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Murine models have provided valuable insights into the pathogenesis of both diabetes and chronic wounds. However, only a few published reports to date have investigated wound healing differences among the differing diabetic mouse models. The goal of the present study was to further define the wound healing deficiency phenotypes of streptozotocin-induced (STZ-induced), Akita, and db/db diabetic mice in comparison with a promising new polygenic strain of Type 2 diabetes (NONcNZO10) by using three specific wound models that targeted different critical processes in the pathogenesis of chronic wounds. Incisional, excisional, and ischemia/reperfusion wound models were established on mice of each strain. Wound healing parameters including tensile strength, epithelial gap, and wound necrosis were evaluated. In contrast to the other diabetic mice, the NONcNZO10 strain was found to have significant wound healing impairments in all wound healing models. Not only do the NONcNZO10 mice appear to better model human Type 2 diabetes, these provocative findings suggest that the mice may show more clinically relevant wound healing deficiencies than previous diabetic mouse models. [ABSTRACT FROM AUTHOR]

Bacterial biofilms have gained increasing visibility in recent years as a ubiquitous form of survival for microorganisms in myriad environments. A number of in vivo models exist for the study of biofilms in the setting of medically relevant implanted foreign bodies. Growing evidence has demonstrated the presence of bacterial biofilms in the setting of a number of chronic wound states including pressure sores, diabetic foot ulcers, and venous stasis ulcers. Here we present a novel murine cutaneous wound system that directly demonstrates delayed reepithelialization caused by the presence of a bacterial biofilm. We established biofilms using either Staphylococcus aureus or Staphylococcus epidermidis in splinted cutaneous punch wounds created on the backs of normal C57Bl6/J mice. Wound reepithelialization was significantly delayed by bacterial biofilms. This effect was specifically dependent on the ability of the bacteria to form biofilms as demonstrated by exogenous administration of biofilm inhibiting peptides and the use of mutant Staphylococcus spp. deficient in biofilm formation. This represents the first direct evidence for the effect of bacterial biofilms on cutaneous wound healing. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic infection after breast reconstruction is not uncommon and can result in loss of the implant pocket and negative patient outcomes. Management of these infections typically involves removal of the prosthesis, treatment with antibiotics, and delayed reconstruction upon infection resolution. The impact of adjunctive use of negative pressure wound therapy with instillation and dwell (NPWTi-d) on breast pocket salvage rates, time to implant reinsertion, and related outcomes was examined., Methods: A systematic literature search using PubMed, Cochrane, OVID, Scopus, and Embase was conducted to identify peer-reviewed articles written in English and published between January 2004 and April 2023 that examined NPWTi-d use in the breast pocket with a history of periprosthetic infection after breast reconstruction., Results: Of the 1703 publications, 6 studies met inclusion criteria, representing 115 patients and 122 breasts. The overall breast pocket salvage rate with NPWTi-d across studies was approximately 92%. In the 6 studies that included prosthesis type and radiation history, overall salvage rates were 97.8% (45 of 46) for pockets containing implants and 93.8% (15 of 16) for pockets containing tissue expanders. Salvage rates were 85.7% (12 of 14) and 91.7% (53 of 58) for irradiated and nonirradiated breasts, respectively. Mean time to implant reinsertion ranged from 2.3 to 10.3 days., Conclusions: In this review, antibiotic therapy along with adjunctive use of NPWTi-d for periprosthetic infections after breast reconstructions was associated with high rates of breast pocket salvage and reduced time to implant reinsertion. Larger prospective and randomized trials are needed to better understand and optimize the effectiveness of NPWTi-d in this population., Competing Interests: Dr. Galiano is a consultant and receives funding from 3M/KCI. Drs. Collinsworth and Griffin are employees of Solventum. The other authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Skin wounds, whether medically or incidentally induced, are always at a risk of becoming infected, but the infection risks are greater when the wounds are recovering under ischemic, poorly perfused conditions. Staphylococcus aureus, which frequently infects cutaneous and soft tissue, can infect to a greater extent when wounds are poorly perfused. Bad as this may be, both MSSA and MRSA strains of S. aureus can cause severe infections, with MRSA being considered more aggressive., Methods: In this study, we used a lagomorph ear excisional wound model to initially test the influence of partial ischemia on uninfected wound healing. We then subsequently test the same ischemic injury model under an active MSSA infection and compared these wounds against normally perfused MSSA-infected wounds. Lastly, we test whether differences in healing exist between MSSA-infected and MRSA-infected wounds, both under the same ischemic model., Results: The data suggest that partial ischemia considerably reduces healing of noninfected wounds (epithelial gap P = ∗∗∗∗ , granulation gap P = ∗∗∗ , and granulation area P = ∗∗∗∗ ). Similarly, partial ischemic wounds coupled with MSSA infection display healing impairments against likewise-infected wounds healing under normal perfusion (epithelial gap P = ∗ , granulation gap P = ∗ , and granulation area P = ∗∗ ). No significant differences were observed between MSSA-infected and MRSA-infected wounds healing under ischemia., Conclusion: The data produced quantitative differences in healing under various conditions consequent to ischemia and S. aureus infection. Although it is well recognized that ischemia and infection adversely influence healing, by testing these conditions, we determined the detrimental magnitude such circumstances inflict on skin healing, thereby providing a relative reference to compare and gauge when met with similar conditions clinically., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Adrian E. Rodrigues et al.)

