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Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects

Bekisz, Jonathan M; Flores, Roberto L; Witek, Lukasz; Lopez, Christopher D; Runyan, Christopher M; Torroni, Andrea; Cronstein, Bruce N; Coelho, Paulo G
PURPOSE/OBJECTIVE:The objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, bioactive ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model. MATERIALS AND METHODS/METHODS:Custom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100 μM concentration dipyridamole (DIPY) solution. Sheep (n = 5) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution. RESULTS:No exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (p = 0.013) and 6 weeks (p = 0.046) in vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, p = 0.046 and p = 0.031, respectively). CONCLUSION/CONCLUSIONS:Dipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.
PMCID:5803375
PMID: 29292126
ISSN: 1878-4119
CID: 2899422

Three-Dimensional Soft Tissue Nasal Changes After Nasoalveolar Molding and Primary Cheilorhinoplasty in Infants With Unilateral Cleft Lip and Palate

Mancini, Laura; Gibson, Travis L; Grayson, Barry H; Flores, Roberto L; Staffenberg, David; Shetye, Pradip R
OBJECTIVE:To quantify 3-dimensional (3D) nasal changes in infants with unilateral cleft lip with or without cleft palate (UCL±P) treated by nasoalveolar molding (NAM) and cheilorhinoplasty and compare to noncleft controls. DESIGN/METHODS:Retrospective case series of infants treated with NAM and primary cheilorhinoplasty between September, 2012 and July, 2016. Infants were included if they had digital stereophotogrammetric records at initial presentation (T1), completion of NAM (T2), and following primary cheilorhinoplasty (T3). Images were oriented in 3dMD Vultus software, and 16 nasolabial points identified. PATIENTS/METHODS:Twenty consecutively treated infants with UCL±P. INTERVENTIONS/METHODS:Nasoalveolar molding and primary cheilorhinoplasty. MAIN OUTCOME MEASURES/METHODS:Anthropometric measures of nasal symmetry and morphology were compared in the treatment group between time points using paired Student t tests. Postsurgical nasal morphology was compared to noncleft controls. RESULTS:Nasal tip protrusion increased, and at T3 was 2.64 mm greater than noncleft controls. Nasal base width decreased on the cleft side by 4.01 mm after NAM and by 6.73 mm after cheilorhinoplasty. Columellar length of the noncleft to cleft side decreased from 2:1 to 1:1 following NAM. Significant improvements in subnasale, columella, and nasal tip deviations from midsagittal plane were observed. Treatment improved symmetry of the alar morphology angle and the nasal base-columella angle between cleft and noncleft sides. CONCLUSIONS:Three-dimensional analysis of UCL±P patients demonstrated significant improvements in nasal projection, columella length, nasal symmetry, and nasal width. Compared to noncleft controls, nasal form was generally corrected, with overcorrection of nasal tip projection, columella angle, and outer nasal widths.
PMID: 29698115
ISSN: 1545-1569
CID: 3053152

Resection of Nasal Glial Heterotopia Using a Nasal Subunit Approach

Friel, Michael T; Flores, Roberto L
Background/UNASSIGNED:In the subunit principle of nasal reconstruction, the valleys and low ridges of the nose are designated as topographic subunits. Surgical scars can be located at the borders of subunits to hide their appearance. Case Report/UNASSIGNED:A 30-month-old female presented with an obstructing nasal glial heterotopia (nasal glioma). Using the nasal subunit approach, the mass was exposed using an incision along the subunit borders of the nose. The nasal glioma was completely resected, and the internal nasal valve and the deformed lower lateral cartilages were reconstructed through the subunit approach access incision. The final scar was placed along the subunit borders of the nose. At 6-month follow-up, the patient demonstrated no airway obstruction, adequate nasal contour, and an esthetic nasal scar. Conclusion/UNASSIGNED:The subunit approach for a large, obstructing nasal glial heterotopia allows direct exposure for tumor resection, framework reconstruction, placement of the incision in an esthetic location, and excision of the expanded skin for recontouring of the skin envelope.
PMCID:6135286
PMID: 30258301
ISSN: 1524-5012
CID: 3315772

