Skin Soft Tissue Research Articles

M2 macrophage-derived exosomes induce angiogenesis and increase skin flap survival through HIF1AN/HIF-1α/VEGFA control

BackgroundSkin flap transplantation is a routine strategy in plastic and reconstructive surgery for skin-soft tissue defects. Recent research has shown that M2 macrophages have the potential for pro-angiogenesis during tissue healing. MethodsIn our research, we extracted the exosomes from M2 macrophages(M2-exo) and applied the exosomes in the model of skin flap transplantation. The flap survival area was measured, and the choke vessels were assessed by morphological observation. Hematoxylin and eosin (H&E) staining and Immunohistochemistry were applied to assess the neovascularization. The effect of M2-exo on the function of Human umbilical vein endothelial cells (HUVECs) was also investigated. We also administrated 2-methoxyestradiol (2-ME2, an inhibitor of HIF-1α) to explore the underlying mechanism. We tested the effects of M2-Exo on the proliferation of HUVECs through CCK8 assay and EdU staining assay. ResultsThe survival area and number of micro-vessels in the skin flaps were increased in the M2-exo group. Besides, the dilation rate of choke vessels was also enhanced in the M2-exo group. Additionally, compared with the control group, M2-exo could accelerate the proliferation, migration and tube formation of HUVECs in vitro. Furthermore, the expression of the pro-angiogenesis factors, HIF-1α and VEGFA, were overexpressed with the treatment of the M2-exo. The expression of HIF1AN protein level was decreased in the M2-exo group. Finally, treatment with HIF-1α inhibitor reverses the pro-survival effect of M2-exo on skin flaps by interfering with the HIF1AN/HIF-1α/VEGFA signaling pathway. ConclusionThis study showed that M2-exosomes promote skin flap survival by enhancing angiogenesis, with HIF1AN/HIF-1α/VEGFA playing a crucial role in this process.

Anatomic study and clinical application of iliac crest chimeric tissue flap

To conduct anatomical study on the iliac crest chimeric tissue flap and summarize its effectiveness of clinical application in repairing limb wounds. Latex perfusion and anatomical study were performed on 6 fresh adult cadaver specimens with 12 sides, to observe the initial location, distribution, quantity, and direction of the common circumflexa iliac artery, the deep circumflexa iliac artery, and the superficial circumflexa iliac artery, and to measure their initial external diameter. Between December 2020 and September 2022, the iliac crest chimeric tissue flap repair was performed on 5 patients with soft tissue of limbs and bone defects. There were 3 males and 2 females, with an average age of 46 years (range, 23-60 years). Among them, there were 3 cases of radii and skin soft tissue defects and 2 cases of tibia and skin soft tissue defects. The length of bone defects was 4-8 cm and the area of skin soft tissue defects ranged from 9 cm×5 cm to 15 cm×6 cm. The length of the iliac flap was 4-8 cm and the area of skin flap ranged from 12.0 cm×5.5 cm to 16.0 cm×8.0 cm. The donor sites were directly sutured. Anatomical studies showed that there were 10 common circumflex iliac arteries in 5 specimens, which originated from the lateral or posterolateral side of the transition between the external iliac artery and the femoral artery, with a length of 1.2-1.6 cm and an initial external diameter of 0.8-1.4 mm. In 1 specimen without common circumflexa iliac artery, the superficial and deep circumflex iliac arteries originated from the external iliac artery and the femoral artery, respectively, while the rest originated from the common circumflex iliac artery. The length of superficial circumflex iliac artery was 4.6-6.7 cm, and the initial external diameter was 0.4-0.8 mm. There were 3-6 perforator vessels along the way. The length of deep circumflex iliac artery was 7.8-9.2 cm, and the initial external diameter was 0.5-0.7 mm. There were 3-5 muscular branches, 4-6 periosteal branches, and 2-3 musculocutaneous branches along the way. Based on the anatomical observation results, all iliac crest chimeric tissue flaps were successfully resected and survived after operation. The wounds at recipient and donor sites healed by first intention. All patients were followed up 8-24 months, with an average of 12 months. The tissue flap has good appearance and soft texture. X-ray film reexamination showed that all the osteotomy healed, and no obvious bone resorption was observed during follow-up. The common circumflex iliac artery, deep circumflex iliac artery, and superficial circumflex iliac artery were anatomically constant, and it was safe and reliable to use iliac crest chimeric tissue flap in repairing the soft tissue and bone defects of limbs.

Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study

The aim of the study described here was to evaluate the safety of Sonazoid-assisted high-intensity focused ultrasound (HIFU) in the treatment of advanced malignant liver lesions. A single-arm study was designed to enroll participants who were diagnosed with advanced primary liver cancer or liver metastases and proposed to receive Sonazoid assistance during HIFU treatment. Serological examination was conducted within 1 wk, and side effects in each patient were monitored for 1 mo. To evaluate therapeutic efficacy, the contrast-enhanced magnetic resonance imaging was performed 1 mo after treatment, and short-term follow-up was conducted a year later. A total of 17 participants (12 male, 5 female) with an average age of 58 y (range: 46-73 y) were enrolled, including 11 patients with hepatocellularcarcinoma, 2 patients with hepaticmetastasis and 4 patients with cholangiocarcinoma. The total volume of tumor mass was 111.82 (11.01-272.30) cm3. The average total ablation time for a patient was 2021 ± 1030 s, and the energy efficiency factor was 5979.7 (3108.0, 45634.5) J/cm3. Immediately after HIFU treatment, 1 patient (5.9%) achieved complete response (CR), 4 patients (23.5%) had a moderate response, 8 patients (47.1%) had partial reperfusion and 4 patients (23.5%) had stable disease (SD). The average ablation rate for all the tumors was 51.5 ± 26.7%. The level of glutamic-pyruvic transaminase (ALT) was mildly increased in 71.6% (12/17) of patients after HIFU therapy. Mean ALT values before and after treatment were 22 (14, 35) U/L and 36 (25, 41) U/L, respectively (Z=1.947, p=0.051). Mild or obvious edema in skin and subcutaneous soft tissues were observed in 76.5% of patients, but no serious side effects were found. Twelve months after treatment, the follow-up results revealed that 1 patient (5.8%) achieved a CR, 8 patients (47.1%) had SD and 8 patients (47.1%) had progressive disease. The estimated median time to progression was 11 mo after treatment, with a 95% confidence interval of 6, 11 for all involved patients. Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions. The therapeutic efficacy of Sonazoid-assisted HIFU needs to be explored in additional controlled clinical investigations.

Clinical results of locking compression plate external fixation for open ulnar and radial shaft fractures

Introduction and importanceOpen ulnar and radial shaft fractures refers to the simultaneous rupture and injury of the skin and subcutaneous soft tissue at the fracture, and is easy to cause wound infection, local soft tissue necrosis or osteomyelitis. The purpose of this paper is to observe the efficacy of external locking compression plate in the treatment of open fractures, so as to provide reference for clinical practice. Case presentationFrom January 2019 to January 2020, 11 patients with open ulnar or radial shaft fractures underwent surgery by a single surgeon. Physical examination, radiography, and functional scores were performed before surgery and the average follow-up was 14 months (range, 12 to16 months) after surgery. Clinical outcome scores were recorded. Six patients obtained excellent Anderson Scores, four of satisfactory and one of Unsatisfactory. No surgical complications, reoperations, nonunion and implant breakage in this series and the fractures can be healed from 6 to 12 months after the operation. All implant removal was requested for all cases. Clinical discussionOpen ulnar and radial shaft fractures refers to the simultaneous rupture and injury of the skin and subcutaneous soft tissue at the fracture, which can connect the fracture site with the outside environment, and is easy to cause wound infection, local soft tissue necrosis or osteomyelitis. The open fracture mostly involves adjacent joints. If it is not treated in time, it is easy to lead to complications such as infection and nonunion. The locking plate is named as “internal fixation”, which means the internal fixation is placed in the soft tissue, and is similar to the external fixator. However, its biomechanical properties still need to be verified, the appropriate screw position and number need to be further defined, and there is a lack of clinical validation of large number of cases. ConclusionIn this study, locking compression plate externaI fixation for technology for the treatment of open ulnar and radial shaft fractures has the advantages of minimal trauma, simple operation, reliable fixation, fewer postoperative complications, and restored stability and function of forearm joints. Level of evidenceLevel IV, therapeutic case series.