The transforming powder dressing (Altrazeal®, Uluru Inc, Addison, TX, USA) is simple to use, painless to apply and has a wear time of up to 30 days. This study aims to review the current literature to elucidate the impact of transforming powder dressing on healing, pain management and overall patient outcomes. We conducted a systematic review following Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines. Data including study characteristics, patient demographics and wound outcomes were extracted. Our systematic review included 26 articles (n = 175). Of these articles, 13 (50%) were case reports, 10 (38.5%) were case series, 2 (7.7%) were randomised controlled trials and 1 (3.8%) was a cohort study. Wound types included venous ulcer (23.9%), pressure sore (19.7%), burn (15.5%), skin graft (13.4%), diabetic foot ulcer (4.2%), Mohs defect (3.5%) and other (19.6%). Complete re-epithelialization occurred in 90.1% of the wounds. A total of 19 studies (73%) discussed pain, each of which reported reduced pain with the use of transforming powder dressing. The evaluated studies collectively suggest that transforming powder dressing offers a promising re-epithelialization rate and analgesic effect across various wound types., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

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., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

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.

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.

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., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

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., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

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., Competing Interests: Robert Galiano is a consultant for MTF Biologics and receives research funding through grants to Northwestern University School of Medicine. Dennis Orgill is a consultant for MTF Biologics and receives research funding through grants to Brigham and Women’s Hospital. Paul Glat is the medical director and owner of Dr. Glat PC and receives research funding from MTF biologics. David G. Armstrong has no financial interest to declare in relation to the content of this article. Marissa Carter receives funds as a consultant to PERI and MTF Biologics to conduct the statistical analysis for this trial. Charles M. Zelen, DPM is the medical director and president of the Professional Education and Research Institute and received funds from MTF Biologics to conduct this clinical trial. This study was supported by MTF Biologics, Edison, New Jersey. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

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 = ∣measurement 6 - measurement 12 ∣). 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 ± 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., Competing Interests: Dr. Galiano is a consultant for MTF Biologics. This study was supported by MTF Biologics. The other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Competing Interests: The authors have no financial interest to declare in relation to the content of this article.

