Complications Following Tissue Expander-Based Reconstruction in Pediatric Burn Injuries: A Retrospective Analysis.

BACKGROUND: Tissue expansion has been widely used to reconstruct soft tissue defects following burn injuries in pediatric patients, allowing for satisfactory cosmetic and functional outcomes. Factors impacting the success of tissue expander (TE)-based reconstruction in these patients are poorly understood. Herein, we aim to determine the risk factors for postoperative complications following TE-based reconstruction in pediatric burn patients. METHODS: A retrospective review of pediatric patients who underwent TE placement for burn reconstruction from 2006 to 2019 was performed. Primary outcomes were major complications (TE explantation, extrusion, replacement, flap necrosis, unplanned reoperation, readmission) and wound complications (surgical site infection and wound dehiscence). Descriptive statistics were calculated. The association between primary outcomes, patient demographics, burn characteristics, and TE characteristics was assessed using the chi-squared, Fisher's exact, and Mann-Whitney U tests. RESULTS: Of 28 patients included in the study, the median [interquartile range (IQR)] age was 6.5 (3.3-11.8) years, with a follow-up of 12 (7-32) months. The majority were males [n = 20 (71%)], Black patients [n = 11 (39%)], and experienced burns due to flames [n = 78 (29%)]. Eleven (39%) patients experienced major complications, most commonly TE premature explantation [n = 6 (21%)]. Patients who experienced major complications, compared to those who did not, had a significantly greater median (IQR) % total body surface area (TBSA) [38 (27-52), 10 (5-19), P = 0.002] and number of TEs inserted [2 (2-3), 1 (1-2), P = 0.01]. Ten (36%) patients experienced wound complications, most commonly surgical site infection following TE placement [n = 6 (21%)]. Patients who experienced wound complications, compared to those who did not, had a significantly greater median (IQR) %TBSA [35 (18-45), 19 (13-24), P = 0.02]. CONCLUSION: Pediatric burn injuries involving greater than 30% TBSA and necessitating an increasing number of TEs were associated with worse postoperative complications following TE-based reconstruction.

Cervical Necrotizing Fasciitis: A Severe Sequela of Open Mandibular Fracture and Delay in Treatment.

Cervical necrotizing fasciitis (CNF) is a rare condition in the United States, with very few cases reported as a sequela of mandibular fracture. The authors describe the case of a 40-year-old man with poor oral health and no significant past medical history who developed CNF following delayed treatment of an open mandibular fracture, leading to life-threatening septic shock, thrombophlebitis of the internal jugular vein, and septic emboli to the lungs. Successful management of this patient was accomplished by serial surgical debridement, the administration of broad-spectrum antibiotics, and hemodynamic support. Eventual reconstruction was performed with external fixation of the mandible fracture and split-thickness skin grafting for the left neck and chest wound. The authors recommend early treatment of open mandibular fractures for immunocompromised patients or patients with poor oral hygiene to avoid the rare but potentially fatal complication of CNF and highlight external fixation as a useful technique in select cases of complex mandibular fractures.

Management of Bilateral Edentulous Mandible Fractures Through an Intraoral Approach Using CAD/CAM Technology: A Case Report.

The surgical management of edentulous mandible fractures presents unique challenges secondary to poor bone stock and the absence of dentition to assist with fracture reduction. In complex injury patterns, such as bilateral edentulous mandible fractures, an external approach is often necessary to achieve adequate reduction and adaptation of a load-bearing reconstruction plate. We report a case in which computer-assisted design/computer-assisted manufacturing (CAD/CAM) was applied as an adjunct for the acute management of bilateral edentulous mandible fractures in a 58-year-old man. CAD/CAM technology was used to fabricate a patient-specific reconstruction plate and a maxillomandibular splint, which facilitated the successful treatment of this complex injury through an intraoral approach. This case highlights the potential of CAD/CAM technology to improve operative efficiency and clinical outcomes in the acute management of complex edentulous mandible fractures.

