Surgical management of giant acne keloidalis nuchae lesions.

Acne keloidalis nuchae (AKN) is a progressive inflammatory condition that affects posterior neck and occiput. Treatment options include antibiotics, steroids, lasers, radiotherapy and surgery. We present three patients with advanced 'tumor-stage' AKN that underwent radical local excision followed by either immediate or delayed skin resurfacing, and briefly review existing literature.

Immediate allograft reconstruction of the infraorbital nerve following resection of polyostotic fibrous dysplasia lesion.

Processed nerve allografts (PNA) have increasingly been used as alternative to autogenous nerve grafts to repair nerve injuries in oral-maxillofacial surgeries. This case report describes an immediate PNA reconstruction of infraorbital nerve injury sustained during the ablation of a large expansile polyostotic fibrous dysplasia centered in the left maxilla.

Ameloblastoma: clinical presentation, multidisciplinary management and outcome.

We studied 21 patients who underwent radical ameloblastoma excision followed by immediate reconstruction. Comorbidities, consumption of alcohol and/or tobacco and BMI status did not contribute to an unfavorable outcome. Giant ameloblastoma (≥5 cm) and/or tumor involving bony curvatures increased surgical complexity, the incidence of complications and hospital stay.

Use of cervicothoracic rotation flap and osteocutaneous radial forearm free flap for a complex multilayered cheek defect reconstruction.

We report the combination of osteocutaneous radial forearm free flap and extensive cervicothoracic flap to reconstruct a large through-and-through cheek and mandibular defect. In patients with difficult clinical settings, this approach reduces operative time and complications without compromising the functional and cosmetic outcomes.

Closed Incisional Negative Pressure Wound Therapy Sponge Width and Tension Off-Loading: A Laboratory Model.

Closed incisional negative pressure wound therapy (ciNPWT) has become commonplace in surgery. One mechanism ciNPWT may prevent incision site complications is by off-loading tension. This study aimed to find what width sponge using ciNPWT provides the most tension off-loading.A model was designed to test tension off-loading of a wound using ciNPWT. An incision was made in an anatomy model and closed with single stitch at the central axis. Force was applied tangentially using a force gauge at a steady rate until the wound dehisced at a peak force indicated by the 5-0 suture breaking. This was repeated 10 times for the following 4 trials: no ciNPWT and ciNPWT sponges cut a 3-, 6-, and 9-cm widths with 125 mm Hg of negative pressure.The mean peak force to dehisce the wound without ciNPWT was the lowest, 28.7 N. The mean force for the ciNPWT trials was 43.0, 38.7, and 36.4 N for V.A.C. sponges of 3, 6, and 9 cm in width, respectively. There was a statically significant difference among all the trials using one-way analysis of variance with Tukey posttest analysis with a P value of less than 0.0001.Closed incisional negative pressure wound therapy was shown to increase peak force required to dehisce an incision of up to 49.7% compared with closure without. There is an inverse relationship with sponge width and tension off-loading. The smaller the sponge, the more tension is off-loaded across the incision. Closed incisional negative pressure wound therapy with a 3-cm-wide sponge required the greatest peak force for dehiscence.

An unusual and delayed complication of hyaluronic acid filler injection: a case report.

48-year-old female with facial granulomatous nodules and fungal/bacterial infection after hyaluronic acid injection. She underwent anti-fungal/antibacterial therapy and local excision. The proposed mechanisms include inflammatory foreign body reaction and pathogen contamination. Providers must exercise caution with the use of facial fillers and demonstrate expertise in avoiding and managing potential complications.

Management of two major postoperative bleeding complications after mandible reconstruction with fibula free flap in a patient under chronic warfarin treatment.

We present a case of two separated life-threatening postoperative bleeding complications after mandible cancer resection and microsurgical fibula flap in a patient under permanent warfarin treatment. We used fresh frozen plasma, prothrombin complex concentrate to control bleedings. We consider to maintain similar patients in heparin/enoxaparin bridging for 1-2 weeks.

Total Nose and Upper Lip Replantation: A Case Report and Literature Review.

The nose plays a critical role in olfaction, air filtration and humidification, and facial aesthetics. Most nasal amputations result from animal bites, human bites, and lacerations from glass. Successful replantation yields the best aesthetic and functional outcomes and is preferred compared with multistage nasal reconstruction. However, nasal replantation is technically challenging; establishing venous outflow can be particularly difficult. A 17-year-old male sustained a complete nose and upper lip amputation in a motor vehicle accident. The midface segment was emergently replanted. Two arteries (left dorsal nasal artery, left superior labial artery) and 1 vein (branch of the left supratrochlear artery) were anastomosed using microsurgical technique. A vein graft, systemic anticoagulation, and postoperative leeching were important adjuncts. Total operative time was 10 hours. Cold ischemia time was 2 hours and warm ischemia time was 1 hour. Two arteries were anastomosed to minimize the risk of ischemia of the nose and/or upper lip. Complete survival of the replanted segment was achieved. Eighteen months postoperatively, the patient has bilateral nasal patency, intact septal support, and an excellent aesthetic result. All efforts should be made to establish a venous anastomosis during nasal replantation to maximize functional and aesthetic outcomes. Partial necrosis is common following artery-only replantation, leading to tissue loss and contracture.

