Nipple-areola complex prosthesis as a new arsenal for breast reconstruction.

Nipple and areola complex (NAC) recreating is primordial to achieve a complete breast reconstruction. Some patients would not benefit or choose to undergo surgical or tattoo NAC reconstruction. Recently, innovative NAC silicone prostheses have been developed that are applied over the skin and come in various shapes, sizes, and colors to match different NAC tones and sizes. Our prospective study aims to evaluate for the first time, to our knowledge, the safety of these prostheses and patients' and surgeons' satisfaction using a 30-day survey. Twenty patients using these NAC prostheses after unilateral breast reconstruction postmastectomy with NAC excision were included. All patients except one (95%) were satisfied/very satisfied with the aspect and symmetry of NAC prostheses compared with native contralateral NAC. All patients were more/much more satisfied with their body image and self-esteem using the NAC prostheses. Except for 2 (90%), no participant presented any skin reaction, infection, or erosion. Most patients (68.75%) used the prosthesis every day, and others-occasionally. All participants stated they would recommend these prostheses to other women as a temporary or definitive solution. With these promising results demonstrating a high safety and satisfaction rate, we are confident that this simple, safe, noninvasive, and cost-effective device should be proposed to all patients to improve the management of breast reconstruction and offer body integrity to patients. Health insurance should consider reimbursement for these prostheses in patients after mastectomy or with NAC deformation after trauma, surgery, or congenital.

Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds.

This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with the inflammatory and angiogenic factors. Proteomics on conditioned media showed that gelatin also acted as a concentrator and reservoir of the regenerative ASC secretome. This secretome promoted fibroblast survival and epithelialization, and significantly increased the migration and tubular assembly of endothelial cells within fibronectin. ASC in gelatin on a chick chorioallantoic membrane were more connected to vessels than an empty sponge, confirming an increased angiogenesis in vivo. No tumor formation was observed in immunodeficient nude mice to which an ASC gelatin sponge was transplanted subcutaneously. Finally, ASC in a gelatin sponge prepared from outbred rats accelerated closure and re-vascularization of ischemic wounds in the footpads of rats. In conclusion, we provide here preclinical evidence that a cross-linked porcine gelatin sponge is an optimal carrier to concentrate and increase the regenerative activity of ASC, notably angiogenic. This formulation of ASC represents an optimal, convenient and clinically compliant option for the delivery of ASC on ischemic wounds.

NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing.

Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-ß) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix (ECM) and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-ß-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-ß in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-ß treatment, Nox4 did not influence skin myofibroblast differentiation although a putative NOX4 inhibitor GKT137831 and a flavoprotein inhibitor diphenylene iodonium mitigated this mechanism. Transcriptomic analysis revealed upregulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3 in Nox4-deficient fibroblasts, which had however no impact on fibroblast bioenergetics. Altogether, we provide extensive evidence that NOX4 is dispensable for wound healing and skin fibroblast to myofibroblast differentiation, and suggest that another H2O2-generating flavoprotein drives this mechanism.

Isolation and Characterization of Stem Cells from the Anal Canal Transition Zone in Pigs.

BACKGROUND: Utilization of autologous stem cells has been proposed for the treatment of anal incontinence despite a lack of understanding of their mechanism of action and of the physiological healing process of anal sphincters after injury. AIMS: We aim to develop a technique allowing isolation and further study of local mesenchymal stem cells, directly from anal canal transition zone in pig. METHODS: Anal canal was resected "en bloc" from two young pigs and further microdissected. The anal canal transition zone was washed and digested with 0.1% type I collagenase for 45 min at 37 °C. The isolated cells were plated on dishes in mesenchymal stem cell medium and trypsinized when confluent. Cells were further used for flow cytometry analysis and differentiation assays. RESULTS: The anal canal transition zone localization was confirmed with H&E staining. Following culture, cells exhibited a typical "fibroblast-like" morphology typical of stem cells. Isolated cells were positive for CD90 and CD44 but negative for CD14, CD34, CD45, CD105, CD106, and SLA-DR. Following incubation with specific differentiation medium, isolated cells differentiated into adipocytes, osteoblasts, and chondrocytes, confirming in vitro multipotency. CONCLUSIONS: Herein, we report for the first time the presence of mesenchymal stem cells in the anal canal transition zone in pigs and the feasibility of their isolation. This preliminary study opens the path to the isolation of human anal canal transition zone mesenchymal stem cells that might be used to study sphincters healing and to treat anal incontinence.

