Advanced Facial Rejuvenation: Synergistic Effects of Lower Blepharoplasty and Ultrasound Guided Mid-Face Lift Using Polydioxanone (PDO) Threads.

BACKGROUND: Traditional facial aging surgeries have risks and extended recovery times, leading to a demand for minimally invasive alternatives. PDO (polydioxanone) threads, which are absorbable sutures that stimulate collagen production and tissue contraction, offer improved aesthetic outcomes. This paper evaluates the combined use of PDO thread mid-cheek lift and lower blepharoplasty for facial rejuvenation. METHODS: This retrospective study compared outcomes in patients undergoing lower blepharoplasty combined with a mid-face lift using PDO threads versus those undergoing only lower blepharoplasty. Focused on individuals with baggy lower eyelids and pronounced nasolabial folds, outcome measures included the Modified Fitzpatrick wrinkle scale, Allergan® midface volume deficit scale, Width of inter zygomatic distance, Patient and Observer Scar Assessment Scale, and patient satisfaction questionnaires, assessed at baseline, 3 months, and 1 year postoperatively. RESULTS: The combined procedure demonstrated superior aesthetic outcomes and higher patient satisfaction compared to lower blepharoplasty alone. Improvements were more significant in wrinkle reduction, midface volume, and inter-zygomatic distance in the combined procedure group. Although the combined procedure had a longer mean operation time, scar assessment scores were similar between both groups, with no complications reported. CONCLUSION: The combination of lower blepharoplasty and mid-face lift using PDO threads is a comprehensive and effective approach for facial rejuvenation. It significantly enhances wrinkle reduction, mid-face lifting, and patient satisfaction. Ultrasound-guided thread lifting, a method of assessing and performing mid-face lifting, proves to be safe and efficient. This approach holds promise as a future option in cosmetic anti-aging surgery, presenting a minimally invasive alternative with natural-looking results and reduced downtime. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Revisiting metformin therapy for the mitigation of diabetic foot ulcer in patients with diabetic kidney disease from real-world evidence.

Diabetic foot ulcer and diabetic kidney disease are diabetes-related chronic vascular complications that strongly correlate with high morbidity and mortality. Although metformin potentially confers a wound-healing advantage, no well-established clinical evidence supports the benefit of metformin for diabetic foot ulcer. Thus, this study investigated the effect of metformin on diabetic foot ulcer from a large diabetic kidney disease cohort for the first time. This retrospective cohort study enrolled 10 832 patients who visited the nephrology department more than twice at two South Korean tertiary-referral centers between 2001 and 2016. The primary outcome was diabetic foot ulcer events; secondary outcomes included hospitalization, amputation, a composite of amputation or vascular intervention, and Wagner Grade ≥ 3. Multivariate Cox analysis and propensity score matching (PSM) were used to balance baseline intergroup differences between metformin users and non-users. In total, 4748 patients were metformin users, and 6084 patients were metformin non-users. Over a follow-up period of 117.5 ± 66.9 months, the diabetic foot ulcer incidence was 5.2%. After PSM, metformin users showed a lower incidence of diabetic foot ulcer events than metformin non-users (adjusted hazard ratio 0.41; p < 0.001). In a sensitivity analysis of 563 patients with diabetic foot ulcer, metformin usage was associated with lower severity in all four secondary outcomes: hospitalization (adjusted hazard ratio 0.33; p < 0.001); amputation (adjusted hazard ratio 0.44; p = 0.001); composite of amputation or vascular intervention (adjusted hazard ratio 0.47; p < 0.001); and Wagner Grade ≥ 3 (adjusted hazard ratio 0.39; p < 0.001). In conclusion, metformin therapy in patients with diabetic kidney disease can lower diabetic foot ulcer incidence and progression.

