Stephen M Warren

NYU Langone Medical Center, New York, New York, United States

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Publications (235)674.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Asher-McDade system is a 5-point ordinal scale frequently used to rate the components of nasolabial appearance, including nasal form and nasal symmetry, in unilateral cleft lip and palate. Although reference photographs illustrating this scale have been identified for the frontal and right profile view, no reference photographs exist for the basal view. The aim of this study was to identify reference photographs for nasal form and nasal symmetry from the basal view to illustrate this scale and facilitate its use. Four raters assessed nasolabial appearance (form and symmetry) on basal view photographs of 50 children (average age 8 years) with a repaired cleft lip. Intraclass correlation coefficients show fair to moderate inter-rater reliability. Cronbach α indicated strong agreement between raters (0.77 nasal form; 0.78 nasal symmetry; 0.80 overall), along with low duplicate measurement error and strong internal consistency between the measures. The photographs with the highest agreement among raters were selected to illustrate each point on the 5-point scale for nasal form and for nasal symmetry, resulting in the selection of 10 reference photographs. The basal view reference photograph set developed from this study may complement existing reference photograph sets for other views and facilitate rating tasks.
    No preview · Article · Jul 2015 · The Journal of craniofacial surgery
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    ABSTRACT: The present study aims to determine the risk of early secondary nasal revisions in patients with complete unilateral and bilateral cleft lip and palate (U/BCLP) treated with and without nasoalveolar molding (NAM) and examine the associated costs of care. A retrospective cohort study from 1990 to 1999 was performed comparing the risk of early secondary nasal revision surgery in patients with a CLP treated with NAM and surgery (cleft lip repair and primary surgical nasal reconstruction) versus surgery alone in a private practice and tertiary level clinic. The NAM treatment group consisted of 172 patients with UCLP and 71 patients with BCLP, whereas the non-NAM-prepared group consisted of 28 patients with UCLP and 5 with BCLP. The risk of secondary nasal revision for patients with UCLP was 3% in the NAM group and 21% in the non-NAM group. The risk of secondary nasal revision for patients with BCLP was 7% in the NAM group compared with 40% in the non-NAM group. Using multicenter averages, the non-NAM revision rates were calculated at 37.8% and 48.5% for U/BCLP, respectively. Applying these risks of revision, NAM treatment led to an estimated savings of between $491 and $4893 depending on the type of cleft. In conclusion, NAM can reduce the number of early secondary nasal revision surgeries and, therefore, reduce the overall cost of care.
    No preview · Article · Jun 2015 · The Journal of craniofacial surgery
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    ABSTRACT: Acellular dermal matrix (ADM) is widely used for structural or dermal replacement purposes. Given its innate biocompatibility and its potential to vascularize, we explored the possibility of ADM to function as a small interfering RNA (siRNA) delivery system. Specifically, we sought to improve ADM vascularization by siRNA-mediated inhibition of prolyl hydroxylase domain-2 (PHD2), a cytoplasmic protein that regulates hypoxia inducible factor-1α, and improve neovascularization. Fluorescently labeled siRNA was used to rehydrate thin implantable ADM. Pharmacokinetic release of siRNA was determined. Twelve millimeter sections of ADM reconstituted with PHD2 siRNA (nonsense siRNA as control) and applied to dorsal wounds of 40 FVB mice. Grafts were sewn in, bolstered, and covered with occlusive dressings. Photographs were taken at 0, 7, and 14 d. Wounds were harvested at 7 and 14 d and analyzed (messenger RNA, protein, histology, and immunohistochemistry). Release kinetics was first-order with 80% release by 12 h. By day 14, PHD2-containing ADM appeared viable and adherent, whereas controls appeared nonviable and nonadherent. Real-time reverse transcription-polymerase chain reaction demonstrated near-complete knockdown of PHD2, whereas