Epigenetic remodeling of downstream enhancer regions is linked to selective expression of the IL1F10 gene in differentiated human keratinocytes.

Interleukin (IL)-38, encoded by the IL1F10 gene, is a member of the IL-1 family of cytokines. IL-38 is constitutively expressed in epithelia in healthy humans, and in particular in epidermal keratinocytes in the skin. IL-38 expression is closely correlated with keratinocyte differentiation. The aim of this study was to further characterize the regulation of IL1F10 expression and the mechanisms involved in its selective induction in differentiated human keratinocytes. We observed coordinated expression of two IL1F10 transcripts, transcribed from two different promoters, upon differentiation of primary human keratinocytes. Using ENCODE datasets and ChIP-qPCR on ex vivo isolated normal human epidermis, we identified regulatory regions located downstream of the IL1F10 gene, which displayed features of differentiated keratinocyte-specific enhancers. Expression of the IL1F10 gene was linked to changes in the epigenetic landscape at these downstream enhancer regions in human epidermis. Overexpression of the transcription factors KLF4 and TAp63ß in an immortalized normal human keratinocyte (iNHK) cell line promoted the expression of mRNA encoding the differentiation markers keratin 10 and involucrin, and of IL1F10. ChIP-qPCR experiments indicated that KLF4 and TAp63ß overexpression also modified the chromatin state of the proximal downstream enhancer region, suggesting a role for KLF4 and TAp63ß in directly or indirectly regulating IL1F10 transcription. In conclusion, expression of the IL1F10 gene in differentiated keratinocytes in normal human epidermis involves coordinated transcription from two promoters and is linked to epigenetic remodeling of enhancer regions located downstream of the gene.

Operative Planning of Chest Wall Reconstructions Illustrated by a Large Defect in a Child.

Reconstruction of large chest wall defects is challenging. Here we discuss the process of decision-making in planning chest wall reconstruction, considering the requirements of tumor removal, stabilization of the chest wall, and soft tissue coverage, illustrated by a case of a hemi-chest wall defect in a child. Ewing sarcoma measuring 10 × 9 × 13 cm was resected in a 9-year-old boy, followed by stabilization using a Gore-Tex patch. Due to extension of the oncologic resection far into the superomedial quadrant of the chest, tension-free coverage with a classical latissimus-dorsi flap could not be achieved. Integrating the serratus-anterior muscle into the flap creating a chimeric latissimus-dorsi/serratus-anterior flap allowed for excellent soft tissue coverage of the foreign body. As the skin could be preserved, careful incision planning was necessary to allow for best possible exposure during oncologic resection and flap harvest, while ensuring skin vascularization impaired by underlying tumor resection. Two vertical skin incisions were chosen, one presternal and a second in the mid-axillary fold delineating a large bipedicled skin flap. Postoperative recovery was excellent. Solid skin vascularization and adequate soft tissue coverage of the alloplastic material allowed for the patient to receive two cycles of postoperative radiotherapy without developing wound dehiscence. Careful interdisciplinary planning of skin incisions allowed for good exposure for tumor resection and flap harvest while preserving skin vascularization. Choosing a chimeric latissimus-dorsi/serratus-anterior flap provided larger coverage than a classical latissimus-dorsi flap with minimal additional donor site morbidity. Taken together, we here present a pragmatic solution to a complex problem.

Defining the Ideal Breast Reconstruction Procedure After Mastectomy From the Patient Perspective: A Retrospective Analysis.