Contemporary Management of Mandibular Fracture Nonunion-A Retrospective Review and Treatment Algorithm.

PURPOSE: Nonunion is an uncommon complication after mandibular fractures. The purpose of this investigation was to compare outcomes of patients with mandibular fracture nonunion who were treated with a 1- versus 2-stage approach and propose a pragmatic treatment algorithm for surgical management based on preoperative characteristics. MATERIALS AND METHODS: The authors conducted a retrospective study consisting of patients who presented to 2 level 1 trauma centers for the management of mandibular fracture nonunion over a 10-year period. The primary predictor variable was 1- versus 2-stage treatment. Outcomes were examined to propose a treatment algorithm. RESULTS: Eighteen patients were included in the study. The sample's mean age was 44.0 ± 19.3 years and most were men (88.9%). Mandibular angle and body accounted for 77.8% of cases. A single-stage approach was used in 13 patients (72.2%). Bone grafts or vascularized bone flaps were required in 13 patients (72.2%). Patients who required 2-stage treatments had intraoral soft tissue defects. Mean length of follow-up was 13.3 ± 20.4 months. All patients achieved bony union, with complications occurring in 5 patients (27.8%). The authors' 10-year experience was used to formulate a treatment algorithm based on bony defect size and soft tissue status, which can be used to inform optimal surgical management. CONCLUSIONS: Nonunion of mandibular fractures is an infrequent and complex condition requiring careful and deliberate surgical management. A single-stage approach is appropriate in most cases and does not negatively affect outcomes. Bony defect size and soft tissue status are essential parameters for determining the approach and timing of reconstruction.

Vascular Endothelial Growth Factor Induction of Muscle-Derived Stem Cells Enhances Vascular Phenotype While Preserving Myogenic Potential.

BACKGROUND: Previous work by our group and other laboratories have revealed that muscle-derived stem cells (MDSCs) may contain both myogenic and endothelial progenitors, making MDSCs a promising option for skeletal muscle regeneration. The purpose of this study was to investigate the impact of vascular endothelial growth factor (VEGF) induction on the vascular and myogenic potential of MDSCs. METHODS: Muscle-derived stem cells were isolated from 4- to 8-week-old C57BL/6J mice using a preplate technique and recombinant human VEGFa was used as the induction agent. Cellular proliferation and migration were assessed using serial imaging and wound healing assays, respectively. Myosin heavy chain staining was performed to assess MDSC myotube formation. Vascular potential of MDSCs was measured by expression of CD31 and in vitro capillary tube formation. RESULTS: Vascular endothelial growth factor stimulation led to a dose-dependent increase in MDSC proliferation (P < 0.05) and migration kinetics (P < 0.01). Control MDSCs had low levels of baseline expression of CD31, which was significantly upregulated by VEGF stimulation. Similarly, MDSCs demonstrated a basal capability for capillary tube formation, which was significantly increased after VEGF induction as evidenced by increased branches (5.91 ± 0.58 vs 9.23 ± 0.67, P < 0.01) and total tube length (11.73 ± 0.97 vs 18.62 ± 1.57 mm, P < 0.01). Additionally, the myogenic potential of MDSCs as measured by fusion index remained unchanged with increasing concentration of VEGF up to 250 ng/mL (P = 0.77). CONCLUSIONS: Vascular endothelial growth factor induction enhances MDSC proliferation, migration, and endothelial phenotypes without negatively impacting myogenic potential. These results suggest that VEGF stimulation may improve vascularization of MDSC-based strategies for skeletal muscle regeneration.

A modified approach to component separation using biologic graft as a load-sharing onlay reinforcement for the repair of complex ventral hernia.