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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

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., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking. Much research into fibrotic pathophysiology has focused on dermal pathology, but less research has been performed to understand aberrations in fibrotic epidermis, leading to an incomplete understanding of dermal fibrosis. Herein, literature on occlusion, a treatment modality known to reduce dermal fibrosis, in part through accelerating wound healing and regulating aberrant epidermal inflammation that otherwise drives fibrosis in the dermis, is reviewed. The review focuses on epidermal-dermal crosstalk, which contributes to the development and maintenance of dermal fibrosis, an underemphasized interplay that may yield novel strategies for treatment if understood in more detail., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. The study received funding through the Musculoskeletal Transplant Foundation., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

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., Competing Interests: Disclosures: The authors have no conflict of interest to disclose.

Chronic or delayed healing wounds constitute an ever-increasing burden on healthcare providers and patients alike. Thus, therapeutic modalities that are tailored to particular deficiencies in the delayed wound healing response are of critical importance to improve clinical outcomes. Human amnion-derived viable and devitalized allografts have demonstrated clinical efficacy in promoting the closure of delayed healing wounds, but the mechanisms responsible for this efficacy and the specific wound healing processes modulated by these tissues are not fully understood. Here, we utilized a diabetic murine excisional wound model in which healing is driven by granulation and re-epithelialization, and we applied viable (vHAMA) or devitalized (dHAMA) amnion-derived allografts to the wound bed in order to determine their effects on wound healing processes. Compared to control wounds that were allowed to heal in the absence of treatment, wounds to which vHAMA or dHAMA were applied demonstrated enhanced deposition of granulation tissue accompanied by increased cellular proliferation and increased de novo angiogenesis, while vHAMA-treated wounds also demonstrated accelerated re-epithelialization. Taken together, these data suggest that both vHAMA and dHAMA facilitate wound healing through promoting processes critical to granulation tissue formation. Further understanding of the cellular and tissue mechanisms underlying the effects of tissue-derived matrices on wound healing will enable tailored prescription of their use in order to maximize clinical benefit., (© 2022 The Authors. Clinical and Experimental Pharmacology and Physiology published by John Wiley & Sons Australia, Ltd.)

The incidence and economic burden of diabetic foot ulcers continues to rise throughout the world. In this prospective study, a unique device designed to offload the wound, enhance circulation and monitor patient compliance was evaluated for safety and efficacy. The device provides offloading and intermittent plantar compression to improve the pedal flow of oxygenated blood and support wound healing while recording patient use. Ten patients with non-healing diabetic foot ulcers UTgrade 1A/Wagner grade 1 were treated weekly for up to 12 weeks. The primary endpoint was complete wound closure at 12 weeks, and secondary endpoints included healing time, percent area reduction and changes in pain using the visual analogue pain scale. Eight out of ten wounds healed within 12 weeks(80%), and the mean healing time was 41 days(95% CI:24.3-58.3). The percent area reduction was 75(SD:53.9). The baseline visual analogue pain scale was 4.5(2.9) as compared with 3.3(3.4) at end of study. No device-related or serious adverse events were reported. This unique intermediate plantar compression and offloading device may be considered as an alternative for safe and effective for treatment of non-healing diabetic foot ulcers. During treatment, wound healing was significantly accelerated, and pain was improved. Larger randomised controlled trials are underway to validate these early findings., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Because of the high volume of Asian eyelid operations performed and the complexity of the Asian eye, there is a need to define exactly what anthropometric measurements determine attractiveness., Methods: Eye photographs of young East Asian women were collected from publicly available sources online. Photographs were evaluated on a Likert scale ranging from 1 to 5 for attractiveness. Thirty-seven anthropometric measurements were collected using ImageJ from the most attractive and least attractive eyes to discover which features play the most important role in attractiveness., Results: A total of 322 right eye photographs were evaluated for attractiveness. Sixty-six eyes received a median score of greater than or equal to 4.0 and were included in the attractive cohort. Forty-three eyes received a score of less than or equal to 2.0 and were included in the unattractive cohort. The superior brow peak was more lateralized compared to the upper lid crease and upper lash line peaks in attractive eyes. A greater palpebral aperture height-to-upper lid show ratio was found to be more associated with attractive eyes than with unattractive eyes. At the midpupillary line, the ratio was on average 1.58 ± 0.32 in attractive eyes and 1.22 ± 0.43 in unattractive eyes ( p < 0.001). Eyes with convergence of the upper lid crease with the upper lash line were more likely to be deemed unattractive ( p < 0.001)., Conclusions: East Asian eyes have specific anthropometric measurements that are more associated with attractiveness. These ideal measurements are different from those in Caucasians, suggesting ethnic variability in features defining attractiveness and a need to tailor surgical care appropriately., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: This randomized controlled trial evaluated the safety and effectiveness of weekly and biweekly applications of dehydrated human amnion and chorion allograft (dHACA) plus standard of care compared to standard of care alone on chronic venous leg ulcers., Methods: This open-label randomized controlled trial included patients with chronic venous leg ulcers at eight wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40 percent closure at 4 weeks and the incidence of adverse events., Results: Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more venous leg ulcers healed in the two dHACA-treated groups (75 percent) than in the standard-of-care group (30 percent) ( p = 0.001) even after adjustment for wound area ( p = 0.002), with an odds ratio of 8.7 (95 percent CI, 2.2 to 33.6). There were no significant differences in the proportion of wounds with percentage area reduction greater than or equal to 40 percent at 4 weeks among all groups. The adverse event rate was 63.5 percent. Among the 38 adverse events, none were graft or procedure related, and all were resolved with appropriate treatment., Conclusions: dHACA and standard of care, either applied weekly or biweekly, significantly healed more venous leg ulcers than standard of care alone, suggesting that the use of aseptically processed dHACA is advantageous and a safe and effective treatment option in the healing of chronic venous leg ulcers., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)

