Skin fibrosis is accompanied by increased expression of secreted frizzled-related protein-2.

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis.

The use of acellular products in venous leg ulcers: a narrative review.

BACKGROUND: Venous leg ulcers (VLUs) are the most common type of chronic wound in the lower extremity and are often associated with redness, swelling, and pain at the site of the wound. The primary focus of VLU treatment is the promotion of wound healing through compression therapy, wound debridement, and elevation of the affected limb. Acellular matrices have gained traction as a potential adjunct to wound healing in diabetic foot ulcers. However, the clinical effect of acellular products in the setting of VLUs has not been well reported. OBJECTIVE: To review the published evidence on the use of acellular products in the management of VLUs. METHODS: PubMed, Embase, Cochrane, and Google Scholar databases were initially searched on March 2, 2023, for literature on VLU and acellular dermal matrix. Later, the search was broadened to include any and all acellular matrices, and a secondary search of the same databases was conducted on February 20, 2024. Articles obtained through collateral methods were also included. RESULTS: A total of 27 articles were identified for review. All studies were human studies. Four articles had level I evidence and 7 articles had level II evidence, while the remaining articles had level III or IV evidence. Studies included both large and small wound sizes ranging from 0.5 cm² to 100 cm2. Product application occurred once to twice weekly for 4 weeks to up to 36 months. Overall, regardless of ulcer size, the majority of studies reported favorable wound healing outcomes with the use of a variety of acellular skin coverage products with few complications. Some studies also reported pain reduction with the use of acellular skin substitutes in a small cohort of patients. CONCLUSION: Acellular products appear to have the potential to support healing in VLUs. However, more large-scale randomized controlled trials that provide level I evidence are needed.

Understanding Staphylococcus aureus in hyperglycaemia: A review of virulence factor and metabolic adaptations.

Staphylococcus aureus is one of the most commonly detected bacteria in diabetic skin and soft tissue infections. The incidence and severity of skin and soft tissue infections are higher in patients with diabetes, indicating a potentiating mechanism of hyperglycaemia and infection. The goal of this review is to explore the metabolic and virulence factor adaptations of S. aureus under hyperglycaemic conditions. Primary data from identified studies were included and summarised in this paper. Understanding the nexus of hyperglycaemia, metabolism, and virulence factors provides insights into the complexity of diabetic skin and soft tissue infections attributed to S. aureus.

Exploring the Efficacy of Selected Allografts in Chronic Wound Healing: Evidence from Murine Models and Clinical Data for a Proposed Treatment Algorithm.

Significance: Chronic wounds can lead to poor outcomes for patients, with risks, including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary health care costs. Recent Advances: Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown that dermal allografts promote reepithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings confirm their effectiveness and illuminate their therapeutic mechanisms. Critical Issues: Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach toward a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial. Future Directions: Recent advances in allografts provide a framework for further investigations into patient-specific allograft selection. This requires additional research to identify which allografts support the best outcomes during each stage of wound healing and in which wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.

The Cost-effectiveness of Enhanced Recovery after Surgery Protocols in Abdominally Based Autologous Breast Reconstruction.

Background: The purpose of this study was to conduct a systematic review on the cost-effectiveness of enhanced recovery after surgery (ERAS) protocols in abdominally based autologous breast reconstruction. Further, we reviewed the use of liposomal bupivacaine transversus abdominis plane (TAP) blocks in abdominal autologous reconstruction. Methods: PubMed, Embase, Cochrane, and Scopus were used for literature review, and PRISMA guidelines were followed. Included articles had full-text available, included cost data, and involved use of TAP block. Reviews, case reports, or comparisons between immediate and delayed breast reconstruction were excluded. Included articles were reviewed for data highlighting treatment cost and associated length of stay (LOS). Cost and LOS were further stratified by treatment group (ERAS versus non-ERAS) and method of postoperative pain control (TAP versus non-TAP). Incremental cost-effectiveness ratio (ICER) was used to compare the impact of the above treatments on cost and LOS. Results: Of the 381 initial articles, 11 were included. These contained 919 patients, of whom 421 participated in an ERAS pathway. The average ICER for ERAS pathways was $1664.45 per day (range, $952.70-$2860). Average LOS of ERAS pathways was 3.12 days versus 4.57 days for non-ERAS pathways. The average ICER of TAP blocks was $909.19 (range, $89.64-$1728.73) with an average LOS of 3.70 days for TAP blocks versus 4.09 days in controls. Conclusions: The use of ERAS pathways and postoperative pain control with liposomal bupivacaine TAP block during breast reconstruction is cost-effective. These interventions should be included in comprehensive perioperative plans aimed at positive outcomes with reduced costs.

