Proteomic and secretomic comparison of young and aged dermal fibroblasts highlights cytoskeleton as a key component during aging.

Crucial for skin homeostasis, synthesis and degradation of extracellular matrix components are orchestrated by dermal fibroblasts. During aging, alterations of component expression, such as collagens and enzymes, lead to reduction of the mechanical cutaneous tension and defects of skin wound healing. The aim of this study was to better understand the molecular alterations underwent by fibroblasts during aging by comparing secretomic and proteomic signatures of fibroblasts from young (<35years) and aged (>55years) skin donors, in quiescence or TGF-stimulated conditions, using HLPC/MS. The comparison of the secretome from young and aged fibroblasts revealed that 16 proteins in resting condition, and 11 proteins after a 24h-lasting TGF-ß1-treatment, were expressed in significant different ways between the two cell groups (fold change>2, p-value <0.05), with a 77% decrease in the number of secreted proteins in aged cells. Proteome comparison between young and aged fibroblasts identified a significant change of 63 proteins in resting condition, and 73 proteins in TGF-ß1-stimulated condition, with a 67% increase in the number of proteins in aged fibroblasts. The majority of the differentially-expressed molecules belongs to the cytoskeleton-associated proteins and aging was characterized by an increase in Coronin 1C (CORO1C), and Filamin B (FLNB) expression in fibroblasts together with a decrease in Cofilin (CFL1), and Actin alpha cardiac muscle 1 (ACTC1) detection in aged cells, these proteins being involved in actin-filament polymerization and sharing co-activity in cell motility. Our present data reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.

Reduction Mammoplasties: Risk Factors and Early Complications-About 1442 Cases.

BACKGROUND: Breast reduction surgery is a widely performed plastic surgery procedure. The incidence of such complications has been steadily decreasing in recent years but is still nonetheless 5.6%. The primary aim of this study was to analyze the incidence of the main postoperative complications of breast reduction surgery. In addition, we identified cause-and-effect links between complications and characteristics of the patients, such as smoking, age, weight resection, BMI, and wound drainage. MATERIALS AND METHODS: This retrospective study was performed on a population of 1442 women who underwent breast reduction surgery between January 2016 and October 2022 in the plastic surgery unit at Saint-Louis Hospital, Paris, France. At the follow-up examination, we evaluated the patients for complications. RESULTS: The average resection weight was 1297.7 g in a population for which the average BMI was 28.9. We found 19.9% rate of total complications, of which 3.5% were major complications. We found that only the resection weight was a risk factor for complications. DISCUSSION: The main strength of our study is the size of our sample. The large number of patients allowed us to conduct numerous analyses and obtain significant results despite the rarity of certain events. This large cohort was also responsible for the high statistical power of our results. CONCLUSION: The risk of developing a postoperative infection was 7.5% for resections of less than 2.4 kg, increasing to 13.9 % when greater than that. Thus, the administration of prophylactic antibiotic therapy to affected women to reduce the risk of infection is a distinct consideration. For the other factors, while none of them appeared to promote the occurrence of adverse events and, therefore, do not formally contraindicate breast reduction surgery, some preventive measures still strike us as being relevant, such as blade drainage, weight loss, diabetes control, and smoking cessation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses.

Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A- or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B-coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.

Description of the Pedicled Osteo-Muscular Flap of Split Temporal Muscle.

Background: Reconstruction of the head and neck is dominated by free flaps, and for bone reconstruction by fibula and scapula flaps. However, this choice is sometimes difficult to make in patients who cannot tolerate an extensive and lengthy surgical procedure. In addition, vascular micro-anastomoses are sometimes complicated in patients who have been previously irradiated. Pedicle flaps remain an option and can sometimes be considered as first choice for head and neck reconstruction. Purpose: In this study, we describe the feasibility of a split temporal muscle pedicled flap with coronal harvesting for a reconstruction that can reach the midline. Study design sample covariates: Ten fresh-frozen human cadaver heads were dissected, and the length of the split flap was noted, followed by the length of the non-split flap. Results: The mean length was 155.7 mm (± 20.0) for the split flap, from the point of rotation to the tip of the coronoid process. These results coincide with the tragus-midline distance, which makes it possible to consider reconstruction of the midline, especially the maxilla and the mandible, which has not yet been described in the literature. Conclusions and relevance: This technique would then allow a supply of pedicled vascularized bone for loco-regional reconstruction.

