Lessons Learned From Twenty-Eight Cases of Burns Following Breast Reconstruction: An Underestimated Complication Requiring Inclusion in Consent Information.

BACKGROUND: There has over recent years been a constant increase in annual breast reconstruction figures. Although reports indicate that burns following breast reconstruction are a rare occurrence, there has nevertheless been a relative increase in cases. The key underlying causes of this type of condition remain unknown. OBJECTIVES: The authors launched a new study on the demographic characteristics of burns in the breast reconstruction population with the inclusion of up-to-date data to assess cases and contributing factors. METHODS: The study was a multicenter retrospective review of patients who underwent any type of breast reconstruction and subsequently sustained burn injuries. RESULTS: Twenty-eight cases of burn injury following breast reconstruction were documented; 6 involved autologous flaps and 22 involved implants. Nine of the 10 implant exposure cases had previous history of radiotherapy, but there was no statistically significant difference between previous radiotherapy history and implant exposure (P = 0.32). Of the 13 cases sustaining full-thickness burns, a large number included implant-based reconstruction (n = 12, 92%), although no statistically significant difference was observed between type of reconstruction and incidence of full-thickness burns (P = 0.17). CONCLUSIONS: Each patient undergoing breast reconstruction should be advised of the potential risks and instructed to avoid significant heat exposure and steer clear of dark-colored bathing suits. At the time of writing, this information has yet to be included in the vast majority of surgery-related informed consent documents.

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16- Human Blood Monocytes in Serum-Free Condition.

Langerhans cells (LCs) are epithelial APCs that sense danger signals and in turn trigger specific immune responses. In steady-state, they participate in the maintenance of peripheral tolerance to self-antigens whereas under inflammation LCs efficiently trigger immune responses in secondary lymphoid organs. It has been demonstrated in mice that LC-deprived epithelia are rapidly replenished by short half-life langerin-expressing monocyte-derived LCs (MDLCs). These surrogate LCs are thought to be progressively replaced by langerin(high) LCs arising from self-renewing epithelial precursors of hematopoietic origin. How LCs arise from blood monocytes is not fully understood. Hence, we sought to characterize key factors that induce differentiation of langerin(high)-expressing monocyte-derived Langerhans-like cells. We identified GM-CSF and TGF-ß1 as key cytokines to generate langerin(high)-expressing cells but only in serum-free conditions. These cells were shown to express the LC-specific TROP-2 and Axl surface markers and contained Birbeck granules. Surprisingly, E-cadherin was not spontaneously expressed by these cells but required a direct contact with keratinocytes to be stably induced. MDLCs induced stronger allogeneic T cell proliferations but released low amounts of inflammatory cytokines upon TLR stimulation compared with donor-paired monocyte-derived dendritic cells. Immature langerin(high) MDLCs were responsive to MIP-3ß/CCL20 and CTAC/CCL27 chemokine stimulations. Finally, we demonstrated that those cells behaved as bona fide LCs when inserted in a three-dimensional rebuilt epithelium by becoming activated upon TLR or UV light stimulations. Collectively, these results prompt us to propose these langerin(high) MDLCs as a relevant model to address LC biology-related questions.

Eight-Year Safety Data for Round and Anatomical Silicone Gel Breast Implants.

BACKGROUND: The safety and efficacy of all medical devices, including breast implants, is important and consistent performance is best shown by undertaking long-term clinical and vigilance studies. Local complications such as capsular contracture and rupture are risks often associated with breast implant surgery. OBJECTIVES: The authors investigate and evaluate the safety and performance of Eurosilicone's (Eurosilicone S.A.S, Apt Cedex, France) Cristalline Paragel breast implants at 8 years postimplantation. METHODS: In this prospective clinical study, 995 Eurosilicone textured cohesive Cristalline Paragel mammary implants were implanted in 526 women undergoing augmentation and reconstructive surgery at 17 centers across France. Complications were recorded at 3 months and annually thereafter for 8 years. Descriptive statistics were used and key complications were analysed using the Kaplan-Meier method. RESULTS: Capsular contracture was reported in 8.5% of implants across all cohorts through 8 years. The Kaplan-Meier risk of capsular contracture (Baker Grade III/IV) per implant was 8.4% in the primary augmentation cohort and 18.0% in the primary reconstruction cohort. Eight implant ruptures were identified by surgeon examination during this follow-up period. The Kaplan-Meier risk of rupture occurring within 8 years postimplantation, across all cohorts, was 1.4% per patient and 0.9% per implant. Actual implant removal rate (explantation/exchange) was 6.0% and 13.8% for primary augmentation and primary reconstruction, respectively. Actual rates of local complications including infection and seroma were low with risk rates of 0.6% and 0.2% by subject. CONCLUSIONS: This multicenter clinical study involving Eurosilicone's silicone gel breast implants in both round and shaped profiles demonstrates an excellent safety and efficacy profile through 8 years.