vascular endothelial growth factor and FGF-2 were increased 2.3- and 4.7-fold. On enzyme-linked immunosorbent assay, vascular endothelial growth factor was increased more than fourfold and stromal cell-derived factor doubled. Histology demonstrated improved graft incorporation in treated groups. Immunohistochemical demonstrated increased vascularity measured by CD31 staining and increased new cell proliferation by denser proliferating cell nuclear antigen staining in treated versus controls. We concluded that ADM is an effective matrix for local delivery of siRNA. Strategies to improve the matrix and/or genetically alter the local tissue environment can be envisioned. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Journal of Surgical Research
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    ABSTRACT: Obtaining an esthetic and functional primary surgical repair in patients with complete cleft lip and palate (CLP) can be challenging because of tissue deficiencies and alveolar ridge displacement. This study aimed to describe surgeons' assessments of presurgical deformity and predicted surgical outcomes in patients with complete unilateral and bilateral CLP (UCLP and BCLP, respectively) treated with and without nasoalveolar molding (NAM). Cleft surgeon members of the American Cleft Palate-Craniofacial Association completed online surveys to evaluate 20 presurgical photograph sets (frontal and basal views) of patients with UCLP (n = 10) and BCLP (n = 10) for severity of cleft deformity, quality of predicted surgical outcome, and likelihood of early surgical revision. Five patients in each group (UCLP and BCLP) received NAM, and 5 patients did not receive NAM. Surgeons were masked to patient group. Twenty-four percent (176/731) of surgeons with valid e-mail addresses responded to the survey. For patients with UCLP, surgeons reported that, for NAM-prepared patients, 53.3% had minimum severity clefts, 58.9% were anticipated to be among their best surgical outcomes, and 82.9% were unlikely to need revision surgery. For patients with BCLP, these percentages were 29.8%, 38.6%, and 59.9%, respectively. Comparing NAM-prepared with non-NAM-prepared patients showed statistically significant differences (P < 0.001), favoring NAM-prepared patients. This study suggests that cleft surgeons assess NAM-prepared patients as more likely to have less severe clefts, to be among the best of their surgical outcomes, and to be less likely to need revision surgery when compared with patients not prepared with NAM.
    No preview · Article · Dec 2014 · Journal of Craniofacial Surgery
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    ABSTRACT: Although bone repair is often a relatively rapid and efficient process, many bone defects do not heal. Because an adequate blood supply is essential for new bone formation, we hypothesized that augmenting new blood vessel formation by increasing the number of circulating vasculogenic progenitor cells (PCs) with AMD3100 and enhancing their trafficking to the site of injury with recombinant human parathyroid hormone (rhPTH) will improve healing. Critical-sized 3-mm cranial defects were trephined into the right parietal bone of C57BLKS/J 6 mice (N = 120). The mice were divided into 4 equal groups (n = 30 for each). The first group received daily subcutaneous injections of AMD3100 (5 mg/kg). The second group received daily subcutaneous injections of rhPTH (5 mg/kg). The third group received both AMD3100 and rhPTH. The fourth group received subcutaneous injections of saline. Circulating vasculogenic PC numbers, new blood vessel formation, and bony regeneration were assessed. Progenitor cell adhesion, migration, and tubule formation were assessed in the presence of rhPTH and AMD3100. Flow cytometry demonstrated that combination therapy significantly increased the number of circulating PCs compared with all other groups. In vitro, AMD3100-treated PCs had significantly increased adhesion migration, and tubule formation was assessed in the presence of rhPTH. Combination therapy significantly improved new blood vessel formation in those with cranial defect compared with all other groups. Finally, bony regeneration was significantly increased in the combination therapy group compared with all other groups. The combination of a PC-mobilizing and traffic-enhancing agent improved bony regeneration of calvarial defects in mice.
