of NASHA gel, and reveals that this is a promising treatment option for rejuvenation of the skin.

The history of aesthetic medicine and surgery.

The history of beauty is as old as mankind itself--throughout history people have tried to improve their attractiveness and to enhance their beauty. The technical basis for many of nowadays procedures like lipoplasty, breast augmentation or rhinoplasty was thereby initiated more than a hundred years ago and evolved to the modern standards of today. The aim of this article is to recall the early days of aesthetic medicine and show the swift progress up to the highly specialized medical discipline of our modern time. Combining the past, present and future of aesthetic medicine, allows to incorporate this perspective and ultimately to delivery better patient care.

New-generation radiofrequency technology.

Radiofrequency (RF) technology has become a standard treatment in aesthetic medicine with many indications due to its versatility, efficacy, and safety. It is used worldwide for cellulite reduction; acne scar revision; and treatment of hypertrophic scars and keloids, rosacea, and inflammatory acne in all skin types. However, the most common indication for RF technology is the nonablative tightening of tissue to improve skin laxity and reduce wrinkles. Radiofrequency devices are classified as unipolar, bipolar, or multipolar depending on the number of electrodes used. Additional modalities include fractional RF; sublative RF; phase-controlled RF; and combination RF therapies that apply light, massage, or pulsed electromagnetic fields (PEMFs). This article reviews studies and case series on these devices. Radiofrequency technology for aesthetic medicine has seen rapid advancements since it was used for skin tightening in 2003. Future developments will continue to keep RF technology at the forefront of the dermatologist's armamentarium for skin tightening and rejuvenation.

A novel approach to structural facial volume replacement.

UNLABELLED: Improved understanding of the anatomy and physiology of the aging face has laid the foundation for adopting an earlier and more comprehensive approach to facial rejuvenation, shifting the focus from individual wrinkle treatment and lift procedures to a holistic paradigm that considers the entire face and its structural framework. This article presents an overview of a comprehensive method to address facial aging. The key components to the reported strategy for improving facial cosmesis include, in addition to augmentation of volume loss, protection with sunscreens and antioxidants; promotion of epidermal cell turnover with techniques such as superficial chemical peels; microlaser peels and microdermabrasion; collagen stimulation and remodeling via light, ultrasound, or radiofrequency (RF)-based methods; and muscle control with botulinum toxin. For the treatment of wrinkles and for the augmentation of pan-facial dermal lipoatrophy, several types of fillers and volumizers including hyaluronic acid (HA), autologous fat, and calcium hydroxylapatite (CaHA) or injectable poly-L-lactic acid (PLLA) are available. A novel bimodal, trivector technique to restore structural facial volume loss that combines supraperiosteal depot injections of volume-depleted fat pads and dermal/subcutaneous injections for panfacial lipoatrophy with PLLA is presented. The combination of treatments with fillers; toxins; light-, sound-, and RF-based technologies; and surgical procedures may help to forestall the facial aging process and provide more natural results than are possible with any of these techniques alone. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Regenerative and progressing lesions in lungs and lung-associated lymph nodes from fourteen 90-day inhalation studies with chemically different particulate materials.

Rat lungs and lung-associated lymph nodes from 14 inhalation studies with chemically different particulate materials were histopathologically re-evaluated, and the bronchoalveolar lavage fluid (BALF) data and lung burden analyses were compared. All investigated substances caused similar lesions. For most substances, 1 mg/m3 of respirable particulate matter was established as the borderline for adverse morphological changes after the 90-day exposure period, confirmed by the increase in polymorphonuclear neutrophils in BALF. Possible reversibility was demonstrated when recovery groups are included in the study especially allowing the differentiation between regeneration or progressing of inflammatory changes during the recovery period. It was concluded, that the major driver of toxicity is not an intrinsic chemical property of the particle but a particle effect. Concerning classification for specific target organ toxicant (STOT) repeated exposure (RE), this paper highlights that merely comparing the lowest concentration, at which adverse effects were observed, with the Classification Labelling and Packaging (CLP) regulation (EC) no. 1272/2008 guidance values is inappropriate and might lead to a STOT classification under CLP for a large part of the substances discussed in this paper, on the basis of typically mild to moderate findings in rat lung and lung-associated lymph nodes on day 1 after exposure. An in-depth evaluation of the pathologic findings is required and an expert judgement has to be included in the decision on classification and labeling, evaluating the type and severity of effects and comparing these with the classification criteria.