Comparison of limb reconstruction with vascularized fibula flap versus induced membrane technique in 54 pediatric cases over 16 years.

BACKGROUND: Children's bone loss of limbs represents a significant challenge for surgeons, especially given that children are growing individuals. In the pediatric population, we compared bone reconstruction using vascularized fibula flaps with the induced membrane technique. The primary purpose of this study was to evaluate the delay and quality of consolidation. METHODS: Data from patients who underwent limb reconstruction using either the fibula flap or the induced membrane were retrospectively collected from files across two centers. Perioperative and long-term complications were documented, along with functional and aesthetic outcome. RESULTS: Between 2004 and 2020, 31 children underwent limb reconstruction using a fibula flap, and 13 patients were treated using the induced membrane technique. The etiologies included 76% tumors, 20% congenital pseudarthroses, and 3.7% infections. The median size of the bone resection was 12.5 cm (range: 1.8 to 31 cm). The median time to consolidation after free fibula flap transfer was 10 months (range: 2 to 55 months) versus 7.5 months (range: 1 to 64 months) for the Masquelet technique (p = 0.54). Limb length inequality occurred in 52% of fibula cases and 39% of the induced membrane cases (p = 0.55). CONCLUSIONS: Both of free fibula flap and the induced membrane technique are effective options for bone reconstructing long bones in children. These techniques yield good functional outcomes and have comparable consolidation times.

Reduction of skin closure time without loss of healing quality: a multicenter prospective study in 100 patients comparing the use of Insorb absorbable staples with absorbable thread for dermal suture.

The authors report the results of a multicenter prospective study evaluating a novel technology: dermal suture using absorbable staples composed of polylactic and polyglycolic acids. From January to June 2009, 59 dermal sutures were performed with Insorb absorbable staples and 41 with absorbable thread. All patients in the study underwent abdominal dermolipectomy (N = 65) or surgery for breast hypertrophy (N = 35). The purpose of the study was to compare the closure time and healing quality obtained with the 2 methods. Ninety-five patients were reexamined by the surgeon after 1 year of follow-up to assess scar width, suppleness, inflammation, and hypertrophy. The overall results were good and quite similar for the 2 groups. Thus, the use of Insorb staples reduced closure time while ensuring good healing quality.

Avant-propos.

Hard-to-heal wounds are a problem for both patients and caregivers. The biofi lm is one of the local factors of delayed healing. Wound hygiene carried out in 4 steps (cleansing, debridement, refashion - care of the edges, and dressing) constitutes the basis of proactive and curative anti-biofi lm strategies.

IL-34 deficiency impairs FOXP3+ Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis.

BACKGROUND: Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remains to be determined. METHODS: We generated Il34-/- rats and using both Il34-/- rats and mice, we investigated their phenotype under inflammatory conditions. Using Il34-/- rats, we further analyzed the impact of the absence of expression of IL-34 for CD4+ Tregs suppressive function. We investigated the potential of IL-34 in human disease to prevent xenogeneic GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, taking advantage of a biocollection, we investigated the correlation between presence of IL-34 in the serum and kidney transplant rejection. RESULTS: Here we report that the absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with production of multiple auto-antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS- and TNBS-colitis in Il34-/- animals. Moreover, we revealed the striking inability of Il34-/- CD4+ Tregs to protect Il2rg-/- rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34+/+ CD4+ Tregs. We also showed that IL-34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL-34 in the serum is associated with a longer rejection-free period in kidney transplanted patients. CONCLUSION: Altogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL-34 in human transplantation and auto-immunity. HIGHLIGHTS: -Absence of expression of IL-34 in Il34-/- rats and mice leads to an unstable immune phenotype, with a production of multiple auto-antibodies and exacerbated immune pathology under inflammatory conditions. -Il34-/- CD4+ Tregs are unable to protect Il2rg-/- rats from colitis induced by transfer of pathogenic cells. -IL-34 treatment delayed EAE in mice, as well as acute GVHD and human skin allograft rejection in immune-humanized immunodeficient NSG mice.

Risk factors and therapeutic strategy after failure of free flap coverage for lower-limb defects.

