Faculty Bibliography

INTRODUCTION: A multidisciplinary conference was convened in March 2010 with the charge to develop parameters of care for patients with craniosynostosis. The 52 participants represented 16 medical specialties and 16 professional societies. Herein, we present the dental, orthodontic, and surgical care recommendations for those with craniosynostosis, with special emphasis on craniosynostosis syndromes. METHODS: Plenary and small-group iterative discussions were held to draft specialty-specific parameters of care. All participants reviewed and discussed each specialty-specific document. Special care was taken to ensure cross-discipline interactions, recognizing the importance of interdisciplinary team care. RESULTS: A unified document was produced delineating longitudinal care parameters from prenatal assessment and consultation to adulthood in all the represented specialty areas. The dental and orthodontic care parameters from infancy to adulthood are explained in terms of stages of development and coordinated with interdisciplinary assessments and interventions. CONCLUSIONS: The consensus document provides a detailed description of physical, functional, and cognitive development in persons with craniosynostosis and recommends staged team observations and interventions. The expectation is that the document will help to ensure state-of-the-art care for patients with craniosynostosis and provide a generally acceptable framework for collaborative studies.

ABSTRACT: There is tremendous interest in autologous fat grafting for the management of soft tissue volume deficiencies, treatment of cutaneous injuries, and regeneration of missing parts. Given its relative abundance and proximity to the surface of the skin, adipose tissue seems an excellent choice for the treatment of both congenital and acquired soft tissue defects, but the mesenchymal stem cells contained within the fat may provide unexpected opportunities for tissue replacement and repair. Although adipose transfer has been successfully used for reconstructive purposes since the end of the 19th century, numerous controversies about adipose harvesting, processing, delivery, survival, and efficacy still persist today. The purpose of this article was to highlight current practices, areas of controversy, and near-term future applications of fat grafting for reconstruction of the face.

Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of diabetes and its effects on wound healing. Over half of diabetic patients who develop a single ulcer will subsequently develop another ulcer of which the majority will become chronic non-healing ulcers. One-third will progress to lower extremity amputation. Over the past decade, the outcomes for patients with DFUs ulcers have not improved, despite advances in wound care. Successful treatment of diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on the healing processes dysregulated by diabetes. Stem cells are a promising treatment for DFUs as they are capable of targeting, as well as bypassing, the underlying abnormal healing mechanisms and deranged cell signaling in diabetic wounds and promote healing. This review will focus on existing stem cell technologies and their application in the treatment of DFUs.

BACKGROUND: : A multidisciplinary meeting was held from March 4 through 6, 2010, in Atlanta, Georgia, to conceptualize, map out, and operationalize the variables most relevant to the care of patients with craniosynostosis. In this article, the authors highlight the development of the craniofacial and neurologic surgery parameters of care. METHODS: : Fifty-two conference attendees, representing a broad range of expertise in craniosynostosis care and 16 professional societies, participated in this working group. Literature and expert opinion were used to identify the variables important for the care of patients with craniosynostosis. In an iterative manner, specialty-specific data were compiled into draft recommendations and presented to all conference attendees. Cross-discipline analysis was used to assess the completeness of the data, facilitate exchange of ideas, and achieve consensus. RESULTS: : Consensus was reached among the 52 conference attendees and two post hoc reviewers in 18 areas of craniosynostosis care. Longitudinal parameters of care were developed for the diagnosis, treatment, and management of craniosynostosis in each of the specialty areas of care, from prenatal evaluation to completion of care in adulthood. CONCLUSIONS: : To our knowledge, this is the first multidisciplinary effort to develop parameters of care and best practices for craniosynostosis. In conjunction with patient input, these parameters may help to heuristically develop core outcome sets that are important not only to patients and their families, but also to health care providers and health services and outcome researchers. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.

BACKGROUND: : Patients with syndromic craniosynostosis and midface hypoplasia are often treated with Le Fort III advancement. The authors present four patients with extraordinarily long-term follow-up (in excess of 20 years). METHODS: : An institutional review board-approved retrospective chart review was performed on all patients with syndromic craniofacial synostosis who underwent Le Fort III advancement. Patients with greater than 20 years of cephalometric and photographic records were identified. Lateral cephalograms were obtained preoperatively, immediately postoperatively, at 1-year follow-up, and at long-term follow-up. Cephalograms were traced, digitized, and averaged. Fifty cephalometric landmarks were identified for serial measurements. RESULTS: : Of the four patients identified, one had Apert syndrome and three had Crouzon syndrome. Average age at the time of Le Fort III advancements was 11 years (range, 4 to 20 years). Average length of postoperative follow-up was 25 years (+/-5 years). No patient had significant anterior midfacial growth following Le Fort III advancement. Both young patients (<10 years) had substantial vertical inferior midfacial growth after advancement. CONCLUSIONS: : These data demonstrate that the Le Fort III segment of children with syndromic craniosynostosis does not grow significantly forward. Moreover, the traditional Le Fort III osteotomy does not provide the amount of midface advancement necessary to avoid phenotypic recidivism in these syndromic patients. This study also suggests that patients undergoing Le Fort III advancement appear to have zygomatic effacement and ptosis of the overlying soft tissue with deepening of the facial folds; collectively, it is suggested that these changes give the appearance of accelerated facial aging. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V