Cephalometric Predictors of Clinical Severity in Treacher Collins Syndrome

Esenlik, Elcin; Plana, Natalie M; Grayson, Barry H; Flores, Roberto L
BACKGROUND: The aim of this study is to identify cephalometric measurements associated with clinical severity in patients with Treacher Collins Syndrome (TCS). METHODS: A retrospective single-institutional review of patients with TCS was conducted. Pre-operative cephalograms and computed tomography scans (n=30) were evaluated. 50 cephalometric measurements were compared to age-specific normative data using ANOVA. These cephalometric measurements and the patient's Pruzansky classification were correlated to clinical severity using Spearman analysis. Clinical severity was defined as: severe (required tracheostomy), moderate (obstructive sleep apnea, oral cleft, or gastrostomy-tube), or mild (absence of listed co-morbidities). Cephalometric measurements with a strong correlation (rs>0.60) were identified as predictors of clinical severity. RESULTS: Cephalograms of the study population contained thirty measurements that were found to be significantly different from normative data (p<0.01). These measurements were largely related to maxillary/mandibular projection, maxillary/mandibular plane angle, mandibular morphology, facial height, facial convexity and mandible/throat position. Ten of these 30 statistically significant measurements in addition to Pruzansky classification were found to be strongly correlated (rs>.60) to clinical severity. These measurements include: Mandibular projection/position [Sella-Nasion-Pogonion (SN-Pg) rs=-0.64; Hyoid-Menton (Hy-Me) rs=-0.62]; Posterior facial height [Posterior Facial Height/Anterior Facial Height (PFH/AFH) rs=0.60; Condyle-Gonion (Co-Go) rs=-0.66]; Maxillary/mandibular plane angle [Sella-Nasion-Mandibular Plane (SN-MP) rs=0.62; Frankfort Horizontal-Mandibular Plane (FH-MP) rs=0.61; Sella-Nasion-Palatal Plane (SN-PP) rs=0.69; Sella-Nasion-Symphysis (SN-Symph) rs=-0.69; Pruzansky classification rs=0.82. CONCLUSIONS: Specific cephalometric measurements of increased mandibular retrognathia, decreased posterior facial height, more obtuse maxillary/mandibular plane angle and more obtuse symphasis notch angle are strongly correlated to increased clinical severity in patients with Treacher Collins syndrome.
PMID: 28820843
ISSN: 1529-4242
CID: 2670552

"Does the Organization of Plastic Surgery Units into Independent Departments Affect Academic Productivity?"

Loewenstein, Scott N; Duquette, Stephen; Valsangkar, Nakul; Avula, Umakanth; Lad, Neha; Socas, Juan; Flores, Roberto L; Sood, Rajiv; Koniaris, Leonidas G
BACKGROUND: There is an increased push for plastic surgery units in the United States to become independent departments administered autonomously rather than as divisions of a multispecialty surgery department. The purpose of this research was to determine if there are any quantifiable differences in the academic performance of departments versus divisions. METHODS: Using a list of the plastic surgery units affiliated with The American Council of Academic Plastic Surgeons (ACAPS), unit websites were queried for departmental status and to obtain a list of affiliated faculty. Academic productivity was then quantified using the SCOPUS database. National Institute of Health (NIH) funding was determined through the Research Portfolio Online Reporting Tools database. RESULTS: Plastic surgery departments were comparable to divisions in academic productivity, evidenced by a similar number of publications per faculty (38.9 versus 38.7; p=0.94), number of citations per faculty (692 versus 761; p=0.64), H-indices (9.9 versus 9.9; p=0.99), and NIH grants (3.25 versus 2.84; p=0.80), including RO1 grants (1.33 versus 0.84; p=0.53). There was a trend for departments to have a more equitable male to female ratio (2.8 versus 4.1; p=0.06), and departments trained a greater number of integrated plastic surgery residents (9.0 versus 5.28; p=0.03). CONCLUSIONS: This study demonstrates that the academic performance of independent plastic surgery departments is generally similar to divisions, but with nuanced distinctions.
PMID: 28746240
ISSN: 1529-4242
CID: 2654322

Optimizing Safety of Iliac Bone Harvest Using an Acumed Drill: A Simulated Radiographic Study of 100 Patients

