Faculty Bibliography

Background/Purpose: Previous in vivo and in vitro animal studies demonstrate that the adenosine A2A receptor (A2AR) agonist dipyridamole (DIPY) stimulates robust osteogenic differentiation and proliferation without adverse effects on craniofacial suture development. However, no studies to date have been performed on human tissue. This study compares the effects of DIPY, BMP-2, and standard osteogenic media on osteogenic differentiation by human mesenchymal stem cells to lay the foundation for translating this bone tissue engineering approach to pediatric craniofacial reconstruction. Methods/Description: Pediatric mesenchymal stem cells were isolated from surplus bone taken from consented patients undergoing craniofacial surgery. Cells were cultured at early passage for 3 weeks in 1 of 7 experimental conditions: control media; osteogenic media (control + 100 muM beta-glycerophosphate, 0.1 muM dexamethasone and 100 mg/ mL L-ascorbic acid); osteogenic media + 200 ng/mL BMP-2; osteogenic media + 10, 100, 1000, or 10 000 muM DIPY. All experiments were performed in biological triplicates. Samples were analyzed using Alkaline phosphatase (ALP) assay at 6 hours, 24 hours, 48 hours, and 7 days as a marker of early osteogenic differentiation. At the end of the 3-week differentiation period, cells underwent immunocytochemistry to verify phalloidin, osteocalcin, and collagen I expression. Alizarin red staining was used to detect mineralization. Statistical analysis used 1-way ANOVA with Tukeys post hoc correction and multiple t test comparison of means.
Result(s): In all osteogenic conditions, relative peak ALP activity occurred at 48 hours. One thousand micrometer DIPY showed significantly increased peak ALP activity compared to BMP-2 (3.6 +/- 0.1 fold increase vs 3.1 +/- 0.1; P = .006). There was no significant difference between 1000 muM DIPY and osteogenic media (4.1 +/- 0.1; P = .36). At 3 weeks, immunocytochemistry revealed differentiation in all osteogenic conditions compared to control. One thousand micrometer DIPY cells showed greater evidence of mature osteogenic differentiation including cuboidal cell morphology and deposition of collagen I in an extracellular fibrillar network pattern compared to both control osteogenic media and BMP-2. Alizarin red quantification demonstrated significantly increased extracellular matrix mineralization at 100 muM(2.4+/-0.4; P = .002), 1000 muM (4.3+/-0.6; P = .001), and 10 000 muM (5.1 +/- 0.2; P < .0001) DIPY compared to nonosteogenic control medium (1.0 +/- 0.1). Matrix mineralization was not significantly different between BMP-2 (2.4 +/- 0.2) and 1000 muM DIPY (P = .08). ImageJ analysis revealed increased proportion of osteocalcin expressing cells (40.0% +/- 2.8%) in stem cells treated with 1000 muM of dipyridamole compared to control (1.0% +/- 0.6%), osteogenic (5.8% +/- 1.0%), and BMP-2 (16.9% +/- 2.2%; P < .0001).
Conclusion(s): Dipyridamole promotes early osteogenic differentiation and maturation of human bone-derived mesenchymal stem cells. These data suggest that dipyridamole may be an effective tissue engineering strategy for pediatric craniofacial reconstruction

Background/Purpose: Our goal is to present to mental health professionals and craniofacial center providers a 2-part workshop series called "Social Stories." Social Stories are a creative and effective tool for helping children with craniofacial conditions cope with feelings that arise in new and/or stressful situations: such as surgery, doctor visits, and school transitions. This presentation will teach psychosocial teams at other craniofacial centers how to develop workshops using Social Stories as a platform for helping school-age children and their parents cope with stressful and/or novel situations. The first workshop of the 2-part series was developed for parents of children with craniofacial conditions. Parents learned about the concept of Social Stories and identified situations that their child was struggling with. Parents were asked to provide detailed information for these situations and help collect images and photos to be used in their child's Social Story Workbooks. The second workshop was developed for children ages 8 to 12 years old with craniofacial conditions. In this workshop, the children created their Social Story Workbooks, utilizing a combination of ideas, images, and photographs from home (provided by parents) and collected by the psychosocial team. Parent participants completed a psychological screening questionnaire to help us assess how this intervention impacted their child's level of coping with stressful and novel situations. Methods/Description: The concept of Social Stories, initially developed for children and adolescents with autism, was created and trademarked by Carol Gray in 1991. Our team modified this modality for children with craniofacial conditions to help improve their ability to cope with distressing or novel situations. Social Stories can include specific information about expectations, emotions, and feelings and why they occur, and empower children to gain mastery and resilience

