Intralesional 5-Fluorouracil for Keloids: A Systematic Review.

Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been employed for the treatment of keloids; however, there is no one gold standard approach. Five-fluorouracil, a potent chemotherapeutic agent, has emerged as a promising therapeutic option. Therefore, this systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focused on providing a broad overview of the use of 5-fluorouracil for the management of keloids. Forty studies (2325 patients) met inclusion criteria and investigated 5-fluorouracil for keloid management, with 19 studies (1043 patients) including a 5-fluorouracil monotherapy group. Five-fluorouracil monotherapy demonstrated consistent keloid improvement with >254 keloids injected across various anatomical regions. Five-fluorouracil monotherapy was most often compared to intralesional triamcinolone acetonide, utilizing the Patient and Observer Scar Assessment Scale and the Vancouver Scar Scale. The most common keloid parameters assessed were height, size, volume, width, length, induration, pruritus, and erythema. Five-fluorouracil monotherapy exhibited substantial improvements, with weight averages of 73% of patients experiencing >25% improvement and 67% achieving >50% improvement. Relapse rate was 16% at 27 weeks after 5-fluorouracil monotherapy treatment. Limitations included potential selection bias, language restrictions, and heterogenous data analysis among studies. Overall, our findings underscore the potential effectiveness of 5-fluorouracil monotherapy in the management of keloids, with an encouraging safety profile. Larger prospective trials are needed to determine optimal therapy or combination therapy for the management of keloids. This detailed compilation of treatment protocols, outcomes, and relapse rates stand as a valuable resource for further research and clinical applications.

Efficacy and Safety of Corticosteroid in Combination with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Addressing hypertrophic scars and keloids poses a significant challenge in the realm of preventive and curative medicine. Combination corticosteroid with 5-fluorouracil (5-FU) is presumed to enhance the treatment of hypertrophic scars and keloids, although supportive evidence is lacking. This study is aimed at comparing the efficacy and safety profile of a combined corticosteroid and 5-FU regimen in treating hypertrophic scars and keloids. METHODS: A comprehensive search was conducted for pertinent studies across various databases, including Web of Science, PubMed, Google Scholar, Cochrane Library, and Medline. The calculation of weighted mean difference (WMD), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CIs) was executed. Additionally, the Cochrane Collaboration's Risk of Bias Tool was utilized to evaluate potential bias risks. RESULTS: A total of 15 studies were involved. The effectiveness based on patient self-assessment and the effectiveness based on observer assessment were significantly higher in the corticosteroid+5-FU group compared to those treated with control. A meta-analysis of scar height showed that the corticosteroid+5-FU group performed better than the control group (WMD = -0.38, 95% CI -0.58 to -0.18). There was no significant difference between the corticosteroid+5-FU group and the control group in improving scar vascularity, pliability and pigmentation. The result revealed that the corticosteroid+5-FU group of patients had less adverse effect of hypopigmentation, skin atrophy and telangiectasia than the control group. CONCLUSION: The combined use of corticosteroids and 5-FU appears to be a more effective strategy for the treatment and prevention of hypertrophic scars and keloids, as evidenced by greater improvements in scar height and overall effectiveness, coupled with a reduced incidence of side effects. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Potential of Chat-Based Artificial Intelligence Models in Differentiating Between Keloid and Hypertrophic Scars: A Pilot Study.

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 .

The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Fibrosis in burns: an overview of mechanisms and therapies.

Scar development remains a common occurrence and a major healthcare challenge affecting the lives of millions of patients annually. Severe injuries to the skin, such as burns can lead to pathological wound healing patterns, often characterized by dermal fibrosis or excessive scarring, and chronic inflammation. The two most common forms of fibrotic diseases following burn trauma are hypertrophic scars (HSCs) and keloids, which severely impact the patient's quality of life. Although the cellular and molecular mechanisms are similar, HSC and keloids have several distinct differences. In this review, we discuss the different forms of fibrosis that occur postburn injury, emphasizing how the extent of burn influences scar development. Moreover, we highlight how a systemic response induced by a burn injury drives wound fibrosis, including both the role of the inflammatory response, as well as the fate of fibroblast during skin healing. Finally, we list potential therapeutics aimed at alleviating pathological scar formation. An understanding of the mechanisms of postburn fibrosis will allow us to effectively move studies from bench to bedside.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

Ear keloids: An innovative 3-steps combined treatment.