Zwitterionic polymer on silicone implants inhibits the bacteria-driven pathogenic mechanism and progress of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) occurs in the capsule surrounding breast implants. Malignant transformation of T cells by bacteria-driven chronic inflammation may be underlying BIA-ALCL mechanism. Here, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on a silicone surface and examined its effects against BIA-ALCL pathogenesis. MPC grafting strongly inhibited the adhesion of bacteria and bacteria-causing inflammation. Additionally, cancer T cell proliferation and capsule-derived fibroblast-cancer cell communication were effectively inhibited by MPC grafting. We further demonstrated the effect of MPC against the immune responses causing BIA-ALCL around human silicone implants in micro-pigs. Finally, we generated a xenograft anaplastic T cell lymphoma mouse model around the silicone implants and demonstrated that MPC grafting could effectively inhibit the lymphoma progression. This study is the first to show that bacteria-driven induction and progression of BIA-ALCL can be effectively inhibited by surface modification of implants. STATEMENT OF SIGNIFICANCE: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a major concern in the field of plastic and reconstructive surgery. In this study, we demonstrate strong inhibitory effect of zwitterionic polymer grafting on BIA-ALCL pathogenesis and progression, induced by bacterial infection and inflammation, both in vitro and in vivo. This study provides a molecular basis for the development of novel breast implants that can prevent various potential complications such as excessive capsular contracture, breast implant illness, and BIA-ALCL incidence, as well as for expanding the biomedical applications of zwitterionic polymers.

Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.

Flap monitoring with incisional negative pressure wound therapy (NPWT) in diabetic foot patients.

Various types of flaps are considered as reconstructive options for patients with diabetic foot ulcer. However, flap reconstruction for diabetic foot ulcer treatment is particularly challenging because of the relatively limited collateral perfusion in the distal lower extremity. This study evaluated the efficacy and safety of a novel postoperative monitoring procedure implemented in conjunction with negative pressure wound therapy immediately after flap operations for treating diabetic foot. A retrospective analysis was performed on diabetic foot patients who underwent free flaps and perforator flaps from March 2019 through August 2021. The surgical outcomes of interest were the rates of survival and complications. On the third postoperative day, patients underwent computed tomography angiography to check for pedicle compression or fluid collection in the sub-flap plane. Monitoring time, as well as comparisons between NPWT and conventional methods, were analyzed. Statistical analysis was performed between the two groups. This study included 26 patients. Among patients, the negative pressure wound Therapy treated group included 14 flaps and the conventional monitoring group included 12 flaps. There was no significant intergroup difference in flap survival rate (p = 0.83). In addition, there was no significant intergroup difference in the diameters of perforators or anastomosed vessels before and after negative pressure wound therapy (p = 0.97). Compared with conventional monitoring, flap monitoring with incisional negative pressure wound therapy was associated with a significantly lower mean monitoring time per flap up to postoperative day 5. Although conventional monitoring is widely recommended, especially for diabetic foot ulcer management, the novel incisional negative pressure wound therapy investigated in this study enabled effortless serial flap monitoring without increasing complication risks. The novel flap monitoring technique is efficient and safe for diabetic foot patients and is a promising candidate for future recognition as the gold standard for flap monitoring.

Cystic Salivary Duct Carcinoma Penetrated by Facial Nerve.

Salivary duct carcinoma is a rare malignant salivary gland tumor that mainly has solid features. When it occurs in the parotid gland, it can invade the facial nerve and cause facial nerve paralysis. However, in our case, the salivary duct carcinoma exhibited cystic features on computed tomographic imaging, and the facial nerve passed through the cyst. Total parotidectomy with level-I to -III dissections was performed and nerve passing through the tumor was sacrificed. The patient received postoperative radiotherapy and was clinically and radiologically followed-up for every 3 months. Recurrence or distant metastasis was not reported. To the best of our knowledge, this is the first case involving a salivary duct carcinoma with cystic features and facial nerve invasion. Here, we report a first case of cystic salivary duct carcinoma of the parotid gland which uncommonly undergo cystic change and penetrated by facial nerve and successfully resected without causing facial nerve injury.

Comprehensive Evaluation of the Current Knowledge on Breast Implant Associated-Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently spotlighted T-cell origin non-Hodgkin's lymphoma with an increasing incidence of over 800 cases and 33 deaths reported worldwide. Development of BIA-ALCL is likely a complex process involving many factors, such as the textured implant surface, bacterial biofilm growth, immune response, and patient genetics. As the incidence of BIA-ALCL is expected to increase, it is important for all surgeons and physicians to be aware of this disease entity and acquire thorough knowledge of current evidence-based guidelines and recommendations. Early detection, accurate diagnosis, and appropriate treatment are the foundations of current care.

Novel Chitosan Dermal Filler with Enhanced Moldability and Elasticity.