BACKGROUND: Components separation has been proposed as a means to close large ventral hernia without undue tension. We report a modification on open components separation that allows for the incorporation of onlaid noncrosslinked porcine acellular dermal matrix (Strattice, LifeCell Corp, Branchburg, NJ) as a load-sharing structure. METHODS: This was a retrospective case series including all cases using Strattice from July 2008 through December 2009. Data evaluated included patient demographics, comorbidities associated with risk of recurrence, hernia grade, and postoperative complications. The primary outcomes were hernia recurrence and surgical site occurrences. RESULTS: There were 58 patients; 60.8% presented with a recurrent incisional hernia. Average length of follow-up was 384 days. There were 4 hernia recurrences (7.9%). Complications included surgical site infection (20.7%), seroma (15.5%), and hematoma (5%) requiring intervention. Four deaths occurred in the series due to causes unrelated to the hernia repair, only 1 within 30 days of operation. CONCLUSIONS: This series demonstrates that components separation reinforced with noncrosslinked porcine acellular dermal matrix onlay is an efficacious, single-stage repair with a low rate of recurrence and surgical site occurrences.

Contemporary Management of Zygomaticomaxillary Complex Fractures.

Zygomaticomaxillary complex fracture is one of the most commonly treated facial fractures. Accurate reduction and stable fixation of the zygoma are required to restore facial symmetry and projection and avoid functional sequalae from changes in orbital volume. Achieving optimal outcome is challenging due to the complex three-dimensional anatomy and limited visualization of all affected articulations of the zygoma. This article provides an updated overview of the evaluation and management of zygomaticomaxillary complex fractures based on available evidence and clinical experience at our center. The importance of soft tissue management is emphasized, and approaches to internal orbital reconstruction are discussed. While evidence remain limited, intraoperative imaging and navigation may prove to be useful adjuncts in the treatment of zygomaticomaxillary fractures.

Le Fort II Distraction with Simultaneous Zygomatic Repositioning.

Severe midface hypoplasia is often managed by Le Fort III distraction. Le Fort II distraction with zygomatic repositioning is a modification of the Le Fort III distraction operation aimed to correct abnormal facial ratios of patients with greater central than lateral midface deficiency. The operation starts with Le Fort III osteotomies and is followed by separation and fixation of bilateral zygomas. The central nasomaxillary Le Fort II segment is then distracted to achieve independent movements of the central and lateral midface. The Le Fort II zygomatic repositioning operation has become our procedure of choice for patients with Apert facial dysmorphology.

Counterclockwise Craniofacial Distraction Osteogenesis.

Anatomic studies have identified that patients with Treacher Collins syndrome and some cases of bilateral craniofacial microsomia are characterized by multilevel airway obstruction as a result of hypoplasia and clockwise rotation of the maxillomandibular complex. Patients often remain tracheostomy-dependent despite multiple airway surgeries. Counterclockwise craniofacial distraction osteogenesis aims to correct the facial skeletal deformity and expand the upper airway volume by rotating the subcranial complex en bloc around the nasofrontal junction. Early results have demonstrated significant increases in the nasopharyngeal and oropharyngeal airway volumes with successful decannulation in a majority of patients who have undergone this operation.

What Is the Impact of Postoperative Antibiotic Prophylaxis on Tissue Expander Infection Rates in Pediatric Patients?

