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BACKGROUND: The optimal radiotherapy doses for postoperative treatment of ear keloids are currently a topic of debate. OBJECTIVE: The authors compared the efficacy of 9.5-Gy and 10-Gy single-fraction electron beam radiation therapy after surgical excision and evaluated the impact of radiation timing on outcomes. MATERIALS AND METHODS: This study was conducted on patients with ear keloid who underwent surgical excision and postoperative electron beam radiotherapy between May 2021 and June 2024. Patients were divided into groups based on radiation dose (9.5 vs 10) and timing (within 8 hours vs 24 hours postoperatively). Recurrence rates and complications were also compared. RESULTS: The study included 182 patients (21 men and 161 women). The overall recurrence rate was 3.3% (6/182). The 10-Gy group had a significantly lower recurrence rate than the 9.5-Gy group (0.81% vs 8.47%; p =.014). Radiation timing did not significantly influence recurrence rates (2.59% vs 3.80%, p = 1). Complications were not significantly different. CONCLUSION: A postoperative single dose of 10 Gy is the most effective low-dose single fractional electron beam radiotherapy for preventing ear keloid recurrence. Once administered within 24 hours after surgery, the timing of radiotherapy has no significant impact on treatment outcomes. [ABSTRACT FROM AUTHOR]

Keloid scars (KS) and hypertrophic scars (HS) are fibroproliferative wound healing defects characterized by excessive accumulation of extracellular matrix (ECM) in the dermis of affected individuals. Although transforming growth factor (TGF)-β is known to be involved in the formation of KS and HS, the molecular mechanisms responsible for its activation remain unclear. In this study we investigated Granzyme B (GzmB), a serine protease with established roles in fibrosis and scarring through the cleavage of ECM proteins, as a potential new mediator of TGF-β activation in KS and HS. Increased GzmB-positive mast cells were identified in the dermis of KS and HS but not healthy skin controls. Elevated levels of substance P, a neuropeptide involved in mast cell degranulation, suggest that GzmB is released extracellularly, as confirmed by the significant reduction of the established extracellular GzmB substrate decorin in KS and HS. Similarly, presence of latent TGF-β binding protein 1 (LTBP1), a protein involved in the extracellular tethering of latent TGF-β, was disrupted proximal to the dermal-epidermal junction (DEJ) of GzmBhigh KS and HS lesions. Using LTBP1-enriched medium as well as purified LTBP1, its cleavage by GzmB was confirmed in vitro. Increased TGF-β/Smad signaling pathway was observed in keratinocytes treated with GzmB-digested LTBP1 and was abolished by the addition of a pan-TGF-β inhibitor, suggesting that GzmB cleavage of LTBP1 contributes to TGF-β activation. In dermal fibroblasts, GzmB also cleaved cell-derived LTBP1 and induced TGF-β activation through the cleavage of one or more unidentified fibroblast-secreted proteins. Altogether, the present results suggest that GzmB contributes to KS and HS through ECM remodeling and TGF-β activation. Graphical Abstract. [ABSTRACT FROM AUTHOR]

Background: Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix components. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been used to explore the composition and functionality of immune cells present in fibrotic skin diseases. However, these studies detected the gene expression of all cells in fibrotic skin diseases and did not enrich immune cells. Thus, the precise immune cell atlas in fibrotic skin diseases remains unknown. In this study, we plan to investigate the intricate cellular landscape of immune cells in keloid, a paradigm of fibrotic skin diseases. Methods: CD45+ immune cells were enriched by fluorescence-activated cell sorting. Single-cell RNA sequencing was used to analyze the cellular landscape of immune cells in keloid and normal scar tissues. Ki-67 staining, a scratch experiment, real-time PCR, and Western blotting were used to explore the effect of the Th17 cell supernatant on keloid fibroblasts. Results: Our findings revealed the intricate cellular landscape of immune cells in fibrotic skin diseases. We found that the percentage of Th17 cells was significantly increased in keloids compared to normal scars. All the subclusters of macrophages and dendritic cells (DCs) showed similar proportions between keloid samples and normal scar samples. However, upregulated genes in keloid M1 macrophages, M2 macrophages, and cDC2 are associated with the MHC class II protein complex assembly and antigen assembly, indicating that macrophages and cDC2 are active in keloids. Functional studies suggested that the supernatant of Th17 cells could promote proliferation, collagen expression, and migration of keloid fibroblasts through interleukin 17A. Importantly, increased Th17 cells are also found in other fibrotic skin diseases, such as hypertrophic scars and scleroderma, suggesting this represents a broad mechanism for skin fibrosis. Conclusion: In summary, we built a single-cell atlas of fibrotic skin diseases in this study. In addition, we explored the function of Th17 cell-fibroblast interaction in skin fibrosis. These findings will help to understand fibrotic skin disease pathogenesis in depth and identify potential targets for fibrotic skin disease treatment. [ABSTRACT FROM AUTHOR]

Several treatment modalities have been used for the treatment of keloid scarring but the optimal treatment has not yet been identified. Corticosteroids reduce excessive scarring by reducing collagen synthesis. Vitamin D can curb inflammation by inhibiting the activation and migration of leukocytes. Pentoxifylline is a methyl xanthine derivative initially developed for its vasodilatory properties. Evaluation and comparison between three modalities of treatment for keloid; intralesional vitamin D, pentoxifylline, and steroid. Forty-five patients with keloid lesions were divided into 3 groups; The first group: 15 patients were treated with intralesional triamcinolone acetonide. The second group: 15 patients treated with intralesional pentoxifylline. The third group: 15 patients treated with intralesional vitamin D. The response was evaluated clinically, Vancouver scar scale and patient satisfaction scale. At the end of the study, all groups showed highly statistically significant improvement compared to the baseline. The first group which was treated with triamcinolone acetonide showed excellent and good improvement 53% and 47% respectively. The second group which was treated with pentoxifylline showed excellent and good improvement 6.7% and 73.3% respectively. The third group which was treated with vitamin D showed excellent and good 6.7% and 86.7% respectively. Intralesional vitamin D and pentoxifylline are safe and effective therapeutic options for keloid lesions. [ABSTRACT FROM AUTHOR]

Background: Keloid is a fibro-proliferative dermal benign growth affecting the Asian population. In India, ear keloids are common, often resulting from ear piercing, a prevalent cultural practice. The resultant ear keloids pose aesthetic concerns, leading to significant psychological distress, and necessitating effective treatment. While various treatment options are available, their outcomes and recurrence rates vary, highlighting the need for individualized and optimal management strategies. Our study aimed to observe the combined effect of intralesional triamcinolone with hyaluronidase on keloid regression. Methods: This prospective observational study was conducted at our tertiary care institute over 1 and a half years. Fifty patients who met the inclusion criteria were enrolled and received intralesional triamcinolone injection with hyaluronidase. Keloid regression was assessed using the Vancouver Scar Scale (VSS), while the visual analogue score (VAS) and patient satisfaction score (PSS) provided subjective evaluations of symptom relief. All patients underwent compression therapy. Patients were evaluated at every visit and then at 1 year for symptom relief, keloid regression, and complications if any. Results: Demographic data of all patients were recorded. Ear keloids were predominantly observed in females, with a male-to-female ratio of 18:32. The most common etiology was trauma following ear piercing, accounting for 46% of cases. All patients showed improvement in VSS, VAS, and PSS scores in the follow-up visits. A total of 98% of patients demonstrated a complete treatment response, with only a single instance of recurrence. Conclusion: Intralesional triamcinolone with hyaluronidase provides satisfactory symptomatic relief and has lower recurrence rates. All patients showed improvement in the Vancouver Scar Scale and had enhanced VAS and PSS scores. [ABSTRACT FROM AUTHOR]