Background: An increasing number of breast cancer patients undergo immediate or secondary breast reconstruction, but the ideal method in terms of patient satisfaction remains ambiguous. We compared the 3 most common breast reconstruction techniques to determine patient satisfaction and objective outcomes. Methods: Retrospective study of 184 patients with breast cancer who underwent a reconstructive procedure between 1993 and 2011 at our institution. Procedures evaluated were implant-based reconstruction (IBR) alone, latissimus dorsi (LD) flap reconstruction with/without implant, and deep inferior epigastric perforator (DIEP) free flap reconstruction. A retrospective patient satisfaction questionnaire was sent to all women. Twenty patients from each subgroup were matched to conduct a standardized objective assessment of the sensitivity of their reconstructed breast. A blinded photographic evaluation was also performed by 3 independent observers to assess the esthetic aspect and symmetry. Results: DIEP obtained significantly higher average scores regarding the esthetic outcome, immediate reconstruction impact, and overall score in the questionnaire evaluation. The IBR had the best results in the somatosensory evaluation, with DIEP scoring better than LD. DIEP received higher scores on average than LD for the criteria of size and symmetry in the esthetic evaluation. No statistically significant differences were observed between IBR and DIEP. Conclusions: Good results were reported overall for all breast reconstruction procedures, with more reserved scores for LD. The DIEP reconstruction appeared to be the most satisfactory and best experienced reconstruction method for patients, despite the complexity of the intervention. Clinicians should be encouraged to consider DIEP as the principal choice for breast reconstruction.

Adipose-derived stem cell spheroids are superior to single-cell suspensions to improve fat autograft long-term survival.

Autologous fat transplantation is a widely used procedure for surgical reconstruction of tissues. The resorption rate of this transplantation remains high and unpredictable, reinforcing the need of adjuvant treatments that increase the long-term stability of grafts. Adipose-derived stem cells (ASC) introduced as single cells in fat has been shown clinically to reduce the resorption of fat grafts. On the other hand, the formulation of ASC into cell spheroids results in the enhancement of their regenerative potential. In this study, we developed a novel method to produce highly homogeneous ASC spheroids and characterized their features and efficacy on fat transplantation. Spheroids conserved ASC markers and multipotency. A regenerative gene expression profile was maintained, and genes linked to autophagy were upregulated whereas proliferation was decreased. Their secreted proteome was enriched in comparison with single-cell ASC suspension. Addition of spheroids to fat graft in an animal model of transplantation resulted in a better graft long-term stability when compared to single ASC suspension. In conclusion, we provide a novel method to manufacture homogenous ASC spheroids. These ASC spheroids are superior to ASC in single-cell suspension to improve the stability of fat transplants, reinforcing their potential in reconstructive surgery.

IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in systemic sclerosis epidermis.

OBJECTIVES: Evidence shows that dysfunctional SSc keratinocytes contribute to fibrosis by altering dermal homeostasis. Whether IL-25, an IL-17 family member regulating many epidermal functions, takes part in skin fibrosis is unknown. Here we address the role of IL-25 in skin fibrosis. METHODS: The expression of IL-25 was evaluated by immunofluorescence and in situ hybridization in 10 SSc and seven healthy donor (HD) skin biopsies. Epidermal equivalents (EE) reconstituted by primary HD keratinocytes were used as a model to study transcriptomic changes induced by IL-25 in the epidermis. RNA expression profile in EEs was characterized by RNAseq. The conditioned medium (CM) from primary SSc and HD keratinocytes primed with IL-25 was used to stimulate fibroblasts. IL-6, IL-8, MMP-1, type-I collagen (Col-I), and fibronectin production by fibroblasts was assessed by ELISA. RESULTS: SSc epidermis expressed lower levels of IL-25 compared with HDs. In EEs, IL-25 regulated several molecular pathways related to wound healing and extracellular matrix remodelling. Compared with control CM, the CM from IL-25-primed keratinocytes enhanced the fibroblast production of MMP-1, IL-6 and IL-8, but not of Col-I nor fibronectin. However, IL-25 significantly reduced the production of Col-I when applied directly to fibroblasts. The activation of keratinocytes by IL-25 was receptor-dependent and evident after a very short incubation time (10 min), largely mediated by IL-1, suggesting enhanced and specific release of preformed mediators. CONCLUSIONS: These results show that IL-25 participates in skin homeostasis, and its decreased expression in SSc may contribute to skin fibrosis by favouring extracellular matrix deposition over degradation.