    No preview · Article · Dec 2014 · Journal of Craniofacial Surgery
  • Raj M Vyas · Stephen M Warren
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    ABSTRACT: Modern cleft surgery requires four-dimensional and functional anatomic understanding of the cleft (and noncleft) lip, nose, and alveolus. Some techniques for nasolabial repair rely more on precise anatomic geometry, whereas others afford the surgeon a more flexible design. Consistent anthropometry enables accurate assessment and reporting of long-term outcomes; such reports are needed to guide perioperative care, delineate optimal repair principles, and resolve ongoing controversies.
    No preview · Article · Apr 2014 · Clinics in plastic surgery
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    ABSTRACT: Non-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis.
    Full-text · Article · Mar 2014 · PLoS ONE
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    Sheila N. Blumberg · Stephen M. Warren
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    ABSTRACT: Background: Disparities in diabetic foot ulcer (DFU) treatment outcomes are well described, although few studies identify risk factors contributing to disparate healing and amputation rates. In a unique academic center serving urban public, private, and veteran patients, we investigated amputation and healing rates and specific risk factors for disparate treatment outcomes. Methods: A retrospective chart review of diabetic patients with a new diagnosis of a foot ulcer at geographically adjacent, but independent public, private, and Veterans Administration (VA) hospitals was conducted. Healing and lower extremity amputation outcomes were assessed. Results: Across the three hospitals, 234 patients met the inclusion criteria. Patients at the VA hospital were older (mean 72.5 years; P < 0.001) and had gangrenous ulcers (mean 14.1%; P < 0.001) compared with patients in the private and public hospitals. Public hospital patients were mostly Hispanic (mean 54%; P < 0.001) with a shorter duration of diabetes (mean 12.8 years; P = 0.02), but were more poorly controlled than VA and private hospital patients (P ≤ 0.001). Prior amputation (odds ratio [OR] 1.97; P = 0.016) and non-Caucasian race (OR 2.42; P = 0.004) increased the risk of amputation on multivariate analysis. Osteomyelitis (P = 0.0371) and gangrene (P < 0.001) are independent risk factors for amputation. Across all three hospitals, 42.3% of patients were treated by amputation (6.8% private, 12% public and 23.5% VA; P < 0.001). Conclusion: In a single triumvirate health care system where the patient population is stratified primarily by insurance, VA patients have significantly higher amputation rates compared with patients at adjacent private and public hospitals. The VA patients are largely racial minorities with advanced DFU progression to gangrenous ulcers.
    Preview · Article · Jan 2014 · Journal of Diabetes
  • Parit A Patel · Stephen M Warren · Joseph G McCarthy
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    ABSTRACT: Maxillary mucoceles are a relatively rare entity especially following surgical procedures involving osteotomies of the maxilla. The etiology of maxillary mucoceles has been ascribed to facial trauma (fractures), sinus surgery, and chronic inflammatory diseases or infections. Mucoceles can follow injury to the sinus mucosa and/or sinus outflow tract with a resulting expansile cystic mass. The clinical presentation ranges from swelling, pain, a palpable mass, proptosis, enophthalmos, and diplopia. The treatment involves either open or endoscopic incision and drainage of the cyst, mucosal resection, and an antrostomy for drainage.We report the case of a patient with Pfeiffer syndrome who underwent Le Fort III distraction osteogenesis and developed a symptomatic mucocele 15 years postoperatively.
