Facial Skin Revitalization with Cohesive Polydensified Matrix-HA20G: Results from a Randomized Multicenter Clinical Study.

BACKGROUND: There is a growing interest in the application of hyaluronic acid (HA) derivatives in skin quality improvement. The aim of this study was to confirm safety and effectiveness of cohesive polydensified matrix-hyaluronic acid + glycerol (CPM-HA20G; Belotero Revive) in revitalization of early-onset photodamaged facial skin. METHODS: A total of 159 subjects with early signs of facial photodamaged skin were randomized in a 2:1 ratio to multiple- or single-dose treatment with CPMHA20G. Effectiveness assessments included biophysical measurements of skin hydration; elasticity, firmness, and roughness; investigator- and subject-assessed Global Aesthetic Improvement Scales; and FACE-Q Skin Changes and Treatment Satisfaction questionnaires. RESULTS: In both treatment groups, skin hydration improved from baseline to all follow-up visits in subjects with dry or very dry skin. This improvement was significant at week 16 after initial treatment in the multiple-dose group (P = 0.0013). Investigator- and subject-reported outcomes showed that the majority of subjects across all skin hydration types benefited from treatment, with higher satisfaction rates observed in the multiple-dose group. According to investigator-assessed Global Aesthetic Improvement Scale, 90.7% of subjects at week 12 in the multiple-dose and 74.6% of subjects at week 4 in the single-dose group were rated as at least "improved." All related treatment-emergent adverse events were transient, expected injection-site reactions of mild to moderate intensity. CONCLUSIONS: Effectiveness of CPM-HA20G for skin hydration in subjects with dry or very dry skin was demonstrated up to 9 months after last injection. Overall, CPM-HA20G demonstrated effective and safe use in facial skin revitalization among subjects with early-onset photodamaged skin.

Safety and Performance of Etermis 3 and 4 in Wrinkles/Folds Treatment and Facial Volume Enhancement: A Prospective, Evaluator-Blinded, Open-Label Study.

BACKGROUND: Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas. OBJECTIVE: To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement. METHODS: Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment. RESULTS: In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥76.6%, marionette lines ≥61%, lips ≥36%) and ET3 (marionette lines ≥50% and lips ≥21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions. CONCLUSION: Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.

Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm.

BACKGROUND AND OBJECTIVES: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. MATERIALS AND METHODS: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. RESULTS: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. CONCLUSION: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.

A novel concept for the treatment of couperosis based on nanocrystals in combination with solid lipid nanoparticles (SLN).

For the post laser treatment of couperosis a new dermal formulation was developed combining three actives: vitamin K1, A1 and rutin, where both vitamins were incorporated into solid lipid nanoparticles (SLN) and the poorly soluble antioxidant rutin formulated as nanocrystal. All three formulations were stable over 6 months either on their own or after their incorporation into a hydrogel. Vitamin A1 at 0.3% in emulsions shows local skin irritation due to very rapid release. By forming SLN, prolonged release with less irritation potential but deeper penetration was achieved in porcine ear skin. Due to the nanosized rutin, the new hydrogel showed clearly increased antioxidant activity, representing a stronger protection potential against reactive oxygen species (ROS), compared to marketed anti-redness products with rutin as raw drug powder or water-soluble derivative. In addition, rutin nanocrystals showed up to 5 times pronounced penetration compared to µm-sized raw drug powder. The orientating in-vivo case study revealed a three to six times faster recovery after laser treatment of couperosis by twice daily application of the new hydrogel, regarding scabbed-over areas and erythema. Continued use of the new gel also showed preventive properties against recurrences of veins for at least 8 month.

Hyaluron Filler Containing Lidocaine on a CPM Basis for Lip Augmentation: Reports from Practical Experience.