A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

Current Trends in Breast Cancer Treatment in Chinese and Chinese American Women: The Disparity Between Mastectomy and Breast Reconstruction.

BACKGROUND: Breast cancer screening and surgical interventions are often underutilized in the Chinese community. For both Chinese American (CA) and native Chinese (NC) patients, screening rates are well below medical recommendations, which places these patients at risk for late diagnoses and larger tumors. There is also a notable reluctance to breast reconstruction after mastectomy. We investigated the role of sociodemographic and cultural barriers in breast treatment trends among Chinese breast cancer survivors. METHODS: A literature search for full-text articles published between 2011 and 2021 was performed using PubMed, The Web of Science, and Embase. The articles that were selected contained information regarding Chinese individuals in the United States or China who had undergone breast cancer screening or diagnosis of breast cancer and received treatment with or without reconstructive surgery. RESULTS: Both patient populations exhibited screening rates that were significantly lower than national recommendations. Of the CA patients, 25% reported never receiving a mammogram, whereas 450 million NCs have been left unscreened despite efforts made by the Chinese government. Misinformation, cultural beliefs, and fear significantly contributed to diminished breast health care among CA and NC women. Fear of recurrence, breast value, community influence, and limited health care resources were found to be the primary drivers of low breast reconstruction uptake. CONCLUSIONS: In both NC and CA women, there is a critical need for improved breast health information dissemination and overall quality of care. The findings summarized in this review can guide such efforts.

Rates of breast reconstruction uptake and attitudes toward breast cancer and survivorship among south asians: A literature review.

Our aim in this review was to ascertain rates of breast reconstruction among South Asian patients and identify attitudes towards breast cancer, survivorship, and breast reconstruction. Mastectomy rates for South Asian patients ranged from 52% to 77% and reconstruction following mastectomy varied from 0% to 14%. A negative perception of cancer, fears of social isolation, and taboos around breasts can prevent South Asian women from receiving surgical care after a breast cancer diagnosis.

A Prospective Multicenter Study of a Weekly Application Regimen of Viable Human Amnion Membrane Allograft in the Management of Nonhealing Diabetic Foot Ulcers.

Background: Diabetic foot ulcers (DFUs) pose a significant clinical challenge for providers and patients, and often precede devastating complications such as infection, hospitalization, and amputation. Therefore, advanced treatment options are needed to facilitate the healing of chronic DFUs and improve outcomes in this high-risk population. Cryopreserved viable human amnion membrane allograft (vHAMA) has shown great promise in the treatment of recalcitrant DFUs as a supplement to standard of care (SOC). Placental grafts are rich in extracellular matrix proteins, growth factors, and cytokines, which can induce angiogenesis and dermal fibroblast proliferation, resulting in accelerated healing. Methods: In this prospective, multicenter single arm trial, 20 patients with nonhealing DFUs received weekly application of vHAMA, in addition to SOC, for up to 12 weeks. The primary study endpoint was proportion of healed wounds at 12 weeks. Secondary endpoints included proportion of wounds healed at 6 weeks, time to heal, and percentage area wound reduction. Subjects were evaluated for ulcer healing and assessed for adverse events at every treatment visit. Results: At study conclusion, 85% of patients receiving vHAMA healed. Ten wounds healed (50%) by 6 weeks, and 17 wounds (85%) healed by 12 weeks. The mean time to heal was 46.6 days (95% CI: 35.1-58.0), and the average number of vHAMAs used was 5.4 (SD: 3.25). The mean PAR was 86.3% (SD: 40.51). Conclusions: Aseptically processed, cryopreserved vHAMA should be considered as a safe and effective option for DFUs refractory to SOC therapy.