BACKGROUND: Tissue expansion in the pediatric population can be complicated by high rates of infection and extrusion. The aim of this study was to examine the impact of postoperative antibiotic prophylaxis on infectious complications. METHODS: A retrospective study of all pediatric patients who underwent tissue expander insertion at a children's hospital over a 12-year period was performed. Predictor variables included age, sex, race, indication, anatomical location, number of expanders inserted, serial expansion, history of infection or extrusion, and postoperative antibiotics. Outcome variables included infection and extrusion. Bivariate and multivariate analyses were performed to identify factors associated with infection and/or extrusion. RESULTS: A total of 180 patients who underwent 317 operations for tissue expander insertion were included in this study. Postoperative infection and/or extrusion occurred after 73 operations (23 percent). Postoperative prophylactic antibiotics were prescribed after 232 operations (75 percent), and only perioperative (≤24 hours) antibiotics were administered in 85 cases (25 percent). There were no significant differences in the rate of infection (12.1 percent versus 8.9 percent; p = 0.46), extrusion (16.8 percent versus 17.7 percent; p = 0.88), or infection and/or extrusion (23.7 percent versus 24.1 percent; p = 0.95) between these two groups. Multivariate analysis revealed that postoperative antibiotics did not have a significant association with infection and/or extrusion (OR, 0.84; 95 percent CI, 0.44 to 1.63; p = 0.61). CONCLUSIONS: The rates of infection/extrusion were similar between pediatric patients who received only perioperative antibiotics (≤24 hours) and those who were prescribed a course of postoperative antibiotics. Based on these results, a course of postoperative prophylactic antibiotics may be unnecessary after insertion of tissue expanders in pediatric patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Pediatric Tissue Expansion: Predictors of Premature Expander Removal in a Single Surgeon's Experience with 472 Expanders.

BACKGROUND: Tissue expansion is used for soft-tissue reconstruction in pediatric patients. The expansion process can be complicated by infection and extrusion, leading to premature expander removal. The aim of this study was to identify risk factors associated with premature expander removal caused by infection or extrusion in pediatric patients. METHODS: A retrospective study of pediatric patients who underwent tissue expansion performed by the senior author (R.J.R.) over a 12-year period was performed. Predictor variables included age, sex, race, indication, anatomical location, number of expanders, serial expansion, and expander size. Bivariate and multivariate analyses were performed to identify risk factors for premature expander removal. RESULTS: A total of 139 patients with 472 expanders were included in this study. Complications occurred with 78 expanders (16.5 percent). Premature expander removal caused by infection or exposure occurred with 51 expanders (10.8 percent). In terms of location, the highest rates of premature removal occurred in the lower extremity (20.0 percent) and scalp (16.3 percent). Multivariate analysis identified younger age (0 to 6 years compared with 13 to 17 years; OR, 3.98; 95 percent CI, 1.13 to 14.08; p = 0.03), greater number of expanders (OR, 1.45; 95 percent CI, 1.03 to 2.03; p = 0.03), and lower extremity location (OR, 4.27; 95 percent CI, 1.45 to 12.53; p = 0.008) were associated with an increased odds of premature expander removal. CONCLUSIONS: Expander removal occurred in approximately 10 percent of tissue expanders. Odds of premature removal is increased with younger age, greater number of expanders, and lower extremity location. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Muscle-Derived Stem Cell-Enriched Scaffolds Are Capable of Enhanced Healing of a Murine Volumetric Muscle Loss Defect.

BACKGROUND: Volumetric muscle loss secondary to traumatic or surgical causes can lead to functional and aesthetic impairments. The authors hypothesize that an implantable muscle-derived stem cell-enriched collagen scaffold could significantly augment muscle regeneration in a murine model of volumetric muscle loss. METHODS: Murine muscle-derived stem cells were isolated using a modified preplating technique and seeded onto type 1 collagen scaffolds to create the muscle-derived stem cell-enriched collagen scaffolds. Murine rectus femoris defects of 5 mm were created and randomized to one of three conditions (n = 6 per group): untreated controls, collagen scaffold only, and muscle-derived stem cell-enriched collagen scaffolds. In vivo muscle healing was quantified using micro-computed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks. RESULTS: In vivo experiments demonstrated significantly greater quadriceps cross-sectional area in the muscle-derived stem cell-enriched collagen scaffold group compared with controls on micro-computed tomography (0.74 ± 0.21 versus 0.55 ± 0.06 versus 0.49 ± 0.04 ratio of experimental to naive quadriceps cross-sectional area; p < 0.05). Muscle explants of the muscle-derived stem cell-enriched collagen scaffold group demonstrated significantly higher cellular density compared with controls (1185 ± 360 versus 359 ± 62 versus 197 ± 68 nuclei/high-power field; p < 0.01). Immunofluorescence for laminin and myosin heavy chain confirmed formation of organized muscle fibers within the defect of the muscle-derived stem cell-enriched collagen scaffold group only. However, appreciable confocal colocalization of myosin heavy chain with green fluorescent protein expression was low. CONCLUSIONS: The results of this study indicate that muscle-derived stem cell-enriched scaffolds significantly improved skeletal muscle regeneration in a murine muscle defect model. Based on the low fluorescent colocalization, host progenitor cells appear to contribute significantly to intradefect myogenesis, suggesting that deployment of a viable muscle-derived stem cell-enriched scaffold stimulates a regenerative mitogen response in native tissues.