Currently, dermal fillers are largely based on commercialized cross-linked hyaluronic acid (HA) injections, which require a large injection force. Additionally, HA can be easily decomposed by enzymes, and HA-treated tissues present a risk of developing granuloma. In this study, a chitosan-based dermal filler is presented that operates on a liquid-to-gel transition and allows the injection force to be kept ≈4.7 times lower than that required for HA injections. Evaluation of the physical properties of the chitosan filler indicates high viscoelasticity and recovery rate after gelation at 37 °C. Furthermore, in an in vivo evaluation, the liquid injection-type chitosan filler transitions to a gel state within 5 min after injection into the body, and exhibits a compressive strength that is ≈2.4 times higher than that of cross-linked HA. The filler also exhibits higher moldability and maintains a constant volume in the skin for a longer time than the commercial HA filler. Therefore, it is expected that the chitosan filler will be clinically applicable as a novel material for dermal tissue restoration and supplementation.

An Agonistic Monoclonal Antibody Targeting cMet Attenuates Inflammation and Up-Regulates Collagen Synthesis and Angiogenesis in Type 2 Diabetic Mice Wounds.

BACKGROUND: Diabetic wounds account for 25 to 50 percent of total diabetic health care costs annually, and present overall healing rates of less than 50 percent. Because delayed diabetic wound healing is associated with impaired fibroblast function, the authors hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody will promote diabetic wound healing by means of stable activation of hepatocyte growth factor/cMet signaling. METHODS: Two 6-mm dorsal wounds were created in each mouse (6-week-old, male BKS.Cg-Dock7 m +/+Lepr db /J; n = 5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72 hours, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histologic and immunohistochemical analyses were performed at day 10 (cMet, α-smooth muscle actin, CD68, and transforming growth factor-ß). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with or without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42 mitogen-activated protein kinase, p-mTOR, p-cMet, and ROCK-1 expression. RESULTS: The cMet agonistic monoclonal antibody-treated group showed 1.60-fold lower wound area ( p = 0.027), 1.54-fold higher collagen synthesis ( p = 0.001), and 1.79-fold lower inflammatory cell infiltration ( p = 0.032) than the saline-treated control. The agonist increased cMet (1.86-fold; p = 0.029), α-smooth muscle actin (1.20-fold; p = 0.018), and vascular endothelial growth factor (1.68-fold, p = 0.029) expression but suppressed CD68 (1.25-fold; p = 0.043), transforming growth factor-ß (1.25-fold; p = 0.022), and matrix metalloproteinase-2 (2.59-fold; p = 0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold ( p = 0.029) and activated the hepatocyte growth factor/cMet pathway. CONCLUSIONS: Tyrosine kinase Met agonistic monoclonal antibody treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials. CLINICAL RELEVANCE STATEMENT: Although further clinical studies are necessary to evaluate its therapeutic efficacy, our study suggested that cMet agonistic monoclonal antibody can be the alternative modality in order to improve wound healing cascade in diabetic foot patients.

High-Efficient Production of Adipose-Derived Stem Cell (ADSC) Secretome Through Maturation Process and Its Non-scarring Wound Healing Applications.

Recently, the stem cell-derived secretome, which is the set of proteins expressed by stem cells and secreted into the extracellular space, has been demonstrated as a critical contributor for tissue repair. In this study, we have produced two sets of high concentration secretomes from adipose-derived mesenchymal stem cells (ADSCs) that contain bovine serum or free of exogenous molecules. Through proteomic analysis, we elucidated that proteins related to extracellular matrix organization and growth factor-related proteins are highly secreted by ADSCs. Additionally, the application of ADSC secretome to full skin defect showed accelerated wound closure, enhanced angiogenic response, and complete regeneration of epithelial gaps. Furthermore, the ADSC secretome was capable of reducing scar formation. Finally, we show high-dose injection of ADSC secretome via intraperitoneal or transdermal delivery demonstrated no detectable pathological conditions in various tissues/organs, which supports the notion that ADSC secretome can be safely utilized for tissue repair and regeneration.

Association between socioeconomic position and diabetic foot ulcer outcomes: a population-based cohort study in South Korea.

