RNA-seq unravels distinct expression profiles of keloids and Dupuytren's disease.

Keloid scars and Dupuytren's disease are two common, chronic, and incurable fibroproliferative disorders that, among other shared clinical features, may induce joint contractures. We employed bulk RNA sequencing to discern potential shared gene expression patterns and underlying pathological pathways between these two conditions. Our aim was to uncover potential molecular targets that could pave the way for novel therapeutic strategies. Differentially expressed genes (DEGs) were functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein-interaction (PPI) networks were constructed by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Molecular Complex Detection (MCODE) plugin was used for downstream analysis of the PPI networks. A total of 1922 DEGs were identified within Dupuytren's and keloid samples, yet no overlapping gene expression profiles were detected. Significantly enriched GO terms were related to skin development and tendon formation in keloid scars and Dupuytren's disease, respectively. The PPI network analysis revealed 10 genes and the module analysis provided six protein networks, which might play an integral part in disease development. These genes, including CDH1, ERBB2, CASP3 and RPS27A, may serve as new targets for future research to develop biomarkers and/or therapeutic agents.

Scars.

Wound healing occurs as a response to disruption of the epidermis and dermis. It is an intricate and well-orchestrated response with the goal to restore skin integrity and function. However, in hundreds of millions of patients, skin wound healing results in abnormal scarring, including keloid lesions or hypertrophic scarring. Although the underlying mechanisms of hypertrophic scars and keloid lesions are not well defined, evidence suggests that the changes in the extracellular matrix are perpetuated by ongoing inflammation in susceptible individuals, resulting in a fibrotic phenotype. The lesions then become established, with ongoing deposition of excess disordered collagen. Not only can abnormal scarring be debilitating and painful, it can also cause functional impairment and profound changes in appearance, thereby substantially affecting patients' lives. Despite the vast demand on patient health and the medical society, very little progress has been made in the care of patients with abnormal scarring. To improve the outcome of pathological scarring, standardized and innovative approaches are required.

Systematic review of molecular pathways in burn wound healing.

Depending on extent and depth, burn injuries and resulting scars may be challenging and expensive to treat and above all heavily impact the patients' lives. This systematic review represents the current state of knowledge on molecular pathways activated during burn wound healing. All currently known molecular information about gene expression and molecular interactions in mammals has been summarized. An ample interaction of regenerative cytokines, growth factors, ECM-regenerative molecules and proinflammatory immune response became apparent. We identified three molecules to be most often involved in the pathways: TGFB1, ACTA1 and COL1A1. Yet, other factors including FLII, AKT1 and miR-145 were shown to play pivotal roles in burn wound healing as well. This systematic review helps to explain the fundamental molecular proceedings participating in burn wound healing. A number of new molecular interactions and functional connections were identified yielding intriguing new research targets. An interactive version of the first network about molecular pathways and interactions during burn wound healing is provided in the online edition and on WikiPathways.

Keloids are transcriptionally distinct from normal and hypertrophic scars.

Wound healing and skin regeneration after injury are complex biological processes, and deep injuries with a high degree of tissue destruction may result in severe scar formation. Clinically, scars can be classified into normal, hypertrophic and keloid scars. However, the molecular signature of each scar type is currently not known. The aim of this study was to reveal the transcriptional landscape of normal, hypertrophic and keloid skin scars following hand and plastic surgery based on total RNA sequencing. Eighteen skin scar samples from hand and plastic surgeries of human donors were minced directly after removal and stored in TRIzol (Thermo Fisher, USA). Samples were then subjected to RNA isolation, cDNA library preparation, bulk RNA sequencing and bioinformatics analysis. We show that keloid scars transcriptionally differed from normal and hypertrophic scars. Normal and hypertrophic scars presented overlapping clustering, and eight genes were shown to be commonly expressed between hypertrophic and normal scars. No genes were specifically expressed at a higher level in keloid and normal scars. Based on gene ontology pathway analysis, genes with a higher level of expression in keloid scars lead to increased (extra-) cellular matrix proliferation and cell interaction. Moreover, tumour-like genes were more highly expressed in keloid scars, supporting the clinical impression of strong and diffuse growth. This study furthers our understanding of the classification of differential scar types based on molecular signature, which may shed light on new diagnostic and therapeutic strategies for keloid scars in the future.