Background/Purpose: Informed decision-making in cleft care relies heavily on available information, including online resources. The American Medical Association (AMA) recommends that the readability of these resources does not exceed the sixth grade reading level. We evaluated the comprehensiveness and readability of patientoriented online resources provided by American Cleft Palate- Craniofacial Association (ACPA) Approved cleft lip and/or palate (CLP) Teams in the United States. Methods/Description: ACPA Approved CLP Team listings were reviewed between July 16, 2018, and July 30, 2018. Listings with nonfunctional website links prompted an Internet search for the corresponding websites. Teams with no accessible website or <30 sentences of content were excluded. Content comprehensiveness was scored by presence/absence of 20 variables derived from ACPA team approval standards. Content readability, defined as estimated reading grade level, was evaluated with 8 validated scales using a Professional Readability Software (Oleander Software, Ltd, Vandalia, Ohio). Readability was then compared to AMA recommendations. Linear regression was used to assess the relationship between comprehensiveness and readability.
Result(s): From 167 reviewed teams, 47 (28.1%) had nonfunctional links. After an Internet search, 17 (10.2%) had no accessible website, and 39 (23.4%) had <30 sentences. A total of 56 teams were thus excluded. The average comprehensiveness score for all 111 team websites included was 14.5 +/- 2.6 out of 20. The combined average reading level across all scales (10.7 +/- 1.9) exceeded the AMArecommended sixth grade reading level; this finding held true for each individual website. Children's Hospital-affiliated teams (n = 86) had a significantly higher comprehensiveness 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 comprehensiveness score significantly predicted better readability (beta = -0.226; P < .001; 95% CI: -0.359 to -0.092).
Conclusion(s): Online resources of ACPA Approved CLP Teams vary in accessibility and comprehensiveness, and exceed the recommended reading level. In order to better serve and educate patients with cleft lip and/or palate and their caregivers, future efforts should be directed toward developing standardized, comprehensive, accessible, and intelligible online resources, while ensuring validation of their content and language

Background/Purpose: Knowledge of cleft lip (CL) surgical markings is essential prior to performing the repair. Work hours restrictions, increased patient care documentation time, and requests by patients not to have trainees involved in their care are limiting the acquisition of this skill in the operating room. Textbooks provide 2-dimensional illustrations of CL markings; while the cost of 3-dimensional (3D) printed CL models prohibit their widespread utilization for this purpose. We propose 3D stone models as simple and affordable tools to teach surgical trainees unilateral CL markings. Methods/Description: Polyvinyl siloxane (PVS) impression material was used to create a negative of a patient with unilateral CL. Snapstone mixed with water was poured into the PVS impression to create unilateral CL stone models. Eleven plastic surgery residents were prospectively recruited in the study. They were provided with a textbook chapter and online module detailing surgical markings for unilateral CL repair, and were given 15 minutes of study time, before providing them with a unilateral CL stone model for performing the CL markings within 10 minutes. The participants were then provided with a standardized patient photograph for the same purpose. Learner satisfaction with the stone model and patient photograph as educational tools for learning surgical markings were evaluated using a modified survey based on the Student Evaluation of Educational Quality (SEEQ) survey, a validated tool for measuring higher education student satisfaction. Learner satisfactions with each tool were compared using a Mann-Whitney U test.
Result(s): The total production time of one stone model, including the PVS impression, was 10 minutes. The cost of one PVS impression and one stone model were 64 and 83 cents respectively, for a total of $1.47. Participants reported that when compared to the standardized patient photograph, the stone model was more stimulating (4.72 +/- 0.47 vs 3.82+/-0.87; U = 25.5; P = .01), increased their interest in the subject (4.63 +/- 0.50 vs 3.45 +/- 1.29; U = 26.5; P = .02), allowed better learning of the subject matter (4.54 +/- 0.52 vs 2.91 +/- 0.83; U = 5.0; P < .001), had greater clarity (4.64 +/- 0.50 vs 3.00 +/- 0.89; U = 6.0; P < .001), and was a more effective means of teaching CL markings (4.73 +/- 0.47 vs 2.91 +/- 1.04; U = 6.0; P < .001). Participants were also more likely to recommend the stone model (4.82+/-0.40) over the standardized patient photograph (3.00 +/- 1.10; U = 5.0; P < .001).
Conclusion(s): 3D stone models of the unilateral cleft lip deformity are affordable and simple to produce. Plastic surgery residents report that these models are superior training tools to learn cleft lip markings compared to patient photographs. These educational tools have the potential to overcome significant financial, logistic, and time constraints in teaching cleft lip surgery markings