Some studies have confirmed that pathogens can cause infection through bacterial cultures on the surface of infectious keloids. However, further exploration of the comparison between infectious and non-infectious keloids and the bacterial flora of infectious foci is lacking. To investigate the differential flora of purulent secretions on the surface of infectious keloids compared to non-infectious keloids and to determine the microbial composition within the infectious foci. This case–control study involved 17 patients and obtained swab specimens from the surface of keloids in two groups, and from the infectious foci in the infectious group. Bacterial composition was analyzed using 16S ribosomal RNA sequencing. There were no statistical differences in the general condition of patients between the two groups. The presence of the phylum Actinobacteriota, and the orders Propionibacteriales and Corynebacteriales, as well as the genus Taibaiella, was greater on the surface of keloids in the infectious group. The most prevalent genera in infective sites were Staphylococcus, Peptoniphilus, and Cutibacterium. Microbial-associated gene pathways indicated a correlation with inflammation and tumor-like growth in keloids. There is a connection between infectious keloids and microorganisms, providing insights for predicting and treating keloid infections. [ABSTRACT FROM AUTHOR]

Pathological scars are classified into hypertrophic scars and keloids, and currently have poor treatment outcomes and high recurrence rates. Bleomycin has received widespread attention in scar treatment in recent years, but there is currently no exploration on its real-world data. PubMed, Embase, and Cochrane databases were searched, and eight retrospective studies on the use of bleomycin for treatment were included, covering a total of 562 patients with keloids and hypertrophic scars. The meta-analysis results revealed that 90% of patients had significant flattening of scars after treatment with bleomycin, 5% had moderate flattening, and 4% had mild flattening. The recurrence rate after treatment was only 3%. The major adverse reaction was hyperpigmentation, with an incidence rate of 8%, and no significant ulcers or skin atrophy were reported. Subgroup analysis showed that the significant flattening rate treated with bleomycin alone was 91%, which was significantly different from the 79% treated with bleomycin in combined with triamcinolone acetonide, but the difference was not statistically significant. In addition, the significant flattening rate was 99% in Western patients and 57% in Asian patients, reflecting the impact of racial differences on treatment outcomes. There was no statistically significant difference in curative effects between males and females (RR: 0.95; P = 0.77). Overall, bleomycin has good curative effect in treating scars and has high safety, especially showing more significant effects in Western populations. However, racial differences, treatment plans, and other factors may affect the therapeutic effect of bleomycin. Future research can further explore the mechanisms of these factors and provide more personalized treatment plans for patients with scar. [ABSTRACT FROM AUTHOR]

Cryotherapy, the use of cold temperatures for therapeutic purposes, has long been utilized across medical disciplines for pain management, reducing inflammation, and enhancing recovery. This narrative review aims to evaluate its role within plastic surgery, particularly its effectiveness and safety in improving patient outcomes. Cryotherapy's mechanisms, such as vasoconstriction and inflammation modulation, offer potential advantages in postoperative care, wound healing, and non-invasive aesthetic treatments. Literature reveals its efficacy in managing postoperative pain and reducing swelling, making it particularly beneficial in procedures like rhinoplasty and keloid treatment. Intralesional cryotherapy particularly, shows promise in reducing keloid scar volumes after a single session, offering improved patient satisfaction. Despite these promising applications, cryotherapy remains underutilized within plastic surgery, and research into its broader implementation is limited. Further studies are needed to explore its long-term effects, specific applications in reconstructive surgeries, and to address the challenges of variability in outcomes across different skin types. As non-invasive and minimally invasive procedures gain popularity, cryotherapy may play an increasingly central role in both reconstructive and aesthetic plastic surgery, offering a low-risk, high-reward option for enhancing patient care. This review identifies gaps in current knowledge and suggests areas for future investigation, positioning cryotherapy as a promising adjunctive therapy within the evolving field of plastic surgery. Level of Evidence: Not gradable [ABSTRACT FROM AUTHOR]

Disruption of the molecular pathways during physiological wound healing can lead to raised scar formation, characterized by rigid, thick scar tissue with associated symptoms of pain and pruritus. A key mechanical factor in raised scar development is excessive tension at the wound site. Recently, microneedles (MNs) have emerged as promising tools for scar management as they engage with scar tissue and provide them with mechanical off-loading from both internal and external sources. This review explores the mechanisms by which physical intervention of drug-free MNs alleviates mechanical tension on fibroblasts within scar tissue, thereby promoting tissue remodeling and reducing scar severity. Additionally, the role of MNs as an efficient cargo delivery system for the controlled and sustained release of a wide range of therapeutic agents into scar tissue is highlighted. By penetrating scar tissue, MNs facilitate controlled and sustained localized drug administration to modulate inflammation and fibroblastic cell growth. Finally, the remaining challenges and the future perspective of the field have been highlighted. [ABSTRACT FROM AUTHOR]

Aberrant activation of dermal fibroblasts during wound healing often leads to debilitating fibrotic changes in the skin, such as scleroderma and keloids. However, the underlying cellular and molecular mechanisms remain elusive. Here, we established a wound‐induced skin fibrosis (WISF) mouse model in mature adult mice, characterised by excessive deposition of collagen bundles, loss of dermal adipocytes, and enrichment of DPP4+Ly6A+THY1+ hypodermal interstitial adipocyte progenitors (HI‐APs) and pericytes, resembling human fibrotic skin diseases. This WISF model exhibited an age‐dependent gain of fibrotic characteristics, contrasting with the wound‐induced hair neogenesis observed in younger mice. Through comprehensive analyses of the WISF, we delineated a trajectory of fibroblast differentiation that originates from HI‐APs. These progenitors highly expressed several extracellular matrix (ECM) genes and exhibited a TGFβ pathway signature. TGFβ was identified as the key signal to inhibit the adipogenic potential and maintain the fibrogenic potential of dermal APs. Additionally, administering a TGFβ receptor inhibitor to wound scar reduced the abundance of ECM‐producing APs. Finally, analysis of human scleroderma skin tissues revealed a negative correlation between the expression of AP‐, ECM‐, and TGFβ pathway‐related genes and PPARG. Overall, this study establishes a wound‐induced skin fibrosis mouse model and demonstrates that TGFβ‐mediated blockage of HI‐AP differentiation is crucial for driving fibrotic pathology. Targeting HI‐APs and adipogenesis may provide novel avenues for developing disease‐modifying therapies for fibrotic skin diseases. [ABSTRACT FROM AUTHOR]

