Voice Pitch Shaping and Genderization: New Needs of Cosmetic Phonoplastic Surgery.

Voices can convey content, emotion, and essential information about an individual's gender and social information. Closely related to gender identification and sexual attraction, voices also positively affect many psychological factors of individuals. Surgeries have evolved from treating congenital diseases to fulfilling an individual's aesthetic needs for voice. Voice shaping is emerging as the next cosmetic surgery hotspot after skincare and appearance and body shaping. This paper summarizes the development of voice pitch shaping and genderization procedures out of the cosmetic need. 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 https://www.springer.com/00266 .

Triple-negative breast cancer survival prediction using artificial intelligence through integrated analysis of tertiary lymphoid structures and tumor budding.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease. Accumulating evidence indicates that tertiary lymphoid structures (TLSs) and tumor budding (TB) are significantly correlated with the outcomes of patients who have TNBC, but no integrated TLS-TB profile has been established to predict their survival. The objective of this study was to investigate the relationship between the TLS/TB ratio and clinical outcomes of patients with TNBC using artificial intelligence (AI)-based analysis. METHODS: The infiltration levels of TLSs and TB were evaluated using hematoxylin and eosin staining, immunohistochemistry staining, and AI-based analysis. Various cellular subtypes within TLS were determined by multiplex immunofluorescence. Subsequently, the authors established a nomogram model, conducted calibration curve analyses, and performed decision curve analyses using R software. RESULTS: In both the training and validation cohorts, the antitumor/protumor model established by the authors demonstrated a positive correlation between the TLS/TB index and the overall survival (OS) and relapse-free survival (RFS) of patients with TNBC. Notably, patients who had a high percentage of CD8-positive T cells, CD45RO-positive T cells, or CD20-positive B cells within the TLSs experienced improved OS and RFS. Furthermore, the authors developed a comprehensive TLS-TB profile nomogram based on the TLS/TB index. This novel model outperformed the classical tumor-lymph node-metastasis staging system in predicting the OS and RFS of patients with TNBC. CONCLUSIONS: A novel strategy for predicting the prognosis of patients with TNBC was established through integrated AI-based analysis and a machine-learning workflow. The TLS/TB index was identified as an independent prognostic factor for TNBC. This nomogram-based TLS-TB profile would help improve the accuracy of predicting the prognosis of patients who have TNBC.

Nomogram predicts survival and surgical benefits for patients with breast cancer with initial bone metastasis: A population-based study.

BACKGROUND: Primary stage IV breast cancer is associated with a poor prognosis. At present, the value of local surgical treatment for patients with stage IV breast cancer remains uncertain; therefore, treatment principles remain controversial. Because of the high heterogeneity of these patients, it is often difficult to evaluate their prognoses. As a result, this study aimed to establish a prognostic nomogram to evaluate the prognosis of patients with breast cancer experiencing primary bone metastasis. METHODS: The clinical characteristics and follow-up data of patients with primary breast cancer and bone metastasis from 2010 to 2018 were collected from the Surveillance, Epidemiology, and End Results database and from 2013 to 2021 at the Peking Union Medical College Hospital. Patients were divided into training and validation groups. Multivariate Cox regression analysis was used to identify the independent prognostic variables for predicting cancer-specific survival (CSS). On the basis of these independent risk factors, a nomogram was developed and used calibration curves to evaluate its accuracy. Patients were divided into three risk groups according to their scores and surgery-related survival curves plotted using the log-rank test. RESULTS: Overall, 6372 patients were included, with 6319 from the Surveillance, Epidemiology, and End Results database and 53 from the Peking Union Medical College Hospital Breast Surgery Department. Multivariate analysis showed that age, race, marital status, grade, tumor stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and burden of other metastatic lesions were all associated with CSS. Based on these results, a nomogram that predicted the 1-, 3-, and 5-year CSS rates in patients with primary breast cancer and bone metastasis (concordance index > 0.69) was developed. After dividing patients into low-risk, high-risk, or super-high-risk groups based on nomogram scoring criteria, survival analysis revealed that patients in the low- and high-risk groups had significant survival benefits from primary focal surgery. CONCLUSION: Independent risk factors for primary breast cancer in patients with bone metastasis were analyzed and a nomogram established to predict CSS. The prognostic tool derived in this study can assist clinicians in predicting the survival and surgical benefits of these patients through scoring, thereby providing further guidance for treatment strategies.

Dermal Filler Hypersensitivity Post-COVID-19 Illness: Case Series and Literature Review.