S2k guideline: Laser therapy of the skin.

This guideline aims to improve the efficiency and safety of lasers and optical radiation sources with similar effects (especially IPL). Laser therapy of skin lesions with an increased amount of melanocytes should be performed with caution. Laser treatment of pigmented melanocytic nevi is not recommended. The guideline contains recommendations regarding the treatment of lentigines and café-au-lait spots, non-pigmented dermal nevi, Becker nevus, nevus of Ota/Hori/Ito and melasma. Further recommendations focus on the treatment of skin lesions without an increased amount of melanocytes (ephelides, postinflammatory hyperpigmentation including berloque dermatitis, seborrheic keratoses, traumatic/decorative tattoos and metallic deposits), hypopigmentation (vitiligo), benign non-pigmented neoplasms (fibrous papule of the nose, nevus sebaceus, epidermal nevus, neurofibroma, sebaceous gland hyperplasia, syringoma, xanthelasma palpebrarum), inflammatory dermatoses (acne papulopustulosa/conglobata, acne inversa, granuloma faciale, lichen sclerosus, lupus erythematosus, psoriasis vulgaris, rosacea, rhinophyma), wrinkles/dermatochalasis/striae, hypertrichosis, scars (atrophic, hypertrophic; keloids, burn/scald scars), laser-assisted skin healing, onychomycosis, precancerous lesions and malignant tumors (actinic keratoses/field cancerization, cheilitis actinica, basal cell carcinoma), vascular skin lesions (angiokeratoma, angioma, hemangioma, malformation, spider veins, granuloma telangiectaticum (pyogenic granuloma), rubeosis (erythrosis interfollicularis colli, ulerythema ophryogenes), nevus flammeus, telangiectasias and Osler's disease (hereditary hemorrhagic telangiectasia) and viral skin lesions (condylomata acuminata, mollusca contagiosa, verrucae planae juveniles/vulgares/ verrucae palmares et plantares).

Calcium Hydroxyapatite Filler With Integral Lidocaine CaHA (+) for Soft Tissue Augmentation: Results from an Open-Label Multicenter Clinical Study.

BACKGROUND: Soft tissue augmentation with calcium hydroxylapatite (CaHA) is a versatile technique for line filling, skin tightening, lifting, contouring, and volumizing. The present study was designed to confirm safety and effectiveness of the product with lidocaine (CaHA (+)) in a holistic treatment of nasolabial folds (NLFs), marionette lines, and/or cheeks. METHODS: A total of 207 subjects with moderate to severe facial volume deficit were treated with CaHA(+) in this open-label study. Effectiveness assessments included Merz Aesthetics Scales® (MAS), investigator- and subject-assessed Global Aesthetic Improvement Scales (iGAIS/sGAIS), and FACE-QTM questionnaires. Responder rates were defined as at least one-point improvement on MAS according to blinded rating. Safety was assessed through adverse event reporting. RESULTS: Primary endpoint was evaluated 12 weeks after last injection. Responder rates were 93.6%, 88.7%, and 81.9% in the NLFs, marionette lines, and cheeks, respectively, and were statistically significant above the pre-defined 60% threshold (P< 0.0001). Investigator- and subject-assessed GAIS were consistent and showed high rates of improvement throughout the study, with peak values of 98.0% at week 4 on iGAIS and 93.5% at 12 weeks after last injection on sGAIS. After 18 months, the majority of subjects (52.5%) still perceived improvement via sGAIS. Moreover, total FACE-Q scores demonstrated high subject satisfaction with treatment. All related treatment emergent adverse events were transient and expected injection-site reactions mostly of mild to moderate intensity. CONCLUSION: CaHA (+) has demonstrated safety and effectiveness in the treatment of NLFs, marionette lines, and cheek volume loss in real-life conditions up to 18 months. J Drugs Dermatol. 2022;21(5):481-487. doi:10.36849/JDD.6737.

Individualized Treatment Algorithm Using Hyaluronic Acid Fillers for Lifting, Contouring and Volumizing the Midface.