Community-associated methicillin-resistant Staphylococcus aureus infection of diabetic foot ulcers in an eastern diabetic foot center in a tertiary hospital in China: a retrospective study

BackgroundDiabetic foot concerns are a major public health problem. Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in diabetic foot ulcers. Community-associated MRSA has become notorious for skin and skin soft tissue infections over the last two decades. This study investigated MRSA infection in diabetic foot patients at a tertiary hospital, focusing on the epidemiology and characteristics of community-associated MRSA.MethodsA total of 149 patients with diabetic foot infection whose culture results indicated Staphylococcus aureus as the source were selected. Epidemiological investigations, clinical characteristics, laboratory index records, antibiotic susceptibility analysis, and clinical outcome tracking were performed in all cases. Based on oxacillin resistance using the Vitek Compact 2 system, cases were divided into methicillin-sensitive Staphylococcus aureus and MRSA groups. Subgroup analysis of the MRSA group was performed in accordance with the Centers for Disease Control definition: community-associated MRSA and hospital-associated MRSA.ResultsThe MRSA group (n = 41, 27.5%) had a longer duration of ulcers and hospital stay and higher hospitalization costs than the methicillin-sensitive Staphylococcus aureus group (n = 108, 72.5%). According to the classification criteria of Infectious Diseases Society of America, the severity of infection in the community-associated MRSA group was higher than that in the hospital-associated MRSA group. The analysis of antimicrobial susceptibility of 41 MRSA isolates showed that the resistance rates to erythromycin, clindamycin, quinolone, gentamicin, tetracycline, and rifampicin were 78.0%, 68.3%, 31.7%, 17.1%, 9.8%, and 2.4%, respectively. All the MRSA strains were sensitive to linezolid, tigecycline, and vancomycin. The resistance rates to quinolones and gentamycin in the community-associated MRSA group (both 0%) were lower than those in the hospital-associated MRSA group.ConclusionEmergence of MRSA in diabetic foot ulcer was associated with a prolonged wound duration and increased consumption of medical resources. Community-associated MRSA strains predominated among MRSA isolates from diabetic foot wounds and caused more severe infections.

Design and fabrication of gelatin-based hydrogel loaded with modified amniotic extracellular matrix for enhanced wound healing

Trauma can damage the structural integrity of skin leading to its function being affected. There is an urgent clinical need for innovative therapeutic wound dressings. However, several challenges persist despite the current demands. The development and application of functional dressings offer a novel approach to address skin and subcutaneous soft tissue defects. Amniotic membrane as an ideal biological multifunctional material covering wound surface has been reported in clinic. However, current clinical applications of amniotic membrane still have limitations, such as thinness and mechanically weak. In this paper, we employed decellularized human amniotic membrane (dHAM) as a bioactive extracellular matrix (ECM) and modified it through methacrylate (MA) grafting for engineering purposes, resulting in the photosensitive dECMMA. Subsequently, we utilized a photosensitizer to achieve photopolymerization of dECMMA with GelMA hydrogel, successfully creating a novel composite hydrogel termed dECMMA/GelMA. This composite hydrogel not only inherits the favorable physicochemical properties of hydrogels but also maintains comparable levels of bioactivity to dHAM itself, supporting cell proliferation, migration, angiogenesis, and retaining significant anti-inflammatory capacity.Additionally, we evaluated the reparative effect of the designed dECMMA/GelMA composite hydrogel on rabbit wound defects. We demonstrated that the dECMMA/GelMA promoted wound healing and re-epithelization. These findings highlight the substantial benefits and therapeutic potential of the dECMMA/GelMA composite hydrogel as a practical solution for clinical applications in the treatment of soft tissue damage. Furthermore, this research provides a new strategy for designing and manufacturing bioactive dressings with exceptional clinical efficacy in the future.

An Overview of Scaffolds and Biomaterials for Skin Expansion and Soft Tissue Regeneration: Insights on Zinc and Magnesium as New Potential Key Elements.

The utilization of materials in medical implants, serving as substitutes for non-functional biological structures, supporting damaged tissues, or reinforcing active organs, holds significant importance in modern healthcare, positively impacting the quality of life for millions of individuals worldwide. However, certain implants may only be required temporarily to aid in the healing process of diseased or injured tissues and tissue expansion. Biodegradable metals, including zinc (Zn), magnesium (Mg), iron, and others, present a new paradigm in the realm of implant materials. Ongoing research focuses on developing optimized materials that meet medical standards, encompassing controllable corrosion rates, sustained mechanical stability, and favorable biocompatibility. Achieving these objectives involves refining alloy compositions and tailoring processing techniques to carefully control microstructures and mechanical properties. Among the materials under investigation, Mg- and Zn-based biodegradable materials and their alloys demonstrate the ability to provide necessary support during tissue regeneration while gradually degrading over time. Furthermore, as essential elements in the human body, Mg and Zn offer additional benefits, including promoting wound healing, facilitating cell growth, and participating in gene generation while interacting with various vital biological functions. This review provides an overview of the physiological function and significance for human health of Mg and Zn and their usage as implants in tissue regeneration using tissue scaffolds. The scaffold qualities, such as biodegradation, mechanical characteristics, and biocompatibility, are also discussed.

