Outcomes of Fat Grafting in the Active Versus Quiescent Phase of Localized Scleroderma.

Introduction: Progressive hemifacial atrophy (PHA) and linear scleroderma (LS) are both rare conditions and defined by atrophy and/or sclerosis of the skin and subcutaneous tissue. The ideal timing of reconstructive intervention in these patients is controversial. We compared the outcome and satisfaction of autologous lipofilling performed during active and stable phases of the diseases in adults. Methods: A retrospective chart review was conducted with all patients diagnosed with PHA or LS between 2007 and 2019 in our department. We analysed demographic data, clinical features, and surgical procedures. The changes in symmetry, volume and skin texture were rated by surgeons at 1 week, 3 months and 6 months compared to the preoperative presentation. We compared the outcomes of patients treated during the active and the stable phase of the disease. Additionally, patients were asked to fill out a quality-of-life questionnaire. Results: We found a total of 11 patients diagnosed with PHA and LS, 8 of whom had undergone autologous fat injections to correct facial asymmetry. Of those, 4 patients were treated in their active and 4 in their stable phase. We found similar treatment outcomes in both groups. The social component had the greatest negative effect on patient's quality of life. Conclusion: In this small cohort, autologous fat grafting during the active phase did not appear to be inferior to fat grafting during the stable phase. It could be a safe technique for correction of PHA and LS during the active phase of disease.

Introduction: L'hémiatrophie faciale progressive (HFP) et la sclérodermie linéaire (SL) sont toutes deux des affections rares définies par l'atrophie ou la sclérose de la peau et des tissus sous-cutanés. Le moment idéal pour procéder à une intervention reconstructive chez ces patients. Les auteurs comparent les résultats et la satisfaction associés à un lipofilling autologue effectué pendant les phases active et stable de la maladie chez les adultes. Méthodologie: Les auteurs ont procédé à une analyse rétrospective des dossiers de tous les patients ayant obtenu un diagnostic d'HFP ou de SL entre 2007 et 2019 au sein de leur département. Ils ont analysé les données démographiques, les caractéristiques cliniques et les interventions chirurgicales. Les chirurgiens ont évalué les changements de symétrie, du volume et de la texture de la peau par rapport à la présentation préopératoire au bout d'une semaine, de trois mois et de six mois. Les auteurs ont comparé les résultats chez les patients traités pendant les phases active et stable de la maladie. De plus, les patients ont été invités à remplir un questionnaire sur leur qualité de vie. Résultats: Les auteurs ont recensé un total de onze patients ayant un diagnostic d'HFP ou de SL, dont huit ont subi des injections de graisse autologues pour corriger une asymétrie faciale. De ce nombre, quatre ont été traités pendant la phase active et quatre, pendant la phase stable. Les auteurs ont observé des résultats thérapeutiques semblables dans les deux groupes. L'aspect social avait l'incidence la plus négative sur la qualité de vie des patients. Conclusion: Dans cette petite cohorte, la greffe de graisse autologue pendant la phase active ne semblait pas donner de moins bons résultats que la greffe de graisse pendant la phase stable. Cette technique pourrait être sécuritaire pour corriger une HFP ou une SL pendant la phase active de la maladie.

Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells.

INTRODUCTION: Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA. MATERIALS AND METHODS: Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways. RESULTS: Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control. CONCLUSION: LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation. 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 .

Lambda Repair: A Novel Repair Technique for Chronic Boutonnière Deformity.

SUMMARY: Correction of a boutonnière deformity is one of the most demanding challenges in hand surgery. Surgical interventions are usually considered when functional use of the finger cannot be obtained after intense hand therapy. The authors introduce their newly described lambda (λ) repair, which is an easy-to-learn, straightforward surgical technique. The method involves an end-to-side tenorrhaphy of the lateral bands, resembling the Greek λ. Patients who underwent a lambda repair were retrospectively evaluated with preoperative and postoperative measurements of proximal interphalangeal (PIP) joint movement. Four patients (two male, two female; median age, 35.5 years) with a median follow-up period of 9.1 months were included. Three patients underwent lambda repairs for isolated boutonnière deformities, and one patient received a vascularized free toe transfer combined with a lambda repair. The preoperative average PIP joint extension lag or deficit was 28.75 degrees and could be reduced to 15 degrees. Preoperative average PIP joint active flexion was 60 degrees, which was improved to 88.75 degrees. No complications were observed. The lambda repair is a new tool in the reconstruction of boutonnière deformity, further expanding the armamentarium of hand surgeons.