Scarring negatively impacts patient mental health, causing worsened self-confidence, body image, and social interactions, as well as anxiety and depression. The objective of this study is to evaluate the scarring impact after facial surgery, breast surgery, and full abdominoplasty for symptoms, appearance, psychosocial health, career, and sexual well-being using validated patient-reported outcome measures., Method: A total of 901 patients from five providers completed the SCAR-Q (covering symptoms, appearance, and psychosocial) and Career/Sexual Well-being assessments via phone or email where a higher score indicated a more positive scar perception., Results: Of the 901 patients, 38.1% had abdominoplasty surgery, 38.1% breast reduction, 15.3% facial surgery, 4.7% breast lift, and 3.9% breast augmentation. The differences in SCAR-Q, appearance, and symptom scores between the five procedures were statistically significant. Breast augmentation SCAR-Q scores (median = 256) and facial surgery (median = 242) were significantly higher than those of abdominoplasty patients (median = 219; P = 0.003 and P = 0.001, respectively). Duration after surgery was positively correlated with improved symptom scale scores for abdominoplasty (r = 0.24, P < 0.001), breast augmentation (r = 0.71, P = 0.015), and facial surgery patients (r = 0.28, P = 0.001), but not for other procedures., Conclusions: This study is the first to show that breast augmentation and facial surgery patients have a more positive perception of their scars in terms of appearance, symptoms, psychosocial, career, and sexual well-being impact than abdominoplasty patients. Furthermore, the data suggest that symptoms may improve over time for abdominoplasty, breast augmentation, and facial surgery patients. This study highlights the need for further follow-up, counseling, or other improvements to postoperative scar care., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Clinical options are lacking for the management of chronic wounds or ulcers following failed debridement, skin grafting, or negative pressure wound therapy dressings., Objective: This retrospective case series evaluated the efficacy of injectable AAM in the management and closure of chronic wounds., Materials and Methods: Patients with nonhealing wounds of any etiology, anatomic location, and length of chronicity were included; those with multiple chronic wounds or prior skin grafting for wound repair were excluded. Data on location, etiology, chronicity, and number of AAM applications were collected for each wound. Patients were evaluated for possible complications related to wound healing and infection. Eleven patients (7 males, 4 females), each with 1 chronic wound, were recruited (average age, 65 years). Wound etiologies were postoperative (n = 7), traumatic (n = 2), and foot ulcer (n = 2). Average wound dimensions were 8.45 mm × 7.36 mm, and the average chronicity was 3.77 months. Ten patients received only 1 application of AAM, and 1 patient received 2 treatments 5 days apart. Average follow-up time was 6.6 weeks., Results: Seven patients (63%) achieved wound closure, 4 of which (57%) healed within 1 week of application., Conclusion: Most patients with chronic wounds treated with AAM experienced complete wound closure. AAM shows promising results for enhancing wound healing by providing scaffolding for cell growth.