Background A common complication of wounds is the excessive production of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. Currently, no treatments with good evidence for preventing excessive scar tissue formation are available. We explored the use of microneedle patches containing small interfering RNA (siRNA) to inhibit SPARC mRNA in reducing the volume of postoperative scars. Objectives To compare differences in postoperative scar volume with the daily application of siRNA-embedded dissolving microneedle patches vs. silicone sheets. Methods This was an 8-week, single-blinded intraindividually controlled randomized trial at a tertiary dermatological centre. Patients with 2-week-old postoperative wounds were included. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at days 0, 30 and 60. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000558729). Results At day 30, scars treated with microneedle patches had a lower geometric mean volume of 0.79 mm3 vs. scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.7%. At day 60, scars treated with microneedle patches had a statistically significant lower volume (8.88 mm3) compared with the side treated with silicone sheets (12.77 mm3; P = 0.005), with a difference in mean percentage reduction of 9.7%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume vs. baseline on the side treated with microneedle patches (mean 83.8%) compared with the side treated with silicone sheets (mean 74.1%). Conclusions There was a significantly greater reduction in the volume of postoperative scars on the side of the scar treated with microneedle patches compared with the side treated with silicone sheets. This demonstrates the use of transdermal gene-silencing technology in scar inhibition and that siRNA microneedle patches can be effective and safe in reducing scar tissue formation. [ABSTRACT FROM AUTHOR]

Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing. We found that the dominant fibroblast subgroup in keloids is mechanoresponsive group, which showed enhanced mechanotransduction and migration. This mechanoresponsive fibroblast subgroup is likely to be the key cell population and confer aggressive growth of keloids. The results also indicate that the endothelial cells and keratinocytes in keloid involve in endothelial-mesenchymal and epithelial-mesenchymal transitions. This study demonstrated the mechanoresponsive fibroblasts and multiple cellular mesenchymal processes could pave the way for further investigations into the keloid aggressiveness. Single-cell RNA sequencing reveals mechanoresponsive fibroblasts as a key driver of keloid aggressiveness, with endothelial cell and keratinocyte transitions also involved, paving the way for deeper investigations into keloid pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Lasting scars such as keloids and hypertrophic scars adversely affect a patient's quality of life. However, these scars are frequently underdiagnosed because of the complexity of the current diagnostic criteria and classification systems. This study aimed to explore the application of Large Language Models (LLMs) such as ChatGPT in diagnosing scar conditions and to propose a more accessible and straightforward diagnostic approach. Methods: In this study, five artificial intelligence (AI) chatbots, including ChatGPT-4 (GPT-4), Bing Chat (Precise, Balanced, and Creative modes), and Bard, were evaluated for their ability to interpret clinical scar images using a standardized set of prompts. Thirty mock images of various scar types were analyzed, and each chatbot was queried five times to assess the diagnostic accuracy. Results: GPT-4 had a significantly higher accuracy rate in diagnosing scars than Bing Chat. The overall accuracy rates of GPT-4 and Bing Chat were 36.0% and 22.0%, respectively (P = 0.027), with GPT-4 showing better performance in terms of specificity for keloids (0.6 vs. 0.006) and hypertrophic scars (0.72 vs. 0.0) than Bing Chat. Conclusions: Although currently available LLMs show potential for use in scar diagnostics, the current technology is still under development and is not yet sufficient for clinical application standards, highlighting the need for further advancements in AI for more accurate medical diagnostics. 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. [ABSTRACT FROM AUTHOR]

Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy. [ABSTRACT FROM AUTHOR]

Keloid scarring is a fibroproliferative disease of the skin, which can significantly impact one's quality of life through cosmetic concerns, physical discomfort (itchy; painful), restricted movement, and psychological distress. Owing to the poorly understood pathogenesis of keloids and their high recurrence rate, the efficacy of keloid treatment remains unsatisfactory, particularly in patients susceptible to multiple keloids. We conducted fecal metagenomic analyzes and both untargeted and targeted plasma metabolomics in patients with multiple keloids (MK, n = 56) and controls with normal scars (NS, n = 60); tissue-untargeted metabolomics (MK, n = 35; NS, n = 32), tissue-targeted metabolomics (MK, n = 41; NS, n = 36), and single-cell sequencing analyzes (GSE163973). Differences in the gut microbiota composition, plasma metabolites, and tissue metabolites were observed between the MK and NS groups; the core gut microbiota, Oxalobacter formigenes , Bacteroides plebeius , and Parabacteroides distasonis , were identified via the gut microbiome co-occurrence network. Single-cell data helped clarify the specific cells affected by plasma metabolites. An area under the curve analysis using a random forest model based on fecal metagenomics, plasma metabolomics, and tissue metabolomics revealed that gut bacteria, plasma, and tissue metabolites were effective in distinguishing between MK and NS groups. Decreased Bacteroides plebeius could lower uracil levels, altering systemic lipid metabolism, which may change the metabolic phenotype of secretory reticular fibroblasts in wounds, potentially leading to MK. These findings may open new avenues for understanding the multifactorial nature of keloid formation from the gut-skin axis and highlight the potential for novel therapeutic strategies targeting keloid lesions and the underlying systemic imbalances affected by the gut microbiome. An overview of this study. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusion Pathological scars (PSs), resulting from abnormal skin repair, chronic inflammation, and fibrosis, affect millions of people. Previous studies have demonstrated that skin microbiota (SM) plays a role in cutaneous inflammation and healing, but the interplay between PSs and SM remains unclear yet.To investigate the causal associations between SM and two specific PSs: hypertrophic scars (HSs) and keloids.A bidirectional two‐sample mendelian randomization (MR) analysis using genetic data for SM, HS, and keloids was conducted. The random‐effects inverse variance weighted (IVW) method was used as the primary approach, along with multiple MR methods. False discovery rate (FDR) correction was employed to address multiple testing.In forward analysis, the family Moraxellaceae and order Pseudomonadales exhibited the same significant protective effects on keloids (odds ratio [OR]: 0.849, 95% confidence interval [CI]: 0.770–0.935, q2 = 0.03626). The class Betaproteobacteria (OR: 0.938, 95% CI: 0.894–0.985, q1 = 0.01965) and genus Bacteroides (OR: 0.928, 95% CI: 0.884–0.973, q1 = 0.00889) each demonstrated a suggestive protective effect on HSs and keloids, respectively. Some limited evidence suggested that order Actinomycetales contributes to an increased risk of keloids. In reverse analysis, keloids were found to have negative effects on the class Gammaproteobacteria with limited evidence. There was no detectable evidence of horizontal pleiotropy or heterogeneity.This study provided evidence for the causalities between SM and PSs, which laid foundation for furthering clinical practice and research of microorganism–skin interaction. [ABSTRACT FROM AUTHOR]