Free-flap breast reconstruction: cost analysis in the Swiss healthcare system

AIM OF THE STUDY: Breast cancer is the most common type of malignancy among women. Mastectomy maintains an essential role in oncological therapy and led to the development of breast reconstruction procedures. The deep inferior epigastric perforator (DIEP) free flap became in the last decade a popular approach for breast reconstruction. Although this procedure is known to be more complex than other techniques, it offers one of the highest patient satisfaction rates. However, the cost-effectiveness of this technique has rarely been assessed; and the real cost coverage by health insurance has never been studied. This study estimated the real cost of immediate DIEP free flap breast reconstruction after unilateral mastectomy and evaluated the cost coverage by healthcare insurers according to the diagnosis-related group (DRG) reimbursement scheme in Switzerland. METHODS: Medical files of 20 consecutive patients who underwent immediate DIEP free-flap breast reconstruction between 2012 and 2017 were reviewed retrospectively. Billing data according to DRG rates were compared with an estimation of the real cost generated by the procedure. RESULTS: The mean charge according to the DRG model for one-stage DIEP free-flap reconstruction was CHF 29,573 (CHF 19,256­64,741). The mean real estimated cost was CHF 33,416 (CHF 20,633­47,036). Seven different DRG codes were used between 2012 and 2017, each offering a different definition and compensation. CONCLUSION: The DRG pricing scheme evolves through annual revisions. Progressively, more specific codes were created and used, allowing a better cost coverage for the procedure. Since 2017, the use of the dedicated code J01B has resulted in adequate cost coverage of the procedure. Since it has been widely accepted that DIEP breast reconstruction has advantages such as high patient satisfaction, we encourage the inclusion of this procedure in the reconstructive arsenal of breast cancer centres in Switzerland.

Transverse cervical vessels as a recipient site for microvascular reconstruction in vessel-depleted necks: a safe option.

BACKGROUND: Free flap reconstruction is the gold standard in complex head and neck reconstruction. The branches of the external carotid vessels (ECVs) are considered the most suitable recipients, but they may be unavailable in patients presenting "frozen necks" or "vessel-depleted necks" due to previous treatments. We report our experience using the transverse cervical vessels (TCV) in these situations. METHODS: Retrospective chart review of microsurgical head and neck reconstructions from 2005 to 2017. We focused our analysis on secondary procedures and compared the complication rate according to whether the TCV or the ECVs were used. RESULTS: A total of 97 free flaps were performed for secondary procedures in 89 patients, mainly due to oncological recurrence and fistulae. TCV were used in 14 procedures when external carotid vessel branches were unavailable. The overall complication rate (all grade III Dindo-Clavien) was of 21% versus 35%, respectively, in the TCV and ECVs group. Grade IIIb Dindo-Clavien complications, i.e., microsurgical complications (10%) and flap loss (1%), were only recorded in the ECVs group. Other complications recorded were seroma (7% versus 1%) and hematoma (17% versus 6%) in the TCV and ECVs groups, respectively, and corresponded to grade IIIa Dindo-Claviens. CONCLUSIONS: The use of TCV is a safe second-line recipient site for microsurgical head and neck reconstruction in vessel-depleted necks. Major advantages are their anatomical position outside the previous surgical and radiation zone, lower affinity for atherosclerotic damage, and similar diameter to the pedicles of the most used flaps.

[Training in reconstructive surgery in sub-Saharan Africa : the « 2nd Chance ¼ model]. / Formation en chirurgie réparatrice en Afrique subsaharienne : le modèle « 2nd Chance ¼.

