Faculty Bibliography

This retrospective cohort study aimed to determine the impact of a nasoalveolar molding (NAM) protocol on midface growth in school-aged children with non-syndromic unilateral cleft lip and palate (UCLP). Data from 56 consecutively treated, NAM-prepared, Caucasian patients with non-syndromic UCLP from a single US cleft palate center were compared to pooled center data based on 56 patients with non-syndromic UCLP treated at 2 Eurocleft centers that did not use presurgical infant orthopedics (non-PSIO). Lateral cephalograms were obtained and 28 landmarks were identified. Published cephalometric measurements from Eurocleft centers were used for comparison. Seven cephalometric measurements (SNA, SNB, ANB, A'N'B', G'-Sn'-Pg', Sn-CT-LS, ANS-Me/N-Me%), available or derivable for both centers, were analyzed. Means and standard deviations for the 7 measurements were calculated for the NAM center. Student's t-tests were used to compare group means for 6 of the measures and a test of proportion was used for ANS-Me/N-Me%. No significant differences were found between the NAM protocol-prepared group and the Eurocleft non-PSIO centers on any of the 7 analyzed cephalometric relationships after accounting for false discovery rate. The NAM treatment protocol does not appear to impact skeletal or soft tissue facial growth in school-aged children with non-syndromic UCLP.

BACKGROUND:Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade. METHODS:The authors' team has successfully treated patients with extensive thermal and ballistic facial injuries with allotransplantation. The authors further validate facial transplantation as a reconstructive solution for irreparable facial injuries. Following informed consent and institutional review board approval, a partial face and double jaw transplantation was performed in a 25-year-old man who sustained ballistic facial trauma. Extensive team preparations, thorough patient evaluation, preoperative diagnostic imaging, three-dimensional printing technology, intraoperative surgical navigation, and the use of dual induction immunosuppression contributed to the success of the procedure. RESULTS:The procedure was performed on January 5 and 6, 2018, and lasted nearly 25 hours. The patient underwent hyoid and genioglossus advancement for floor-of-mouth dehiscence, and palate wound dehiscence repair on postoperative day 11. Open reduction and internal fixation of left mandibular nonunion were performed on postoperative day 108. Nearly 1 year postoperatively, the patient demonstrates excellent aesthetic outcomes, intelligible speech, and is tolerating an oral diet. He remains free from acute rejection. CONCLUSIONS:The authors validate facial transplantation as the modern answer to the classic reconstructive challenge imposed by extensive facial defects resulting from ballistic injury. Relying on a multidisciplinary collaborative approach, coupled with innovative emerging technologies and immunosuppression protocols, can overcome significant challenges in facial transplantation and reinforce its position as the highest rung on the reconstructive ladder. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, V.

BACKGROUND:Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds. METHODS:Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 μm of dipyridamole (n = 6), 10,000 μm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test. RESULTS:Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-μm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-μm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 μm versus 10,000 μm dipyridamole; p = 0.104), and rhBMP-2-coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 μm dipyridamole, and p = 0.938 versus 10,000 μm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone. CONCLUSION/CONCLUSIONS:Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available.

Craniosynostosis (CS) is a frequent congenital anomaly featuring the premature fusion of 1 or more sutures of the cranial vault. Syndromic cases, featuring additional congenital anomalies, make up 15% of CS. While many genes underlying syndromic CS have been identified, the cause of many syndromic cases remains unknown. We performed exome sequencing of 12 syndromic CS cases and their parents, in whom previous genetic evaluations were unrevealing. Damaging de novo or transmitted loss of function (LOF) mutations were found in 8 genes that are highly intolerant to LOF mutation (P = 4.0 × 10^-8); additionally, a rare damaging mutation in SOX11, which has a lower level of intolerance, was identified. Four probands had rare damaging mutations (2 de novo) in TFAP2B, a transcription factor that orchestrates neural crest cell migration and differentiation; this mutation burden is highly significant (P = 8.2 × 10^-12). Three probands had rare damaging mutations in GLI2, SOX11, or GPC4, which function in the Hedgehog, BMP, and Wnt signaling pathways; other genes in these pathways have previously been implicated in syndromic CS. Similarly, damaging de novo mutations were identified in genes encoding the chromatin modifier KAT6A, and CTNNA1, encoding catenin α-1. These findings establish TFAP2B as a CS gene, have implications for assessing risk to subsequent children in these families, and provide evidence implicating other genes in syndromic CS. This high yield indicates the value of performing exome sequencing of syndromic CS patients when sequencing of known disease loci is unrevealing.

Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.