OBJECTIVE: To report two cases of dermal filler hypersensitivity post-COVID-19 illness and review the literature. METHODS: A literature review was performed. Data were extracted from the articles: the author, year of publication, age and sex of the patient, filler substance, injection site, symptoms and signs, onset time, diagnostic results, treatment, and prognosis. RESULTS: Six cases from six literatures were included in the review. All of them were female and were confirmed infected with COVID-19. Five of them received hyaluronic acid injection and one patient received polyacrylamide. Time after injection ranged from 8 months to 9 years. Onset of symptoms ranged from two to four weeks post-infection. The clinical manifestations included swelling, edema, induration, erythema, and tenderness. The site where the symptoms appeared was the injection site, and symptoms appeared at each injection site at the same time, including cheeks, periocular area, and lips. CONCLUSION: Dermal filler hypersensitivity may occur post-COVID-19 illness. A detailed history and clinical examination can help confirm the diagnosis. LEVEL OF EVIDENCE V: 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 .

Knockdown of ZEB1 Inhibits Hypertrophic Scarring through Suppressing the Wnt/ß-catenin Signaling Pathway in a Mouse Model.

BACKGROUND: Hypertrophic scars (HS) cause functional impairment and cosmetic deformities following surgeries or burns (30% to 94%). There is no target therapy yet because the pathogenesis of HS progression is not well-known. In tissue fibrosis, Zinc finger E-box binding homeobox 1 (ZEB1) abnormal upregulation is an important cause for extracellular matrix (ECM) overexpression, which is the main molecular change in HS. Therefore, we hypothesized that ZEB1-knockdown inhibits HS formation. METHODS: ZEB1 expression in human HS and TGF-ß1-induced fibroblasts were identified by PCR and western blotting. ZEB1 was knockdown by siRNA in HS fibroblasts (HSFs) and mouse HS model (C57/BL6, male, 8-12 weeks). After 8-hour-transfection, HSFs were subjected to PCR, western blotting and CCK-8, apoptosis, migration and contraction assays. Mice HS were analyzed by HE staining, PCR and western blotting after 56 days. RESULTS: ZEB1 was upregulated in HS tissue (2.0-fold; p < 0.001). ZEB1 knockdown inhibited HSFs activity (0.6 to 0.7-fold; p < 0.001), the expression of fibrotic markers (0.4 to 0.6-fold; p < 0.001) and ß-catenin, cyclinD1 and c-Myc expression (0.5-fold; p < 0.001). In mouse HS models, HS skin thickness was thinner (1.60 ± 0.40 mm vs. 4.04 ± 0.36 mm; p < 0.001) after ZEB1 knockdown. CONCLUSIONS: Knockdown of ZEB1 inhibits HS formation both in vitro and in vivo. However, this is an in vitro/mouse model and more validation is needed. CLINICAL RELEVANCE STATEMENT: The discovery of ZEB1 as a mediator of HS formation might be a potential therapeutic target in HS treatment.

Fat Grafting Reduces Skin Hyperpigmentation of Localized Scleroderma Patients: A Prospective Self-controlled Study.

BACKGROUND: Localized scleroderma (LS) is characterized by skin fibrosis, hyperpigmentation and soft tissue atrophy. Fat grafting has been widely used to correct LS deformity. OBJECTIVE: To investigate the effect of fat grafting on the skin pigmentation of LS lesions. METHODS: A prospective self-controlled study was conducted. Skin melanin and erythema indexes were measured by Mexameter® MX18 before and 3 months after surgery. Differences between lesions and contralateral normal sites were compared to evaluate changes induced by fat grafting. Localized Scleroderma Cutaneous Assessment Tool and PUMC Localized Scleroderma Facial Aesthetic Index were used for clinical evaluation. RESULTS: Fourteen frontal linear LS patients participated in the study. Before surgery, the melanin index of the lesions was significantly higher than the contralateral sites (p = 0.023), while the erythema indexes were not significantly different (p = 0.426). Three months post-operation, the melanin index of the lesions significantly decreased (p = 0.008). There was no significant change in the erythema index of the lesions before and after fat grafting (p = 0.322). The LoSCAT and PUMC LSFAI scores demonstrated improved disease condition and facial esthetics after surgery. CONCLUSION: Fat grafting could alleviate skin hyperpigmentation and skin damage of LS lesions while having little effect on skin erythema and disease activity. LEVEL OF EVIDENCE III: 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 Reactivation of Scleroderma After Autologous Fat Grafting.