Does Fracture Pattern Influence Functional Outcomes in the Management of Bilateral Mandibular Condylar Injuries?

The purpose of this study was to compare the functional outcomes of different types of bilateral mandibular condylar fractures. This was a retrospective study of patients with bilateral mandibular condylar fractures at a level-1 trauma center over a 15-year period. The primary predictor variable was fracture pattern, classified as type I (bilateral condylar), type II (condylar-subcondylar), or type III (bilateral subcondylar). Secondary predictor variables were demographic, injury-related, and treatment factors. Bivariate associations between the predictors and complication rates were computed; a multiple logistic regression model was utilized to adjust for confounders and effect modifiers. Thirty-eight subjects with bilateral condylar injuries met the inclusion criteria. The sample's mean age was 37.6 + 18.2 years, and 16% were female. The most common mechanisms of injury were motor vehicle collisions (53%) and falls (29%). Seventy-four percent had associated noncondylar mandibular fractures, and 32% of cases had concomitant midface fractures. Fifty-three percent of cases were classified as type I, 21% as type II, and 26% as type III. Ten subjects (26%) were managed with open reduction and internal fixation. The average length of follow-up was 4.5 + 6.3 months. After adjusting for confounders and effect modifiers, the type of fracture was a significant predictor of functional complications with type II injuries having the highest likelihood of a poor functional outcome (odds ratio: 7.77, 95% confidence interval: 1.45-41.53, p = 0.02). Asymmetric bilateral mandibular condylar fractures may be associated with an increased risk of poor functional outcomes.

Activation of RANK/RANKL/OPG Pathway Is Involved in the Pathophysiology of Fibrous Dysplasia and Associated With Disease Burden.

Fibrous dysplasia of bone (FD) is a mosaic disease caused by mutations in GNAS. Constitutive activation of the α-subunit of the Gs stimulatory protein (Gαs) leads to dysregulated proliferation of bone marrow stromal cells (BMSCs), generating expansile lesions of fibrotic tissue and abnormal bone. Local bone remodeling regulation by BMSCs is also altered, and FD tissue is characterized by abundant osteoclast-like cells that may be essential for lesion expansion. Animal models show local expression of RANKL in bone lesions, and treatment with the RANKL neutralizing antibody denosumab decreased lesion expansion rate in a patient with aggressive FD. However, the role of RANKL/osteoprotegerin (OPG) in FD pathophysiology is not yet understood. We measured serum levels of RANKL, OPG, and inactive RANKL-OPG complexes in FD patients of known disease burden and in healthy volunteers (HVs). RANK, RANKL, and Ki67 immunohistochemistry were assessed in FD tissue. Cultured FD and HV BMSCs were stimulated with prostaglandin E2 (PGE2 ) and 1,25 vitamin D3 to increase RANKL expression, and media levels of RANKL and OPG were measured. Osteoclastogenic induction by FD or HV BMSCs was assessed in co-cultures with HV peripheral monocytes. FD patients showed a 16-fold increase in serum RANKL compared to HVs. OPG was moderately increased (24%), although RANKL/OPG ratio was 12-fold higher in FD patients than in HVs. These measurements were positively correlated with the skeletal burden score (SBS), a validated marker of overall FD burden. No differences in serum inactive RANKL-OPG complexes were observed. In FD tissue, RANKL+ and Ki67+ fibroblastic cells were observed near RANK+ osteoclasts. High levels of RANKL were released by FD BMSCs cultures, but were undetectable in HV cultures. FD BMSC released less OPG than HV BMSCs. FD, but not HV BMSCs, induced osteoclastogenesis in monocyte co-cultures, which was prevented by denosumab addition. These data are consistent with the role of RANKL as a driver in FD-induced osteoclastogenesis. © 2018 American Society for Bone and Mineral Research.