Based in Geneva since 2010, 2nd Chance's mission is the development of reconstructive surgery care in resource-limited countries with a focus on sub-Saharan Africa, through teaching and advocacy activities. We develop the surgical management of patients on the one hand, providing training for African surgical teams. On the other hand, we support surgical procedures for patients, in the areas of reconstructive surgery, giant goiters, obstetric fistulas and anesthesia so that quality care is guaranteed for the long term. Despite the hurdles caused by the COVID crisis, training programs resumed at the end of 2020, with the implementation of the 2021-2025 strategy focusing on patient care and follow-up in the surgical setting through improved peri-operative safety and prevention of complications.

Basée à Genève depuis 2010, « 2nd Chance ¼ a pour mission le développement des soins en chirurgie réparatrice dans les pays à ressources limitées avec un focus sur l'Afrique subsaharienne, au moyen d'activités d'enseignement et de plaidoyer. Nous développons la prise en charge chirurgicale des patients tout en assurant la formation des équipes chirurgicales africaines dans les domaines de la chirurgie reconstructive, des goitres géants, des fistules obstétricales et de l'anesthésie afin que des soins de qualité soient garantis à long terme. Malgré les obstacles induits par la crise du Covid-19, les programmes de formation ont repris fin 2020, avec une stratégie 2021-2025 mettant l'accent sur les soins et le suivi du patient dans son contexte chirurgical.

Angiogenesis Is Differentially Modulated by Platelet-Derived Products.

Platelet-derived preparations are being used in clinic for their role in tissue repair and regenerative processes. The release of platelet-derived products such as autologous growth factors, cytokines and chemokines can trigger therapeutic angiogenesis. In this in vitro study, we evaluated and compared the ability of three platelet-derived preparations: platelet-rich-plasma (PRP), PRP-hyaluronic acid (PRP-HA) and platelet lysates (PL) at various concentrations (5-40%) to modulate human umbilical vein endothelial cells (HUVEC) biological effects on metabolism, viability, senescence, angiogenic factors secretion and angiogenic capacities in 2D (endothelial tube formation assay or EFTA) and in 3D (fibrin bead assay or FBA). HUVEC exocytosis was stimulated with PRP and PRP-HA. Cell viability was strongly increased by PRP and PRP-HA but mildly by PL. The three preparations inhibit HUVEC tube formation on Matrigel, while PRP enhanced the complexity of the network. In the fibrin bead assay (FBA), PRP and PRP-HA stimulated all steps of the angiogenic process resulting in massive sprouting of a branched microvessel network, while PL showed a weaker angiogenic response. Secretome profiling revealed modulation of 26 human angiogenic proteins upon treatment with the platelet derived preparations. These in vitro experiments suggest that PRP and PRP-HA are effective biological therapeutic tools when sustained therapeutic angiogenesis is needed.

Production of Autologous Platelet-Rich Plasma for Boosting In Vitro Human Fibroblast Expansion.

There is currently great clinical interest in the use of autologous fibroblasts for skin repair. In most cases, culture of skin cells in vitro is required. However, cell culture using xenogenic or allogenic culture media has some disadvantages (i.e., risk of infectious agent transmission or slow cell expansion). Here, an autologous culture system is developed for the expansion of human skin fibroblast cells in vitro using a patient's own platelet-rich plasma (PRP). Human dermal fibroblasts are isolated from the patient while undergoing abdominoplasty. Cultures are followed for up to 7 days using a medium supplemented with either fetal bovine serum (FBS) or PRP. Blood cell content in PRP preparations, proliferation, and fibroblast differentiation are assessed. This protocol describes the method for obtaining a standardized, non-activated preparation of PRP using a dedicated medical device. The preparation requires only a medical device (CuteCell-PRP) and centrifuge. This device is suitable under sufficient medical practice conditions and is a one-step, apyrogenic, and sterile closed system that requires a single, soft spin centrifugation of 1,500 x g for 5 min. After centrifugation, the blood components are separated, and the platelet-rich plasma is easily collected. This device allows a quick, consistent, and standardized preparation of PRP that can be used as a cell culture supplement for in vitro expansion of human cells. The PRP obtained here contains a 1.5-fold platelet concentration compared to whole blood together, with a preferential removal of red and white blood cells. It is shown that PRP presents a boosting effect in cell proliferation compared to FBS (7.7x) and that fibroblasts are activated upon PRP treatment.