Keloid scars (keloids), a prototypical form of aberrant scar tissue formation, continue to pose a significant therapeutic challenge within dermatology and plastic surgery due to suboptimal treatment outcomes. Gelatinases are a subgroup of matrix metalloproteinases (MMPs), a family of enzymes that play an important role in the degradation and remodeling of the ECM (a pivotal factor for keloids development). Gelatinases include gelatinase A (MMP-2) and gelatinase B (MMP-9). Since accumulating evidence has shown that gelatinases played a crucial role in the process of keloid formation, we summarized the current knowledge on the association between MMP-2 and MMP-9 expression and the pathological process of keloids through a comprehensive review. This review demonstrated that the interplay between MMP-2, MMP-9, and their regulators, such as TGF-β1/Smad, PI3K/AKT, and LncRNA-ZNF252P-AS1/miR-15b-5p/BTF3 signaling cascades, involved in the intricate balance governing ECM homeostasis, collectively driving the excessive collagen deposition and altered tissue architecture observed in keloids. In summary, this review consolidates the current understanding of MMP-2 and MMP-9 in keloid pathogenesis, shedding light on their intricate involvement in the dysregulated keloids processes. The potential for targeted therapeutic interventions presents promising opportunities for advancing keloid management strategies. [ABSTRACT FROM AUTHOR]

Keloids, characterized by an excessive accumulation of fibrous tissue, remain a significant dermatological challenge. This study elucidates the role of Reticulocalbin 3 (RCN3) in modulating keloid fibroblasts (KFs) in vitro.The RCN3 expression levels in human KFs and normal dermal fibroblast cells were examined using RT-qPCR and Western blot methods. RCN3 expression was knocked down in keloid fibroblasts after cells were transfected with shRNA targeting RCN3. On the other hand, recombinant RCN3 was added to treat the cells. RT-qPCR, Western blot, flow cytometry, CCK8 assays, and wound healing assays were performed to analyze the fibrotic markers (collagen I, III, MMP2, α-SMA) and TGFβ1/Smad2/6/7 pathway, apoptosis, proliferation and migration.RCN3 was upregulated in KFs. Its knockdown reduced fibrotic marker expression (collagen I, III, MMP2, α-SMA), cell proliferation, and migration, while increasing apoptosis. Conversely, recombinant RCN3 treatment enhanced the fibrotic responses. Changes in TGFβ1/Smad2 pathway, especially in Smad2 phosphorylation and Smad7, were evident following RCN3 modulation.The study reveals RCN3 as a regulator in keloid pathology, affecting fibrosis, cellular behavior through TGFβ1/Smad2/Smad7 signaling. [ABSTRACT FROM AUTHOR]

A large keloid on the right earlobe that extended to the infraauricular region was the reason for the 42-year-old woman's referral for treatment. The entire thickness of the earlobe was implicated in the surgical defect that resulted from the severe keloid excision. We employed a straightforward technique to provide a pleasing appearance while repairing the entire lobe in a single stage without the need for grafts. In addition to being ornamental, ear lobules provide a crucial point of reference for facial symmetry while wearing earrings. It is obviously unnatural from an aesthetic standpoint to lose them. Numerous techniques created to reconstruct this deformity have offered a range of benefits and drawbacks. A case of big ear lobe keloid with whole ear lobe reconstruction employing a new, single-stage, superiorly based Preauricular flap technique that is easy to master and produces good results in terms of absence of recurrence or no any deformity even after a lengthy follow-up period has been presented. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to evaluate mir‐31‐5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health. Methods: Using a tissue microarray, mir‐31‐5p expression was measured with miRNAscope, and mir‐31‐5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir‐31‐5p positive cells and KD recurrence at 1 year. In an independent dataset, associations between mir‐31‐5p and messenger RNA (mRNA) expression were assessed. Ingenuity Pathway Analysis identified target genes and pathways impacted by mir‐31‐5p. Results: Of the 58 KD patients, 42 (72%) received adjuvant triamcinolone injections, and 8 recurred (14%). mir‐31‐5p was expressed in 48 (83%) specimens. Increasing mir‐31‐5p expression was associated with decreased risk of recurrence (p =.031), with an odds ratio of 0.86 (95% CI 0.75–0.98) for each 20% increase in mir‐31‐5p cellular positivity. This effect persisted with triamcinolone treatment (odds ratio 0.82; 95% CI 0.71–0.95; p =.015). mir‐31‐5p correlated with gene expression enriched in KD pathways, including mRNA splicing and autophagy. Conclusion: Taken together, our data supports the association between mir‐31‐5p expression and KD recurrence. Its potential as a prognostic biomarker should be further investigated. Level of Evidence: Level 2. [ABSTRACT FROM AUTHOR]

Wound healing as a result of a skin injury involves a series of dynamic physiological processes, leading to wound closure, re-epithelialization, and the remodeling of the extracellular matrix (ECM). The primary scar formed by the new ECM never fully regains the original tissue's strength or flexibility. Moreover, in some cases, due to dysregulated fibroblast activity, proliferation, and differentiation, the normal scarring can be replaced by pathological fibrotic tissue, leading to hypertrophic scars or keloids. These disorders can cause significant physical impairment and psychological stress and represent significant challenges in medical management in the wound-healing process. The present study aimed to investigate the therapeutic effects of exogenously applied carbon dioxide (CO2) on fibroblast behavior, focusing on viability, proliferation, migration, and differentiation to myofibroblasts. We found that CO2 exposure for up to 60 min did not significantly affect fibroblast viability, apoptosis rate, or proliferation and migration capacities. However, a notable finding was the significant reduction in α-smooth muscle actin (α-SMA) protein expression, indicative of myofibroblast differentiation inhibition, following CO2 exposure. This effect was specific to CO2 and concentration as well as time-dependent, with longer exposure durations leading to greater reductions in α-SMA expression. Furthermore, the inhibition of myofibroblast differentiation correlated with a statistically significantly reduced glycolytic and mitochondrial energy metabolism, and as a result, with a reduced ATP synthesis rate. This very noticeable decrease in cellular energy levels seemed to be specific to CO2 exposure and could not be observed in the control cultures using nitrogen (N2)-saturated solutions, indicating a unique and hypoxia-independent effect of CO2 on fibroblast metabolism. These findings suggest that exogenously applied CO2 may possess fibroblast differentiation-reducing properties by modulating fibroblast's energy metabolism and could offer new therapeutic options in the prevention of scar and keloid development. [ABSTRACT FROM AUTHOR]