Short- and long-term morbidity after Taylor flap (oblique rectus abdominis flap) for perineal reconstruction after abdominoperineal resection: A single-center series of 140 patients.

BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.

Specificities of Management of Perineal Burns.

There is a paucity of articles addressing the management strategy for perineal burns. Pelvic floor burns present a multitude of problems. These relate to the management of stool, urine, areas of maceration, significant strain, and the risk of infection. The objective of this study was to analyze a consecutive series of perineal burns by studying their characteristics, treatment, and management of urine and feces. This was a retrospective study including 100 patients between January 2018 and December 2022. The patients had all been hospitalized after suffering burns to the perineum. In 28% of the patients, the perineal burn was complicated by infection. In 61% of cases, a cutaneous infection, in 32% of cases, a urinary tract infection, in 25% of cases, a respiratory tract infection, and in 7% of cases, an infection of the digestive tract. Superinfection is associated with an increased risk of poor engraftment. A total of 100% of the patients with poor or average engraftment had an infection in the aftermath of the burn, compared with 20% of the patients with excellent engraftment and 61% of the patients with good engraftment. In our series, the analysis revealed that, in 95% of cases, no specific procedures were implemented for stool management. Perianal involvement was associated with a risk of sub-excellent engraftment. The results were statistically significant, with P = .005 and an OR = 8.72 after multivariate analysis. We favor the least invasive approach to stool management. Indications for a rectal catheter arise in patients with the following characteristics: the patient must be sedated, the burns must be deep and close to the anal opening, and the stools must be watery and abundant. In 95% of cases, we do not install a stool management device. Colostomies should remain exceptional.

The Use of Hydrogel Dressings in Sulfur Mustard-Induced Skin and Ocular Wound Management.

Over one century after its first military use on the battlefield, sulfur mustard (SM) remains a threatening agent. Due to the absence of an antidote and specific treatment, the management of SM-induced lesions, particularly on the skin and eyes, still represents a challenge. Current therapeutic management is mainly limited to symptomatic and supportive care, pain relief, and prevention of infectious complications. New strategies are needed to accelerate healing and optimize the repair of the function and appearance of damaged tissues. Hydrogels have been shown to be suitable for healing severe burn wounds. Because the same gravity of lesions is observed in SM victims, hydrogels could be relevant dressings to improve wound healing of SM-induced skin and ocular injuries. In this article, we review how hydrogel dressings may be beneficial for improving the wound healing of SM-induced injuries, with special emphasis placed on their suitability as drug delivery devices on SM-induced skin and ocular lesions.

Evidence of inter- and intra-keloid heterogeneity through analysis of dermal fibroblasts: A new insight in deciphering keloid physiopathology.