Objective: Obturator nerve injury can occur as a complication of gynecologic surgeries, occurring most frequently in patients with endometriosis and genitourinary malignancies. The resulting injury causes paresthesia and major weakness in adduction and atrophy of the adductor group of lower extremity muscles. The objective of this study was to conduct a systematic review and meta-analysis of the effectiveness of end-to-end repair, nerve grafting, and nerve transfer in improving motor function in patients with obturator nerve injury., Methods: PubMed, Cochrane, Medline, and Embase libraries were searched from May 1994 to August 2020 according to the PRISMA guidelines for articles that present functional outcomes after obturator nerve injury in patients treated with nerve grafting, end-to-end repair, or nerve transfer., Results: A total of 25 patients from 22 studies were included in the study, 15 of whom were treated with end-to-end repair (60%), nine with nerve grafting (36%), and one with nerve transfer (4%). Of the 15 patients with transection data, two had incomplete (13%) and 13 had complete (87%) nerve transections. The patients underwent pelvic lymphadenectomy (n=24) and radical cystectomy (n=1) operations. The mean Medical Research Council (MRC) score was 2.95±1.7 immediately after treatment and 4.77±0.6 at the final follow-up. All patients achieved good outcomes (MRC ≥3) at the final follow-up. The mean MRC score for end-to-end repair (n=15), nerve grafting (n=9), and nerve transfer (n=1) was 4.8±0.6, 4.7±0.8, and 5, respectively. Patients with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting (p=0.03) and tended to achieve full functional recovery after shorter periods of time (rho=-0.65, p=0.049). Other parameters did not correlate with MRC., Conclusion: End-to-end repair, nerve grafting, and nerve transfer are equally effective in restoring function in patients with obturator nerve injury. However, patients treated with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting., Competing Interests: Competing interests: JHK is on the Scientific Advisory Board for Mesh Suture Inc and Checkpoint Surgical Inc. He is also a Consultant for Integra Lifesciences Inc and Neuraptive Therapeutics Inc. No disclosures are reported by any of the other authors., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetic foot infections continue to be a major challenge for health care delivery systems. Following encouraging results from a pilot study using a novel purified reconstituted bilayer matrix (PRBM) to treat chronic diabetic foot ulcers (DFUs), we designed a prospective, multi-centre randomised trial comparing outcomes of PRBM at 12 weeks compared with a standard of care (SOC) using a collagen alginate dressing. The primary endpoint was percentage of wounds closed after 12 weeks. Secondary outcomes included assessments of complications, healing time, quality of life, and cost to closure. Forty patients were included in an intent-to-treat (ITT) and per-protocol (PP) analysis, with 39 completing the study protocol (n = 19 PRBM, n = 20 SOC). Wounds treated with PRBM were significantly more likely to close than wounds treated with SOC (ITT: 85% vs 30%, P = .0004, PP: 94% vs 30% P = .00008), healed significantly faster (mean 37 days vs 67 days for SOC, P = .002), and achieved a mean wound area reduction within 12 weeks of 96% vs 8.9% for SOC. No adverse events (AEs) directly related to PRBM treatment were reported. Mean PRBM cost of healing was $1731. Use of PRBM was safe and effective for treatment of chronic DFUs., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Aggregated data show that Black patients undergo disproportionately lower rates of cosmetic surgery than their Caucasian counterparts. Similarly, laboratory findings indicate that social media representation is lower among Black patients for breast reconstruction surgery, and it is expected that this could be the case in cosmetic surgery as well., Objectives: The aim of this study was to explore the social media representation of Black patients and physicians in the 5 most common cosmetic surgery procedures: rhinoplasty, blepharoplasty, abdominoplasty, breast augmentation, and liposuction., Methods: Data were collected from RealSelf (Seattle, WA), the most popular social media site for sharing cosmetic