From 2004 to 2007, 148 limb free flaps were performed in a series of 138 patients at the University Hospital in Nantes, France. Flaps were successful in 127 instances (rate: 86%; group A) and failed in 21 (group B). An analysis of the various factors (pre-, intra-, and postoperative) in both groups that may have influenced the outcome of surgery identified the following: operating time, cold ischemia time, and the interval before reoperation. This report is based on our experience in managing 21 free flap failures during reconstructive surgery of the limbs. The causes of failure were analyzed, and possible therapeutic strategies defined (i.e., a second free flap procedure, a pedicle flap, coverage with artificial dermis, or amputation). In our opinion, careful analysis of the causes of flap failure is essential to an appropriate choice of subsequent therapeutic strategy.

Preliminary Results of the "Capasquelet" Technique for Managing Femoral Bone Defects-Combining a Masquelet Induced Membrane and Capanna Vascularized Fibula with an Allograft.

We describe the preliminary results of a novel two-stage reconstruction technique for extended femoral bone defects using an allograft in accordance with the Capanna technique with an embedded vascularized fibula graft in an induced membrane according to the Masquelet technique. We performed what we refer to as "Capasquelet" surgery in femoral diaphyseal bone loss of at least 10 cm. Four patients were operated on using this technique: two tumors and two traumatic bone defects in a septic context with a minimum follow up of one year. Consolidation on both sides, when achieved, occurred at 5.5 months (4-7), with full weight-bearing at 11 weeks (8-12). The functional scores were satisfactory with an EQ5D of 63.3 (45-75). The time to bone union and early weight-bearing with this combined technique are promising compared to the literature. The osteoinductive role of the induced membrane could play a positive role in the evolution of the graft. Longer follow up and a larger cohort are needed to better assess the implications. Nonetheless, this two-stage technique appears to have ample promise, especially in a septic context or in adjuvant radiotherapy in an oncological context.

A Novel Absorbable Stapler Provides Patient-Reported Outcomes and Cost-Effectiveness Noninferior to Subcuticular Skin Closure: A Prospective, Single-Blind, Randomized Clinical Trial.

BACKGROUND: Deep dermal suturing is critical for scar quality outcomes. The authors evaluated a new, fast medical device for dermal suturing, with the hypothesis of noninferiority with regard to clinical scar and cost-effectiveness. METHODS: A prospective, patient-blind, randomized, multicenter noninferiority study in 26 French hospitals was conducted. Patients were randomized 1:1 to suturing with conventional thread or a semiautomatic stapler. The Patient Scar Assessment Scale was rated at 3 months for primary endpoint effectiveness. Secondary endpoints were cost-effectiveness of the two suturing methods, prevalence of complications, suturing/operating time, Observer Scar Assessment Scale and Patient Scar Assessment Scale score, scar aesthetic quality 18 months after surgery, and occupational exposure to blood during surgery. RESULTS: Six hundred sixty-four patients were enrolled, 660 were randomized, and 649 constituted the full analysis (stapler arm, n = 324; needle arm, n = 325). Primary endpoint Patient Scar Assessment Scale score in the stapler arm was not inferior to that in the needle arm at 3 months or after 18 months. The mean operating time was 180 minutes in the stapler arm and 179 minutes in the needle arm (p = not significant). The mean suturing time was significantly lower in the stapler arm (p < 0.001). There were seven occupational exposures to blood in the needle arm and one in the stapler arm. The two arms did not differ significantly in terms of complications (p = 0.41). The additional cost of using the device was &OV0556;51.57 for the complete-case population. CONCLUSION: Wound healing outcome was no worse than with conventional suturing using a semiautomatic stapler and associated with less occupational exposure to blood. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

ALGINATE versus NPWT in the Preparation of Surgical Excisions for an STSG: ATEC Trial.

A calcium alginate dressing (ALGINATE) and negative pressure wound therapy (NPWT) are frequently used to treat wounds which heal by secondary intention. This trial compared the healing efficacy and safety of these 2 treatments. METHODS: This randomized, non-inferiority trial enrolled patients who underwent skin excision (>30 cm2), which was left open to heal by secondary intention. They received ALGINATE or NPWT by a centralized randomization. Follow-up was performed weekly until optimal granulation tissue was obtained. The primary outcome was time to obtain optimal granulation tissue for a split thickness skin graft take (non-inferiority margin: 4 days). Secondary outcomes were occurrence of adverse events (AEs) and impact of the treatments on the patient's daily life. RESULTS: ALGINATE and NPWT were applied to 47 and 48 patients, respectively. The mean time to optimal granulation was 19.98 days (95% CI, 17.7-22.3) with ALGINATE and 20.54 (95% CI, 17.6-23.5) with NPWT. Between group difference was -0.56 days (95% CI -4.22 to 3.10). The non-inferiority of ALGINATE versus NPWT was demonstrated. No AE related to the treatment occurred with ALGINATE versus 14 AEs with NPWT. There was no difference in the impact of the treatments on the patient's daily life. CONCLUSION: This trial demonstrates that ALGINATE has a similar healing efficacy to that of NPWT and that is markedly better with regard to patient safety.