Lip augmentation with hyaluronic acid fillers is established. As monophasic polydensified hyaluronic acid products with variable density, CPM-HAL1 (Belotero Balance Lidocaine, Merz Aesthetics, Raleigh, NC) and CPM-HAL2 (Belotero Intense Lidocaine, Merz Aesthetics, Raleigh, NC) are qualified for beautification and particularly natural-looking rejuvenation, respectively. The aim of this article was to assess the handling and outcome of lip augmentation using the lidocaine-containing hyaluronic acid fillers, CPM-HAL1 and CPM-HAL2. Data were documented from patients who received lip augmentation by means of beautification and/or rejuvenation using CPM-HAL1 and/or CPM-HAL2. Observation period was 4 months, with assessment of natural outcome, evenness, distribution, fluidity, handling, malleability, tolerability, as well as patient satisfaction and pain. A total of 146 patients from 21 German centers participated. Physicians rated natural outcome and evenness as good or very good for more than 95% of patients. Distribution, fluidity, handling, and malleability were assessed for both fillers as good or very good in more than 91% of patients. At every evaluation point, more than 93% of patients were very or very much satisfied with the product. A total of 125 patients (85.6%) experienced transient injection-related side effects. Pain intensity during the procedure was mild (2.72 ± 1.72 on the 0-10 pain assessment scale) and abated markedly within 30 minutes (0.42 ± 0.57). Lip augmentation with hyaluronic acid fillers produced a long-term cosmetic result. Due to the lidocaine content, procedural pain was low and transient. Accordingly, a high degree of patient satisfaction was achieved that was maintained throughout the observation period.

Recommendations for the best possible use of botulinum neurotoxin type a (Speywood units) for aesthetic applications.

The botulinum neurotoxin (BoNT) product Azzalure (manufactured by Ipsen Biopharm Limited, Wrexham, UK; distributed by Galderma), measured in Speywood units (s.U) has been available since 2009 for temporary improvement in the appearance of moderate to severe glabellar lines. Although we know much about the use of Azzalure for aesthetic indications, some aspects of product use in the clinic still require an update based on continuing and prevailing misconceptions and new clinical data. Therefore, a group of experts experienced with the use of Azzalure convened to formulate the following recommendations: (1) The key to an optimal effect is adequate dosing per injection point. Ten s.U are indicated for strong muscular activity, 5 s.U for medium activity, and approximately 2 s.U for minor activity. (2) The main factor that influences the area of effectiveness is the dosage per injection point. (3) In contrast to former beliefs, we know now that Azzalure works very fast, with some patients reporting initial drug activity after hours. (4) Various volumes can be used for dilution. However, the first choice is the recommended volume, 0.63 mL per vial of 125 s.U. Nevertheless, for clinicians changing products, keeping the volume they are used to might be an option. (5) Clinicians changing products have to be very careful not to confuse the units between different products. (6) In aesthetic BoNT-A usage, the development of antibodies is very rare and is not the common reason for insufficient results. (7) Probably the most common reason when BoNT-A is not working is the absolute or relative underdosage. The present adjunctive recommendations elaborated in an informal expert meeting should help physicians to optimize their treatment with Speywood unit products.

A European evaluation of cosmetic treatment of facial volume loss with Juvéderm™ Voluma™ in patients previously treated with Restylane Sub-Q™.

BACKGROUND: Juvéderm™ VOLUMA™ (Voluma) is a new injectable, long-lasting, resorbable hyaluronic acid filler. It restores facial volume, resulting in a more youthful appearance. AIMS: To evaluate current in-market perceptions of the aesthetic result and use of Voluma. PATIENTS/METHODS: Men and women >30 years who had received Restylane SubQ™ (Restylane) <2 years previously, now requiring re-treatment and who consented to Voluma treatment were included. RESULTS: Eighty-four patients (mean age 51 years, 88% women) were recruited. The mean total volume of Voluma injected was 2.73 mL/patient. This included treatment to both sides of the face, specifically in the malar and chin areas or both (mean 1.36 mL each to the right and left sides of the face). Seventy-five percent of injectors found Voluma fairly/very easy to inject and 84.5% found it easy to sculpt/massage. Most patients (98%) and physicians (98%) rated the aesthetic effect of Voluma as improved. Injectors rated Voluma as better than previous Restylane use in 69.1% of patients (P < 0.001), and preference for Voluma was expressed in 61% of patients (P < 0.001). Ninety-nine percent of injectors would recommend Voluma to colleagues and patients (100%); 96.4% of patients would recommend it to friends. Treatment was well tolerated. CONCLUSIONS: Voluma is easy to use, sculpt, and massage. Physicians and patients rated the cosmetic effects highly, and both groups reported a preference for Voluma in those patients previously treated with Restylane.