Important Developments in Burn Care.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Explain the epidemiology of severe burn injury in the context of socioeconomic status, gender, age, and burn cause. 2. Describe challenges with burn depth evaluation and novel methods of adjunctive assessment. 3. Summarize the survival and functional outcomes of severe burn injury. 4. State strategies of fluid resuscitation, endpoints to guide fluid titration, and sequelae of overresuscitation. 5. Recognize preventative measures of sepsis. 6. Explain intraoperative strategies to improve patient outcomes, including hemostasis, restrictive transfusion, temperature regulation, skin substitutes, and Meek skin grafting. 7. Translate updates in the pathophysiology of hypertrophic scarring into novel methods of clinical management. 8. Discuss the potential role of free tissue transfer in primary and secondary burn reconstruction. SUMMARY: Management of burn-injured patients is a challenging and unique field for plastic surgeons. Significant advances over the past decade have occurred in resuscitation, burn wound management, sepsis, and reconstruction that have improved outcomes and quality of life after thermal injury. However, as patients with larger burns are resuscitated, an increased risk of nosocomial infections, sepsis, compartment syndromes, and venous thromboembolic phenomena have required adjustments in care to maintain quality of life after injury. This article outlines a number of recent developments in burn care that illustrate the evolution of the field to assist plastic surgeons involved in burn care.

Characterization of heterotopic ossification in burn patients.

Heterotopic ossification (HO) is a clinical condition of ectopic bone formation in soft tissue. This clinical entity has been associated with genetic disorders, traumatic injuries, and musculoskeletal surgeries. In this regard, functional impairments secondary to scar contractures seen in burn injuries may be exacerbated with underlying HO. The appropriate prevention or management of this complication is crucial to optimize outcome in burn patients. This clinical study reviews the incidence of HO in our burned patients, diagnostic methods, therapeutic approaches including surgical timing and techniques.

Deep dermal fibroblast profibrotic characteristics are enhanced by bone marrow-derived mesenchymal stem cells.

Hypertrophic scars are a significant fibroproliferative disorder complicating deep injuries to the skin. We hypothesize that activated deep dermal fibroblasts are subject to regulation by bone marrow-derived mesenchymal stem cells (BM-MSCs), which leads to the development of excessive fibrosis following deep dermal injury. We found that the expression of fibrotic factors was higher in deep burn wounds compared with superficial burn wounds collected from burn patients with varying depth of skin injury. We characterized deep and superficial dermal fibroblasts, which were cultured from the deep and superficial dermal layers of normal uninjured skin obtained from abdominoplasty patients, and examined the paracrine effects of BM-MSCs on the fibrotic activities of the cells. In vitro, deep dermal fibroblasts were found higher in the messenger RNA (mRNA) levels of type 1 collagen, alpha smooth muscle actin, transforming growth factor beta, stromal cell-derived factor 1, and tissue inhibitor of metalloproteinase 1, an inhibitor of collagenase (matrix metalloproteinase 1). As well, deep dermal fibroblasts had low matrix metalloproteinase 1 mRNA, produced more collagen, and contracted collagen lattices significantly greater than superficial fibroblasts. By co-culturing layered fibroblasts with BM-MSCs in a transwell insert system, BM-MSCs enhanced the fibrotic behavior of deep dermal fibroblasts, which suggests a possible involvement of BM-MSCs in the pathogenesis of hypertrophic scarring.

Local expression of indoleamine 2,3 dioxygenase in syngeneic fibroblasts significantly prolongs survival of an engineered three-dimensional islet allograft.

OBJECTIVE: The requirement of systemic immunosuppression after islet transplantation is of significant concern and a major drawback to clinical islet transplantation. Here, we introduce a novel composite three-dimensional islet graft equipped with a local immunosuppressive system that prevents islet allograft rejection without systemic antirejection agents. In this composite graft, expression of indoleamine 2,3 dioxygenase (IDO), a tryptophan-degrading enzyme, in syngeneic fibroblasts provides a low-tryptophan microenvironment within which T-cells cannot proliferate and infiltrate islets. RESEARCH DESIGN AND METHODS: Composite three-dimensional islet grafts were engineered by embedding allogeneic mouse islets and adenoviral-transduced IDO-expressing syngeneic fibroblasts within collagen gel matrix. These grafts were then transplanted into renal subcapsular space of streptozotocin diabetic immunocompetent mice. The viability, function, and criteria for graft take were then determined in the graft recipient mice. RESULTS: IDO-expressing grafts survived significantly longer than controls (41.2 +/- 1.64 vs. 12.9 +/- 0.73 days; P < 0.001) without administration of systemic immunesuppressive agents. Local expression of IDO suppressed effector T-cells at the graft site, induced a Th2 immune response shift, generated an anti-inflammatory cytokine profile, delayed alloantibody production, and increased number of regulatory T-cells in draining lymph nodes, which resulted in antigen-specific impairment of T-cell priming. CONCLUSIONS: Local IDO expression prevents cellular and humoral alloimmune responses against islets and significantly prolongs islet allograft survival without systemic antirejection treatments. This promising finding proves the potent local immunosuppressive activity of IDO in islet allografts and sets the stage for development of a long-lasting nonrejectable islet allograft using stable IDO induction in bystander fibroblasts.