Purpose: Patients seeking treatment for the midface are individuals with different objectives and characteristics of skin and soft tissue. In this study, patients were treated in the midface with one of three products with different properties; HARV, HARD, or HARL, using a treatment algorithm based on primary need for treatment (volumizing, lifting or contouring) and tissue coverage (thin or thick tissue). The aim was to optimize the treatment outcome and to provide an individualized treatment approach that distinguishes different types of patients seeking midfacial treatment. Materials and Methods: Subjects were treated in the midface at baseline to achieve optimal aesthetic results (≤2 mL per side of the face), and touch-up was allowed after 4 weeks (≤1 mL per side of the face). Study visits were scheduled at Weeks 8, 16 and 24. Assessments included aesthetic improvement of the midface, evaluation of midface fullness, and subject satisfaction. Safety evaluations included local tolerability symptoms collected at 4 weeks after treatment and adverse events. Results: A total of 90 subjects were included in the study, mean age was 45 years (range 29-55) and 82% of subjects were female. Mean total injected volume for the products was 4.4 mL (HARV and HARL) and 4.2 mL (HARD). At least 92% of subjects were assessed as aesthetically improved throughout the study. Assessment of midface fullness showed ≥90% of subjects being responders until Week 24. In addition, subject satisfaction was high throughout the study. Tenderness, bruising and swelling were the most reported local tolerability symptom for all study products, and no adverse events related to study product/treatment were reported. Conclusion: Midface treatment with either HARV, HARD, or HARL using a treatment algorithm to guide the choice of product to individual subject needs was effective and safe for up to 24 weeks after treatment.

Energy-based devices for the treatment of Acne Scars: 2022 International consensus recommendations.

BACKGROUND AND OBJECTIVES: Acne scars are one of the most distressing and long-term consequences of acne vulgaris, with damaging effect on a person's physical, mental, and social well-being. Numerous treatment options are available including surgical and nonsurgical techniques, depending on the clinical presentation. Although considerable advances in the development of new treatment technologies and applications have been made in the last decade, international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the potential utility of energy-based devices (EBDs) for acne scarring, offer recommendations for safe and efficacious treatment, and provide consensus-based EBD treatment options based on varying presentations demonstrated in a series of real-life clinical photographs. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 24 dermatologists and plastic surgeons from 12 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the treatment of acne scars. A two-step modified Delphi method took place between March 2020 and February 2021 consisting of two rounds of emailed questionnaires. The panel members approved the final manuscript via email correspondence. RESULTS: The manuscript includes a comprehensive discussion and panel recommendations regarding the following topics: 1. the role of EBD in mitigating and treating acne scars in a patient with active acne, 2. the use of various EBDs for the treatment of different acne scar types with special focus on commonly used laser platform such as vascular lasers, ablative fractional lasers (AFLs) and non-AFLs (NAFLs), 3. treatment combinations, and 4. acne scar treatments in skin of color. The last part comprised of 10 photos of real-life clinical cases with the panel recommendation treatment plan to achieve best aesthetic outcome. CONCLUSION: Panel members were unanimous in their view that EBDs have a role in the management of acne scars, with AFLs, NAFLs, vascular lasers, and RF devices preferentially selected by most of the panel experts. EBDs are considered a first-line treatment for a variety of acne scar types and patients without access to these treatments may not be receiving the best available care for optimal cosmetic results. Future high-quality research and updated international treatment guidelines and reimbursement schemes should reflect this status.

Safety of Cohesive Polydensified Matrix Cross-Linked Hyaluronic Acid Volumizing Gel in Temporal Hollows and Cheeks: A Prospective, Open-Label, Postmarket Study.