The Combination of Mechanically Isolated Stromal Vascular Fraction and Fibrin Hydrogel: A Processing Protocol.

The regenerative potential of adipose-derived stromal cells (ASCs) has gained significant attention in regenerative and translational research. In the past, the extraction of these cells from adipose tissue required a multistep enzyme-based process, resulting in a heterogenous cell mix consisting of ACSs and other cells, which are jointly termed the stromal vascular fraction (SVF). More recently introduced mechanical SVF (mSVF) isolation protocols are less time-consuming and bypass regulatory concerns. We recently proposed a protocol that generates mSVF rich in stromal cells based on a combination of emulsification and centrifugation. One current issue in mSVF application for wound therapy application is the lack of a scaffold providing protection from mechanical manipulation and desiccation. Fibrin hydrogels have been shown to be a useful adjunct in cell transfer for wound healing purposes in the past. In the work herein, we delineate the preparation steps of an mSVF-fibrin hydrogel construct as a novel approach for translational research and clinical application.

Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice.

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm2). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-ß1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future.

Basic Principles in the Management of Acute Burn Injuries in Adults.

INTRODUCTION: This review outlines an overview of up-to-date, stage-appropriate treatment methods for burn injuries as practiced at the National Burn Center of the University Hospital Zurich. It intends to provide practitioners with recommendations for the management of acute minor to severe burn injuries based on scientific evidence as well as the long-term experience of the Burn Center. The focus is on a practical guideline and various options including novel, innovative conceptual approaches.

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair.

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation.

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study.

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.

Outcome of Facial Burn Injuries Treated by a Nanofibrous Temporary Epidermal Layer.

BACKGROUND: The face is commonly affected in thermal injuries, with a demand for proper recognition and the correct choice of treatment to guarantee optimal aesthetic and functional outcomes. It is highly vascularized and often heals conservatively, highlighting the particular relevance of conservative treatment modalities, many of which require daily re-applications or dressing changes, which can be painful and tedious for both the patient and the healthcare providers. Motivated by encouraging results of a novel temporary nanofibrous epidermal layer, we herein present a case series of this technology in a case series of patients suffering from facial burns and treated in our Burn Center. PATIENTS AND METHODS: Patients with superficial partial-thickness facial burns and mixed pattern burns, which were treated with SpinCare™, an electrospun nanofibrous temporary epidermal layer, between 2019 and 2021, at our institution were analyzed retrospectively. The Manchester scar scale (MSS) and numeric rating scale (NRS) were used for scar, pain, and outcome evaluation at different time points by five independent board-certified plastic surgeons with profound experience in burn surgery. RESULTS: Ten patients (m = 9; f = 1) were treated and evaluated retrospectively. The mean age was 38.8 ± years (SD ± 17.85). The mean healing time was 6.4 days (SD ± 1.56). The mean follow-up was 16.4 months (SD ± 11.33). The mean MSS score was 5.06 (SD ± 1.31), and the mean NRS Score for pain was significantly reduced from initially 7 to 0.875 upon application (mean (pre-application) 7 ± 0.7 and (application) 0.875 ± 1.26; p ≤ 0.0001). Patients reported a NRS score of 10 in terms of functional and cosmetic outcomes at their final follow-up appointment. No adverse effects were observed. CONCLUSIONS: The application of a nanofibrous temporary epidermal layer such as SpinCare™ represents a relatively easy-to-use, well-tolerated, and effective alternative for the treatment of partial-thickness facial burns.