Potential predictive effect of mechanical properties of the plantar skin and superficial soft tissue, and vibration perception on plantar loading during gait in individuals with diabetes

BackgroundThis exploratory study aimed to investigate the extent to which mechanical properties of the plantar skin and superficial soft tissue (hardness, stiffness, and thickness) and vibration perception thresholds (VPTs) predict plantar pressure loading during gait in people with diabetes compared to healthy controls.MethodsMechanical properties, VPTs, and plantar loadings during gait at the heel and first metatarsal head (MTH) of 20 subjects with diabetes, 13 with DPN, and 33 healthy controls were acquired. Multiple regression analyses were used to predict plantar pressure peaks and pressure-time integrals at both locations based on the mechanical properties of the skin and superficial soft tissues and VPTs.ResultsIn the diabetes group at the MTH, skin hardness associated with 30-Hz (R2 = 0.343) and 200-Hz (R2 = 0.314) VPTs predicted peak pressure at the forefoot. In the controls at the heel, peak pressure was predicted by the skin thickness, hardness, and stiffness associated with 30-Hz (R2 = 0.269, 0.268, and 0.267, respectively) and 200-Hz (R2 = 0.214, 0.247, and 0.265, respectively) VPTs.ConclusionThe forefoot loading of people with diabetes can be predicted by the hardness of the skin when combined with loss of vibration perception at low (30-Hz) and high (200-Hz) frequencies. Further data from larger sample sizes are needed to confirm the current findings.

Distal positioning of the skin paddle of pectoralis major myocutaneous flap in head and neck reconstruction.

To assess outcomes of pectoralis major myocutaneous flap (PMF) wherein the skin paddle (SP) was positioned with its distal portion extending beyond the lower border of pectoralis major by ≥2 cm (PMF-d). Consecutive head and neck reconstructions with PMF-d (n = 110). SP dimensions l2 (distal extent below the lower border of pectoralis major), l1 (proximal extent above lower border of pectoralis major), and b (breadth) were recorded. Endpoints were SP necrosis, recipient dehiscence, early fistula, and persistent fistula. Median values of l2 , l1 , and b were 3.0, 6.0, and 6.0 cm, respectively. When l2 = 2.0-3.0 cm, SP necrosis occurred in only one (1%) subject (with obesity). When l2 was ≥3.5 cm, necrosis occurred in four (16%) subjects, three of whom also had l1 /l2 < 2.0 (proximal SP < 67% of entire SP). Statistically, increased l2 was the only risk factor for necrosis (p = 0.001). Overall, incidence of recipient dehiscence, early fistula, and persistent fistula were 32 (29%), 20 (20%), and 3 (3%), respectively. Persistent fistula occurred only in the setting of SP necrosis and/or re-irradiation. Careful patient selection, adequate proximal SP, and l2 = 2.0-3.0 cm is associated with a negligible risk of necrosis. The enhanced reach and laxity and additional skin surface area and soft tissue volume conferred with PMF-d facilitate recipient wound healing.

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

Localized scleroderma (LS) is characterized by skin fibrosis, hyperpigmentation and soft tissue atrophy. Fat grafting has been widely used to correct LS deformity. To investigate the effect of fat grafting on the skin pigmentation of LS lesions. A prospective self-controlled study was conducted. Skin melanin and erythema indexes were measured by Mexameter® MX18 before and 3months 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. 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. Fat grafting could alleviate skin hyperpigmentation and skin damage of LS lesions while having little effect on skin erythema and disease activity. 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 .