BACKGROUND: Low socioeconomic position (SEP) is associated with a high incidence of diabetic foot ulcers (DFUs). However, reports on the association between SEP and DFU outcomes are limited. Therefore, in this study, we investigated this association and determined the prognostic factors of DFU outcomes. METHODS: The total cohort comprised 976,252 individuals. Using probability sampling, we randomly selected a sample of patients by reviewing the data from the Health Insurance Review and Assessment Service database of South Korea during 2011-2015. Residence, household income, and insurance type represented SEP. The primary outcome was amputation, and the secondary outcome was mortality. A multivariate model was applied to identify the predictive factors. Amputation-free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: Among 976,252 individuals in the cohort, 1362 had DFUs (mean age 62.9 ± 12.2 years; 42.9% were women). Overall amputation and mortality rates were 4.7 and 12.3%, respectively. Male sex (hazard ratio [HR], 2.41; p < 0.01), low SEP (HR 5.13, 5.13; p = 0.018), ophthalmopathy (HR, 1.89; p = 0.028), circulatory complications (HR, 2.14; p = 0.020), and institutional type (HR, 1.78; p = 0.044) were prognostic factors for amputation. Old age (HR, 1.06; p < 0.01), low SEP (HR, 2.65; p < 0.01), ophthalmopathy (HR, 1.74; p < 0.01), circulatory complications (HR, 1.71; p < 0.01), and institution type (HR 1.84; p < 0.01) were predictors of mortality. CONCLUSIONS: DFU patients with a low SEP are strongly associated with increased amputation and mortality rates. Along with age and comorbidities, SEP could provide the basis for risk assessment of adverse outcomes in DFU. Providing targeted care for this population considering SEP may improve the prognosis.

A selective small-molecule inhibitor of c-Met suppresses keloid fibroblast growth in vitro and in a mouse model.

Keloids, tumor-like lesions that result from excessive scar formation, have no definitive treatment modality. Activation of c-mesenchymal-epithelial transition factor (c-Met) promotes cell proliferation and survival. Selective c-Met inhibitors, such as PHA-665752, may attenuate the activity of keloid fibroblasts and reduce keloid formation. Here, we aimed to evaluate the effect of PHA-665752, a second-generation selective small-molecule inhibitor of c-Met, on human keloid fibroblasts in vitro and in a mouse model. We performed in vitro cytotoxicity assays, scratch tests, western blotting, and immunofluorescence on human keloid fibroblasts. We also injected human fibroblasts into severe combined immunodeficient mice and measured the degree of nodule formation and skin histologic characteristics. We found that keloid fibroblast migration was inhibited by PHA-665752. Inhibitor treatment was also associated with lower expression of members of the hepatocyte growth factor/c-Met pathway, and lower fibroblast activity and collagen synthesis. In the in vivo experiments, PHA-665752-treated mice had lower nodule volumes and weights, accompanied by less inflammatory cell infiltration and collagen deposition, than those in control mice. These findings showed that although an in vivo model may not accurately represent the pathophysiology of human keloid development, PHA-665752 suppressed keloid fibroblast activity by inhibiting the c-Met-related tyrosine kinase pathway.

AI-based localization and classification of skin disease with erythema.

Although computer-aided diagnosis (CAD) is used to improve the quality of diagnosis in various medical fields such as mammography and colonography, it is not used in dermatology, where noninvasive screening tests are performed only with the naked eye, and avoidable inaccuracies may exist. This study shows that CAD may also be a viable option in dermatology by presenting a novel method to sequentially combine accurate segmentation and classification models. Given an image of the skin, we decompose the image to normalize and extract high-level features. Using a neural network-based segmentation model to create a segmented map of the image, we then cluster sections of abnormal skin and pass this information to a classification model. We classify each cluster into different common skin diseases using another neural network model. Our segmentation model achieves better performance compared to previous studies, and also achieves a near-perfect sensitivity score in unfavorable conditions. Our classification model is more accurate than a baseline model trained without segmentation, while also being able to classify multiple diseases within a single image. This improved performance may be sufficient to use CAD in the field of dermatology.

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing.

Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.

Covalently Grafted 2-Methacryloyloxyethyl Phosphorylcholine Networks Inhibit Fibrous Capsule Formation around Silicone Breast Implants in a Porcine Model.