Objective To evaluate the possibility of improving and preventing the formation of postoperative hypertrophic and keloid scars using botulinum toxin type A (BTA). Materials and Methods Scientific articles published in English have been systematically screened in PubMed/MEDLINE database over the entire period. The following information about the studies was analyzed: first author surname; year of publication; number of patients; average age; scar location; dosage of the drug administered; follow-up duration; scar assessment methods; results, incidence of hypertrophic and keloid scars formation. The odds ratio and 95% confidence interval were calculated for each of the estimated parameters. The statistical heterogeneity of publications assessed using the criteria of chi-square test and I2. The differences were considered significant at p < 0.05. Results A total of 18 prospective randomized studies were selected for evaluation, containing data on the use of BTA in 363 cases. Patients receiving botulinum toxin had a lower Vancouver scar scale index, higher visual analog scale index, and higher Stony Brook scar evaluation scale score. The use of BTA reduces the risk of perceptible scar formation, the incidence of hypertrophic and keloid scars. Conclusion The use of BTA to obtain imperceptible scar and prevent hypertrophic and keloid postoperative scars demonstrates good prospects. However, there is no consensus regarding the pathophysiological mechanisms underlying the positive effect of BTA on the prevention of hypertrophic and keloid scars. [ABSTRACT FROM AUTHOR]

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Copyright of Chinese Journal of Dermatovenereology is the property of Xi'an Jiaotong University Periodicals Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Wound healing is a complex biological process that can lead to chronic wounds, keloids, and hypertrophic scars when disrupted. Chronic wounds result from a prolonged inflammatory phase and impaired re-epithelialization. Keloids are characterized by excessive collagen deposition beyond the original wound boundaries, driven by persistent inflammation and fibroblast hyperactivity. Hypertrophic scars, on the other hand, are confined to the wound edges and are caused by an imbalance in collagen synthesis and degradation, typically resolving over time. The therapeutic approach to wound healing impairment involves a range of strategies, including non-invasive (which focus on supporting the natural healing process), minimally invasive, and aggressive interventions (such as surgical approach, often reserved for severe or refractory cases). Emerging therapies, including stem cell treatments and botulinum toxin injections, offer new hope for improving outcomes in patients with wound healing impairments. This review highlights the distinct mechanisms underlying chronic wounds, keloids, and hypertrophic scars and discusses their respective therapeutic approaches, focusing on both established and emerging therapies. Understanding these mechanisms is crucial for optimizing treatment strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Keloid and hypertrophic scars are a result of aberrant wound healing responses within the reticular dermis. They are thought to be secondary to the formation of a disorganized extracellular matrix due to excessive fibroproliferative collagen response. Prevention of these scars focuses on avoiding elective or cosmetic procedures such as piercings in patients at high risk, reducing tension across the lesion, and decreasing the inflammatory response. Topical treatments, including tension reduction with gel sheets, inflammatory reduction with corticosteroid ointments, and combined treatment with corticosteroid-infused tapes and plasters, can reduce scarring. Liquid nitrogen is beneficial, especially when injected into the scar through intralesional cryotherapy. Corticosteroid injection is effective for prevention and treatment. OnabotulinumtoxinA appears to be superior to both fluorouracil and corticosteroid injections for treating keloids and hypertrophic scars. Advanced treatment includes laser therapies (direct ablation, postsurgical, or laser-assisted drug delivery). Surgical revisions can be successful when tension-reducing techniques are used and when combined with other treatments such as postoperative steroid injection, laser ablation, and radiation therapy. For keloid prevention, corticosteroid injections administered 10 to 14 days postsurgery is superior to injections administered before or during surgery. Radiation therapy is considered safe with low cancer risk and can be used alone or in combination with other therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids. Method We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20–22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo. Results ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments. Conclusions Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars. Graphical Abstract

ABSTRACT Background Methods Results Conclusions Keloids, characterized by excessive collagen deposition, often recur despite various treatments. This study explores the association between preoperative serum vitamin D levels and keloid recurrence in a Korean population.A retrospective cohort of 160 patients who underwent keloid excision was analyzed. Preoperative serum 25(OH) vitamin D and 1,25(OH)2 vitamin D levels were measured. Recurrence rates were compared using hierarchical logistic regression, adjusting for potential confounders.Age was significantly associated with keloid recurrence (OR: 0.934, p = 0.009), indicating older age was linked to lower recurrence risk. No significant association was found between preoperative 25(OH) vitamin D (p = 0.395) and 1,25(OH)2 vitamin D levels (p = 0.925) and keloid recurrence.Preoperative vitamin D levels do not predict keloid recurrence in this Korean cohort, while age is a significant predictor. Understanding the multifactorial nature of keloid pathogenesis requires further investigation into other potential risk factors. [ABSTRACT FROM AUTHOR]

The pathological mechanism of pathological scar is highly complex, encompassing the abnormalities of diverse cytokines, signaling pathways and regulatory factors. To discover more preferable scar treatment options, a variety of distinct approaches have been utilized clinically. Nevertheless, these treatments possess certain side effects and are inclined to relapse. Presently, pathological scar treatment remains a clinical conundrum, and there is an urgent demand for treatment methods that are safe, less traumatic and have lower recurrence rates. New drug delivery systems, novel therapeutic drugs and therapy strategies can enable drugs to permeate the skin effectively, decrease side effects, enhance drug efficacy and even achieve pain-free self-administration. Currently, novel nanotechnologies such as nanomicroneedles, photodynamics mediated by novel photosensitizers, bioelectrical stimulation and 3D printed dressings have been developed for the effective treatment of pathological scars. Additionally, innovative nanoscale fillers, including nano-fat and engineered exosomes, can serve as novel therapeutic agents for the efficient treatment of pathological scars. The intervention of nanomaterials can enhance drug absorption, stabilize and safeguard the active ingredients of drugs, delay or control drug release and enhance bioavailability. This article reviews these new treatment strategies for scar to explore novel approaches for efficient and safe for keloid treatment. Article highlights The pathological mechanism of pathological scars is highly complex, encompassing abnormalities in various cytokines, signaling pathways and regulatory factors. The treatment of pathological scars remains a challenging clinical issue and there is an urgent demand for methods that are safe, less traumatic and have a low recurrence rate. Nanomicroneedles constitute an emerging therapeutic modality that can be utilized either independently or as a delivery system for directly transporting drugs to the epidermis or dermis. It possesses the merits of being painless, minimally invasive, efficient, safe and convenient. The newly developed photosensitizers can ensure the depth of treatment and prompt PDT response. Particularly, the combination of photosensitizer-mediated PDT and nanozymes boosts the efficacy of PDT. The integration of the self-powered system and the nanocarriers is capable of generating bioelectrical stimulation and achieving synergistic antibacterial and anti-inflammatory effects, thereby significantly expediting wound healing and preventing the formation of scar tissue. By integrating 3D printing technology with nanomaterials, it becomes feasible to acquire a dressing scaffold featuring a complex structure, precise size and the ability to promote wound healing and to achieve personalized wound dressings for facilitating wound healing. The treatment involving nanofat and combined platelet components can inhibit scar formation through influencing the signaling pathway, which constitutes a potential therapeutic strategy for scar treatment as well. Mesenchymal stem cell-derived exosomes and their derivatives suppress ECM deposition in keloids through influencing the TGF-β/Smad and Notch-1 signaling pathways. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Isotretinoin is widely used for moderate to severe acne vulgaris. Despite its broad application, isotretinoin carries a risk of permanent scarring and keloid formation following various skin procedures. As a result, a delay of at least 6–12 months after completing or discontinuing isotretinoin treatment is commonly recommended before undergoing skin procedures.This study aims to evaluate the necessity of delaying skin procedures performed concurrently with or soon after isotretinoin treatment at different dosages in patients with acne vulgaris, based on the dermatological side effects associated with combination therapy.A literature search was conducted using PubMed, Scopus, Web of Science, and Embase databases for original studies up until June 2023.A total of 34 eligible studies, including 1563 patients treated with isotretinoin, were reviewed to assess the timing of various skin procedures, safe dosages, and potential adverse effects, such as keloid formation and persistent hyperpigmentation which were reported in a few cases.Based on our review, there is insufficient evidence to support delaying laser hair removal, ablative fractional lasers, nonablative fractional lasers, superficial to medium‐depth chemical peels, manual dermabrasion, cutaneous surgeries, fractional microneedling radiofrequency, microdermabrasion, and dermaroller treatments. However, fully ablative lasers, mechanical dermabrasion, and ablative radiofrequency procedures are not recommended during isotretinoin use. Further studies are needed to establish the safety and optimal interval for these procedures. For all skin procedures, especially more aggressive and deeper ones, a lower dose of isotretinoin is recommended. [ABSTRACT FROM AUTHOR]