Coverage of clavicular area by a pectoralis minor pedicle flap: anatomical study and description of three clinical cases.

As the data in the literature concerning the vascularization of the pectoralis minor were conflicting, we conducted a new anatomic study on cadavers preliminary to clinical application of a pedicle flap for clavicular coverage in 3 patients. Twenty flaps were dissected, yielding numerous anatomic variations. In all cases, the principal arteries penetrated the muscle in its upper part, either posteriorly or posterolaterally. This anatomic study justified the use of the pectoralis minor as a pedicle flap, with turnover just below the coracoid process. Accordingly, 3 cases of clavicular defects were treated successfully. Reports in the literature propose an adipofascial turnover flap or a pectoralis major flap for clavicular coverage. The pectoralis minor pedicle flap is easy to dissect and reproducible, involving minor esthetic sequelae and no functional complications. This flap, which has never been described in this application, would appear to be suitable for first-line treatment in this indication.

Ten-Year Safety Data for Eurosilicone's Round and Anatomical Silicone Gel Breast Implants.

BACKGROUND: Although silicone breast implants have been available for over 60 years, their safety and efficacy continue to be assessed via long-term clinical and vigilance studies. Complications often associated with breast implant surgery include but are not limited to capsular contracture and rupture. OBJECTIVE: The authors investigate and evaluate the safety and performance of Eurosilicone's (Eurosilicone S.A.S, Apt Cedex, France) Cristalline Paragel breast implants at least 10 years postimplantation. METHODS: Nine hundred and ninety-five of Eurosilicone's textured mammary implants were implanted in 526 women undergoing primary (423 patients) and revision surgery (103 patients) at 17 centers throughout France. Complications were recorded at 3 months and annually thereafter for 10 years. Descriptive statistics were used and the Kaplan-Meier method was utilized to analyze key complications. RESULTS: Seventy-four women (98 implants) experienced capsular contracture across all cohorts. The Kaplan-Meier 10-year cumulative risk of capsular contracture (Baker Grade III/IV) per implant was 11.5% in the primary augmentation cohort and 25.2% in the primary reconstruction cohort. Sixteen implant ruptures were observed by surgeon examination giving a Kaplan-Meier risk of 3.8% per patient and 3.5% per implant. Surgical re-intervention (explantation/exchange) was reported 80 times resulting in a Kaplan-Meier cumulative risk of 13.3% and 31.6% for primary augmentation and primary reconstruction, respectively, per patient. Local complication rates including infection and seroma were low with risk rates of 0.6% and 0.2% by subject. CONCLUSIONS: This multicenter clinical study demonstrates the long-term safety and efficacy profile through 10 years for Eurosilicone round and anatomical silicone gel breast implants.

Human CD8+ Tregs expressing a MHC-specific CAR display enhanced suppression of human skin rejection and GVHD in NSG mice.

Polyclonal CD8+CD45RClow/- Tregs are potent regulatory cells able to control solid organ transplantation rejection and even induce tolerance. However, donor major histocompatibility complex (MHC)-specific Tregs are more potent than polyclonal Tregs in suppressing T-cell responses and preventing acute as well as chronic rejection in rodent models. The difficulty of identifying disease-relevant antigens able to stimulate Tregs has reduced the possibility of obtaining antigen-specific Tregs. To bypass this requirement and gain the advantage of antigen specificity, and thus improve the therapeutic potential of CD8+ Tregs, we stably introduced a chimeric antigen receptor (CAR) derived from a HLA-A*02 antigen-specific antibody (A2-CAR) in human CD8+ Tregs and developed a clinically compatible protocol of transduction and expansion. We demonstrated that A2-CAR CD8+ Tregs were not phenotypically altered by the process, were specifically activated, and did not exhibit cytotoxic activity toward HLA-A*02+ kidney endothelial cells (ECs). We showed that A2-CAR CD8+ Tregs were more potent suppressors of immune responses induced by HLA-A*02 mismatch than control-CAR CD8+ Tregs, both in vitro and in vivo, in models of human skin graft rejection and graft-versus-host disease (GVHD) in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. We showed that integrity of human skin graft was preserved with A2-CAR CD8+ Tregs at least 100 days in vivo after administration, and that interaction between the A2-CAR CD8+ Tregs and HLA-A*02+ kidney ECs resulted in a fine-tuned and protolerogenic activation of the ECs without cytotoxicity. Together, our results demonstrated the relevance of the CAR engineering approach to develop antigen-specific CAR-CD8+ Tregs for clinical trials in transplantation, and potentially in other diseases.