Transdifferentiated circulating monocytes release exosomes containing 14-3-3 proteins with matrix metalloproteinase-1 stimulating effect for dermal fibroblasts.

Fibroblasts are major cellular components of healing wounds. In this regard, it remains to be fully understood how different paracrine signals may influence the final collagen/matrix metalloproteinase (MMP) balance in resident fibroblasts. Our previous reports have demonstrated that circulating stem cells and monocytes can be transdifferentiated into "keratinocyte-like cells" under certain culture conditions. These transformed cells are able to stimulate MMP-1 expression in dermal fibroblasts. However, the underlying mechanism of this cell-to-cell interaction is unknown. This study describes exosomes as a major delivery system that keratinocyte-like cells use to release proteins into the conditioned media. The exosomes exhibited distinctive size, density, and saucer-like morphology. Using PKH-26 and GFP-adenovirus infection, we demonstrated that exosomes are able to fuse and then release their protein content into dermal fibroblasts. Mass spectrometry and Western blotting identified five 14-3-3 isoforms (beta, gamma, epsilon, tau, and zeta) as MMP-1 stimulating factors for dermal fibroblasts. Immunoprecipation assays confirmed that these 14-3-3 isoforms account for almost the entire MMP-1 up-regulation induced by exosomes. In summary, our results demonstrated that circulating monocytes stimulated to be transformed into "keratinocyte-like cells" could promote an anti-fibrogenic commitment of dermal fibroblasts via exosomal 14-3-3 proteins.

Circulating monocytes have the capacity to be transdifferentiated into keratinocyte-like cells.

Transdifferentiation is a process in which the original commitment of a cell is changed to give rise to unexpected peripheral mature cells. Our previous report showed that circulating stem cells can generate keratinocyte-like cells (KLCs). However, it remains to be determined whether or not other peripheral blood mononuclear cells (PBMC) subsets have the potential to follow the same cell fate. In this study, the cell transdifferentiation of circulating CD14(+) monocytes into KLCs and their regulatory effect on matrix metalloproteinase-1 (MMP-1) expression in dermal fibroblasts were evaluated. The results showed that monocytes isolated from peripheral blood mononuclear cells have the capacity to generate KLCs. These transdifferentiated cells exhibited, along with a keratinocyte-like morphology, a characteristic profile consisting in stratifin(+), cytokeratins(+) (types I and II), CD14(low), and involucrin(+) on day 21 in culture. Similar to keratinocyte-conditioned media, KLC-derived conditioned media were able to induce an increase in the MMP-1 expression in dermal fibroblasts. This effect was significantly reduced by using 14-3-3 protein-depleted KLC-conditioned media. Our findings show the potential transdifferentiation of circulating CD14(+) monocytes into KLCs and their regulatory effect on MMP-1 expression in dermal fibroblasts.

Transdifferentiation of peripheral blood mononuclear cells into epithelial-like cells.

Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3varsigma for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3varsigma and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P

The role of stratifin in fibroblast-keratinocyte interaction.

Stratifin is a member of 14-3-3 protein family, a highly conserved group of proteins constituted by seven isoforms. They are involved in numerous crucial intracellular functions such as cell cycle and apoptosis, regulation of signal transduction pathways, cellular trafficking, cell proliferation and differentiation, cell survival, and protein folding and processing, among others. At epidermal level, stratifin (also called 14-3-3 sigma) has been described as molecule with relevant functions. For instance, this isoform is a marker associated with keratinocyte differentiation. In this maturation process, the presence of dominant negative molecules of p53 induces a "stemness condition" of keratinocyte precursor cells and suppression of stratifin expression. In addition, the recently described keratinocyte-releasable form of stratifin is involved in dermal fibroblast MMP-1 over-expression through c-Fos and c-Jun activity. This effect is mediated, at least in part, by p38 mitogen-activated protein kinase (MAPK). Other MMP family members such as stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), neutrophil collagenase (MMP-8), and membrane-type MMP-24 (MT5-MMP) are also up-regulated by stratifin. Within fibroproliferative disorder of skin, hypertrophic scar and keloids exhibit a high content of collagen, proteoglycans, and fibronectin. Thus, the MMP profile induced by stratifin is an interesting starting point to establish new therapeutic tools to control the process of wound healing. In this review, we will focus on site of synthesis and mode of action of stratifin in skin and wound healing.