Issues in the inhalation toxicity testing and hazard assessment for low density particulate materials such as synthetic amorphous silica (SAS).

Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

Does carbon black disaggregate in lung fluid? A critical assessment.

Carbon black is an industrially produced particulate form of nearly pure elemental carbon. The basic building blocks of carbon black are (1) primary particles, minute pieces of matter with defined physical boundaries; (2) aggregates, collections of strongly bound or fused particles; and (3) agglomerates, collections of weakly bound aggregates. Industrial carbon black is produced within a closed reactor where the primary particles form aggregates, which become the indivisible entities of carbon black. These aggregates then form agglomerates, which are the typical form of carbon black in commerce. Carbon black is often used in in vitro and in vivo particle toxicology investigations as a reference nanoparticle. The toxicology studies often report the sizes of the primary particles but rarely the sizes of the aggregates or agglomerates. It appears in many cases that there is a limited understanding of the fact that carbon black typically does not exist as primary particles but instead exists as aggregates and agglomerates. Moreover, many toxicology studies manipulate carbon black particles in order to disperse them so that the form of carbon black used in these toxicology studies may be substantially different from the form that may be encountered in the workplace environment. Since the main exposure route for carbon black is inhalation, the question arose as to whether inhaled carbon black may deagglomerate or disaggregate to either smaller aggregates or primary particles when in contact with lung fluids. This question relates to the concern that there may be additional hazards of smaller particles, such as their ability to translocate to tissues and organs beyond the lung and the ability to pass through the blood-brain barrier. The purpose of this assessment is to review the existing literature for evidence as to whether carbon black deagglomerates or disaggregates into smaller aggregates or primary particles when in contact with lung fluid. On the basis of a review of the physical characteristics of commercial carbon black and various toxicology studies, it appears that commercially produced carbon black in contact with lung fluid is unlikely to deagglomerate or disaggregate into smaller aggregates or primary particles.

Safety and efficacy of a new device combining radiofrequency and low-frequency pulsed electromagnetic fields for the treatment of facial rhytides.

BACKGROUND: A distinct trend in aesthetic medicine is the patient's demand for efficient, noninvasive treatments with no downtime. Ongoing with this, these so-called lunchtime procedures are expected to be as safe and painless as possible. A new technique based on a combination of radiofrequency (RF) and pulsed electromagnetic fields (PEMF) was recently introduced and is supposed to be effective in the treatment of facial wrinkles and virtually pain free. The objective of this study was to investigate the safety and efficacy of this technology for the treatment of facial rhytides. METHODS: Thirty-one subjects with facial wrinkles and rhytides were entered into this study. Every subject received 10 treatments of the face with a device that combines 1 MHz radiofrequency with PEMF with a flux of 15 gauss. Patients rated the pain level immediately after the treatment by using a visual analog scale (VAS) for pain. Side effects were recorded at every visit. The study's efficacy end point was evaluated by 2 blinded physicians who rated the standardized pictures from baseline and 3-month follow-up using the Fitzpatrick Wrinkle and Elastosis Scale (FWES). RESULTS: No unexpected adverse side effects were detected or reported for the duration of the study. Both raters recognized improvements of at least 1 grade on the FWES in 30 of 31 subjects (97%). The score decreased from 5.2 before the first treatment to 3.6 at 3 months after the last treatment. Furthermore, all patients rated the treatment to be free of pain on the VAS pain scale. CONCLUSION: The results of this study show that the combination of multipolar RF with PEMF is a safe, effective, and painless approach to treat facial rhytides and is suitable to answer the demands of patients for safe treatments without pain or downtime.

Surface Treatment With Hydrophobic Coating Reagents (Organosilanes) Strongly Reduces the Bioactivity of Synthetic Amorphous Silica in vitro.