CICAFAST: comparison of a biological dressing composed of fetal fibroblasts and keratinocytes on a split-thickness skin graft donor site versus a traditional dressing: a randomized controlled trial.

BACKGROUND: Wound repair is one of the most complex biological processes of human life. Allogeneic cell-based engineered skin substitutes provide off-the-shelf temporary wound coverage and act as biologically active dressings, releasing growth factors, cytokines and extracellular matrix components essential for proper wound healing. However, they are susceptible to immune rejection and this is their major weakness. Thanks to their low immunogenicity and high effectiveness in regeneration, fetal skin cells represent an attractive alternative to the commonly used autologous and allogeneic skin grafts. METHODS/DESIGN: We developed a new dressing comprising a collagen matrix seeded with a specific ratio of active fetal fibroblasts and keratinocytes. These produce a variety of healing growth factors and cytokines which will increase the speed of wound healing and induce an immunotolerant state, with a slight inflammatory reaction and a reduction in pain. The objective of this study is to demonstrate that the use of this biological dressing for wound healing at the split-thickness skin graft (STSG) donor site, reduces the time to healing, decreases other co-morbidities, such as pain, and improves the appearance of the scar. This investigation will be conducted as part of a randomized study comparing our new biological dressing with a conventional treatment in a single patient, thus avoiding the factors that may influence the healing of a graft donor site. DISCUSSION: This clinical trial should enable the development of a new strategy for STSG donor-wound healing based on a regenerative dressing. The pain experienced in the first few days of STSG healing is well known due to the exposure of sensory nerve endings. Reducing this pain will also reduce analgesic drug intake and the duration of sick leave. Our biological dressing will meet the essential need of surgeons to "re-crop" from existing donor sites, e.g., for thermal-burn patients. By accelerating healing, improving the appearance of the scar and reducing pain, we hope to improve the conditions of treatment for skin grafts. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03334656 . Registered on 7 November 2017.

Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acid.

Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6-1 prostate tumor cells were characterized in vitro at the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studied in vivo on bone lesion development and in vitro on AT6-1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6-1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observed in vivo after intraosseous AT6-1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation.

Management of finger deep burns: The interest of local flaps.

INTRODUCTION: The management of finger deep burns is still problematic for the surgeon. Due to the fineness and the thickness of the subcutaneous tissue, after excision there is an important risk of exposure of the underlying tissue like bone, nerve or tendons. Local flaps (random pattern flap and pedicle flap) allowed ensuring a good quality covering with a tissue with many advantages (good thickness, sensitivity). On the contrary of all other techniques, flaps can be used independently from the vascular quality of the wound bed. Despite those advantages, the literature is poor to report the experience of flap in the management of finger deep burn. MATERIAL AND METHODS: We report our experience in the use of such technique with a series of 49 flaps. The cohort consisted of 34 patients (22 men and 12 women) who were treated in our unit between 2003 and 2012. RESULTS: Of the 49 flaps made, 71,4% were homodactyl flaps. 22,5% were heterodactyl flaps and 6,1% were intermetacarpian (second space) flaps. The rate of success was 87,8%. We reviewed 16 patients out of 34 patients operated, 20 of the 49 flaps performed (40,8%). The patients were reviewed by an independent surgeon. The average follow-up at this consultation was 4,25±2,46 years. The monofilament test was positive for 17 flaps (85% of cases). For the Weber's test, we found a normal perception threshold for 11 flaps (55%), with an average test at 2,8mm (2-4mm). Normal motricity was found at the donor site in 14 of the 16 patients evaluated for 18 of the 20 revised flaps (90% of cases). In terms of cosmetic result, the average overall score obtained at the patient's own evaluation was 0.85. That obtained by the evaluator was equal to 0.55, with no significant difference (scale range from 0 best results to 5 worse results). DISCUSSION: Hand and finger burns are frequent and benefit from rapid, high-quality coverage, enabling early mobilization to combat secondary stiffness problems. The high success rate of our series, as well as the quality of the functional and cosmetic results obtained, demonstrate the reliability and the interest of the digital flaps.