Desensitization and Prevention of Antibody-Mediated Rejection in Vascularized Composite Allotransplantation by Syngeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection. Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent antibody-mediated rejection in VCA. METHODS: Skin transplants from Dark Agouti to Lewis rats were performed for sensitization. Orthotopic hind limb transplants from Dark Agouti donors were performed to sensitized and nonsensitized recipients, and the animals were treated with either daily tacrolimus or no immunosuppression. A desensitization protocol consisting of total body irradiation, fludarabine, and syngeneic HSCT was applied to sensitized animals. Graft rejection was monitored by clinical assessment and histological analysis. Serum levels of donor-specific antibodies (DSA IgG) were measured using flow cytometry. RESULTS: Sensitized recipients exhibited accelerated rejection by 5.5 ± 1.2 days without immunosuppression and 10.2 ± 3.6 days with daily tacrolimus compared with 8.7 ± 1.2 days and longer than 30 days in nonsensitized recipients, respectively. Serum levels of DSA IgG were markedly elevated (37.3 ± 3.34-fold from baseline) in sensitized recipients after VCA and correlated with histologic evidence of rejection and C4d deposition. Desensitization significantly reduced DSA compared with sensitized controls (2.6 ± 0.5-fold vs 6.0 ± 1.2-fold, P < 0.01) and along with daily tacrolimus led to improved VCA survival longer than 30 days without evidence of C4d deposition (n = 6). CONCLUSIONS: In summary, sensitization leads to accelerated rejection of VCA, and syngeneic HSCT combined with conventional immunosuppression effectively reduces DSA and improves allograft survival in sensitized rats.

Versatility of Free Cutaneous Flaps for Upper Extremity Soft Tissue Reconstruction.

The goals of upper extremity soft tissue reconstruction should go well beyond providing coverage and restoring function. As the field of reconstructive microsurgery has evolved, free cutaneous flaps (FCFs) are gaining wider application. The advantages of FCF include minimizing donor-site morbidity by preserving the muscle and fascia, improving versatility of flap design, and superior aesthetic results. This review highlights the application of anterolateral thigh, superficial circumflex iliac artery, deep inferior epigastric perforator, superficial inferior epigastric artery, and flow-through flaps for reconstruction of upper extremity defects. These flaps share several qualities in common: well-concealed donor sites, preservation of major arteries responsible of providing inflow to distal extremity, and potential for a two-team approach (donor and recipient sites). While the choice of flaps should be decided based on individual patient and defect characteristics, FCF should be considered as excellent options to achieve the goals of upper extremity reconstruction.

Which Factors Are Associated with Open Reduction of Adult Mandibular Condylar Injuries?