Keloids are characterized histologically by excessive fibroblast proliferation and connective tissue deposition, and clinically by scar tissue extending beyond the original site of skin injury. These scars can cause pruritus, pain, physical disfigurement, anxiety, and depression. As a result, keloid patients often have a diminished quality of life with a disproportionate burden on ethnic minorities. Despite advances in understanding keloid pathology, there is no effective Food and Drug Administration (FDA)-approved pharmacotherapy. Recent studies have highlighted the possible pathologic role of T helper (Th)17 cells and interleukin (IL)-17 in keloid formation, as well as their implication in other inflammatory disorders. This systematic review characterizes the role of Th17 cells and IL-17 in keloid pathogenesis, highlighting this pathway as a potential therapeutic target. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search on PubMed, Embase, MEDLINE, and Web of Science databases on June 5, 2024. The search included terms related to Th17 cells, IL-17, and keloids. Thirteen studies met the inclusion criteria, comprising basic science and bioinformatic studies focusing on Th17 cells and IL-17. Key findings include increased Th17 cell infiltration and IL-17 expression in keloids, IL-17's role in amplifying the inflammatory and fibrotic response via the promotion of IL-6 expression, and IL-17's involvement in upregulating fibrotic markers via SDF-1 and HIF-1α pathways. IL-17 also activates the transforming growth factor beta (TGF-β)/Smad pathway in keloid fibroblasts. Th17 cells and IL-17 significantly contribute to the inflammatory and fibrotic processes in keloid pathogenesis. Therefore, targeting the IL-17 pathway offers a potential new therapeutic target to improve keloid patients' outcomes. Future research could further elucidate the role of Th17 cells and IL-17 in keloid pathogenesis and assess the safety and efficacy of targeting this pathway in human studies. [ABSTRACT FROM AUTHOR]

The use of postoperative radiotherapy (PORT) for the treatment of keloids in the pediatric population is rare, despite being a common pathology at this age. Recurrences after surgery are very common. The absence of a standardized protocol for the management of recurrent keloids further complicates therapeutic decision‐making. Here, we present a clinical case involving a recurrent giant retroauricular keloid in a pediatric patient, demonstrating a satisfactory response to a comprehensive approach involving surgery, PORT, and periodic injections of 5‐fluorouracil with corticosteroid. We believe that reporting this case adds value as a potential therapeutic option in the absence of established protocols for recurrent keloids in pediatric patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Background/Objectives Methods Results Conclusions There are scant established data on the cause, distribution, treatment options, and recurrence rate of pediatric keloids in Asian populations. We characterized clinical features by comprehensively categorizing pediatric keloid patients into prepubertal and postpubertal groups at a single tertiary center.We searched the database of Kangbuk Samsung Hospital for pediatric patients (< 18 years) with clinically proven keloids who underwent outpatient‐based treatment from 2007 to 2021. Clinical features, including demographics, distribution, underlying cause, treatment modality, and recurrence, were analyzed.Of the 93 patients (total 110 keloids), 42 females (45.2%) and 51 males (54.8%), with a mean age of 14.5 ± 4.1 years (range, 1–18 years), were retrospectively analyzed. The mean length of follow‐up was 22.0 ± 14.2 months (range, 6–63). Of the 100 keloids with assessable causes, piercing (22%) and acne (19%) were the most common. In the prepubertal group, the lower and upper limbs (n = 7, 28%; n = 6, 24%) were the two most common locations, suggesting that post‐traumatic keloids are common during this developmental period. In the postpubertal group, the ear (n = 25, 29.4%) was the most common site, which corresponds to the frequency of cosmetic piercing at this age. No differences were found between the effects of treatment methods on relapse rate.Understanding the clinical features of pediatric keloids is important in the therapeutic considerations for pediatric keloids. Future studies should analyze a larger number of children with keloids over longer observation periods. [ABSTRACT FROM AUTHOR]

Keloid formation in toes area is rare. However, occurrence of this phenomenon in toes after the surgery of syndactyly repair has been reported. Risk factors of keloid formation in toes after syndactyly reconstructions are currently unknown. This study aimed to investigate the risk factors of keloid formation after the surgery of syndactyly repair of the toes. We retrospectively reviewed our case series including patients who were treated surgically at our institution. We hypothesized some key factors of keloid formation and analyzed each of them statistically. A total of 105 patients were treated surgically at our hospital, and 9 patients were involved keloid formations after operations. Among our hypothesized key factors, the results of multivariate logistic regression analysis revealed the number of affected web spaces (OR 0.031; 95%CI 0.001–0.684; p = 0.028) was significantly different. Digital enlargement was not a significant factor (OR 17.731; 95%CI 0.686–458.174; p = 0.091). Involving multiple web space was associated with keloid formation after syndactyly release, on the other hand, toe enlargement did not show a significant difference. However, the digital enlargement showed high Odds ratio, we could not deny its high relativity for keloid formation. Further investigations are needed to clarify the key risk factors of keloid formation after the surgery of syndactyly repair of the toes. [ABSTRACT FROM AUTHOR]