INTRODUCTION: An excessive proliferation of fibroblasts and collagen synthesis after an injury may lead to a benign fibrous tumor, known as keloid, which does not regress spontaneously. Earlobes are a very frequent site of onset, since after a trauma (i.e., piercing) keloids may develop either on the helix and on the anterior or posterior lobe, from a few months up to several years after the injury. OBJECTIVES: To report the effectiveness of a combined protocol of CO2 laser + Dye laser + a portable Blue LED Light medical device for Photobiomodulation Therapy (EmoLED®). METHODS: Fifty-two patients with a total of 56 ear keloids have been treated in the same session with a single CO2 laser procedure + a pulsed Dye laser procedure with an adjunctive EmoLED® procedure for 3 up to 6 min. A monthly follow-up has been performed with an adjunctive EmoLED® session in case of signs of inflammation. RESULTS: Among 56 treated keloids, 89.3% of them (50/56) did not recur during a follow-up period (from 6 up to 24 months, mean 16.3 months) while six keloids recurred (6/56, 10.7%) with mild thickening of the scar, thus requiring further treatments. CONCLUSIONS: Even if an excellent outcome obtained by the synergistic effect of combined laser treatments has already been described (i.e., CO2 laser + Dye Laser), the present study showed the adjuvant procedure with EmoLED® can reduce significantly the risk of keloids recurrences.

Efficacy of a multimodal approach of laser therapy for earlobe keloids management in dark population.

BACKGROUND: Patients with keloids are often younger than 30 years old and have darker skin. AIM: To evaluate the efficacy and safety of CO2 laser therapy in the management of earlobe and helix keloids in dark subjects. METHODS: A total of 21 dark patients (five men and 16 women) presented with the earlobe and ear helix keloids, with a mean age of 30.5 (±6.7) years and with phototype between III-VI, were enrolled. In order to improve their earlobe and helix keloids, all patients underwent a single session of CO2 laser therapy immediately followed by a pulsed Dye laser procedure. A single well-experienced doctor performed all treatment sessions and the response to treatment. Patients were followed-up for 6 months after termination of therapy. Clinical images were examined and collected: all patients were examined clinically and with Dermoscopy. RESULTS: The majority of the patients treated show complete remission of keloid lesions. Clinical photographs show a visible aesthetic improvement of several types of keloids in dark subjects. CONCLUSIONS: Our data demonstrate that this combined laser therapeutic protocol appears to be effective and well tolerated for the management of earlobe and helix keloids in dark subjects, with no high recurrence rate and avoiding the adverse effects and lengthy recovery time.

A Nomogram with the Keloid Activity Assessment Scale for Predicting the Recurrence of Chest Keloid after Surgery and Radiotherapy.

BACKGROUND: Patients with chest keloids undergoing surgery and adjuvant radiotherapy still have a high recurrence rate, which is a critical problem. The level of keloid activity has not been studied, and a nomogram model for predicting keloid recurrence has not been established in previous studies. METHODS: A total of 145 patients with chest keloids who underwent surgery and radiotherapy between January 2015 and January 2019 at Peking Union Medical College Hospital were included in our study. Demographic and clinical features and the score of KAAS were analyzed. We compared the area under the curve (AUC) and decision curve analysis (DCA) between KAAS and the Vancouver scar scale (VSS) and established a nomogram model for predicting the risk of recurrence. We used bootstrap and calibration plots to evaluate the performance of the nomogram. RESULTS: The KAAS can predict recurrence in patients with chest keloids after surgery and radiotherapy. Areas under the curve (AUCs) of KAAS and VSS were 0.858 and 0.711, respectively (p < 0.001). Decision curve analysis (DCA) demonstrated that the KAAS was better than the VSS. Complications after treatment may be risk factors for keloid recurrence. We created a nomogram by using complications and KAAS. The AUC was 0.871 (95% CI 0.812-0.930). The ROC of the model's bootstrap was 0.865 and was well calibrated. CONCLUSIONS: The KAAS can be used to predict the recurrence and we developed a nomogram for predicting the recurrence of chest keloids after surgery and adjuvant radiotherapy. 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 .