Background/Purpose: Intraoral myomucosal flaps such as the facial artery myomucosal (FAMM) flap and the buccal flap can provide effective palatal lengthening for the management of velopharyngeal insufficiency (VPI). This surgical approach is not without limitations and can result in increased postoperative burden to the patient and caregiver and frequently involves a second anesthetic event for pedicle division and flap inset. We sought to analyze the postoperative speech and functional outcomes of patients undergoing such procedures at our institution. Methods/Description: A retrospective assessment of all patients undergoing intraoral myomucosal flaps by a single surgeon at a tertiary academic institution was conducted. Only patients undergoing bilateral FAMM or buccal flaps for VPI were included. Data included demographic characteristics, flap-related complications, and postoperative speech and oral function. Results were compared between 2 age groups (group 1: <13, group 2: >=13). Analysis was performed over 5 clinical time points: preoperatively (T0), and postoperatively at 1 to 4 weeks (T1), 3 to 6 months (T2), and 1 to 3 years (T3).
Result(s): Of 54 patients reviewed, 24 met inclusion criteria: fourteen (58.3%) underwent bilateral FAMM flaps and 10 (41.7%) buccal flaps. Group 1 included 15 (62.5%) patients (median age: 6; range: 4-12) and group 2 included 9 (37.5%; median age: 23; range: 13-52). Group 1 patients were more likely to undergo buccal (60%), whereas group 2 were more likely to undergo FAMM flaps (88.9%). No intraor postoperative donor site complications, bleeding, flap necrosis, or dehiscence were noted. Subsequent pedicle division was performed in 66.7% of patients in group 1 (median: 35 days, range: 18-174) and 55.6% in group 2 (median: 46 days, range: 35-980) for interference with mastication in 10 (41.7%) patients, timing with other elective procedures in 3 (12.5%), or molar eruption in 1 patient. Ten (41.7%) patients had longitudinal speech follow-up, 70% of which were from group 1. Structural hypernasality had completely resolved in 80% of patients at T1, and in the rest by T3. At T1, >50% displayed abnormal occlusion or tongue placement and weak articulatory contact, which subsequently resolved. Dysphagia, drooling, or reduced oral opening were noted at T1 in most patients but had largely resolved on follow-up.
Conclusion(s): FAMM and buccal flaps are effective palatal lengthening procedures with 100% resolution of structural hypernasality and minimal complications in our series. Patient age and timing of division of flap pedicles may have an effect on postoperative oral function. Our findings support the early division of FAMM and buccal flap pedicles

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

Background/Purpose: To develop guidelines for oral hygiene procedures following cleft lip/palate (CL/P) surgery. To share post surgical oral hygiene protocols with other organizations/institutions to stimulate dialogue between their Surgical and Dental Teams. Methods/Description: Global Smile Foundation (GSF), a registered nonprofit organization, whose volunteers have over 3 decades of follow-up care, would like to develop a parallel OHI protocol after each stage of CL/P surgery. GSF has explored the use of various combined OHI methods (including toothbrush, sponge, chlorhexidine, and CPC). GSF's surgical and dental team are developing their own OHI protocol(s) specific to the age of patient and type of surgery, including: (a) type of instrument (toothbrush, sponge on a stick) to use initially postsurgery, (b) timing to restart toothbrushing postsurgery, (c) type of toothpaste (fluoridated or not-fluoridated) to use initially postsurgery, (d) use of mouth rinse postoperatively, such as chlorhexidine (alcohol or alcohol-free) or cetylpyridinium chloride (CPC), (e) location/surfaces of tooth brushing and which surgical sites to avoid, (f) liquid or soft food diet recommendations, and (g) timing of when normal routine should be resumed. A literature review was conducted of surgical and nonsurgical methods, along with a review of the existing OHI protocols from 30 registered US cleft centers, and guidelines of various national and international organizations/institutions (ACPA, ICHOM, CLEFTSIS, etc).
Result(s): Literature search revealed that most cleft care organizations have a set of protocols for postoperative care of the wound site after surgery. However, a specific OHI protocol wasn't found. Rinsing with water, traditional protocols and what NOT to do (pacifier, bottle, thumb, etc) was the extent of the information found. There is a wide range of post surgical protocols among clinicians and different centers. Despite these contradictory approaches (liquid diet vs soft food, brushing vs rinse only, chlorhexidine vs no rinsing), there seems to be no difference in outcome of surgery and long-term oral health. Nonetheless, this is an area that has not been formerly studied.
Conclusion(s): The goal of postsurgical OHI protocol should be to reduce the burden of bacterial load /bio film and to keep the wound site as healthy as possible, allowing for optimal healing. The post surgical OHI protocol should be mutually supported by both the surgical and dental teams. However, does the specific OHI protocol affect the surgical outcome? Further testing to measure the markers of post surgical oral hygiene and its impact on the outcome of surgery is needed