Prospective Clinical Trial Evaluating the Outcomes Associated with the Use of Fresh Frozen Allograft Cartilage in Rhinoplasty.

Background: There are different types of grafts for rhinoplasty, each with certain advantages and disadvantages. Fresh frozen cadaveric costal allograft (CCA) provides an alternative to rhinoplasties. The aim of this study was to compare the outcomes of fresh frozen CCA and traditional autologous costal cartilage in cosmetic and reconstructive rhinoplasty procedures. Methods: This is a prospective, single-center, nonrandomized, open-label clinical trial. Objective assessment to evaluate warping, resorption, and displacement of the cartilage was achieved by measuring the differences of standardized values (deviation angle, nasofrontal angle, total facial convexity, nasofacial angle, and nasolabial angle) obtained at 6-months and 12-months postoperative follow-up on standard two-dimensional photographs (Δ = ∣measurement6 - measurement12∣). Subjective assessment was measured by the FACE-Q assessment. Results: Fifty eligible patients between March 2017 and October 2020 were included. The average age was 43.9 ±â€…16.6 years and the mean follow-up period was 14.8 months. In the control group, the changes (Δ) in the deviation angle and nasolabial angle were greater than in the CCA group (P < 0.05). In the CCA group, the mean score of satisfaction with nose improved at 6 months and 1 year postoperatively (P < 0.05). The mean score of satisfaction with nostrils and overall facial appearance also increased in the CCA group at 6 months postoperatively (P < 0.05). Six patients from the CCA group and 10 patients from the control group experienced postoperative complications. Conclusions: Fresh frozen CCA is a safe and reliable source of rhinoplasty grafts. It is aseptic, readily available, and free of donor site complications.

Evaluating skin colour diversity in the validation of scar assessment tools.

Across scar studies, there is a lack of dark-skinned individuals, who have a predisposition for keloid formation, altered pigmentation and poorer quality of life (QOL). There is a need for patients of colour to be included in scar scale development and validation. In this study, we evaluate the racial diversity of patients included in the validation of scar assessment scales. A systematic review was conducted for articles reporting on the validation of a scar assessment tool. Racial, ethnic and Fitzpatrick skin type (FST) data were extracted. Fifteen scar scale validation studies were included. Nine of the studies did not mention FST, race or ethnicity of the patients. Two of the studies that reported FST or race information only included White patients or included no FST V/VI patients: mapping assessment of scars (MAPS) and University of North Carolina '4P'. Only four studies included non-White patients or dark-skinned patients in the validation of their scar scale: the modified Vancouver Scar Scale (VSS), modified Patient and Observer Scar Assessment Scale (POSAS), acne QOL and SCAR-Q scales. The patients included in the modified VSS validation were 7% and 13% FST V/VI, 14% African in the modified POSAS and 4.5% FST V/VI in the SCAR-Q. We highlight the severe lack of diversity in scar scale validation, with only 4 out of 15 studies including dark-skinned patients. Given the susceptibility of darker-skinned individuals to have poorer scarring outcomes, it is critical to include patients of colour in the very assessment tools that determine their scar prognosis. Inclusion of patients of colour in scar scale development will improve scar assessment and clinical decision-making.

Content Validity of a Novel Scar Assessment Tool Evaluating the Career and Sexual Well-being Impact of Scars.