A Working Classification and a Simple Effective Management Protocol for Ear Keloids.

BACKGROUND: The unpredictable behavior of scars in the ear makes it a nightmare in planning the management protocol for ear keloids. To understand and classify the ear keloid, a simple working classification based on the anatomical location has been proposed. Low recurrence rate should be the primary determinant in choosing a management protocol. The scar control protocol includes complete excision of the keloid, taking care not to extend to normal skin which was followed by a round-the-clock 24×7 management protocol for 6 months to 1 year. PATIENTS AND METHODS: This study presents a prospective analysis of 71 patients with 106 ear keloids who underwent surgery in our clinic between 2007 and 2022. The management included complete excision, postoperative adjuvant therapy in the form of self-managed scar stabilization with bi-digital, bi-dimensional, bi-directional massage and corticosteroid therapy if warranted. Complete keloid excision with primary reconstruction was followed up to 1 year, and recurrence rates were tracked during this period. RESULTS: Of the 71 patients, 91.54% were women. All lesions (n = 106) were treated by complete excision. The average age was between 15 and 30 years. The overall recurrence rate was 5.6%. CONCLUSION: With our classification and protocol, we were able to achieve a consistent recurrence free state in 94.4% of patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Anti-Fibrotic Effects of RF Electric Currents.

Hypertrophic scars and keloids are two different manifestations of excessive dermal fibrosis and are caused by an alteration in the normal wound-healing process. Treatment with radiofrequency (RF)-based therapies has proven to be useful in reducing hypertrophic scars. In this study, the effect of one of these radiofrequency therapies, Capacitive Resistive Electrical Transfer Therapy (CRET) on biomarkers of skin fibrosis was investigated. For this, in cultures of human myofibroblasts treated with CRET therapy or sham-treated, proliferation (XTT Assay), apoptosis (TUNEL Assay), and cell migration (Wound Closure Assay) were analyzed. Furthermore, in these cultures the expression and/or localization of extracellular matrix proteins such as α-SMA, Col I, Col III (immunofluorescence), metalloproteinases MMP1 and MMP9, MAP kinase ERK1/2, and the transcription factor NFκB were also investigated (immunoblot). The results have revealed that CRET decreases the expression of extracellular matrix proteins, modifies the expression of the metalloproteinase MMP9, and reduces the activation of NFκB with respect to controls, suggesting that this therapy could be useful for the treatment of fibrotic pathologies.

Comparing intralesional triamcinolone and verapamil-triamcinolone injections in keloids: A single-blinded randomised clinical trial.

INTRODUCTION: In this clinical trial, we investigated the efficacy of two treatment methods for keloids resulting from surgical incisions: intralesional triamcinolone injections alone versus in combination with verapamil. MATERIAL AND METHODS: Patients were divided into two groups: one received triamcinolone alone (Group T) and the other received a triamcinolone-verapamil blend (Group VT). Regular treatments were conducted until the keloids were nearly flat or for a maximum of eight sessions. RESULTS: Both groups showed significant improvements, but Group VT saw quicker resolution of skin redness and needed fewer sessions. Though the Vancouver Scar Scale (VSS) scores were generally similar across both groups, Group VT exhibited greater improvements, leading to lower final scores. The VT group also attained normal scar flexibility faster than the T group. CONCLUSION: These findings suggest that the combination of verapamil and triamcinolone provides a more effective treatment for keloids, thereby highlighting the potential of verapamil in scar reduction.

[Keloid nomogram prediction model based on weighted gene co-expression network analysis and machine learning].

Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.

Important role of mechanical microenvironment on macrophage dysfunction during keloid pathogenesis.