Dysfunctional Keratinocytes Increase Dermal Inflammation in Systemic Sclerosis: Results From Studies Using Tissue-Engineered Scleroderma Epidermis.

OBJECTIVE: Evidence suggests that keratinocyte-fibroblast interactions are abnormal in systemic sclerosis (SSc). The present study was undertaken to investigate potential epidermal dysfunction in SSc and its effects on dermal homeostasis. METHODS: Epidermal equivalents (EEs) were generated using keratinocytes from 6 healthy donors and 4 individuals with SSc. Skin and EE expression of markers of proliferation, differentiation, and activation was evaluated by immunohistochemistry. The transcriptomic profile of SSc EEs and healthy donor EEs was identified by RNA sequencing. EE conditioned medium (CM) was used to stimulate fibroblasts, and their production of interleukin-6 (IL-6), IL-8, matrix metalloproteinase 1 (MMP-1), type I collagen, and fibronectin was assessed by enzyme-linked immunosorbent assay. RESULTS: Compared to healthy donor EEs, SSc EEs exhibited aberrant differentiation, enhanced expression of activation markers, and a lower rate of basal keratinocyte mitosis, reproducing most of the abnormalities observed in SSc epidermis. RNA sequencing analysis revealed that, compared to healthy donor EEs, SSc EEs were characterized by lower expression of homeobox gene family members and by enhanced metabolic and oxidative stress molecular pathways. EE CM enhanced fibroblast production of IL-6, IL-8, MMP-1, type I collagen, and fibronectin (P < 0.05). Except for type I collagen and fibronectin, this effect was 2-fold higher in the presence of CM generated form SSc EEs. IL-1 was responsible, at least in part, for keratinocyte-dependent fibroblast activation. CONCLUSION: SSc EEs recapitulate the in vivo characteristics of SSc epidermis, demonstrating that SSc keratinocytes have an intrinsically altered differentiation program, possibly due to the dysregulation of genes from the homeobox family. The increased metabolic and oxidative stress associated with SSc epidermis may contribute to chronic inflammation and fibrosis of the dermis.

Quantitative magnetic resonance imaging: differentiating soft tissue implants and fillers used in cosmetic and reconstructive surgery.

OBJECTIVE: To evaluate the value of synthetic magnetic resonance imaging (MRI) and T2 mapping in distinguishing between different types of fillers in soft tissues. MATERIALS AND METHODS: Ex vivo fillers of buttock soft tissues (silicone, collagen, and different types of hyaluronic acid) were scanned using a synthetic MRI sequence at 1.5 and 3 T and an optimized T2 mapping sequence to measure the T2 relaxation times of the fillers ex vivo. Three patients addressed to assess complications with buttock fillers underwent MRI with the standard morphological sequences and an additional synthetic MRI sequence; T2 mapping was not performed for the patients. Two patients had silicone fillers, whereas the exact filler composition for the third patient was unknown. RESULTS: Measurements of T1 and T2 relaxation times of ex vivo fillers at 1.5 and 3 T using synthetic MRI showed that the silicone, collagen, and hyaluronic acid had distinct relaxation time characteristics. In vivo, the synthetic MRI correctly identified silicone in the two patients with known silicone fillers, showing low T1 and T2 values, whereas in the third patient with an unknown filler type, the synthetic MRI suggested a collagen filler, with intermediate relaxation time values. CONCLUSION: Quantitative sequences have the potential to differentiate between filler types in a noninvasive fashion.

Granulomas and nongranulomatous nodules after filler injection: Different complications require different treatments.