BACKGROUND: Patients with localized scleroderma (LS) often have to seek plastic surgery to improve facial esthetic impairment. AIMS: The authors reported a case of the reactivation of LS after autologous fat grafting (AFG). PATIENT: A man presented with facial atrophy and skin fibrosis on the cheek with a history of LS. The disease had remained stable for 9 years and he was suggested to stop oral medication. With irreversible esthetic impairment on the face, he sought plastic surgery for improvement. He underwent twice AFG into the right cheek with about 60 mL fat graft each. The donor sites were the abdomen and both thighs. RESULTS: Six months after the last AFG, the patient found new lesions occur on the lateral forehead. The patient was later diagnosed with reactivation of LS. CONCLUSION: The understanding of the surgical risk and perioperative management for patients with LS needs more research.

What factors will influence patients when choosing plastic surgeons? A behaviour analysis of Chinese patients.

PURPOSE: To analyze the factors that patients consider when choosing plastic surgeons and investigate patients' attitudes toward physicians' aesthetic ability and their adherence toward same-gender physicians. METHODS: A cross-sectional study was conducted. All patients who presented for evaluation and management between January and April 2022 were eligible for study enrolment. Data collected include demographical information and specific questions related to choosing plastic surgeons, including physician's education, surgical ability, research, title, appearance, dress, age, aesthetics, the patient's preference for physicians' gender, and the way of learning about physicians. RESULTS: 1006 valid respondents participated, and the average age was 46.44 ±â€¯15.51 years old (participation rate 99.60%). 72.5% were female. Plastic surgery history (OR 3.242, 95%CI: 1.664-6.317, p = 0.001), education (OR 1.895, 95%CI: 1.064-3.375, p = 0.030), income (OR 1.340, 95%CI: 1.026-1.750, p = 0.032), sexual orientation (OR 1.662, 95%CI: 1.066-2.589, p = 0.025), and concern for the physicians' appearance (OR 1.564, 95%CI: 1.160-2.107, p = 0.003) were significantly associated with patients' tendency to value physicians' aesthetic ability. Marital status (OR 0.766, 95% CI: 0.616-0.951, p = 0.016), income (OR 0.896,95% CI: 0.811-0.990, p = 0.031), the attention to physicians' age (OR 1.191,95% CI: 1.031-1.375, p = 0.017), and the attention to physicians' aesthetic ability (OR 0.775,95% CI: 0.666-0.901, p = 0.001) were significantly associated with the respondents' same-gender adherence degree. CONCLUSION: These findings suggest that patients with plastic surgery history, higher income, higher education background, and more diverse sexual orientation paid more attention to physicians' aesthetic ability. Marriage and income would affect the same-gender adherence degree, which would further influence patients' attention to the doctor's age and aesthetic ability.

Platelet-Rich Plasma Combined Fat Transplantation for the Treatment of Bleomycin-Induced Murine Scleroderma.

BACKGROUND: Low-fat retention induced by inflammation limits the clinical application of fat grafting for treating localized scleroderma (LS) patients. Novel methods to improve the therapeutic outcome are needed. OBJECTIVE: The aim of the study is to investigate the effect of platelet-rich plasma (PRP)-assisted fat transplantation on skin fibrosis and adipose survival in the LS model. METHODS: The LS model was established by the injection of bleomycin into BALB/C nude mice, which were randomly divided into the following 4 groups: healthy control, LS disease group model, fat transplantation group, and PRP+ fat transplantation group. The mice received a subcutaneous injection at back with phosphate-buffered saline, fat, or 20% PRP+ fat. Factors of immunoregulation, angiogenesis and adipogenesis were measured. RESULTS: Platelet-rich plasma-combined fat transplantation significantly attenuated dermis fibrosis by reducing the production of type III collagen. The fat retention in the PRP+ fat transplantation group was 43 ± 4 mg, significantly higher than 22 ± 15 mg in the fat transplantation group (P = 0.0416). The level of tumor necrosis factor α and interleukin 2 showed no significant difference between the groups. The expression of angiogenesis factors, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, and CD31, significantly increased in the PRP+ fat transplantation group. The expression of adipogenesis factors, insulin-like growth factor 1 receptor, extracellular signal-regulated kinase, anti-CCAAT-enhancer-binding proteins, and peroxisome proliferator-activated receptor γ, also significantly increased in the PRP+ fat transplantation group. CONCLUSIONS: The results demonstrated that PRP-combined fat transplantation attenuated dermis fibrosis and raised fat survival in the LS model by promoting angiogenesis and adipogenesis through insulin-like growth factor 1 receptor/extracellular signal-regulated kinase signaling pathway.