BACKGROUND: Facial aging is characterized by volume loss and progressive hollowing of temples and cheeks. Biodegradable filler materials are preferred over nonabsorbable materials; of these, hyaluronic acid (HA) fillers are the most often used because of their favorable effectiveness and safety profile. OBJECTIVE: To confirm the safety and effectiveness of Cohesive Polydensified Matrix (CPM)-HA26 gel in the treatment of volume deficiency. METHODS: Subjects received up to 2 treatments in the temples and/or cheeks. A blinded investigator assessed improvement according to the Merz Temple Volume Scale (MTVS) and Merz Cheek Fullness Assessment Scale (MCFAS). Subjects were followed for 48 weeks after the last treatment. RESULTS: In total, 87 healthy subjects were enrolled. The proportion of subjects achieving at least a 1-grade improvement on MTVS and/or MCFAS was above 70% for each (MTVS: Weeks 4, 24, and 48 = 95.4%, 94.2%, and 77.0%; MCFAS: Weeks 4, 24, and 48 = 92.3%, 83.1%, and 71.8%). Based on MTVS and MCFAS scores at Visit 5, improvement remained visible at up to 48 weeks. No treatment-related serious AEs occurred. CONCLUSION: CPM-HA26 demonstrated both a favorable safety and effectiveness profile, with improvement in facial volume evident for up to 48 weeks. It was well tolerated and had a positive, long-lasting effect.

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.

[Personal preference, experience, intuition and school of surgery dominate the use of wound drainage in dermatosurgery]. / Persönliche Präferenz, Erfahrung, Intuition und operative Schule dominieren die Verwendung postoperativer Wunddrainagen in der Dermatochirurgie.

BACKGROUND: The use of drainage systems in dermatosurgery has so far been carried out without evidence-based data. The indications, complications and contraindications are traditionally passed on from surgeon to surgeon but have so far not been defined. METHOD: An Internet-based survey was created and sent out to members of the German Society for Dermatosurgery (DGDC). The questions were on the general treatment approach in German language countries with reference to the use of wound drainage following dermatological operations as well as the utilization habits and experiences with drainage-associated complications. RESULTS: Of the DGDC members contacted 12.73% completed the questionnaire. Drainages were predominantly used in the clinical environment and all drainage systems in question were used. The extent and complexity of the intervention were essential criteria when evaluating the indications. The use of drainages was dependent on the age of the participant and mostly carried out in patients where complications in the postoperative course were to be expected (e.g. obesity, nicotine use, diabetes). CONCLUSION: In summary, the majority of the participants used wound drainages and mostly intuitively. Uniform and fixed evidence-based parameters for the use of wound drainages are lacking. In the assessment of the necessity for a wound drainage, an individually expressed need of safety seems to play a large role for some dermatosurgeons and an eminence-based action for others.

Safety, Tolerability, and Efficacy of Repeat-Dose Injections of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results from a Prospective, Open-Label, Phase III Study.

In aesthetic practice, wrinkles in the upper face are commonly treated with repeat-dose injections. The objective of this study was to investigate the safety, tolerability, and efficacy of repeat-dose injections of incobotulinumtoxinA in the combined treatment of moder-ate to severe upper facial lines (UFL) [glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL)]. Healthy subjects (≥18 years) with moderate to severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contrac-tion were administered 54 to 64 U of incobotulinumtoxinA (GFL, 20 U; HFL, 10 to 20 U; LPL, 24 U) in up to four, 120-day treatment cycles. Adverse events (AE) were recorded for each cycle until 120 ± 7 days after treatment. Investigator-assessed MAS scores were evaluated for each treated area at maximum contraction on day 30 [responder = score of “none” (0) or “mild” (1)]. Subject-assessed scores for overall appearance of the upper face of “much improved” or “very much improved” were noted at day 30 of each treatment cycle on the Global Impression of Change Scale (GICS). Overall, 140 subjects were treated, and 125 subjects completed the study. Mean injected units per injection cycle ranged from 56.3 U to 57.7 U. During the four-cycle study period 17.1% of total treated subjects experienced a treatment emergent adverse event (TEAE). TEAEs of special interest were documented for 9 subjects (6.4%), in 6 of these subjects (4.3%) the TEAEs were related to treatment. No clinically significant mean changes in laboratory and vital-sign values were observed from screening to final-treatment visit. Over the study interval, a response rate of > 80% on the investigator-assessed MAS was reported for all treated areas except HFL. Greater than 80% of subjects in cycles 1, 3, and 4 and 78.5% of subjects in cycle 2 reported ratings of “much improved” or “very much improved” on the GICS for the overall appearance of the upper face. Incobotu-linumtoxinA for the repeat-dose treatment of UFL is safe and well tolerated with a stable safety profile, without new formation of neutralizing antibodies and has excellent efficacy during prolonged administration. J Drugs Dermatol. 2020;19(5):461-469. doi:10.36849/JDD.2020.5013.