Currently, patient reported outcome scales used to assess scar impact focus solely on psychosocial well-being, symptoms, and appearance. There remains a need to develop a broadened measure of scar impact on patients, focusing on sexual and career aspects. This study investigates the content validity of the novel Career and Sexual Well-being (CS) Scar Impact Scale. Method: The CS scale contains five questions and was developed from previous patient thematic analysis interviews describing scar impact, and covers self-conscious behavior, new partners, hiding of the scar, being hindered in the workplace, and concerns regarding unprofessional appearance. Cognitive interviews and established guidelines were used to ensure that the scale was comprehensive, reproducible, and easily understandable. Results: In total, 86 patients completed cognitive interviews. Patients had a clear understanding of the questions and elicited their intent in the interviews. An estimated 86% of patients rated the CS scale coverage of scar impact on career and sexual health at a three or above out of four; 95% said the specific instructions were clear, and 92% stated it took them less than 4 minutes to complete the scale. After the first round of interviews, a question about "perception/self-consciousness in a professional environment" was added based on patient suggestions. Conclusions: The CS scar scale demonstrated face validity, acceptability, and field-readiness through cognitive interviewing of patients at our institution. Sexual well-being and career performance are important yet often neglected themes with which scars should be assessed. Usage of these tools would serve to improve current scar scales.

A multicenter, randomized controlled clinical trial evaluating the effects of a novel autologous heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Final analysis.

A novel autologous heterogeneous skin construct (AHSC) was previously shown to be effective versus standard of care (SOC) treatment in facilitating complete wound healing of Wagner 1 diabetic foot ulcers in an interim analysis of 50 patients previously published. We now report the final analysis of 100 patients (50 per group), which further supports the interim analysis findings. Forty-five subjects in the AHSC treatment group received only one application of the autologous heterogeneous skin construct, and five received two applications. For the primary endpoint at 12 weeks, there were significantly more diabetic wounds closed in the AHSC treatment group (35/50, 70%) than in the SOC control group (17/50, 34%) (p = 0.00032). A significant difference in percentage area reduction between groups was also demonstrated over 8 weeks (p = 0.009). Forty-nine subjects experienced 148 adverse events: 66 occurred in 21 subjects (42%) in the AHSC treatment group versus 82 in 28 SOC control group subjects (56.0%). Eight subjects were withdrawn due to serious adverse events. Autologous heterogeneous skin construct was shown to be an effective adjunctive therapy for healing Wagner 1 diabetic foot ulcers.

Anti-fibrotic effects of statin drugs: A review of evidence and mechanisms.

Fibrosis is a pathological repair process common among organs, that responds to tissue damage by replacement with non-functional connective tissue. Despite the widespread prevalence of tissue fibrosis, manifesting in numerous disease states across myriad organs, therapeutic modalities to prevent or alleviate fibrosis are severely lacking in quantity and efficacy. Alongside development of new drugs, repurposing of existing drugs may be a complementary strategy to elect anti-fibrotic compounds for pharmacologic treatment of tissue fibrosis. Drug repurposing can provide key advantages to de novo drug discovery, harnessing the benefits of previously elucidated mechanisms of action and already existing pharmacokinetic profiles. One class of drugs with a wealth of clinical data and extensively studied safety profiles is the statins, a class of antilipidemic drugs widely prescribed for hypercholesterolemia. In addition to these widely utilized lipid-lowering effects, increasing data from cellular, pre-clinical mammalian, and clinical human studies have also demonstrated that statins are able to alleviate tissue fibrosis originating from a variety of pathological insults via lesser-studied, pleiotropic effects of these drugs. Here we review literature demonstrating evidence for direct effects of statins antagonistic to fibrosis, as well as much of the available mechanistic data underlying these effects. A more complete understanding of the anti-fibrotic effects of statins may paint a clearer picture of their anti-fibrotic potential for various clinical indications. Additionally, more lucid comprehension of the mechanisms by which statins exert anti-fibrotic effects may aid in development of novel therapeutic agents that target similar pathways but with greater specificity or efficacy.

The Utilization of Fresh Frozen Cartilage in Asian Rhinoplasty: A New Approach.