The surface of human silicone breast implants is covalently grafted at a high density with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. Addition of cross-linkers is essential for enhancing the density and mechanical durability of the MPC graft. The MPC graft strongly inhibits not only adsorption but also the conformational deformation of fibrinogen, resulting in the exposure of a buried amino acid sequence, γ377-395, which is recognized by inflammatory cells. Furthermore, the numbers of adhered macrophages and the amounts of released cytokines (MIP-1α, MIP-1ß, IL-8, TNFα, IL-1α, IL-1ß, and IL-10) are dramatically decreased when the MPC network is introduced at a high density on the silicone surface (cross-linked PMPC-silicone). We insert the MPC-grafted human silicone breast implants into Yorkshire pigs to analyze the in vivo effect of the MPC graft on the capsular formation around the implants. After 6 month implantation, marked reductions of inflammatory cell recruitment, inflammatory-related proteins (TGF-ß and myeloperoxidase), a myoblast marker (α-smooth muscle actin), vascularity-related factors (blood vessels and VEGF), and, most importantly, capsular thickness are observed on the cross-linked PMPC-silicone. We propose a mechanism of the MPC grafting effect on fibrous capsular formation around silicone implants on the basis of the in vitro and in vivo results.

Efficient reduction of fibrous capsule formation around silicone breast implants densely grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers by heat-induced polymerization.

Implants based on silicone elastomers, polydimethylsiloxane (PDMS), have been widely used for breast augmentation and reconstruction, but excessive foreign body reactions around implants often cause serious side effects such as capsular contracture. In our previous study, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on the surface of PDMS blocks by UV-induced polymerization and showed effective reduction of capsular formation around the MPC-grafted PDMS in rats. In the present study, we examined the efficacy of heat-induced polymerization of MPC grafting on silicone breast implants intended for humans, and analyzed the in vivo inhibitory effect against capsular formation and inflammation in pigs, which are closely related to humans in terms of epidermal structures and fibrotic processes. The heat-induced polymerization provided a thicker MPC-grafted surface and was more effective than UV-induced polymerization for the grafting of complex shaped non-transparent implants. After 24-week implantation in the submuscular pockets of Yorkshire pigs, the heat-induced MPC-grafted breast implants showed 45% smaller capsular thickness and 20-30% lower levels of inflammatory markers such as myeloperoxidase (MPO), transforming growth factor-ß (TGF-ß), and α-smooth muscle actin (α-SMA) in surrounding tissues compared to non-grafted implants. This study provides important information for future clinical trials of MPC-grafted silicone implants.

De novo formation of citrate-based fluorophores on N-termini of peptides and proteins in cells and tissues.

We developed a new method for the de novo formation of fluorophores based on citrate (DNFC) in biological samples. Use of an amide coupling reagent and microwave irradiation greatly facilitates the fluorophore formation on peptides and proteins with N-terminal cysteine or serine. Since N-terminal cysteine and serine can form thiazolopyridone- or oxazolopyridone-based fluorophores emitting blue and green fluorescence, respectively, by the DNFC staining, each organelle, cell and tissue exhibited a characteristic fluorescence distribution. The DNFC staining is able to provide a new potential protocol for future cell imaging, histology and diagnosis.

Influence of Microbiota on Diabetic Foot Wound in Comparison with Adjacent Normal Skin Based on the Clinical Features.

Diabetic foot ulcer (DFU) is a complication experienced by diabetic patients and does not heal well in an altered wound environment. Although diverse microbes in DFU were detected, little is known about their influences on diabetic foot wound (DFW) and the association with the skin microbiota in normal tissue from the same patients according to clinical features. We aimed to analyze the microbiota in normal skin and DFW tissue from the same subject and predict their roles based on clinical features. We analyzed the microbiota in normal skin and DFW tissue from the same subject and compared the associated members of microbiota with clinical parameters. The diversity of skin microbiota was higher than that of DFW tissues, along with compositional differences. In addition, different microbes were associated with clinical features. The proportions of Bacteroidetes, Prevotella, Peptoniphilus, Porphyromonas, and Dialister were higher in the severe groups than of the mild groups, whereas that of Firmicutes was lower in the severe groups. According to wound severity, the microbiota could be related to inflammation, damaging host cell membrane, and pathogenicity through lipopolysaccharide biosynthesis, cellular antigens, and protein digestion metabolism. The predicted DFW microbiota functions according to systemic diabetic status defined by ESRD and HbA1c, differed from those presented by wound severity. Results indicate that the microbiota in normal skin is related to the colonizing microbes in DFW tissue according to clinical features and the different microbes can play important roles in DFW prognosis. This information can be applied to prevent and manage DFW by modulating the microbiota.