BACKGROUND: The purpose of this study was to identify factors associated with the decision to perform open reduction and internal fixation of mandibular condylar fractures. METHODS: This was a retrospective cohort study of patients with mandibular condylar fractures managed by the plastic and reconstructive surgery, oral and maxillofacial surgery, and otorhinolaryngology services over a 15-year period. Bivariate associations and a multiple logistic regression model were computed for injury characteristics that were associated with open reduction and internal fixation. For all analyses, a value of p ≤ 0.05 was considered significant. RESULTS: Six hundred fifty-four condylar injuries were identified in 547 patients. The sample's mean age was 36.0 ± 16.5 years, 20.5 percent were women, and 63 percent were Caucasian. The most common mechanisms of injury were motor vehicle collisions (49 percent), 53.4 percent involved the subcondylar region and 20 percent were bilateral injuries. Associated noncondylar mandibular fractures were present in 60 percent of cases; 20.7 percent were managed with open reduction and internal fixation. The overall complication rate was 21.6 percent. In a multiple logistic regression model, factors associated with an increased likelihood of open reduction and internal fixation were the presence of extracondylar mandibular injuries, condylar neck or subcondylar region injuries, increasing dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery (p ≤ 0.04). CONCLUSIONS: Increasing severity of mandibular injury, lower level of fracture, joint dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery are associated with open reduction and internal fixation of mandibular condylar injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Effects of denosumab treatment and discontinuation on human growth plates.

CONTEXT: Denosumab is a humanized monoclonal antibody to receptor activator of nuclear factor-κB ligand used primarily for postmenopausal osteoporosis and skeletal-related events from metastatic cancer. Its safety in children has not been established. OBJECTIVE: The objective of the study was to investigate the effects of denosumab treatment on skeletal growth and histology. DESIGN: This was an observational case report with radiological and histopathological analyses. SETTING: The study was conducted at a clinical research center. PATIENTS: A 9-year-old boy with fibrous dysplasia treated with a 7-month course of denosumab participated in the study. INTERVENTION: Histological analyses were performed and compared on growth plates from limbs that had been amputated before and 17 months after denosumab treatment. MAIN OUTCOME MEASURES: Skeletal radiographs and bone histopathology from before and after treatment were measured. RESULTS: After initiating denosumab, sclerotic metaphyseal bands appeared on radiographs. Posttreatment radiographs revealed migration of the bands away from the growth plates, consistent with continued linear growth. Histologically, the bands were composed of horizontally arranged trabeculae containing calcified cartilage. This cartilage appeared to derive from unresorbed primary spongiosa as a result of osteoclast inhibition by denosumab, similar to what has been observed with bisphosphonates. By 17 months after treatment, active bone resorption and formation had returned, as evidenced by the presence of active osteoclasts in resorption pits and osteoid surfaces. CONCLUSIONS: Further studies are needed to determine the safety of denosumab on the growing skeleton. However, in this child there was continued epiphyseal activity both during and after treatment and reversal of bone turnover suppression after treatment discontinuation, suggesting that denosumab did not have significant adverse effects on growth.

Aesthetic and functional facial transplantation: a classification system and treatment algorithm.

BACKGROUND: As of July of 2013, 27 facial vascularized composite allotransplantations have been performed. The authors developed a classification system and treatment algorithm that is practical and surgically applicable. METHODS: The majority of the transplants have been described in the surgical literature and the media, and a review of the data was performed. A classification system and a treatment algorithm were designed. Skeletal defects were defined by craniofacial osteotomies and soft-tissue defects by aesthetic facial subunits. The soft-tissue defect was subdivided into the following subunits: oral-nasal (type 1), oronasal-orbital (type 2), and full facial (type 3). The bony defects were subdivided into mandibular involvement (M), Le Fort 1 (A), Le Fort 3 (B), and monobloc (C). RESULTS: The mechanisms of injury included trauma (n = 13), burns (n = 8), congenital deformity (n = 3), oncologic resection (n = 1), and unreported (n = 2). According to the proposed classification system: one was type 1; one was type 1-M; one was type 1-MB; two were type 2; two were type 2-B; two were type 2-MB; six were type 3; one was type 3-B; and three were type 3-MB; eight could not be classified due to a lack of data. The treatment algorithm designed a vascularized composite allotransplantation that addressed the bony and soft-tissue components. CONCLUSIONS: Patient selection for these complicated procedures, currently dependent on lifelong immunosuppression, is crucial to their success. The authors describe a classification system and treatment algorithm for facial defects that may be ideally suited for facial transplantation. The proposed classification and algorithm may help centers define indications and ideally improve patient outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.