Objective evaluation of an occlusive overnight intensive patch containing onion extract and allantoin for hypertrophic scars.

BACKGROUND: Patients suffering from hypertrophic scars often describe esthetic, functional, and psychological impairments. While current guidelines for the treatment of pathologic scarring recommend the use of onion extract containing gels and sheets, hard evidence for its efficacy remains scarce due to inconsistent data. Onion extract and allantoin containing occlusive overnight intensive patches (OIP) were introduced as a recent option for noninvasive scar management. However, objective data demonstrating their efficacy are missing. AIMS: This study is the first to objectively evaluate the benefit and safety of an OIP for hypertrophic scars using a three-dimensional imaging device and a standardized scar scale. METHODS: Twelve patients with untreated, three to twelve months old hypertrophic scars received an OIP for 3 months. The assessment was performed using PRIMOS®pico , a three-dimensional imaging device and POSAS, a standardized scar questionnaire at baseline, one and 3 months after the last treatment. RESULTS: Objective evaluation at three months follow-up (FU) showed a significant decrease in scar height of 28.8% (baseline mean: 2.08 ± 0.68 mm, three months FU mean: 1.48 ± 0.52 mm) and a reduction in scar volume of 31.9% (baseline mean: 454.33 ± 265.53 mm3, 3 months FU mean: 309.58 ± 224.28 mm3). Pain and pruritus subsided under treatment. There were no negative side effects. CONCLUSION: Overnight intensive patches is a convenient, painless, safe, affordable and effective prevention and treatment option for hypertrophic scars. Treatment should be performed at least for 3 months for visible effects.

Dermal fillers do not induce upregulation of NLRP3 inflammasomes or expression of inflammatory cytokines in granulomas.

BACKGROUND: Filling materials have increasingly been used in aesthetics over the last decades. Understanding the pathophysiology of granuloma formation as a very relevant unwanted side effect of filler application may be essential to help avoid these adverse events. AIMS: Our aim was to investigate the role of the inflammasome in the formation of filler granuloma, as a central column of the innate immune response. METHODS: RPMI 1640 medium was used for growth of THP-1 cells and the induction of THP-1 macrophages. Sonication was applied in order to crush the acrylic particles of the filler. ELISA was the method of analysis for the specific cytokines. Biopsy specimens of filler granuloma were analyzed by various immunohistochemical methods. GraphPad Prism 5 software was used for the statistical data analysis. RESULTS: Neither was the sensor NALP3 overexpressed, nor could an elevated expression of cleaved IL-1ß, IL-18, or IFN-γ be detected. Furthermore, no increased expression of IL-8 or IL-1ß was detectable in vitro. CONCLUSION: No increased inflammasome activation could be observed; however, filler granulomas were infiltrated with granulocytes and macrophages. Therefore, we speculate that an unspecific immune response might be the key player in the formation of filler granuloma.

Laser Treatment of Traumatic Scars and Contractures: 2020 International Consensus Recommendations.

BACKGROUND AND OBJECTIVES: There is currently intense multidisciplinary interest and a maturing body of literature regarding laser treatments for traumatic scars, but international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the tremendous potential of laser techniques, offer recommendations for safe and efficacious treatment, and promote wider patient access guided by future high-quality research. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the laser treatment of traumatic scars. A three-step modified Delphi method took place between March 2018 and March 2019 consisting of two rounds of emailed questionnaires and supplementary face-to-face meetings. The panel members approved the final manuscript via email correspondence, and the threshold for consensus was at least 80% concurrence among the panel members. RESULTS: The manuscript includes extensive detailed discussion regarding a variety of laser platforms commonly used for traumatic scar management such as vascular lasers and ablative and non-ablative fractional lasers, special considerations such as coding and laser treatments in skin of color, and 25 summary consensus recommendations. CONCLUSIONS: Lasers are a first-line therapy in the management of traumatic scars and contractures, and patients without access to these treatments may not be receiving the best available care after injury. Updated international treatment guidelines and reimbursement schemes, additional high-quality research, and patient access should reflect this status. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.