OBJECTIVE/UNASSIGNED:Informed decision-making relies on available information, including online resources. We evaluated the content and readability of websites published by American Cleft Palate-Craniofacial Association (ACPA)-approved cleft lip and/or palate (CLP) teams in the United States. DESIGN/UNASSIGNED:Team websites were reviewed, and teams with no accessible website or <30 sentences of content were excluded. Website content was scored by presence/absence of 20 variables derived from ACPA approval standards. Readability was evaluated with 8 scales. Readability was then compared to American Medical Association (AMA) recommendations. The relationship between website content and readability was assessed. MAIN OUTCOME MEASURE(S)/UNASSIGNED:Content and readability of team websites. RESULTS/UNASSIGNED:From 167 reviewed teams, 47 (28.1%) had nonfunctional links, 17 (10.2%) had no accessible website, and 39 (23.4%) had <30 sentences. The average content score for all 111 team websites included was 14.5 (2.6) of 20. The combined average reading level across all scales (10.7 [1.9]) exceeded the AMA-recommended sixth-grade reading level; this finding held true for each individual website. Children's Hospital-affiliated teams (n = 86) had a significantly higher content score (14.8 vs 13.5; P = .03) and better readability as evidenced by lower reading grade level (10.5 vs 11.4; P = .04). On linear regression, a higher content score significantly predicted better readability (β = -0.226; P < .001). CONCLUSIONS/UNASSIGNED:Websites published by ACPA-approved CLP teams vary in accessibility and content and exceed the recommended reading level. These findings could inform future efforts to improve patient-oriented resources.

OBJECTIVE/UNASSIGNED:Assess the weight and contribution of each of the parameters of the Asher-McDade Scale to overall subjective assessment of nasolabial aesthetics following cleft lip repair. DESIGN/UNASSIGNED:Retrospective cohort evaluation. SETTING/UNASSIGNED:Cleft and craniofacial center. PARTICIPANTS/UNASSIGNED:Forty-one patients who underwent unilateral cleft lip repair. INTERVENTIONS/UNASSIGNED:Unilateral cleft lip repair. MAIN OUTCOME MEASURES/UNASSIGNED:Nasolabial rating using the Asher-McDade scale and overall subjective assessment of nasolabial aesthetics using a rank score following unilateral cleft lip repair. RESULTS/UNASSIGNED:= .69; P < .001). CONCLUSION/UNASSIGNED:The parameters evaluated in the Asher-McDade scale have different weights and contribute differently to overall subjective assessment of nasolabial aesthetic outcomes following cleft lip repair. Adjusting for their weights results in a modified score that demonstrates superior correlation with overall subjective assessment of nasolabial aesthetic outcomes.

BACKGROUND:Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation. METHODS:Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro-computed tomography/advanced reconstruction software. Micro-computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals. RESULTS:Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups. CONCLUSION:Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold's ability to regenerate bone in a thin bone defect environment.

Background/Purpose: Despite the increasing trend toward ambulatory surgery rate in general, for cleft lip repair, 72.1% of patients in the United States are still hospitalized. Multiple centers have been studying this and with the very recent publishing of 2 large volume studies published in Plastic and Reconstructive Surgery supporting the safety of outpatient cleft lip surgery, it has become a high-profile debatable topic in cleft management. Last year at ACPA in the plastic surgery breakout session there was a heated debate on the topic between surgeons. And just this summer, one of the authors articles was featured as the PRS Journal Club article of the month via Social media, where there were 68 comments, 11 shares, and 40 likes, which placed the article in the TOP 15 most viewed article in PRS Journal's website. So this is a topic that more and more surgeons and craniofacial teams are thinking about and considering changing practice management but that deserves being brought into the spotlight to discuss all the pros and cons. The goal of the presentation are to present a literature review up to date on inpatient versus outpatient cleft lip surgery and have members of the panel share their and data behind their approach to postoperative cleft lip management. We would like to focus on what has been studied and reported versus what people practice because "that is how they were trained" or that is how they "historically" have always done it. Methods/Description: We will start with an overview of the literature surrounding inpatient versus outpatient cleft lip surgery and epidemiology about the numbers of institutions that do inpatients versus outpatient. If possible, we would like to include an audience poll to get an idea of practice patterns in the room. Then based on the recent published studies, each panelist will share different protocols that have been successful for outpatient cleft lip management and how that could be implemented if a center wants to consider outpatient cleft lip surgery. This includes: preoperative education that can be done by the team or nurse managers, perioperative management before, during, and after the operation, and postoperative care after they go home. All are very key components to a successful outpatient cleft lip management. We will also discuss the barriers to doing outpatient cleft lip surgery as well as having a panelist who consistently does inpatient cleft lip surgery to present the rationale behind their practice management and also their barriers to outpatient cleft lip surgery. I have reached out to a few people and will be discussing with them at the upcoming ASPS meeting to see who may be interested in joining the panel to discuss that. We will discuss the economic impact overall of practice changes to a predominantly outpatient surgery and also potential insurance policy impact. We think this will be a very useful topic for any team member participating in the care of a cleft lip patient