Keloid scars are hypertrophic and proliferating pathological scars extending beyond the initial lesion and without tendency to regression. Usually, keloids are considered and treated as a single entity but clinical observations suggest heterogeneity in keloid morphologies with distinction of superficial/extensive and nodular entities. Within a keloid, heterogeneity could also be detected between superficial and deep dermis or centre and periphery. Focusing on fibroblasts as main actors of keloid formation, we aimed at evaluating intra- and inter-keloid fibroblast heterogeneity by analysing their gene expression and functional capacities (proliferation, migration, traction forces), in order to improve our understanding of keloid pathogenesis. Fibroblasts were obtained from centre, periphery, papillary and reticular dermis from extensive or nodular keloids and were compared to control fibroblasts from healthy skin. Transcriptional profiling of fibroblasts identified a total of 834 differentially expressed genes between nodular and extensive keloids. Quantification of ECM-associated gene expression by RT-qPCR brought evidence that central reticular fibroblasts of nodular keloids are the population which synthesize higher levels of mature collagens, TGFß, HIF1α and αSMA as compared to control skin, suggesting that this central deep region is the nucleus of ECM production with a centrifuge extension in keloids. Although no significant variations were found for basal proliferation, migration of peripheral fibroblasts from extensive keloids was higher than that of central ones and from nodular cells. Moreover, these peripheral fibroblasts from extensive keloids exhibited higher traction forces than central cells, control fibroblasts and nodular ones. Altogether, studying fibroblast features demonstrate keloid heterogeneity, leading to a better understanding of keloid pathophysiology and treatment adaptation.

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro.

Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated in vitro herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril® (ALG, pure Ca2+ alginate) and Biatain® Alginate (BIA, Ca2+ alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca2+ via the SOCE Ca2+ permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca2+-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril® enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.

The immunological effects of intradermal particle-based vaccine delivery using a novel microinjection needle studied in a human skin explant model.

For intradermal (ID) immunisation, novel needle-based delivery systems have been proposed as a better alternative to the Mantoux method. However, the penetration depth of needles in the human skin and its effect on immune cells residing in the different layers of the skin has not been analyzed. A novel and user-friendly silicon microinjection needle (Bella-muTM) has been developed, which allows for a perpendicular injection due to its short needle length (1.4-1.8 mm) and ultrashort bevel. We aimed to characterize the performance of this microinjection needle in the context of the delivery of a particle-based outer membrane vesicle (OMV) vaccine using an ex vivo human skin explant model. We compared the needles of 1.4 and 1.8 mm with the conventional Mantoux method to investigate the depth of vaccine injection and the capacity of the skin antigen-presenting cell (APC) to phagocytose the OMVs. The 1.4 mm needle deposited the antigen closer to the epidermis than the 1.8 mm needle or the Mantoux method. Consequently, activation of epidermal Langerhans cells was significantly higher as determined by dendrite shortening. We found that five different subsets of dermal APCs are able to phagocytose the OMV vaccine, irrespective of the device or injection method. ID delivery using the 1.4 mm needle of a OMV-based vaccine allowed epidermal and dermal APC targeting, with superior activation of Langerhans cells. This study indicates that the use of a microinjection needle improves the delivery of vaccines in the human skin.

Autologous Gluteal Augmentation with Parasacral Perforator-Pedicled Propeller Flaps.

BACKGROUND: De-epithelialized flaps have been used in gluteal contouring over the last three decades, but most improve the projection rather than the upper quadrants. The authors provide a detailed description of their method of gluteal augmentation using parasacral perforator-pedicled propeller flaps. This technique achieves a volumetric increase and maximal buttock projection at the midlevel and in the medial half of the buttocks. METHODS: Between January and December of 2019, a series of 18 patients on whom a lower body lift with a parasacral perforator-pedicled propeller flap had been performed by the senior author (F.B.) were prospectively evaluated. Postoperatively, the satisfaction rate was assessed using a 10-point analog scale (1 = unsatisfied, 10 = very satisfied) by the patient and by two independent surgeons based on photographs taken 1 year after surgery. RESULTS: Eighteen patients underwent this procedure. Their mean age was 32.2 ± 5.6 years (range, 24 to 40 years). The mean flap length was 20.3 cm, their mean width was 10.4 cm, and the mean thickness was 3.4 cm. The authors noted only two minor complications, one seroma and two skin dehiscences that healed without surgery. The rate of satisfaction as assessed by the patients was 8.3 out of 10 (±1.1), and by surgeons, 7.9 and 8.1. CONCLUSION: This article describes a gluteal autoaugmentation flap technique using parasacral perforator-pedicled propeller flaps to increase projection and volume in the inferomedial gluteal region after lower body lift. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

A new therapeutic protocol for the treatment of keloid scars: a retrospective study.