Endorphin Massage on Intensity of Pain in the First Stage of Active Labour

Most maternity mothers feel pain during labor; the causes of pain in Indonesia is 16% because they experience complications, and 63% because they did not get information on childbirth preparation. Pain arises due to increased activity of the sympathetic nervous system and results in blood pressure and pulse. A midwife cannot provide analgetic in reducing pain, so complementary treatments are very helpful, one of which is endorphins massage. Massage therapy can systematically affect the skin surface, soft tissues, muscles, and ligaments. It can release of endorphin hormone that can cause muscle relaxation. This study aims to determine endorphin massage's effect on pain intensity in the first stage of active labor at Public Health Center Mampang Prapatan District, South Jakarta. This study used a quasi-experimental design with a pretest-posttest type of control group. This type involved two groups of subjects, one was treated (experimental group) with 15 samples, and the other was not treated (control group) with 15 samples. The total sample is 30 respondents. The research instrument used an observation sheet to measure pain intensity using the FLACC scale (Face, Legs, Activity, Cry, Consolability). Data analysis used the Wilcoxon signed rank test and the Mann-Whitney test. Based on the results of the Mann-Whitney test, it shows that the Assign value sig. (2-tailed) of 0.000. This means that 0,000 &lt; 0,05, there is a significant difference between the pain intensity of the experimental group that was given endorphin massage and the control group that was not treated. There is a difference between the pain intensity in the first stage of active labor at Public Health Center Mampang Prapatan, South Jakarta. It is recommended that services apply non-pharmacological pain control methods of endorphin massage in labor.

Superficial mesenchymal tumours expressing epithelial markers on immunohistochemistry: Diagnostic clues and pitfalls.

The diagnosis of mesenchymal neoplasms arising in the superficial soft tissue can be challenging as some entities are rare and show overlapping features. Moreover, the spectrum of mesenchymal tumours has expanded recently to include potential new entities, some of which have been described after the 5th edition of the World Health Organisation (WHO) classification of soft tissue and bone tumours published in 2020. In the skin and superficial soft tissue, tumours of epidermal, melanocytic and appendageal origin are more commonly encountered than mesenchymal neoplasms. However, specific entities from the latter category can occasionally express epithelial markers on immunohistochemistry, some of them in a strong and diffuse manner. It is therefore crucial to be aware of diagnostic pitfalls when encountering cytokeratin positivity in superficial soft tissue neoplasms. This article provides an overview on the differential diagnosis of these mesenchymal tumours that can sporadically occur also in the skin, including myoepithelial neoplasms, epithelioid sarcoma, keratin positive giant cell tumour of soft tissue / xanthogranulomatous epithelial tumour, superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour, and perineurioma.

Solute Transport across the Lymphatic Vasculature in a Soft Skin Tissue.

Convective transport of drug solutes in biological tissues is regulated by the interstitial fluid pressure, which plays a crucial role in drug absorption into the lymphatic system through the subcutaneous (SC) injection. In this paper, an approximate continuum poroelasticity model is developed to simulate the pressure evolution in the soft porous tissue during an SC injection. This poroelastic model mimics the deformation of the tissue by introducing the time variation of the interstitial fluid pressure. The advantage of this method lies in its computational time efficiency and simplicity, and it can accurately model the relaxation of pressure. The interstitial fluid pressure obtained using the proposed model is validated against both the analytical and the numerical solution of the poroelastic tissue model. The decreasing elasticity elongates the relaxation time of pressure, and the sensitivity of pressure relaxation to elasticity decreases with the hydraulic permeability, while the increasing porosity and permeability due to deformation alleviate the high pressure. An improved Kedem-Katchalsky model is developed to study solute transport across the lymphatic vessel network, including convection and diffusion in the multi-layered poroelastic tissue with a hybrid discrete-continuum vessel network embedded inside. At last, the effect of different structures of the lymphatic vessel network, such as fractal trees and Voronoi structure, on the lymphatic uptake is investigated. In this paper, we provide a novel and time-efficient computational model for solute transport across the lymphatic vasculature connecting the microscopic properties of the lymphatic vessel membrane to the macroscopic drug absorption.

FRONTIER: FAPi radioligand open-label, phase 1 study to evaluate safety, tolerability and dosimetry of [Lu-177]-PNT6555—A dose escalation study for treatment of patients with select solid tumors.