Keloid is considered as a tumor-like skin disease with multiple aetiologies including immunological factors and mechanical microenvironment. Macrophages are plastic and diverse immune cells that play a critical role in maintaining tissue homeostasis by removing dead cells, debris, pathogens and repairing tissues after inflammation. The imbalance of M1/M2 macrophages and disturbances in macrophage functions can steer the progression of chronic inflammation and lead to the development of pathological fibrosis in keloid disease. Recently, it has been shown that macrophages are sensitive to mechanical signals, especially stretching tension and tissue stiffness, which can determine macrophage polarization and functions. Higher stretching tension is known to be an important pathogenic factor of keloid, and the formation of keloid will lead to an increase in tissue stiffness. As little is known about the underlying reasons of macrophages dysfunction in keloid, an understanding of how the mechanical microenvironment interacting with macrophages and affecting their behaviours may help provide mechanism insights into keloid pathogenesis. We thus hypothesize that the synergistic effect of stretching tension and matrix stiffness may contribute to the major pathophysiological niche attributes of macrophages' in vivo mechanical microenvironment in keloids. These mechanism insights of how macrophages sense and respond to their mechanical microenvironment would propel the development of novel strategies for keloid treatment.

Joel Rosenbloom and the revolution in biomedical research.

This biography of Dr. Joel Rosenbloom is published on the occasion of the 50th anniversary of the journal. Dr. Rosenbloom presents the scientific milestones and achievements throughout his career emphasizing events that have spurred him to launch into a career in biomedical research and education. The biography spans several decades of the life and achievements of a distinguished physician scientist whose dedication to science demonstrates the development of new insights into a variety of connective tissues through technological advances and insightful approaches.

Different Types of Auricular Keloids and Treatment by Intralesional Cryosurgery: Best Practice for Obtaining Long-Lasting Clinical Results.

BACKGROUND: Auricular keloids belong to the most perplexing medical conditions, which have significant psychosocial impact on the patient's body image and quality of life. SUMMARY: The article is purposed to provide dermatologists and plastic surgeons with the best proven practice using intralesional cryosurgery for the treatment of the different auricular keloid types in order to obtain superior clinical results by minimizing the probability of recurrence. In the past 20 years, the authors have developed novel procedures in order to increase the effectiveness of intralesional cryosurgery on auricular keloids, including hydrodissection, warm gauze technique, and excision of dangling skin. Long-lasting clinical results with a low recurrence rate and a satisfactory aesthetic outcome are achieved with no deformation of the ear framework.

The Inhibition of Adipose-Derived Stem Cells on the Invasion of Keloid Fibroblasts.

Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation.

Diagnosis and differential diagnosis of dermatofibrosarcoma protuberans: Utility of high-resolution dynamic contrast-enhanced (DCE) MRI.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a kind of low-grade malignant spindle cell neoplasm, the diagnosis, and treatment, which have markedly attracted clinicians' attention for its repeated recurrence. High-resolution magnetic resonance imaging (HR-MRI) has shown unique capabilities in diagnosis of various cutaneous tumors. MATERIALS AND METHODS: Data of 29 patients with clinically suspected DFSPs and undergoing dynamic contrast-enhanced (DCE) HR-MRI preoperatively were prospectively collected. The HR-MRI qualitative features were evaluated and compared. The DCE-associated quantitative parameters and the time-signal intensity curve (TIC) types were provided using DCE sequences. RESULTS: A total of 7 DFSPs, nine dermatofibromas (DF, including four cases of cellular variant [CDF]), 12 keloids, and one nodular fasciitis were enrolled. DFSP showed the largest major diameter and the deepest depth. Five DFSPs (71.4%) showed ill-defined margins as well as infiltration of peripheral adipose. All DFSPs showed irregular shape. Most DFSPs presented hyperintensity on T2 WI (71.4%) and iso-intensity on T1 WI (85.7%). Six cases (85.7%) had significant enhancement, and six cases (85.7%) had homogeneous enhancement. There were significant differences of Ktrans , Kep , Ve and iAUC values among DFSPs, DFs, and keloids, and DFSP had the highest values for these parameters. Six DFSPs (85.7%) and four CDFs (100%) showed type-III TICs, while the other lesions showed type-Ⅰor type-Ⅱ TICs. CONCLUSIONS: DCE-HR-MRI could show the growth characteristics of DFSPs, which was of great value for the diagnosis and differential diagnosis of DFSPs and was helpful for the determination of treatment options, thereby to improve the prognosis of patients.

