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Parameters of care for craniosynostosis: craniofacial and neurologic surgery perspectives
Warren, Stephen M; Proctor, Mark R; Bartlett, Scott P; Blount, Jeffrey P; Buchman, Steven R; Burnett, Whitney; Fearon, Jeffrey A; Keating, Robert; Muraszko, Karin M; Rogers, Gary F; Rubin, Marcie S; McCarthy, Joseph G
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.
PMID: 22373978
ISSN: 1529-4242
CID: 158287
Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury
Sultan SM; Barr JS; Butala P; Davidson EH; Weinstein AL; Knobel D; Saadeh PB; Warren SM; Coleman SR; Hazen A
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
PMID: 21962530
ISSN: 1878-0539
CID: 138703
A Quantitative 3D Analysis of Coronoid Hypertrophy in Pediatric Craniofacial Malformations
Chang CC; Allori AC; Wang E; Farina R; Warren SM; Grayson BH; McCarthy JG
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
PMID: 21987044
ISSN: 1529-4242
CID: 138702
Parameters of Care for Craniosynostosis
McCarthy JG; Warren SM; Bernstein JM; Burnett W; Cunningham ML; Edmond JC; Figueroa AA; Kapp-Simon KA; Labow B; Peterson-Falzone S; Proctor M; Rubin M; Sze RW; Yemen T
Abstract na
PMID: 21848431
ISSN: 1545-1569
CID: 138704
Long-Term Evaluation of Midface Position after Le Fort III Advancement: A 20-Plus-Year Follow-Up
Warren, Stephen M; Shetye, Pradip R; Obaid, Sacha I; Grayson, Barry H; McCarthy, Joseph G
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
PMID: 22186512
ISSN: 1529-4242
CID: 147703
Autologous fat grafting and facial reconstruction
Wetterau, Meredith; Szpalski, Caroline; Hazen, Alexes; Warren, Stephen M
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.
PMID: 22337433
ISSN: 1049-2275
CID: 159350
Craniofacial surgery: innovation, design, and strategy [Editorial]
Warren, Stephen M; Longaker, Michael T
PMID: 22337364
ISSN: 1049-2275
CID: 1217092
A Novel Vacuum Assisted Scaffold System for Bony Regeneration
Zhang D; Santore J; Wootton D; Warren SM
Worldwide, there is a tremendous need to improve the healing of long bone defects and fractures. The purpose of thisstudy was to explore the theoretical feasibility of a novelapproach to bone healing. Using a vacuum assisted scaffoldsystem, we performed a theoretical analysis and computationalmodeling. Results indicate that a standard extracorporeal devicecan create enough negative pressure to develop a pressure dropacross a scaffold that will enhance fluid flow through thescaffold. The velocity of fluid flow is affected by fibrin depositionand scaffold permeability. The fluid flow is predicted to createshear stress that would increase cell growth and migration
INSPEC:12770255
ISSN: 1071-121x
CID: 2030502
Need for standard outcome reporting systems in craniosynostosis
Szpalski, Caroline; Weichman, Katie; Sagebin, Fabio; Warren, Stephen M
Craniosynostosis is the premature fusion of one or more cranial sutures. When a cranial suture fuses prematurely, skull growth is altered and the head takes on a characteristic pathological shape determined by the suture(s) that fuses. Numerous treatment options have been proposed, but until recently there were no parameters or guidelines of care. Establishing such parameters was an important step forward in the treatment of patients with craniosynostosis, but results are still assessed using radiographic measurements, complication rates, and ad hoc reporting scales. Therefore, clinical outcome reporting in the treatment of craniosynostosis is inconsistent and lacks methodological rigor. Today, most reported evidence in the treatment of craniosynostosis is level 5 (expert opinion) or level 4 (case series) data. Challenges in obtaining higher quality level 1 or level 2 data include randomizing patients in a clinical trial as well as selecting the appropriate outcome measure for the trial. Therefore, determining core outcome sets that are important to both patients and health care professionals is an essential step in the evolution of caring for patients with craniosynostosis. Traditional clinical outcomes will remain important, but patient-reported outcomes, such as satisfaction, body image, functional results, and aesthetic outcomes, must also be incorporated if the selected outcomes are to be valuable to patients and families making decisions about treatment. In this article, the authors review the most commonly used tools to assess craniosynostosis outcomes and propose a list of longitudinal parameters of care that should be considered in the evaluation, diagnosis, and treatment evaluation of a patient with craniosynostosis
PMID: 21806340
ISSN: 1092-0684
CID: 135566
Augmenting neovascularization accelerates distraction osteogenesis
Davidson, Edward H; Sultan, Steven M; Butala, Parag; Tutela, John Paul; Canizares, Orlando; Wagner, I Janelle; Knobel, Denis; Saadeh, Pierre B; Warren, Stephen M
BACKGROUND: : Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction. METHODS: : Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.25 mm twice daily), and 21-day consolidation periods. From the beginning of the consolidation period, animals received daily injections of either AMD3100 (bone marrow progenitor cell mobilizing agent) or sterile saline. Animals were euthanized on postoperative day 31; mandibles were harvested; and bone regeneration was assessed using micro-computed tomography, immunohistochemistry, bone morphogenetic protein-2 enzyme-linked immunosorbent assay, and mechanical testing. RESULTS: : Immunohistochemistry demonstrated that AMD3100 treatment increased vascular density and bone formation. Micro-computed tomography and dual-emission x-ray absorptiometry demonstrated that AMD3100-treated animals had improved bone generation compared with sham-treated controls. Greater force was required on three-point testing to break AMD3100-treated bone. Bone morphogenetic protein-2 expression was up-regulated with AMD3100. Interestingly, the nondistracted contralateral hemimandibles treated with AMD3100 were also stronger than sham-treated counterparts. CONCLUSIONS: : Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow
PMID: 21788832
ISSN: 1529-4242
CID: 135583