Asian rhinoplasty generally requires augmentation procedures rather than reduction. Alloplastic grafts are fraught with higher complication rates. Autologous cartilage grafts are safer. However, Asian patients typically do not have adequate septal cartilages, and other autologous cartilage grafts may cause surgical site morbidities, prolonged surgical time, and complications, including warping and infection. Asian rhinoplasties were performed using fresh frozen cartilage by the senior author. Patients' demographics and medical histories were recorded. Anthropometric measurements (nasofrontal angle, nasofacial angle, nasolabial angle, and Goode ratio) were taken on two-dimensional photographs. FACE-Q scales were used to assess patient-reported outcomes. Five Asian patients underwent rhinoplasty using the fresh frozen cartilage and were followed up for an average period of 14.2 ± 3.35 months. There was no resorption, warping, or infection. Anthropometric measurements showed no significant changes 2-4 months or 8-20 months after surgery. At the time of the 1-year follow-up, mean FACE-Q Satisfaction with Nose, and Satisfaction with Nostrils scores improved from 35.2 ± 10.06 to 60 ± 15.48 (P = 0.0002), and 42.6 ± 20.31 to 59.8 ± 38.21 (P = 0.12), respectively. Fresh frozen cadaveric cartilage is a novel option for Asian rhinoplasty. Our study demonstrated its safety and satisfying surgical outcomes.

A Comparative Analysis of Online Reporting of Possible Complications for Minimally Invasive Cosmetic Procedures.

Background: The rise in Botox, fillers, and chemical peel procedures demands transparent online information that discloses all relevant risks and complications. This study assesses the quality of complication disclosure on the most popular cosmetic sites. Methods: The top 50 Google search results for "Botox," "fillers," and "chemical peel" were analyzed for their reporting on relevant complications. Websites were categorized based on their origin. An overall complication, prevention, management, prevalence, and disclaimer score were assigned to each site. Results: A total of 136 websites were analyzed. Of these websites, 31 (22.7%) did not mention any complications or risks associated with the treatment. The most commonly reported complications were bruising (67.0%) for Botox, swelling (79.0%) for fillers, and redness (58%) for chemical peels. The least-reported serious complications were toxin spread effects (31.0%) for Botox, vision loss (23.0%) for fillers, and allergic reaction for chemical peel (18.0%). Reports of serious and rare side effects were significantly lower than those of common side effects (Botox, P = .001; fillers, P = .004; chemical peels, P < .001). The overall mean (standard deviation) complication score across all websites was 2.81/5 (1.31). Online health reference and academic/hospital sites disclosed complications better than sources in most other categories (P < .001). Conclusions: The reporting of online complications for the top 3 cosmetic procedures performed in the US is highly variable, biased, and at times, completely absent. Patients pursuing cosmetic surgery are heavily influenced by the internet and vulnerable to misinformation. Cosmetic procedure websites are in need of drastic improvement to ensure the health and safety of all patients.

Comment on "Scar-Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis".

Cellular therapies show promise for treatment of fibrosis. A recent article presents a strategy and proof-of-concept for delivering stimulated cells to degrade hepatic collagen in vivo. A discussion is presented surrounding the strengths of this approach and the potential to generalize this strategy of optimizing cell sources and activation stimuli to treat other types of fibrosis.

Prediction and Demonstration of Retinoic Acid Receptor Agonist Ch55 as an Antifibrotic Agent in the Dermis.

The prevalence of fibrotic diseases and the lack of pharmacologic modalities to effectively treat them impart particular importance to the discovery of novel antifibrotic therapies. The repurposing of drugs with existing mechanisms of action and/or clinical data is a promising approach for the treatment of fibrotic diseases. One paradigm that pervades all fibrotic diseases is the pathological myofibroblast, a collagen-secreting, contractile mesenchymal cell that is responsible for the deposition of fibrotic tissue. In this study, we use a gene expression paradigm characteristic of activated myofibroblasts in combination with the Connectivity Map to select compounds that are predicted to reverse the pathological gene expression signature associated with the myofibroblast and thus contain the potential for use as antifibrotic compounds. We tested a small list of these compounds in a first-pass screen, applying them to fibroblasts, and identified the retinoic acid receptor agonist Ch55 as a potential hit. Further investigation exhibited and elucidated the antifibrotic effects of Ch55 in vitro as well as showing antiscarring activity upon intradermal application in a preclinical rabbit ear hypertrophic scar model. We hope that similar predictions to uncover antiscarring compounds may yield further preclinical and ultimately clinical success.