BACKGROUND: Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury. METHODS: Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100 degrees C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining. RESULTS: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305+/-15.77mV, saline=242+/-15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3+/-4.39ngml(-1), saline=34.3+/-5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8+/-1.23ngml(-1), saline grafted=10.2+/-3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ss1(TGF-ss): saline=9.30+/-0.93, fat=4.63+/-0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05+/-1.21ngml(-1), fat=6.83+/-1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8+/-3.39 vessels per high power field (hpf), saline=20.0+/-0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69+/-0.10, saline=2.03+/-0.53; p=0.046). CONCLUSIONS: Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers

INTODUCTION:: Coronoid process hypertrophy can be associated with a variety of congenital or acquired anomalies. There is, however, no consensus on a quantitative or objective measure to define coronoid hypertrophy. Here, we describe a novel analytical technique using three-dimensional (3D) computed tomographic data to accurately and reproducibly assess coronoid size and diagnose coronoid:condyle disproportion. METHODS:: A total of 24 patients were analyzed using 3D medial axis analysis: eight cases of unilateral coronoid hypertrophy, 4 cases of bilateral coronoid hypertrophy, and 12 age-matched normal control cases were identified. RESULTS:: Measurement of normal subjects (n=12) demonstrated a coronoid:condyle volumetric ratio </= 0.5. Analysis of patients with coronoid hypertrophy demonstrated that a coronoid:condyle volumetric ratio >/= 1.0 was consistent with marked coronoid:condylar disproportion and a ratio between 0.5 and 1.0 was indicative of modest disproportion. Surface area ratios comparing coronoid to condyle were also elevated (ratio >/= 0.5) in patients with coronoid hypertrophy. CONCLUSIONS:: Quantitative assessment of coronoid size using 3D volume and surface-area analysis of computed tomographic data may be helpful to the clinician in diagnosing coronoid hypertrophy and in guiding treatment. It may also serve a role in monitoring the temporal evolution of coronoid hypertrophy in early cases that have not yet resulted in trismus or decreased interincisal opening

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BACKGROUND: Although different cranioplasty storage methods are currently in use, no study has prospectively compared these methods. The authors compare freezing and subcutaneous storage methods in a rat model. METHODS: Trephine defects (10 mm) were created in 45 Sprague-Dawley rats. The cranial bone grafts were stored in an autologous subcutaneous pocket (n = 15), frozen at -80 degrees C (n = 15), immediately analyzed (n = 12), or immediately replanted into the defect (n = 3). After 10 days of storage, the subcutaneous or frozen grafts were either replanted (subcutaneous, n = 3; frozen, n = 3) or analyzed (subcutaneous, n = 12; frozen, n = 12). Grafts underwent histologic analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase assay, mechanical testing, and micro-computed tomographic imaging. RESULTS: After 10 days of storage, physiologic assays demonstrated a significant decrease in cellular functionality (e.g., alkaline phosphatase assay concentration: fresh, 18.8 +/- 0.77 mM/mg; subcutaneous, 12.2 +/- 0.63 mM/mg; frozen, 8.07 +/- 1.1 mM/mg; p < 0.012 for all comparisons). Mechanical integrity (maximal load) of fresh grafts was greatest (fresh, 9.26 +/- 0.29 N; subcutaneous, 6.27 +/- 0.64 N; frozen, 4.65 +/- 0.29 N; fresh compared with frozen, p < 0.001; fresh compared with subcutaneous, p = 0.006). Replantation of subcutaneously stored and frozen grafts resulted in limited bony union and considerable resorption after 12 weeks; in contrast, replanted fresh grafts demonstrated bony union and little resorption. CONCLUSIONS: Current preservation methods for interval cranioplasty do not maintain bone graft viability. Subcutaneous storage appears to provide a small advantage compared with freezing.