Does injection pattern matter in upper face BoNT-A application? A prospective split-face andomized trial comparing linear and spot technique.

BACKGROUND: Although the efficacy of botulinum toxin type A (BoNT-A) has been shown to vary depending on injection layer, reconstitution volumes, and BoNT-A formulations, the impact of injection patterns has been rarely mentioned. This article compared the therapeutic effects in patients treated with BoNT-A with retrograde linear and traditional spot injection techniques. METHODS: Twenty-eight participants were enrolled in a split-face, patient-blinded randomized clinical trial. Each patient received BoNT-A injected with linear injection technique on one side and with spot injection technique on the other side. Outcomes included the wrinkle improvement rates (WIR) of the two injection techniques determined by the wrinkle scores derived from Antera 3D camera, the muscle activity assessed via ultrasound, and patient-reported pain rating on a numeric pain rating scale (NRS). RESULTS: All participants completed the study. For forehead wrinkles, WIR on the linear side was significantly larger than that on the spot side at 1 week and 1 month (p<0.02). For glabellar wrinkles, WIR on the linear injection side was significantly larger than that on the spot side at 1 week (p=0.04). However, for periorbital wrinkles, WIR on the spot side was significantly larger than that on the linear side at 1 week (p<0.03). No significant difference was observed between the injection patterns in terms of muscle contraction and NRS scores. CONCLUSIONS: Compared with the traditional spot injection, the retrograde linear injection shows to be superior in reducing forehead lines and glabellar lines, but less effective in reducing periorbital lines when identical dosages were injected. TRIAL REGISTRATION: chictr.org.cn: ChiCTR2100046880.

The Dorsal Nasal Complex in Asians: Anatomical Variations and Injection Guide for Botulinum Toxin Type A.

BACKGROUND: Multiple muscles contribute to the formation of dorsal nasal lines (DNLs) and affect nasal aesthetics. Few attempts have been made to explore the range of distribution of DNLs in relation to injection planning. OBJECTIVES: The aim of this study was to classify the distribution types of DNLs and propose a refined injection technique validated by clinical study and cadaver dissection. METHODS: Patients were classified into 4 types according to their DNL distribution type. Botulinum toxin type A injections were administered at 6 regular points and 2 optional points. The effect on wrinkle reduction was assessed. Patient satisfaction was recorded. Cadaver dissection was conducted to explore the anatomical evidence of DNL variation. RESULTS: The study included 349 treatments in 320 patients (269 females and 51 males), whose DNLs were classified into complex type, horizontal type, oblique type, and vertical type. The severity of DNLs was significantly reduced after treatment. Most patients were satisfied. From the cadaver study, connecting muscular fibers were clearly observed among the muscles involved in the formation of DNLs, and these muscles were collectively named the dorsal nasal complex (DNC) by the authors. Four anatomical variations of the DNC were discovered, corroborating the DNL classification system. CONCLUSIONS: A novel anatomical concept, the DNC, and a classification system for DNLs were proposed. Each of the 4 distribution types of DNLs corresponds to a specific anatomical variation of the DNC. A refined injection technique for DNLs was developed, and its efficacy and safety were demonstrated.

Laparoscopic procedures-induced keloids: A retrospective case series study.

The abdominal skin is not a common area for keloid formation. The knowledge of laparoscopically induced keloids (LIK) remains little. This article aimed to review the case series of LIK and analyse the characteristics. A retrospective and descriptive study was conducted. Patients' clinical records in the database were collected, including the demographics, medical history, laparoscopic surgery information, keloid information, and the severity of LIKs recorded using the Patient and Observer Scar Assessment Scale. Twenty-four LIK patients were enrolled. 18 patients were female and 10 had chronic diseases. 11 patients had non-LIKs. 91.6% patients received laparoscopic cholecystectomy. LIKs were mainly located under the xiphoid process (N = 20), followed by the umbilicus (N = 16). 41.7% patients developed keloids at all trocha sites. The severity of the LIK was significantly negatively associated with the presence of the non-LIK. Laparoscopic procedures could lead to the formation of keloids. Two types of LIKs were noticed: extended incisions induced long "spreading" type and trocha induced round bulging type. The presence of non-LIKs could significantly reduce the severity of LIKs.

The Superficial Fascia System: Anatomical Guideline for Zoning in Liposuction-Assisted Back Contouring.