    No preview · Article · Nov 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Purpose: Bilateral craniofacial microsomia is a risk factor for obstructive sleep apnea (OSA)1. We hypothesize that unilateral craniofacial microsomia (UCFM) can also be an unrecognized cause of OSA. In this study, we aim to determine and characterize the etiopathogenesis of OSA in patients with UCFM through the use of three dimensional airflow analysis. Materials and Methods: All pediatric patients diagnosed with UCFM at a tertiary level institution from 1990 to 2010 were reviewed. Patients with confirmed diagnoses of OSA (Apnea Hypopnea Index>1) were compared to control patients with UCFM without OSA otherwise randomly selected. Three dimensional analysis of airflow with a computational fluid analysis model was performed (MIMIC software) on a sample of both affected as well as unaffected individuals. CT data was converted into a 3-dimensional computational model where the Navier-Stokes equations governing fluid flow can yield a variety of objective measures of airflow in the given anatomy. Results: 62 patients were identified as having UCFM, 7 patients were further diagnosed with OSA. 11.5% of the patients diagnosed with UCFM were diagnosed with OSA, compared to 2.5% in the healthy pediatric population (p=0.01). 100% of patients with OSA were Pruzanski grades IIB or higher. OSA presenting symptoms included snoaring (71.4%), failure to thrive (FTT) (57.1%), chronic respiratory infections (42.8%), adenotonsillar hypertrophy (28.6%) or loud breathing (28.5 %). Snoring (p<0.001), presence of Goldenhaar features (p=0.001) and FTT (p=0.004) were identified as significant predictors for OSA in patients with UCFM. Race, obesity, cleft lip/palate, upper respiratory complications, presence of adenotonsillar hypertrophy and side of UCFM were not predictors of OSA in our cohort. Patients with UCFM and OSA had significantly lower total flow rate compare to controls. Conclusions: The prevalence of OSA in UCFM patients is 3.9 times greater then in the otherwise healthy population. Snoring, presence of Goldenhaar features and FTT were shown to be predictive factors for OSA in the presence of UCFM.
    No preview · Conference Paper · Oct 2013
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    ABSTRACT: Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd.
    No preview · Article · Sep 2013 · Journal of Tissue Engineering and Regenerative Medicine
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    ABSTRACT: The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 ± 14 vs 10.3 ± 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.
    No preview · Article · Sep 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Delayed diabetic (DM) wound healing is, in part, the result of inadequate endothelial progenitor cell (EPC) proliferation, mobilization, and trafficking. Recently, we developed a serum free functional culture system called quantity and quality control culture system (QQc) which enhances the number and vasculogenic potential of EPCs. We hypothesize that QQc restoration of DM EPC function will improve wound closure. In order to test this hypothesis, we measured pre/post-QQc DM KSL (e.g. c-kit(+)Sca-1(+)lin(-)) cell activity in vitro as well as the effect of KSL cell adoptive transfer on the rate of euglycemic wound closure. KSL cells were magnetically sorted from control and streptozotocin-induced Type I DM C57BL6J bone marrow. Freshly isolated control and DM KSL cells were cultured in QQc for 7 days and pre/post-QQc KSL function was tested. The number of KSLs significantly increased post QQc for both DM and controls and also increasing DM -KSL vasculogenic potential above fresh control KSL level. Similarly, fresh DM cells form fewer tubules, but QQc increases DM tubule formation to greater than fresh control cell levels (p<0.05). Adoptive transfer of post-QQc DM KSL cells significantly enhance wound closure compared to fresh DM KSL cells and equaled wound closure of post-QQc control KSL cells. Post-QQc DM KSL enhancement of wound closure is mediated, in part, via a vasculogenic mechanism. This study demonstrates that QQc can reverse DM EPC dysfunction and achieve control-levels of EPC function. Finally, post-QQc DM EPC therapy effectively improved euglycemic wound closure and may improve DM wound healing.