Density-equalizing mapping and scientometric benchmarking of European allergy research.

Due to the great socioeconomic burden of allergic diseases, research in this field which is important for environmental medicine is currently increasing. Therefore the European Union has initiated the Global Allergy and Asthma European network (GA2LEN). However, despite increasing research in the past years detailed scientometric analyses have not been conducted so far. This study is the first scientometric analysis in a field of growing interest. It analyses scientific contributions in European allergy research between 2001 and 2007. Three different meetings of the European Academy of Allergy and Clinical Immunology were analysed for contributions and an increase in both the amount of research and networks was found.

Density-equalizing mapping and scientometric benchmarking in Industrial Health.

Bibliometric techniques have been introduced to the field of industrial health in the past two decades. Since then, several studies have assessed progression of science in this area using quantitative measures and qualitative measures such as impact factor or H-indices. Since novel procedures such as density-equalizing mapping have not been used so far, the present study combined classical bibliometric tools with novel scientometric and visualizing techniques. All "INDUSTRIAL HEALTH" entries listed in the ISI database since 1987 were screened and analyzed. Using bibliometric approaches, a continuous increase in qualitative markers such as collaboration numbers or citations were found while quantity markers such as author numbers or publication numbers remained relatively constant. The combination with density equalizing mapping revealed a distinct global pattern of research productivity and citation activity with Japanese institutions at the leading position. Radar chart techniques were used to visualize bi- and multilateral research cooperations and institutional cooperations. In summary, the present study supplies a first scientometric-bibliometric approach that visualizes research activity in "INDUSTRIAL HEALTH" over the past decades.

Mobile Air Quality Studies (MAQS)-an international project.

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"-exposure in relation to non-"traffic zone"-exposure.Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including NO2, SO2, nanoparticles and ozone.

Study of the efficacy, tolerability, and safety of 2 fixed-dose combination gels in the management of acne vulgaris.

This study investigated the efficacy, tolerability, and safety of 2 fixed-dose combination gels for the treatment of facial acne: clindamycin 1%-benzoyl peroxide 5% gel with hydrating excipients (C/BPO HE) and adapalene 0.1%-benzoyl peroxide 25% gel (A/BPO). After 12 weeks of once daily treatment, the mean reduction in inflammatory lesion count was 76.8% and 72.2% in the C/BPO HE group and A/BPO group, respectively (P = .076). Significantly more participants achieved treatment success, which was defined as an improvement of 2 grades or more from baseline to week 12 on the investigator's static global assessment (ISGA) scale, with C/BPO HE (30.5% [58/190]) compared with A/BPO (21.8% [42/192]) (P = .046), and treatment success was achieved more quickly with C/BPO HE (P = .035). Both products also reduced noninflammatory (62.2% C/BPO HE vs 6 1.5% A/BPO) and total lesion counts (69.1% C/BPO HE vs 67.1% A/BPO). Despite the overall similar efficacy profile, C/BPO HE was better tolerated and safer than A/BPO. In the tolerability assessments, erythema, dryness, peeling, pruritus, and burning/ stinging were more frequent in the A/BPO group at all time points from week 1 onward (P < .05). Treatment-related adverse events (AEs) occurred in 48.4% (92/190) of participants in the C/BPO HE group compared with 78.6% (151/192) of the A/BPO group. We conclude that C/BPO HE and A/BPO have similar efficacy in treating inflammatory and noninflammatory acne lesions, but C/BPO HE achieves better overall treatment success in less time coupled with a significantly better tolerability profile and notably better safety profile.

Tobacco control: visualisation of research activity using density-equalizing mapping and scientometric benchmarking procedures.