Dermal fillers are widely used for facial rejuvenation and reconstruction and present fewer risks than surgical approaches. Nevertheless, several complications may occur, including nodule formation. A nodule is a clinical sign corresponding to different etiologies, such as overcorrection, infection, allergic reaction, or granuloma. However, their treatment represents a diagnostic challenge. We present a retrospective review of 26 consecutive patients who underwent a biopsy for facial nodule formation more than 3 months after filler injections, to determine the diagnosis of the nodule and type of filler used. All patients were women (mean age, 57.8 years). Some patients suffered from different localizations: lip, 14 cases; nasolabial folds, 6; cheeks, 5; infraorbital region, 5; the glabella, 2; the temporal region, 1; and chin, 1 case. Only 5 (19.2%) patients knew the type of filler used, and in another 4 cases, the injector was able to provide some information. In 65.4% of cases, the filler type was unknown. Histopathological analysis revealed a "granulomatous" nodule in 30 sites and a "non-granulomatous" nodule in 4 cases. Concerning the type of filler, 5 different histopathological patterns were found. Our results demonstrate that a clinical history and histopathological analysis whether to confirm or not to confirm the diagnosis of granuloma and to identify the type of filler are essential tools to achieve an accurate diagnosis of the problem-oriented treatment of nodules after dermal filler injections. We propose an algorithm for the management of nodules after filler injection.

Severe frostbite complication after cryolipolysis: A case report.

This case report describes a full-thickness frostbite complication following cryolipolysis for subcutaneous fat reduction performed in a non-medical esthetic clinic. The deep and large abdominal wound (15 × 12 cm) required hospitalization and multiple surgical debridement before a two-step direct closure. Even though cryolipolysis is considered as a non-invasive and safe technique to reduce local adiposity, it could present some side-effects and complications. Health-care professionals should be aware of these risks and inform their patients about its potential sequelae.

The renin-angiotensin system in cutaneous hypertrophic scar and keloid formation.

Hypertrophic scar and keloid are two types of fibroproliferative conditions that result from excessive extracellular matrix production. The underlying pathological mechanism is not entirely clear. Activation of the renin-angiotensin system (RAS) is associated with fibrosis in various organs. RAS components including angiotensin II (Ang II), angiotensin AT1 and AT2 receptors, and angiotensin-converting enzyme (ACE) are expressed in the skin and act independently from the plasma RAS. AT1 receptors, which are usually the dominating receptor subtype, promote fibrosis and scar formation, while AT2 receptors inhibit the aforementioned AT1 receptor-coupled effects. Elevated angiotensin II (Ang II) levels acting on the AT1 receptor contribute to skin scar formation through increased expression of inflammatory factors such as interleukin-6 (IL-6), angiogenic factors such as vascular endothelial growth factor (VEGF) and fibrinogenic factors such as transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF), while at the same time suppressing the anti-fibrotic tissue inhibitors of matrix metalloproteinase (TIMPs). First, small clinical trials have provided evidence that inhibition of the ACE/Ang II/ AT1 receptor axis may be effective in the treatment of hypertrophic scars/keloids. This review provides a detailed overview of the current literature on the RAS in skin, wound healing and scar formation and discusses the translational potential of targeting this hormonal system for treatment and prevention of hypertrophic scars and keloids.

IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes.

Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, the expression of which is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes. IL-17E promoted the proliferation of keratinocytes in two-dimensional and three-dimensional cultures and caused the concomitant upregulation of differentiation-associated gene transcripts (e.g., keratin 10), whereas their expression was either inhibited or not changed by IL-17A. Contrary to IL-17A, IL-17E was not involved in the induction of antimicrobial proteins. Time-lapse analysis of cell movement showed that IL-17E influences cell motility, increasing both cell speed and displacement. This was associated with specific changes in the actin cytoskeleton organization and the cell-substrate adhesion. No such effects were observed upon IL-17A stimulation. In summary, we identified effects of IL-17E clearly distinct from IL-17A, pointing toward an important role of IL-17E in the physiology and pathophysiology of the epidermis.