In Vivo Evaluation of Mechanically Processed Stromal Vascular Fraction in a Chamber Vascularized by an Arteriovenous Shunt.

Mechanically processed stromal vascular fraction (mSVF) is a promising source for regenerative purposes. To study the in vivo fate of the mSVF, we herein used a vascularized tissue engineering chamber that insulates the target mSVF from the surrounding environment. In contrast to previous models, we propose an arteriovenous (AV) shunt between saphenous vessels in rats without a venous graft. Mechanical SVF was processed from the fat pads of male Sprague Dawley rats, mixed with a fibrin hydrogel and implanted into an inguinal tissue engineering chamber. An arteriovenous shunt was established between saphenous artery and vein. On the contralateral side, an mSVF-fibrin hydrogel mix without vascular axis served as a non-vascularized control. After two and six weeks, rats were sacrificed for further analysis. Mechanical SVF showed significant numbers of mesenchymal stromal cells. Vascularized mSVF explants gained weight over time. Perilipin and CD31 expression were significantly higher in the mSVF explants after six weeks while no difference in DAPI positive cells, collagen deposition and FABP4 expression was observed. Morphologically, no differentiated adipocytes but a dense cell-rich tissue with perilipin-positive cells was found after six weeks. The phosphorylation of ERK1/2 was significantly enhanced after six weeks while Akt activation remained unaltered. Finally, mSVF explants stably expressed and released VEGF, bFGF and TGFb. Vascularized mSVF is able to proliferate and express adipocyte-specific markers. The AV shunt model is a valuable refinement of currently existing AV loop models in the rat which contributes to the fundamental 3R principles of animal research.

Novel RGAG1-BCOR gene fusion revealed in a somatic soft tissue sarcoma with a long follow-up.

BCOR-rearranged sarcomas are rare and belong to the Ewing-like sarcomas (ELS). Their morphology and histopathological features make the diagnosis challenging. We present a case, initially diagnosed as an unusual extraskeletal myxoid chondrosarcoma (EMC). A 54-year-old male patient developed an asymptomatic swelling of the lower leg. Imaging showed a 9.5-cm large intramuscular soft tissue mass. Due to its morphological and immunohistochemical profile on biopsy, it was initially diagnosed as an EMC. The patient was treated by complete resection and adjuvant radiotherapy and remained free of tumor at 7 years follow-up. Using next-generation sequencing (NGS), we retrospectively identified RGAG1-BCOR gene fusion (confirmed by RT-PCR), which has not been described in somatic soft tissue tumors so far. This finding broadens the spectrum of partner genes in the BCOR-rearranged sarcomas in a tumor with a well-documented, long clinical follow-up.

Fluorescence angiography-assisted debridement of critically perfused glabrous skin in degloving foot injuries: Two case reports.

RATIONALE: Degloving foot injuries are challenging to treat and associated with life-long sequelae for patients. An appropriate debridement of ischemic soft tissues with maximal preservation of glabrous skin is key during the reconstruction of these injuries. Indocyanine green (ICG) fluorescence angiography is an established technique for the intraoperative evaluation of tissue perfusion. PATIENT CONCERNS: Two patients sustained complex foot injuries in traffic accidents, including multiple fracture dislocations and extensive degloving of the plantar skin. DIAGNOSIS: Clinical inspection revealed significant degloving of the glabrous skin in both patients. INTERVENTIONS: After fracture fixation, ICG fluorescence angiography-assisted debridement with immediate latissimus dorsi free flap reconstruction was performed. OUTCOMES: In both cases, this technique allowed a precise debridement with maximal preservation of the glabrous skin. The healing of the remaining glabrous skin was uneventful and the 6-month follow-up was characterized by stable soft tissues and satisfying ambulation. LESSONS: ICG fluorescence angiography is a safe, user-friendly, and quick procedure with minimal risks, expanding the armamentarium of the reconstructive surgeon. It is highly useful for the debridement of extensive plantar degloving injuries and may also help to minimize the number of procedures and the risk of infection.

A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema.

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.