OBJECTIVE: There are few means to treat large keloid scars, as exeresis-even if partial-impedes direct closure without tension in the absence of a flap or a skin graft. This study evaluates the efficacy, indications for use and limitations of a new therapeutic protocol, combining an extralesional keloid excision left to heal by secondary intention with a paraffin dressing and glucocorticoid ointment, followed by monthly intrascar injections of corticosteroids upon full re-epithelialisation. METHOD: A retrospective study of patients treated for keloid scars by using the new therapeutic protocol. Scars were categorised as either healed or recurring. Their recurrence was scored according to the changes in functional signs and the scar volume. RESULTS: A total of 36 scars were studied. The mean follow-up was 14.1 months. Healing occurred in a mean of 6.8 weeks. The mean surface area was 21.6cm2. Healing rate was 30.5%. Scar volume was improved in 60% of recurrent cases and functional signs in 56%. Based on adherence with the corticotherapy, two patient groups could be discerned. For patients in the 'adherent' group, the healing rate was 40%, and scar volume was improved in 75% of recurrent cases and the functional signs in 83% of cases. CONCLUSIONS: The healing rate in this study was close to that reported in the literature. Excision-healing by secondary intention could therefore be offered to patients for whom adherence is uncertain. The protocol in this study offers a straightforward, fast, accessible solution that does not appear to entail any risk of additional keloids. It could potentially offer a treatment option in case of failure of other treatments, large keloid scars or scalp keloids.

Perioperative Management of an Adult Patient With Myoclonic Epilepsy With Ragged Red Fibers Syndrome: A Case Report.

Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is a rare mitochondrial disease potentially associated with increased sensitivity to anesthesia and metabolic decompensation. We present the perioperative management in a 59-year-old man with MERRF scheduled for lipomatosis cure under general anesthesia (GA). Following a reduced fasting period, the patient had an uneventful balanced GA with propofol, sevoflurane, and rocuronium. The patient did not present metabolic decompensation nor malignant hyperthermia but prolonged neuromuscular blockade. Propofol and sevoflurane may be used in asymptomatic MERRF adult patients. Such patients present high risk of residual neuromuscular blockade that should be monitored and reversed.

Epidemiology and Prevention of Breast Prosthesis Capsular Contracture Recurrence.

INTRODUCTION: Baker grade III and IV breast prosthesis capsular contractures represent a major problem for patients undergoing mammoplasties. The risk factors involved in recurrence are debated, and the best surgical approach for their prevention is not established. The objective was to identify these. MATERIALS AND METHODS: We carried out a retrospective study of patients operated on for capsular contracture at the Saint-Louis Hospital in Paris from 2012 to 2014. The characteristics at inclusion were compared so as to determine the risk factors of recurrence. The surgical approaches were compared between the patients with recurrence and those without at 5 years. RESULTS: Of the 100 patients included, 24 had a recurrence. The minimal follow-up was 5 years. No risk factors of recurrence of capsular contracture were identified. The surgical approach associated with the lowest rate of recurrence was anterior capsulectomy [OR total capsulectomy = 2.36 (0.73; 8.037) OR capsulotomy = 4.33 (1.37; 14.81)] (p < 0.040) with alteration of the volume of the implant, whether greater or less than initially [OR greater volume = 0.30 (0.096; 0.83); OR smaller volume = 0.14 (0.008; 0.85)] (p < 0.018). CONCLUSION: The occurrence of capsular contracture is a major problem with prosthetic breast surgery. The main risk factors identified to date are essentially in regard to the occurrence of a first episode. No significant risk factors for recurrence were identified. The best prevention appears to be an anterior capsulectomy with reducing the volume of the implant. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . IV.