Synthetic amorphous silica (SAS) is industrially relevant material whose bioactivity in vitro is strongly diminished, for example, by protein binding to the particle surface. Here, we investigated the in vitro bioactivity of fourteen SAS (pyrogenic, precipitated, or colloidal), nine of which were surface-treated with organosilanes, using alveolar macrophages as a highly sensitive test system. Dispersion of the hydrophobic SAS required pre-wetting with ethanol and extensive ultrasonic treatment in the presence of 0.05% BSA (Protocol 1). Hydrophilic SAS was suspended by moderate ultrasonic treatment (Protocol 2) and also by Protocol 1. The suspensions were administered to NR8383 alveolar macrophages under serum-free conditions for 16 h, and the release of LDH, GLU, H2O2, and TNFα was measured in cell culture supernatants. While seven surface-treated hydrophobic SAS exhibited virtually no bioactivity, two materials (AEROSIL® R 504 and AEROSIL® R 816) had minimal effects on NR8383 cells. In contrast, non-treated SAS elicited considerable increases in LDH, GLU, and TNFα, while the release of H2O2 was low except for CAB-O-SIL® S17D Fumed Silica. Dispersing hydrophilic SAS with Protocol 1 gradually reduced the bioactivity but did not abolish it. The results show that hydrophobic coating reagents, which bind covalently to the SAS surface, abrogate the bioactivity of SAS even under serum-free in vitro conditions. The results may have implications for the hazard assessment of hydrophobic surface-treated SAS in the lung.

Comparison of Biogenic Amorphous Silicas Found in Common Horsetail and Oat Husk With Synthetic Amorphous Silicas.

The present study summarizes the current literature on the presence and the structure of biogenic amorphous silica (BAS) in nature. Based on this review, it is shown that BAS is ubiquitous in nature and exhibits a structure that cannot be differentiated from the structure of synthetic amorphous silica (SAS). The structural similarity of BAS and SAS is further supported by our investigations-in particular, specific surface area (BET) and electron microscope techniques-on oat husk and common horsetail. Many food products containing BAS are considered to be beneficial to health. In the context of the use of SAS in specific applications (e.g., food, feed, and cosmetics), this is of particular interest for discussions of the safety of these uses.

Physical Obstruction of Nasal Cavities With Subsequent Asphyxia, Causes Lethality of Rats in an Acute Inhalation Study With Hydrophobic HMDZ Surface-Treated Synthetic Amorphous Silica (SAS).

The aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) caused the effects observed. Hydrophobic surface-treated SAS was inhaled (flow-past, nose-only) by six Wistar rats (three males and three females) in an acute toxicity study at a concentration of ~500 mg/m3 for an intended 4-hr exposure. Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test- material-exposed animals survived the planned observation time of 4 h; three animals died between 2 34 h after starting exposure and cessation of exposure at 3 14 h, two died after transfer to their cages and the remaining animal was sacrificed due to its poor condition and welfare considerations. Histology accomplished by energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that ultimately blocked the upper respiratory airways, which proved fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. showing a correlation between lethality and hydrophobicity determined by contact angle measurement. The aerosol characterizations associated with this study are provided in detail by Wessely et al.

Age-related changes in skin mechanical properties: a quantitative evaluation of 120 female subjects.

BACKGROUND/PURPOSE: The most commonly used method to determine the mechanical ability of skin is the creep test using suction chamber devices. Until now, there is no scientific consensus upon which skin deformation parameters and which body sites are particularly suitable to describe age-related changes in human skin mechanics. The aim of this study was to find those mechanical skin parameters best representing influence of aging at five different body sites. METHODS: A total of 120 healthy women aged 18-65, divided into four similar age groups, were included in this study. The biomechanical properties of the skin were measured using the Cutometer® MPA 580 on five body sites: cheek, neck, cleavage, volar forearm and back of the hand. In order to analyze parameters referred to 1 mm skin thickness, we also used 20 MHz sonography (DUB 20). RESULTS: A high average correlation with age was found for the parameters U(a)/U(f), U(r)/U(e), U(r), U(r)/U(f) and U(a). Only low correlation with age was found for the parameters U(v)/U(e), U(f)-U(a), U(f5)/U(f), U(d)/U(f) and U(a5). The localizations cheek, forearm and neck showed the highest correlation with age, while cleavage showed only low correlation. CONCLUSION: According to the results of our study, we recommend the parameter ratio of elastic recovery to distensibility (U(r)/U(f) ) as well as the gross elasticity (U(a)/U(f)) for evaluation of aging effects on the mechanical properties of skin. Their high correlation with age makes them particularly applicable to represent the influence of aging onto skin mechanical properties. Most suitable localizations to evaluate skin aging are cheek, forearm and neck.