Relative perfusion index: An objective, quantitative and noninvasive method for evaluating the severity of keloids.

BACKGROUND: Keloids are the result of abnormal wound healing, and they differ from the normal skin of the patient in the level of blood perfusion and the degrees of inflammation, hypoxia, regeneration of vessels, and expression of sensory receptors. However, there is no objective assessment method to accurately characterize the severity of keloids. OBJECTIVES: The purpose of this study was to evaluate the perfusion levels of keloids and the expression levels of various internal cytokines, including hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), interleukin-17 (IL-17), HT2A receptor subtype (5-HT2A R), and H1R, in keloids and nonadjacent normal skin and to propose a laser speckle contrast imaging (LSCI)-based relative perfusion index (RPI), through which keloids can be divided into five grades to objectively characterize their severity. METHODS: This population-based cross-sectional study included 70 untreated keloid patients who each had only one keloid on the chest. LSCI was used to measure the area of each patient's keloid ( K area ${K}_{\mathrm{area}}$ ) and the perfusion level of each patient's keloid ( K perfusion ${K}_{\mathrm{perfusion}}$ ) and normal skin ( N perfusion ${N}_{\mathrm{perfusion}}$ ). The Vancouver Scar Scale (VSS) and Visual Analog Scale (VAS) for pain and pruritus were also used to assess each keloid. Immunohistochemistry and Western blot were used to detect the expression levels of various internal cytokines in keloids and normal skin. We compared the perfusion and expression levels of intrinsic cytokines between keloids and normal skin. We established the RPI to grade the severity of keloids and applied different methods to test the utility of the RPI. RESULTS: The mean perfusion level of keloids was significantly higher than that of normal skin (p < 0.001). The expression levels of HIF-1α, VEGF, IL-17, 5-HT2A R, and H1R in keloids were significantly higher than those in normal skin (p < 0.05). RPI was defined as: [ ( K perfusion - N perfusion ) × 0.03 + K area × 0.001 ] . $[({K}_{\mathrm{perfusion}}-{N}_{\mathrm{perfusion}})\times 0.03+{K}_{\mathrm{area}}\times 0.001].$ The severity of keloids could be divided into five grades based on RPI. The RPI had a higher correlation with the pain-VAS, pruritus-VAS, and the expression levels of internal cytokines in keloids than blood perfusion levels and the VSS. T-SNE (t-distributed stochastic neighbor embedding) was also used to verify the clinical discriminatory abilities of this RPI model. CONCLUSIONS: The proposed RPI based on LSCI showed the highest accuracy, unlike the VSS and assessment of perfusion, and can be utilized as a reliable, objective, quantitative, and noninvasive tool to evaluate the severity of keloids.

Ulvan-Based Nanofibrous Patches Enhance Wound Healing of Skin Trauma Resulting from Cryosurgical Treatment of Keloids.

Keloids are skin fibroproliferative disorders, resulting from abnormal healing of deep cutaneous injuries. Cryosurgery, the most common treatment for keloids, causes skin traumas. Even though the clinical practice of cryosurgery has increased, effective wound healing therapy is still lacking. In this investigation, nonwoven nanofibrous patches composed of ulvan, a marine sulfated polysaccharide exhibiting anti-inflammatory and antioxidant activities, and polyethylene oxide (PEO) were fabricated through electrospinning and characterized. Their wound healing efficacy on skin traumas resulting from cryosurgical treatment of keloids was clinically tested and evaluated in comparison to a reference product. Twenty-four volunteer patients undergoing cryosurgery as a treatment of keloids were selected to apply either the ulvan/PEO patch or the reference product for 21 days. The ulvan/PEO patch, 21 days after cryosurgery, showed significant wound healing, elimination of skin inflammation, restoration of biophysical parameters similar to normal values and significant decrease in haemoglobin concentration, skin texture and volume, while no discomfort or adverse reaction was observed. In contrast, the reference product showed inferior performance in all evaluated parameters. The designed ulvan/PEO patch represents the first wound dressing to effectively heal skin trauma after cryosurgical treatment of keloids.