BACKGROUND: Tobacco smoking continues to be a major preventable cause of death and disease and therefore tobacco control research is extremely important. However, research in this area is often hampered by a lack in funding and there is a need for scientometric techniques to display research efforts. METHODS: The present study combines classical bibliometric tools with novel scientometric and visualizing techniques in order to analyse and categorise research in the field of tobacco control. RESULTS: All studies related to tobacco control and listed in the ISI database since 1900 were identified by the use of defined search terms. Using bibliometric approaches, a continuous increase in qualitative markers such as collaboration numbers or citations were found for tobacco control research. The combination with density equalizing mapping revealed a distinct global pattern of research productivity and citation activity. Radar chart techniques were used to visualize bi- and multilateral research cooperation and institutional cooperation. CONCLUSIONS: The present study supplies a first scientometric approach that visualises research activity in the field of tobacco control. It provides data that can be used for funding policy and the identification of research clusters.

New quality and quantity indices in science (NewQIS): the study protocol of an international project.

Benchmarking systems are important features for the implementation of efficacy in basic and applied sciences. These systems are urgently needed for many fields of science since there is an imbalance present between funding policies and research evaluation. Here, a new approach is presented with an international study project that uses visualisation techniques for benchmarking processes. The project is entitled New Quality and Quantity Indices in Science (NewQIS). The juxtaposition of classical scientometric tools and novel visualisation techniques can be used to assess quality and quantity in science. In specific, the tools can be used to assess quality and quantity of research activity for distinct areas of science, for single institutions, for countries, for single time periods, or for single scientists. Also, NewQIS may be used to compare different fields, institutions, countries, or scientists for their scientific output. Thus, decision making for funding allocation can be made more transparent. Since governmental bodies that supervise funding policies and allocation processes are often not equipped with an in depth expertise in this area, special attention is given to data visualisation techniques that allow to visualize mapping of research activity and quality.

High abundances of neurotrophin 3 in atopic dermatitis mast cell.

BACKGROUND: Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far. OBJECTIVE: Characterize NT-3 on a transcriptional and translational level in individuals with atopic dermatitis with special focus on mast cells. METHODS: To meet this objective NT-3 levels in the serum of AD patients were measured, the effect of NT-3 on keratinocytes was evaluated and the gene expression and regulation assessed using ELISA, immunohistochemistry and RNA quantification. RESULTS: Systemic levels of NT-3 were found to be higher in individuals with AD as compared to healthy controls. A distinct genetic expression was found in the various cells of the skin. In lesional mast cells of individuals with atopic dermatitis an increased amount of NT-3 was apparent. Functional in vitro experiments demonstrated that NT-3 stimulation led to a suppression of IL-8 secretion by HaCat cells. CONCLUSION: These findings could imply a role for NT-3 in the pathogenesis of allergic skin diseases.

Expression, localisation and functional implications of the transporter protein PEPT2 in the upper respiratory tract.

Infectious diseases of the upper respiratory tract are widespread and may initiate exacerbations of chronic respiratory diseases such as bronchial asthma or chronic obstructive pulmonary disease. Nebulisation of antibiotics as a topic treatment may lead to high local drug concentrations. To provide data on drug transport, the present study analysed a specific drug transport system on the molecular and functional level. Messenger RNA of the proton-coupled transporter PEPT2 that mediates physiological transport of oligopeptides as well as peptidomimetics like beta-lactams and aminolevulinic acid was discovered in rat nasal mucosa by RT-PCR. Real-time PCR studies indicated a lower expression level than control kidney samples. PEPT2 immunoreactivity was identified in nasal mucosa tissue. The protein was expressed in epithelial cells, but goblet cells did not exhibit PEPT2 expression. Functional studies with rat preparations led to uptake of a fluorophore-conjugated substrate into epithelial cells of nasal mucosa. Goblet cells did not exhibit uptake activity. The uptake was competitively inhibited by dipeptides demonstrating similar substrate specificity as reported for PEPT2. Together, these data suggest that PEPT2 is likely to play an important role in mucosal peptide metabolism and may represent a novel target for therapeutic efforts in upper airway diseases.

Models of asthma: density-equalizing mapping and output benchmarking.