BACKGROUND:Human monoclonal antibodies that potently and broadly neutralise HIV-1 are under development to prevent and treat HIV-1 infection. In this phase 1 clinical trial we aimed to determine the safety, tolerability, and pharmacokinetic profile of the broadly neutralising monoclonal antibody VRC07-523LS, an engineered variant of VRC01 that targets the CD4 binding site of the HIV-1 envelope protein. METHODS:This phase 1, open-label, dose-escalation clinical trial was done at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Individuals were recruited from the greater Washington, DC, area by IRB-approved written and electronic media. We enrolled healthy, HIV-1-negative adults aged 18-50 years. Inclusion criteria were good general health, measured through clinical laboratory tests, medical history, and physical examination. Participants self-selected into one of seven open groups during enrolment without randomisation. Four groups received a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07-523LS, and one group received a single 5 mg/kg subcutaneous dose. Two groups received three doses of either 20 mg/kg intravenous VRC07-523LS, or 5 mg/kg subcutaneous VRC07-523LS at 12-week intervals. The primary outcome was the safety and tolerability of VRC07-523LS, assessed by dose, route, and number of administrations. This study is registered with ClinicalTrials.gov, NCT03015181. FINDINGS/RESULTS:Between Feb 21, 2017, and September 13, 2017, we enrolled 26 participants, including 11 (42%) men and 15 (58%) women. Two (8%) participants withdrew from the study early: one participant in group 1 enrolled in the study but never received VRC07-523LS, and one participant in group 6 chose to withdraw after a single administration. One (4%) participant in group 7 received only one of the three scheduled administrations. 17 participants received intravenous administrations and 8 participants received subcutaneous administrations. VRC07-523LS was safe and well tolerated, we observed no serious adverse events or dose-limiting toxic effects. All reported local and systemic reactogenicity was mild to moderate in severity. The most commonly reported symptoms following intravenous administration were malaise or myalgia in three (18%) participants and headache or chills in two (12%) participants. The most commonly reported symptoms following subcutaneous administration were pain and tenderness in four participants (50%) and malaise or headache in three (38%) participants. INTERPRETATION/CONCLUSIONS:Safe and well tolerated, VRC07-523LS is a strong and practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. The results from this trial also indicate that an HIV-1 broadly neutralising monoclonal antibody engineered for improved pharmacokinetic and neutralisation properties can be safe for clinical use. FUNDING/BACKGROUND:National Institutes of Health.

BACKGROUND:Apert syndrome is frequently combined with respiratory insufficiency, because of the midfacial deformity which, in turn, is influenced by the malformation of the skull base. Respiratory impairment resulting from Apert syndrome is caused by multilevel limitations in airway space. Therefore, this study evaluated the segmented nasopharyngeal and laryngopharyngeal anatomy to clarify subcranial anatomy in children with Apert syndrome and its relevance to clinical management. METHODS:Twenty-seven patients (Apert syndrome, n = 10; control, n = 17) were included. All of the computed tomographic scans were obtained from the patients preoperatively, and no patient had confounding disease comorbidity. Computed tomographic scans were analyzed using Surgicase CMF. Craniometric data relating to the midface, airway, and subcranial structures were collected. Statistical significance was determined using t test analysis. RESULTS:Although all of the nasal measurements were consistent with those of the controls, the nasion-to-posterior nasal spine, sphenethmoid-to-posterior nasal spine, sella-to-posterior nasal spine, and basion-to-posterior nasal spine distances were decreased 20 (p < 0.001), 23 (p = 0.001), 29 (p < 0.001), and 22 percent (p < 0.001), respectively. The distance between bilateral gonions and condylions was decreased 17 (p = 0.017) and 18 percent (p = 0.004), respectively. The pharyngeal airway volume was reduced by 40 percent (p = 0.01). CONCLUSION/CONCLUSIONS:The airway compromise seen in patients with Apert syndrome is attributable more to the pharyngeal region than to the nasal cavity, with a gradually worsening trend from the anterior to the posterior airway, resulting in a significantly reduced volume in the hypopharynx.