surgery outcomes. The skin tone of 1000 images of patients in each of the top 5 cosmetic surgeries was assessed according to the Fitzpatrick scale, a commonly utilized skin tone range. Additionally, the Fitzpatrick scores of 72 providers who posted photographs within each surgical category were collected., Results: Black patients and providers are underrepresented in rhinoplasty, blepharoplasty, breast augmentation, and liposuction compared with the general population (defined by the US Census Bureau), but were proportionately represented in abdominoplasty. Additionally, it was found that patients most often matched Fitzpatrick scores when both had scores of 2, whereas patients with a score of 5 and 6 rarely matched their provider's score., Conclusions: The underrepresentation of Black patients and providers in social media for cosmetic surgery may well discourage Black patients from pursuing cosmetic surgeries. Therefore, it is essential to properly represent patients to encourage patients interested in considering cosmetic surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The fluid immersion simulation system (FIS) has demonstrated good clinical applicability. This is the first study to compare surgical flap closure outcomes of FIS with an air-fluidised bed (AFB), considered as standard of care. The success of closure after 14 days post-op was the primary endpoint. Secondary endpoints were incidences of complications in the first 2 weeks after surgery and the rate of acceptability of the device. Thirty-eight subjects were in the FIS group while 42 subjects were placed in the AFB group. Flap failure rate was similar between groups (14% vs. 12%; p = 0.84). Complications, notably dehiscence and maceration, were significantly higher in the FIS group (40% vs. 17%; p = 0.0296). The addition of a microclimate regulation device (ClimateCare®) to FIS for the last 43 patients showed a significant decrease in the rate of flap failure (71% vs. 16%; p = 0.001) and incidence of complications (33% vs. 0%; p = 0.011). There was no statistically significant difference between the FIS and air-fluidised bed (AFB) in the rate of acceptability (nurse acceptance: 1.49 vs. 1.72; p = 0.8; patient acceptance: 2.08 vs. 2.06; p = 0.17), which further illustrates the potential implementation of this tool in a patient-care setting. Our results show that the use of ClimateCare® in combination with FIS can be a better alternative to the AFB in surgical closure of pressure ulcers., (© 2022 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Scars can have significant morbidity and negatively impact psychological, functional, and cosmetic outcomes as well as the overall quality-of-life, especially among ethnic minorities. The objective of this study was to evaluate African American and White patients' perception of their scars' impact on symptoms, appearance, psychosocial health, career, and sexual well-being, using validated assessment tools., Method: A total of 675 abdominoplasty and breast surgery patients from four providers completed the SCAR-Q, and Career/Sexual Well-Being scales via phone or email. A higher score on both assessments indicates a more positive patient perception., Results: Of the 675 respondents, 77.0% were White, and 23.0% were African American. White patients scored significantly higher on the SCAR-Q (232 ± 79 versus 203 ± 116), appearance (66 ± 26 versus 55 ± 29), and Career/Sexual Well-Being (16 ± 2 versus 15 ± 5) scales than African American patients ( P < 0.001, P < 0.001, P < 0.001, respectively). There was no significant correlation between duration after surgery and symptoms or appearance scores for African American patients ( P = 0.11, P = 0.37). There was no significant correlation between patient age and SCAR-Q score or time after surgery and psychosocial scores., Conclusions: African American patients are more likely to have lower perceptions of their scarring appearance, symptoms, psychosocial impact, career impact, and sexual well-being impact than White patients. Scar appearance and symptoms are less likely to improve over time for African American patients. This study highlights the need to address patient ethnicity when considering further follow-up, counseling, or other measures to enhance scar perception., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)