Stranix, John T; Cuzzone, Daniel; Ly, Catherine; Topilow, Nicole; Runyan, Christopher M; Ream, Justin; Flores, Roberto L
OBJECTIVE: To determine the potential risk of visceral injury during Acumed drill iliac crest cancellous bone graft harvest. DESIGN: Radiographic iliac crest anatomic analysis with simulated drill course to measure cancellous bone available for harvest and proximity of vulnerable pelvic structures. SETTING: Single institution, tertiary care university hospital. PATIENTS AND PARTICIPANTS: One hundred pelvic computed tomography scans performed on children 8 to 12 years old without traumatic or neoplastic pathology. INTERVENTIONS: Radiographic simulation of Acumed drill course within iliac bone. MAIN OUTCOME MEASURES: (1) Potential for pelvic visceral injury. (2) Volume of cancellous bone safely available for harvest. RESULTS: Superior and medial cortical thickness at the reference point remained stable across age groups; however, lateral cortical thickness increased with age (3.13 to 3.74 mm, P < .001). Cancellous bone width increased with age at all depths measured (P < .001). Through radiographic simulation, the drill could reach the bowel in 4% of cases and only through gross deviation (>30 degrees ) from the plane of the ilium. There were no cases of simulated bowel perforation within 3 cm of the reference point. The maximum cancellous volume safely harvested increased with age: 24 cc in 8-year-olds to 36 cc in 12-year-olds (P < .001). CONCLUSIONS: Acumed assisted iliac crest bone graft harvest is a safe technique in which substantial amount of cancellous bone can be obtained. The low risk of bowel perforation can be further minimized by limiting the depth of drill bit penetration to less than 3 cm.
PMID: 27632764
ISSN: 1545-1569
CID: 2779922

Minor Suture Fusion in Syndromic Craniosynostosis

Runyan, Christopher M; Xu, Wen; Alperovich, Michael; Massie, Jonathan P; Paek, Gina; Cohen, Benjamin A; Staffenberg, David A; Flores, Roberto L; Taylor, Jesse A
BACKGROUND: Infants with craniofacial dysostosis syndromes may present with midface abnormalities but without major (calvarial) suture synostosis and head shape anomalies. Delayed presentation of their calvarial phenotype is known as progressive postnatal craniosynostosis. Minor sutures/synchondroses are continuations of major sutures toward and within the skull base. The authors hypothesized that minor suture synostosis is present in infants with syndromic, progressive postnatal craniosynostosis, and is associated with major suture synostosis. METHODS: The authors performed a two-institution review of infants (<1 year) with syndromic craniosynostosis and available computed tomographic scans. Major (i.e., metopic, sagittal, coronal, and lambdoid) and minor suture/synchondrosis fusion was determined by two craniofacial surgeons and one radiologist using Mimics or Radiant software. RESULTS: Seventy-three patients with 84 scans were included. Those with FGFR2 mutations were more likely to lack any major suture fusion (OR, 19.0; p = 0.044). Minor suture fusion occurred more often in the posterior branch of the coronal arch (OR, 3.33; p < 0.001), squamosal arch (OR, 7.32; p < 0.001), and posterior intraoccipital synchondroses (OR, 15.84; p < 0.001), among FGFR2 versus other patients. Patients (n = 9) with multiple scans showed a pattern of minor suture fusion followed by increased minor and major suture synostosis. Over 84 percent of FGFR2 patients had minor suture fusion; however, six (13 percent) were identified with isolated major suture synostosis. CONCLUSIONS: Minor suture fusion occurs in most patients with FGFR2-related craniofacial dysostosis. Syndromic patients with patent calvarial sutures should be investigated for minor suture involvement. These data have important implications for the pathophysiology of skull growth and development in this select group of patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
PMID: 28574949
ISSN: 1529-4242
CID: 2702532

Distraction of the mandible

Chapter by: McCarthy, Joseph G.; Flores, Roberto L.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 45-88
ISBN: 9783319525624
CID: 2796072

Distraction osteogenesis: Biologic and biomechanical principles

Chapter by: Runyan, Christopher M.; Flores, Roberto L.; McCarthy, Joseph G.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 11-43
ISBN: 9783319525624
CID: 2796112

Distraction of the midface: Le fort III and monobloc

Chapter by: McCarthy, Joseph G.; Flores, Roberto L.
in: Craniofacial Distraction by
[S.l.] : Springer International Publishing, 2017
pp. 135-175
ISBN: 9783319525624
CID: 2796122