Background and Aim: Keloids cannot be effectively treated using monotherapy regimens. This study aimed to evaluate the efficacy and safety of ablation (a novel needle‐assisted electrocoagulation technique) combined with pharmacotherapy (corticosteroid and 5‐fluorouracil [5‐FU] injections) in removing keloids and to investigate the underlying biological mechanisms. Methods: The effects of energy consumption and duration of needle‐assisted electrocoagulation on the ablation zone were tested in porcine liver tissue, which simulates human skin. The regulatory effects of ablation combined with pharmacotherapy on collagen deposition, cell proliferation, and angiogenesis were analyzed in a keloid‐bearing nude mouse model in vivo. In a clinical trial involving six patients with keloids, the Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) scores were graded before treatment and 1 month after one cycle of ablation combined with corticosteroid and 5‐FU therapy. Results: Higher energy consumption and longer duration of electrocoagulation resulted in a larger ablation zone and higher surface temperature. Ablation combined with pharmacotherapy significantly reduced keloid volume in nude mice, upregulated MMP‐1 and MMP‐3, downregulated COL I and COL III, and inhibited angiogenesis and proliferation. This combination also significantly reduced the VSS and POSAS scores in patients with keloids after treatment without any obvious adverse events. Conclusion: Our findings show that electroablation combined with pharmacotherapy effectively reduces keloid volume by inhibiting collagen deposition, angiogenesis, and cell proliferation. Thus, this novel combination may serve as a safe therapeutic approach for keloid removal. [ABSTRACT FROM AUTHOR]

Background: Bleomycin, originally an antitumor drug, was explored as a pathological scar treatment in the mid‐1990s. However, its efficacy and safety profile varies among individuals. Aims: This study aimed to assess topical bleomycin's efficacy and safety in treating hypertrophic scars and keloids. Methods: We reviewed randomized controlled trials (RCTs) and controlled clinical trials (CCTs) published in English, comparing intralesional bleomycin to placebos or common intralesional scar treatments. Primary outcomes included percentage change in scar improvement, pigmentation, recurrence, atrophy, pain, telangiectasia, ulceration, patient self‐assessment, and observer assessment (>50%). Results: Six trials met the criteria. Bleomycin significantly improved scar reduction compared to triamcinolone (p < 0.05). There was no significant difference in pigmentation (p = 0.05) and recurrence (p = 0.21) compared to other treatments. In terms of safety, bleomycin caused less skin atrophy (p < 0.01) and telangiectasia (p < 0.01) but more pain (p = 0.03) than other treatments. Conclusions: Bleomycin was more effective than TAC, 5‐FU, or TAC combined with 5‐FU for treating keloids and hypertrophic scars with lower skin atrophy and telangiectasia risks. However, it may cause more pain than 5‐FU or TAC. Further comprehensive studies, including RCTs, are required for objective analysis. [ABSTRACT FROM AUTHOR]

Background: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results. Objectives: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids. Methods: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale. Results: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection. Conclusions: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved. [ABSTRACT FROM AUTHOR]

Jellyfish stings can cause acute inflammatory skin lesions that may hesitate in keloids. Pulsed dye laser (PDL) represents one of the most effective treatments for newly developed keloids. Aim of this study was to evaluate the efficacy of PDL on newly developed keloids specifically induced by jellyfish stings in pediatric patients.We conducted a retrospective observational study on pediatric patients with newly developed keloids from jellyfish stings, treated in the last two years with 595 nm wavelength PDL with a duration of 0.45–1.5 msec, spot-size 7 mm and fluence 8.5–9.5 J/cm2. PDL therapy was administered for a mean of 7.4 treatment sessions, every 1–3 months. Two expert dermatologists evaluated the vascularity, pigmentation, height, and pliability of keloids, according to the Vancouver Scar Scale (VSS), pre-and-post treatment. A total of 17 patients (7 males, 10 females) were included in the study, mean age of 11 years. Overall, mean pre-treatment global VSS was 11.0 ± 1.50. After treatment, global VSS was 3.88 ± 1.87. At paired t-test, the difference between pre-treatment and post-treatment was highly statistically significant (p <.0001). Commonly, manipulation and therapeutic intervention on jellyfish scars and keloids is feared. The present study supports the use of PDL in keloids secondary to jellyfish stings, though conducted on a limited number of patients. [ABSTRACT FROM AUTHOR]

Fibroblasts, the principal cellular mediators of connective tissue remodeling, play a crucial role in the formation of physiological and pathological scars. Understanding the intricate interplay between fibroblasts and other cellular and molecular components is essential for elucidating the underlying mechanisms driving scar formation. Hypertrophic scars, keloids and atrophic scars arise from dysregulated wound healing processes characterized by persistent inflammation, aberrant collagen deposition, and impaired extracellular matrix remodeling. Fibroblasts play a central role in the pathogenesis of such pathological scars, driving aberrant extracellular matrix remodeling, subsequently contributing to the formation of raised or depressed fibrotic lesions. The investigation of complex interactions between fibroblasts and the microenvironment is crucial for developing targeted therapeutic interventions aimed at modulating fibroblast activity and improving clinical outcomes in patients with pathological scars. Further research into the molecular pathways governing fibroblast behavior and their heterogeneity holds promise for advancing scar management strategies. This narrative review was performed to shed light on the mechanisms behind scar formation, with a special focus on the role of fibroblasts in the formation of different types of scars, providing insights into the pathophysiology of these conditions. Through the analysis of current knowledge, this review seeks to identify the key cellular and molecular mechanisms involved in fibroblast activation, collagen synthesis, and extracellular matrix remodeling in hypertrophic scar, keloid, or atrophic scar formation. [ABSTRACT FROM AUTHOR]

Keloid scarring is a complex fibroproliferative disorder characterised by excessive fibroblast proliferation. Inhibition of cellular glycolysis effectively suppresses the proliferation of keloid fibroblasts (KFs). Neural precursor cell‐expressed developmentally downregulated gene 4‐like (NEDD4L), a ubiquitin ligase, regulates cell proliferation in different diseases. This study investigated the effects of NEDD4L on glucose metabolism, proliferation and migration in KFs. Primary KFs were isolated from keloid skin tissues obtained from patients with active‐stage keloids. Cell transfection was used to upregulate or downregulate NEDD4L and Yin Yang 1 (YY1) in KFs. Protein expression was assessed by immunohistochemistry and western blotting. The viability, proliferative capacity and migration ability of KFs were evaluated using the MTT method and the EdU and wound healing assays, respectively. The regulatory effect of NEDD4L on YY1 ubiquitination was examined by coimmunoprecipitation. The interaction between YY1 and hexokinase 2 (HK2) was confirmed by a dual‐luciferase reporter assay. NEDD4L was downregulated, whereas YY1 and HK2 were highly expressed in keloid tissues compared with normal skin. Overexpression of NEDD4L inhibited the proliferation and migration of KFs. NEDD4L promoted YY1 degradation in KFs by inducing its ubiquitination. Upregulation of YY1 induced glucose consumption and lactate production in KFs via the transcriptional regulation of HK2. Increased expression of YY1 reversed the reduced viability, proliferation, and migration of KFs overexpressing NEDD4L. YY1 also reversed the NEDD4L‐induced inhibition of glucose consumption and lactate production in KFs. Additionally, an in vivo study confirmed the inhibitory roles of NEDD4L overexpression and YY1 knockdown in keloid formation. NEDD4L suppressed the viability, proliferation and migration of KFs by regulating YY1 ubiquitination‐mediated glycolysis through HK2. These findings suggest a novel regulatory axis, NEDD4L/YY1/HK2, that mediates glucose metabolism in keloid formation. [ABSTRACT FROM AUTHOR]