Despite the large amount of experimental studies already conducted on bronchial asthma, further insights into the molecular basics of the disease are required to establish new therapeutic approaches. As a basis for this research different animal models of asthma have been developed in the past years. However, precise bibliometric data on the use of different models do not exist so far. Therefore the present study was conducted to establish a data base of the existing experimental approaches. Density-equalizing algorithms were used and data was retrieved from a Thomson Institute for Scientific Information database. During the period from 1900 to 2006 a number of 3489 filed items were connected to animal models of asthma, the first being published in the year 1968. The studies were published by 52 countries with the US, Japan and the UK being the most productive suppliers, participating in 55.8% of all published items. Analyzing the average citation per item as an indicator for research quality Switzerland ranked first (30.54/item) and New Zealand ranked second for countries with more than 10 published studies. The 10 most productive journals included 4 with a main focus allergy and immunology and 4 with a main focus on the respiratory system. Two journals focussed on pharmacology or pharmacy. In all assigned subject categories examined for a relation to animal models of asthma, immunology ranked first. Assessing numbers of published items in relation to animal species it was found that mice were the preferred species followed by guinea pigs. In summary it can be concluded from density-equalizing calculations that the use of animal models of asthma is restricted to a relatively small number of countries. There are also differences in the use of species. These differences are based on variations in the research focus as assessed by subject category analysis.

Genomic aberrations and survival in cutaneous T cell lymphomas.

Information on chromosomal aberrations in cutaneous T cell lymphomas (CTCL), is scarce. In this study, comparative genomic hybridization (CGH) was used to analyze chromosomal imbalances (CI) in 32 patients with CTCL. CI were detected in 21 patients (66%). Euchromatic loss (dim) was localized most frequently (>16%) at the chromosomal regions 17p (28%), 13q (25%), 10q (16%), and 6q (19%), and gain of chromatin (enh) at 7 (25%), 8q (25%), and 17q (16%). The pattern dim6q-enh7-enh8-dim13 was the most frequent combination of CI. The number of aberrations per tumor sample varied between 0 and 19 and correlated with clinical tumor stages: from none in stage Ia to 8.75+/-1.8 (mean+/-SEM) in stage IVa. CI occurred more frequently in aggressive subtypes (9.33+/-2.16) than in indolent (2.88+/-0.8) subtypes. A high number of CI (>/=5) was associated with shorter survival. Gain of chromatin in 8q and loss of 6q and 13q correlated with a significantly shorter survival, whereas the most frequently observed aberrations (loss in 17p and gain in 7) did not influence the prognosis. In summary, CGH analysis revealed a characteristic pattern of recurring chromosomal gains and losses in CTCL. The association of the imbalances with the clinical course of the disease suggests that genes encoded at these loci may influence tumor development and progression.

Down-regulation of vasoactive intestinal polypeptide receptor expression in atopic dermatitis.

BACKGROUND: Receptors for vasoactive intestinal polypeptide (VIP) have recently been suggested to play a key role in immunomodulation with genetically modified mice. However, it is not known whether changes in receptor gene regulation are involved in the pathogenesis of human immune disorders. OBJECTIVE: We studied the expression of VPAC(2) in acute lesions of the human immune disease atopic dermatitis. METHODS: By using nonradioactive in situ hybridization, quantitative immunohistochemistry, RT-PCR, and gene array studies, the expression status of VPAC(2) was assessed in atopic dermatitis and control tissues and in the human mast cell line HMC-1. RESULTS: In situ hybridization and immunohistochemistry demonstrated VPAC(2) mRNA and protein expression in human mast cells surrounded by VIP positive nerve fibers. Gene array experiments and RT-PCR studies showed high levels of VPAC(2) mRNA expression in mast cells that were increased compared to other receptors such as VPAC(1) or VIP in the human mast cell line HMC-1. Stimulation of HMC-1 cells led to a downregulation of VPAC(2). Similarly, quantitative immunohistochemistry for VPAC(2) in acute atopic dermatitis lesions showed a significantly decreased VPAC(2) immunoreactivity in mast cells. CONCLUSION: The downregulation of VPAC(2) in human mast cells in acute lesions of atopic dermatitis suggests a role of this G-protein;coupled receptor in the pathophysiology of the disease.