TPS3161 Background: Fibroblast activation protein alpha (FAP) is a 170 kDa transmembrane glycoprotein expressed during development, active tissue remodeling, and cancer. Overexpression on cancer-associated fibroblasts in the tumor microenvironment, and on some cancer cells of mesenchymal origin, leads to the presence of FAP in &gt; 90% of epithelial tumors, making FAP a compelling anti-cancer target. PNT6555, a potent FAP-targeting compound with rapid clearance from normal tissues and prolonged tumor retention in preclinical models1, is a radioligand consisting of a DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) and a FAP-targeting moiety (Bz-D-Ala-boroPro) connected via an aminomethyl linker. The corresponding gallium-68 and lutetium-177 chelates constitute the imaging and therapeutic theranostic pair of PNT6555 under evaluation in this phase I study. Methods: FRONTIER (NCT05432193) is a multicenter, open-label, multi-dose phase I study of PNT6555 in participants with pancreatic ductal adenocarcinoma, esophageal cancer, colorectal cancer, melanoma skin cancer, cholangiocarcinoma, or soft tissue sarcoma solid tumors with FAP over-expression. The primary aim is to evaluate the safety and tolerability of [Lu-177]-PNT6555 in order to determine a recommended phase II dose (RP2D). Dosimetry, pharmacokinetics, and tumor and immune responses will also be assessed for [Lu-177]-PNT6555, as well as safety, tolerability, and diagnostic performance of [Ga-68]-PNT6555 PET/CT. Key eligibility criteria include being refractory to prior treatment with no alternative available therapeutic options, having adequate organ function, and being FAP-positive on [Ga-68]-PNT6555 PET/CT scan, defined as ≥50% of lesions with an SUVmax of ≥1.5x the liver SUVmean. [Ga-68]-PNT6555 will be dosed at 120 - 220 MBq (3.2 - 5.9 mCi), with PET/CT initiated 90 (±30) min later. FAP-positive participants will receive [Lu-177]-PNT6555 once every 6 weeks for up to 6 cycles. Starting at 4 GBq (108 mCi) ±10%, [Lu-177]-PNT6555 may be escalated by 4 GBq, with a maximum planned dose of 12 GBq. De-escalation by 2 GBq may also occur. Dose finding will be guided by the modified toxicity probability interval (mTPI-2) statistical design with a targeted toxicity rate of 30%. The planned total sample size is 30, with targets of 3-12 DLT evaluable patients per dose level. Cohort 1 has been completed without a DLT. Enrollment to cohort 2 began in January 2023. 1. Hallet R, et al. Pre-clinical characterization of the novel fibroblast activation protein (FAP) targeting ligand PNT6555 for the imaging and therapy of cancer. Presented at SNMMI Annual Meeting April 2022; Vancouver, BC, Canada. Clinical trial information: NCT05432193 .

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers

Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. ClinicalTrials.gov Identifier: NCT04377360.

Introduction to ECM Advances in Chinese Dermatologic Surgery.

We are pleased to present the Dermatologic Surgery Special Issue, which is focused on the extracellular matrix (ECM) in skin regeneration and dermopathy treatment. Regenerative medicine based on ECM is one of the most promising tools for skin rejuvenation and soft tissue regeneration. In addition, the occurrence of dermopathy is highly related to the disturbance of the ECM. In this issue, we provide the most recent advances in determining the role of the ECM in research and clinical application. This issue presents several articles on the cutting edge of dermatologic surgery. Dermatofibrosarcoma protuberans (DFSP) was discovered to have fibroblastic activity, and a variety of neural features were discovered, which validated DFSP’s fibroblastic origin and tendency toward neural differentiation. The efficacy and safety of picosecond laser therapy (PLT) was proven in the treatment of melasma. In addition, the efficacy and safety assessment found that the ECM is a dressing that promotes wound healing after PLT, which can shorten the downtime by alleviating erythema and edema and proceeding with scab shedding related to PLT. The treatment of keloids, a disease caused by ECM disorder, is an urgent problem in clinical practice. In this special issue, different keloid treatments are presented, including punch excision combined with drug injection, autologous split-thickness skin graft and postoperative radiotherapy, surgical excision with electron beam radiotherapy, and reduced incision tension of keloid surgery by tightening the fascia layer. The illumination of these promising strategies will be conducive to the development of future targeted therapies. Finally, we are fortunate to have several peer-reviewed literatures on the applications of ECM in skin regeneration medicine. Pingping Lin et al elucidated the dynamic composition and potential roles of the extracellular matrix in normal skin, the wound healing process, and abnormal skin scarring. Yixin Wang et al provided an overview of the clinical research, limitations, and potential application of botulinum toxin type A in the prevention and treatment of traumatic or postoperative scars. Weiyuan Zhang et al investigated the mechanism of Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and ECM remodeling during wound healing.

Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients.

Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients. A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed. Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively. Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications. Level IV.

Artificial Skin Therapies; Strategy for Product Development.

Significance: Tissue-engineered artificial skin for clinical reconstruction can be regarded as an established practice. Bi-layered skin equivalents are available as established allogenic or autologous therapy, and various acellular skin replacements can support tissue repair. Moreover, there is considerable commonality between the skin and other soft tissue reconstruction products. This article presents an attempt to create a comprehensive global landscape review of advanced replacement materials and associated strategies for skin and soft tissue reconstruction. Recent Advances: There has been rapid growth in the number of commercial and pre-commercial products over the past decade. In this survey, 263 base products for advanced skin therapy have been identified, across 8 therapeutic categories, giving over 350 products in total. The largest market is in the United States, followed by the E.U. zone. However, despite these advances, and the investment of resources in each product development, there are key issues concerning the clinical efficacy, cost-benefit of products, and clinical impact. Each therapeutic strategy has relative merits and limitations. Critical Issues: A critical consideration in developing and evaluating products is the therapeutic modality, associated regulatory processes, and the potential for clinical adoption geographically, determined by regulatory territory, intellectual property, and commercial distribution factors. The survey identifies an opportunity for developments that improve basic efficacy or cost-benefit. Future Directions: The economic pressures on health care systems, compounded by the demands of our increasingly ageing population, and the imperative to distribute effective health care, create an urgent global need for effective and affordable products.

Introduction of the L-PAP Flap: Bipedicled, Conjoined, and Stacked Thigh-Based Flaps for Autologous Breast Reconstruction.

Thigh-based flaps are increasingly popular options for autologous breast reconstruction in the setting of abdominal donor-site inadequacy, previous surgery, or patient preference, but the volume and skin associated with these flaps are often lacking relative to the abdomen. An individualized, shared decision-making approach to donor-site selection was adopted based on body shape, surgical history, lifestyle, reconstructive needs, and patient expectations. Different thigh-based flaps combined in stacked, bipedicled, or conjoined configurations were selected to maximize efficient use of available soft-tissue skin and volume while optimizing donor-site aesthetics. A total of 23 thigh-based stacked, bipedicled, or conjoined profunda artery perforator (PAP), lateral thigh perforator (LTP), or gracilis musculocutaneous flap components were used in six patients. Configurations included bilateral stacked PAP and LTP flaps, bipedicled posterolateral thigh flaps based on the LTP and PAP (L-PAP), and bipedicled thigh flaps based on the gracilis and PAP pedicles. Most anastomoses were performed to the antegrade and retrograde internal mammary vessels; intraflap anastomoses were performed in one case. There were no partial or total flap losses. There was one donor-site seroma. Design of stacked, bipedicled, and conjoined thigh-based flaps using multiple conventional flap components allows for tailored approaches to donor-site utilization based on individual body shape in selected patients. Bipedicled design with the L-PAP flap represents one strategy in appropriate cases to overcome skin and volume deficiencies while facilitating coning and projection. Therapeutic, IV.

The value of PET/CT for the diagnosis and evaluation of immunotherapy in occult primary renal cell carcinoma: a case report

Skin and soft tissue diffusion metastasis (also known as occult cancer) is rare in renal cell carcinoma (RCC). Here, we report an extremely rare case of a 67-year-old male patient with occult primary RCC who developed metastases to the gums, skin, and diffuse soft tissue. The primary renal lesion was missed by computed tomography (CT), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography (PET)/CT, and the diagnosis was confirmed by biopsy of gums and subcutaneous nodules. Subsequent enhanced CT revealed a lesion in the left kidney. The patient had progression-free survival of 16 months after treatment with axitinib and pembrolizumab. Pseudoprogression and tumor heterogeneity pose major challenges in the evaluation of immunotherapy. PET/CT is indispensable especially for cases with multiple metastases, widespread distribution of lesions, and major heterogeneity. In this case, the total lesion glycolysis was calculated by PET/CT and was used to evaluate systemic tumor load before and after immunotherapy, which was calculated as the product of the metabolic tumor volume and the mean standardized uptake value of the target lesion, which increased the accuracy of assessing diffuse lesions. Total lesion glycolysis can be used as a new method to quantitatively evaluate the efficacy of immunotherapy.