BACKGROUND: Dorsal contour deformity presents with different manifestations in each part of the back, such as back rolls, iliac crest deposit, and buffalo hump. However, scant current literature exists on the anatomical basis of dorsal contour deformity. The aim of this study was to better understand the anatomical characteristics of the back, and to propose evidence-based zoning principles for liposuction-assisted back contouring. METHODS: A total of 12 fresh cadavers were dissected for observation of each hierarchy in the vertical order (skin to deep fascia) and transverse comparison of the superficial fascial system (SFS) in the scapular-infrascapular-lumbar triangle region. Full-dorsum vectorial sections were used for the study of suprascapular fat deposits. RESULTS: The SFS acts as a bridge connecting all levels of the dorsal subcutaneous tissue. Macroscopically, it is denser in the scapular and lumbar triangle regions and looser in the infrascapular region; microscopically, the ultrastructure of the retinaculum cutis consists of loose interlobular fascia and stiff functional fascia. CONCLUSIONS: The regional variation pattern of the SFS in the back was consistent with observed back contour deformities in Asian female patients. A better understanding of the topographic anatomy of the back applied to evidenced zoning is the basis for improving surgical precision and avoiding dorsal contour deformity.

Adipose-Derived Stem Cells Attenuate Skin Fibrosis and Improve Fat Retention of a Localized Scleroderma Mouse Model.

BACKGROUND: Although autologous fat grafting is a feasible surgical technique to improve facial deformity in patients with localized scleroderma, its success is limited by the low graft retention induced by the local inflammatory environment. This study investigated the potential effect of adipose-derived stem cells (ASCs) on skin fibrosis and fat retention in a localized scleroderma mouse model. METHODS: BALB/C nude mice that were induced by bleomycin to establish a localized scleroderma model were divided randomly into five groups: blank control; fat grafting; and low, moderate, and high doses of ASC-assisted fat grafting. The backs of the mice were subcutaneously injected with phosphate-buffered saline or fat, or fat with low, moderate, and high doses of ASCs (1 × 10 5 /mL, 5 × 10 5 /mL, and 25 × 10 5 /mL, respectively). The skin fibrosis and fat retention were analyzed after 1 month or 3 months, respectively. RESULTS: Compared to the disease model group, the fat-grafting group, and the low- and moderate-dose ASC-enriched groups, the high-dose ASCs significantly attenuated skin fibrosis, inhibited the production of type III collagen and transforming growth factor-ß1, increased fat graft retention, enhanced the expression of angiogenesis-related cytokines and angiogenesis, and increased the expression of adipogenesis-related cytokines. CONCLUSIONS: The results demonstrated that high-dose ASCs attenuated skin fibrosis and improved fat retention in a localized scleroderma model by reducing inflammation and by promoting angiogenesis and adipogenesis. The authors further demonstrated that ASCs enhanced adipogenesis through the AKT/ERK signaling pathway. CLINICAL RELEVANCE STATEMENT: Fat grafting has been used to treat localized scleroderma patients but with low fat retention. In this study, ASC attenuated skin fibrosis and improved fat retention in the localized scleroderma model, providing evidence for cell therapy in future application of localized scleroderma treatment.

Nipple ulcers of the nipple retractor technique to correct inverted nipples: A retrospective multivariate analysis.

BACKGROUND: A simple procedure using a nipple retractor to correct inverted nipples has been applied in clinical practice with stable and satisfactory aesthetic outcomes. Nipple ulceration and necrosis are rare and severe, with the causes unclear. OBJECTIVE: This study aimed to investigate the risk factors for the development of nipple ulcers in the nipple retractor technique. METHODS: A retrospective study was conducted on inverted nipple patients between January 2012 and September 2021. Clinical information, including baseline patient demographics, reproductive history, smoking, previous treatment, nipple inversion grades, nipple size, areola size, blood flow perfusion, and ulcer development, was collected. RESULTS: Twenty-five female patients with 44 inverted nipples were enrolled. Nipple ulcers were present in seven patients, four of whom were bilateral. Logistic regression analysis showed nipple inversion grades (Z = 2.105, OR 7.005, 95% CI: 1.144-42.898, p = 0.035) and relative perfusion of nipples (Z = -2.337, OR 0.969, 95% CI: 0.944-0.995, p = 0.019) were significantly associated with ulceration. The structural equation model demonstrated the interaction of related factors: nipple inversion grades increased by 0.411 points for ulcers (p = 0.004), while relative perfusion of nipples decreased by 0.647 points for ulcers (p < 0.001). CONCLUSION: Preoperative nipple inversion severity and post-operative nipple blood supply may be the risk factors for nipple ulcer development in the nipple retractor technique.