The aim of this study is to identify the key biomarker of keloid (KD) with significant diagnostic value and to construct the related competing endogenous RNA (ceRNA) network and disease diagnostic model to provide new ideas for the early diagnosis and prevention of KD. Public databases were used to identify the key gene of KD. Enrichment analysis and immune cell infiltration (ICI) analysis revealed its functional and immune characteristics. Then, a ceRNA network was constructed to explore the potential pathways of it. Random forest (RF) analysis was applied to construct a predictive model for the disease diagnosis of KD. Finally, immunohistochemistry (IHC) and RT‐qPCR were used to verify the differential expression of key gene. ERRFI1 was identified as a key biomarker in KD and was lowly expressed in KD. The ceRNA network revealed that H0TAIRM1‐has‐miR‐148a‐3p‐ERRFI1 may be a potential pathway in KD. Finally, a 2‐gene diagnostic prediction model (ERRFI1, HSD3B7) was constructed and externally validated and the results suggested that the model had good diagnostic performance. ERRFI1 is a downregulated gene in KD and is expected to be a promising predictive marker and disease diagnostic gene. ICI may play a role in the progression of KD. The ceRNA network may provide new clues to the potential pathogenesis of KD. Finally, the new KD diagnostic model could be an effective tool for assessing the risk of KD development. [ABSTRACT FROM AUTHOR]

Background: Congenital muscular dystrophies (CMDs) are diverse early‐onset conditions affecting skeletal muscle and connective tissue. This group includes collagen VI‐related dystrophies such as Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), caused by mutations in the COL6A1, COL6A2 and COL6A3 genes. We report a consanguineous Malian family with three siblings affected by UCMD due to a novel homozygous splice site variant in the COL6A1 gene. Methods: After obtaining consent, three affected siblings and their relatives underwent physical examinations by specialists and laboratory tests where possible. DNA was extracted from peripheral blood for genetic testing, including Whole Exome Sequencing (WES). Putative variants were confirmed through Sanger Sequencing and assessed for pathogenicity using in silico tools. Results: The three siblings and their healthy parents, from a consanguineous marriage, presented with early‐onset progressive muscle weakness, walking difficulty, proximal motor deficits, severe muscle atrophy, hypotonia, skeletal deformities, joint hyperlaxity, ankyloses at the elbows and knees, keloid scars and dental crowding. No cardiac involvement was detected and creatine kinase (CK) levels were normal. All had low serum calcium levels, treated with oral supplements. Needle myography indicated myopathic patterns. WES identified a novel splice site variant in the first intron of COL6A1 (c.98‐1G>C), which segregated with the disease within the family. This variant is predicted to cause exon 2 skipping in COL6A1, with a high CADD score of 33 and Splice AI predicting it as deleterious. Conclusion: We identified a novel COL6A1 variant in a consanguineous family, highlighting the need for further studies in larger African cohorts to enhance genetic epidemiology and prepare for future therapeutic research. [ABSTRACT FROM AUTHOR]

Pathological scars, including hypertrophic scar and keloid are the result of excessive tissue repair and are influenced by biomechanical forces like tension, mechanical pressure, and stiffness. These forces significantly impact scar development and progression, affecting wound healing, collagen deposition, and tissue remodeling. Understanding how these mechanical stimuli contribute to scar development is essential for devising effective therapeutic interventions. Clinically, reducing wound tension and applying mechanical pressure are key strategies for managing pathological scars. Techniques like super-tension-reduction suturing, stress-shielding polymers, and force-modulating tissue bridges (FMTB) have been shown to effectively alleviate tension and reduce scar proliferation. Additionally, Pressure Garment Therapy (PGT) is widely used to treat hypertrophic scars by reducing tissue stiffness, limiting collagen buildup, and promoting collagen realignment. Despite challenges such as discomfort and uneven pressure application, ongoing research focuses on enhancing these therapies through mechanosensitive technologies to improve both efficacy and patient comfort. This review highlights the role of biomechanical forces in scar formation and discusses therapeutic approaches that target these forces to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Cleft lip repair (CLR) can be complicated by hypertrophic scar or keloid. Botulinum toxin type A (BTA) may improve postoperative scarring by reducing muscle tension and cytokine activity at the scar site. This systematic review analyzes the available evidence regarding the effect of BTA on scar quality after CLR. Design: The search was conducted in 6 different databases in accordance with PRISMA guidelines (PubMed, Scielo, Embase, Scopus, Web of Science, and Cochrane) using "botulinum toxin" and "cleft lip" as keywords. Setting: Academic hospital Patients: Exclusive to patients who underwent CLR and BTA injection Outcome measures: Mean visual analog scores (VAS), mean Vancouver scar scale (VSS), scar width, and BTA or CLR-related complications. Results: Five studies for a total of 216 patients met inclusion criteria. Four studies reported on primary CLR during infancy while 1 study recruited older patients seeking revision. All patients had BTA (range: 1-2 units/kg) injected in the orbicularis oris muscle. One study documented BTA injections in additional perioral muscles. All 4 studies that measured scar width and had a saline control arm found a significant decrease in width with BTA injection. Improvement of VAS and VSS with BTA was reported in 3 of 5 studies and 2 of 5 studies, respectively. There were no reports of complications associated with BTA or CLR. Conclusion: The existing studies support the use of BTA injection to improve scar quality following CLR with low concern for complication. Further investigations with a greater number of patients are necessary. [ABSTRACT FROM AUTHOR]

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The healing of human skin wounds is susceptible to perturbation caused by excessive mechanical stretching, resulting in enlarged scars, hypertrophic scars, or even keloids in predisposed individuals. Keloids are fibro‐proliferative scar tissues that extend beyond the initial wound boundary, consisting of the actively progressing periphery and the quiescent center. The stretch‐associated outgrowth and enhanced angiogenesis are two features of the periphery of keloids. However, which cell population is responsible for transducing the mechanical stimulation to the progression of keloids remains unclear. Herein, through integrative analysis of single‐cell RNA sequencing of keloids, we identified CD74+ fibroblasts, a previously unappreciated subset of fibroblasts with pro‐angiogenic and stretch‐induced proliferative capacities, as a key player in stretch‐induced progression of keloids. Immunostaining of keloid cryosections depicted a predominant distribution of CD74+ fibroblasts in the periphery, interacting with the vasculature. In vitro tube formation assays on purified CD74+ fibroblasts ascertained their pro‐angiogenic function. BrdU assays revealed that these cells proliferate upon stretching, through PIEZO1‐mediated calcium influx and the downstream ERK and AKT signaling. Collectively, our findings propose a model wherein CD74+ fibroblasts serve as pivotal drivers of stretch‐induced keloid progression, fueled by their proliferative and pro‐angiogenic activities. Targeting the attributes of CD74+ fibroblasts holds promise as a therapeutic strategy for the management of keloids. [ABSTRACT FROM AUTHOR]