    Full-text · Article · May 2013 · Diabetes
  • Caroline Szpalski · Fabio Sagebin · Marissa Barbaro · Stephen M Warren
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    ABSTRACT: Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
    No preview · Article · May 2013 · Journal of Biomedical Materials Research Part B Applied Biomaterials
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    ABSTRACT: Nonhealing bone defects are difficult to treat. As the bone morphogenic protein and transforming growth factor beta pathways have been implicated in bone healing, we hypothesized that percutaneous Smad7 silencing would enhance signaling through both pathways and improve bone formation. Critical sized parietal trephine defects were created and animals received percutaneous injection of: agarose alone or agarose containing nonsense or Smad7 small interfering RNA (siRNA). At 12 weeks, SMADs1, 2, 3, 5, 7 and 8 levels were assessed. Smad1/5/8 osteogenic target, Dlx5, and SMAD2/3 angiogenic target, plasminogen activator inhibitor-1 (Pai1), transcription levels were measured. Noncanonical signaling through TGFβ activated kinase-1 (Tak1) and target, runt-related transcription factor 2 (Runx2) and collagen1α1 (Col1α1), transcription were also measured. Micro-computed tomography and Gomori trichome staining were used to assess healing. Percutaneous injection of Smad7 siRNA significantly knocked down Smad7 mRNA (86.3±2.5%) and protein levels (46.3±3.1%). The SMAD7 knockdown resulted in a significant increase in receptor-regulated SMADs (R-SMAD) (Smad 1/5/8 and Smad2/3) nuclear translocation. R-SMAD nuclear translocation increased Dlx5 and Pai1 transcription. Additionally, noncanonical signaling through Tak1 increased Runx2 and Col1α1 target transcription. Compared with animals treated with agarose alone (33.9±2.8% healing) and nonsense siRNA (31.5±11.8% healing), animals treated Smad7 siRNA had significantly great (91.2±3.8%) healing. Percutaneous Smad7 silencing increases signal transduction through canonical and noncanonical pathways resulting in significant bone formation. Minimally invasive gene therapies may prove effective in the treatment of nonhealing bone defects.Gene Therapy advance online publication, 18 April 2013; doi:10.1038/gt.2013.15.
    No preview · Article · Apr 2013 · Gene therapy
  • Court B Cutting · Stephen M Warren
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    ABSTRACT: Nearly 60 years ago, Joseph Murray described several advancements to Bradford Cannon's Abbe flap reconstruction of secondary bilateral cleft lips in order to simplify the technique and improve results. Unlike their predecessors, Drs. Cannon and Murray modified the Abbe flap by splitting its apex in order to obtain a symmetrical correction of the upper lip and allow the 2 suture lines to extend vertically and laterally past the base of the columella and disappear within the floor of the nose. Eighteen years later, Dr. Murray reviewed the evolution of his own secondary cleft lip reconstruction experience to include a new approach to advance the maxilla rather than set back the mandible. In this Signature Issue, we reflect on contemporary innovations in secondary bilateral cleft lip Abbe flap reconstruction. Today, we approach the secondary reconstruction of the bilateral cleft lip in 3 stages. First, we establish normal anatomic positioning of the midface. Second, we perform secondary cleft nasal surgery as necessary. Finally, only after the midfacial skeleton and nose have been treated do we proceed with Abbe flap reconstruction of the upper lip. We inset the Abbe flap a quarter of the way out on the columella and wrap the Abbe darts around the sides of the columella. We find that designing the Abbe flap this way avoids the saber cut-like notching at the lip-columella junction, redundant vermilion, and excess flap length, and it also reduces or eliminates the need for upper or lower lip scar revision.
    No preview · Article · Jan 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Preoperative nasoalveolar molding (NAM) in combination with primary gingivoperiosteoplasty (GPP) reduces the need for secondary alveolar bone grafting by 60% in patients with unilateral cleft lip and palate (CL/P). Herein, we investigate the efficacy of NAM and primary GPP in patients with bilateral CL/P. All patients (n = 38) with bilateral CL/P who underwent NAM and primary GPP from 1988 to 1998 with at least 14 years of follow-up were included in this study. Panoramic and periapical radiographs were used to assess dentoalveolar bone formation. A total of 38 patients were identified with median follow-up of 18 years (range 14-26 years). Of the 27 patients who underwent bilateral GPP, 14 (51%) patients had successful dentoalveolar bone formation bilaterally and 13 (49%) had unilateral bone formation. No patient had a bilateral failure. Of the 11 patients who underwent unilateral GPP, 7 (63%) patients had successful dentoalveolar bone formation. Bilateral successful dentoalveolar bone formation following primary bilateral GPP has a dependent probability of 52% and a conditional probability of 82%.
    No preview · Article · Jan 2013 · The Journal of craniofacial surgery
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    ABSTRACT: The incidence of postoperative complications in cleft care is low. In this 19-year retrospective analysis of cleft lip and palate patients treated with preoperative nasoalveolar molding, we examine the incidence of postoperative oronasal fistulae. The charts of 178 patients who underwent preoperative nasoalveolar molding by the same orthodontist/prosthodontist team and primary cleft lip/palate repair by the same surgeon over a 19-year period were reviewed. Millard, Mohler, Cutting, or Mulliken-type techniques were used for cleft lip repairs. Oxford-, Bardach-, or von Langenbeck-type techniques were used for cleft palate repairs. One nasolabial fistula occurred after primary cleft lip repair (0.56% incidence) and was repaired surgically. Four palatal fistulae (3 at the junction between soft and hard palate and 1 at the right anterior palate near the incisive foramen) occurred, but 3 healed spontaneously. Only 1 palatal fistula (0.71%) required surgical repair. All 5 fistulae occurred within the first 8 years of the study period, with 4 (80%) of 5 occurring within the first 3 years. Although fistula rate may be related to surgeon experience and the evolution of presurgical techniques, nasoalveolar molding in conjunction with nasal floor closure contributes to a low incidence of oronasal fistulae.
    No preview · Article · Jan 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Despite significant advances in cleft lip and palate treatment, anatomical controversies remain. Some have proposed that the width of the cleft is due to alveolar segmental displacement. Others suggest that the width is due to palatoalveolar hypoplasia. Improving our understanding of cleft anatomy may have implications for presurgical orthopedics and tissue engineering therapies. Palatoalveolar impressions of 17 noncleft children and 11 children with complete (alveolar, primary, and secondary) unilateral cleft palates were taken. Maxillary tuberosity positions and maxillary volumes were compared. Tuberosity position was determined by facebow transfer of palatoalveolar casts into geodetic datum boxes, and identification of the Cartesian coordinates (x, y, z) of the tuberosities relative to the box surfaces and Frankfurt horizontal. Maxillary volume was determined by immersing the palatoalveolar casts and measuring sand displacement. A significant difference was noted in the average tuberosity to contralateral tuberosity distance between cleft and noncleft cohorts. On average, cleft palate tuberosities were laterally displaced 8.7 mm compared with noncleft palates (P < 0.05). There was neither statistically significant alveolar segment elevation nor retroversion. A significant difference was noted in the average palatoalveolar volumes. The cleft palatoalveolar volume was 5.7 cm, and the noncleft palatoalveolar volume was 7.2 cm (P < 0.05). A palatal cleft is due to both alveolar tissue displacement and deficiency. Therefore, ideal cleft palate care should involve the correction of a displaced and deficient alveolus.
    No preview · Article · Jan 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell (OPEC) populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell (EPEC) populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (VEGFR1), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight co-culture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that co-culture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.
    No preview · Article · Jan 2013 · Tissue Engineering Part A

Publication Stats

3k Citations
674.20 Total Impact Points


  • 2008-2015
    • NYU Langone Medical Center
      • Department of Plastic Surgery
      New York, New York, United States
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2000-2015
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      New York, New York, United States
  • 2001-2014
    • CUNY Graduate Center
      New York, New York, United States
  • 2011
    • Peking University
      Peping, Beijing, China
  • 2009-2011
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 2007
    • Weill Cornell Medical College
      • Division of Plastic and Reconstructive Surgery
      New York, New York, United States
    • Cornell University
      Итак, New York, United States
  • 2005-2007
    • Harvard University
      Cambridge, Massachusetts, United States
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 2000-2005
    • Stanford University
      • • Department of Surgery
      • • Division of Plastic and Reconstructive Surgery
      • • Department of Mechanical Engineering
      Palo Alto, California, United States
  • 2004
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2001-2004
    • Stanford Medicine
      • Department of Surgery
      Stanford, California, United States
  • 2002
    • Harvard Medical School
      Boston, Massachusetts, United States