Faculty Bibliography

BACKGROUND:Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored. METHODS:The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information. RESULTS:The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10-6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10-7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10-4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10-4). CONCLUSIONS:These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, III.

BACKGROUND:Mandibular distraction osteogenesis is effective for the correction of severe tongue-based airway obstruction in infants with Pierre Robin sequence. Involved osteotomies may damage developing tooth buds and/or the inferior alveolar nerve. The authors evaluated the theoretical safety of various osteotomy techniques to better define infantile mandibular anatomy using computer-aided modeling. METHODS:Seven mandibular osteotomy techniques (oblique, inverted-L, multiangular, walking stick, high oblique, vertical/high inverted-L, and horizontal) were simulated using computed tomography studies from infants with Pierre Robin sequence and without other associated conditions. Software was used to manually segment the mandibular bone, inferior alveolar nerve, and tooth buds. RESULTS:Sixty-five computed tomography scans were included, yielding 130 hemimandibles. The horizontal osteotomy pattern had significantly lower theoretical risk of tooth bud (p < 0.001) and inferior alveolar nerve involvement (p < 0.001) than all other patterns. Osteotomies with high vertical components (i.e., vertical, walking stick, and multiangular) had lower theoretical tooth bud involvement than the more proximal oblique and inverted-L osteotomies (p < 0.001). Average lingula location was measured at a point 65 percent of the mandibular width from anterior mandibular border and 63 percent of the mandibular height from the inferior mandibular border. CONCLUSIONS:Surgical planning with computed tomography scans can help evaluate an infant's mandibular anatomy to select an osteotomy that reduces morbidity risks. Regardless of technique, tooth buds and the inferior alveolar nerve are often included in osteotomies. The lingula location in this study demonstrates a position more superior and posterior than that previously described. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, V.

OBJECTIVES/OBJECTIVE:Cleft lip repair has traditionally been performed as an inpatient procedure. There has been an interest toward outpatient cleft lip repair to reduce healthcare costs and avoid unnecessary hospital stay. We report surgical outcomes following implementation of an ambulatory cleft lip repair protocol and hypothesize that an ambulatory repair results in comparable safety outcomes to inpatient repair. DESIGN/SETTING/METHODS:This is a single-institution, retrospective study. PATIENTS/PARTICIPANTS/METHODS:Patients undergoing primary unilateral (UCL) and bilateral (BCL) cleft lip repair from 2012 to 2021 with a minimum 30-day follow-up. A total of 226 patients with UCL and 58 patients with BCL were included. INTERVENTION/METHODS:Ambulatory surgery protocol in 2016. OUTCOME MEASURES/METHODS:Variables include demographics and surgical data including 30-day readmission, 30-day reoperation, and postoperative complications. RESULTS:There were no differences in rates of 30-day readmission, reoperation, wound complications, or postoperative complications between the pre- and post-protocol groups. Following ambulatory protocol implementation, 80% of the UCL group and 56% of the BCL group received ambulatory surgery. Average length of stay dropped from 24 h pre-protocol to 8 h post-protocol. The 20% of the UCL group and 44% of the BCL group chosen for overnight stay had a significantly higher proportion of congenital abnormalities and higher American Society of Anesthesiology (ASA) class. Reasons for overnight stay included cardiac/airway monitoring, prematurity, and monitoring of comorbidities. There were no differences in surgical outcomes between the ambulatory and overnight stay groups. CONCLUSIONS:An ambulatory cleft lip repair protocol can significantly reduce average length of stay without adversely affecting surgical outcomes.

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A_2A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

Background/Purpose: Pediatric mandibular fractures remain a therapeutic challenge due to the presence of tooth buds, the need to preserve the growth centers of the jaw, and the high risk to ankylosis in patients with trauma to the condyles. More specifically, condylar fracture with lateral dislocation out of the temporomandibular joint (TMJ) can pose significant challenges due to the difficulty with application of maxillomandibular fixation (MMF) as well as rigid plate fixation. Furthermore, open reduction of the condyle poses long term risk to dysfunction. Herein, we present a novel transfacial pinning surgical technique for the management of pediatric bilateral condylar fractures with lateral dislocation and concomitant symphyseal fracture in a patient less than 5 years of age. Methods/Description: A healthy 3-year-old male patient, who sustained a complex facial fracture in a golf cart accident in which he was unrestrained. Physical exam was remarkable for panfacial edema with no soft tissue injuries and limited oral excursion. Craniofacial computed tomography (CT) revealed a tripartite mandibular fracture, including bilateral condylar fractures with lateral dislocation of the left condyle and a symphyseal fracture. There were no other facial fractures and the patient's cervical spine was cleared both clinically and radiographically. The deciduous teeth precluded the use of traditional MMF and the presence of tooth buds within the entirely of the mandibular body and symphysis made the use of rigid fixation not feasible. The operative plan entailed a staged lower jaw reconstruction with: closed reduction of the laterally dislocated condyle; transfacial pinning with a 2.8 mm threaded Steinman pin between the mandibular angles to secure the medial location mandibular ramus and angle; application of MMF using circummandibular wiring and intermaxillary fixation screws. Two weeks later, MMF was released and the patient started a soft diet and oral excursion exercises with the transfacial pin in place. Two months after the first surgery, the transfacial pin was removed.
Result(s): The patient tolerated all procedures well. Immediate postoperative CT taken after placement of the transfacial pin (first surgery) revealed appropriate reduction of the laterally displaced condyle. At the time of transfacial pin removal (8 weeks after the initial repair), the patient demonstrated full and pain free oral excursion and stable class I occlusion. Follow-up CT analysis after removal of the transfacial pin demonstrates a stable reduction of the dislocated condyle and bony union of all three fractures.
Conclusion(s): Transfacial pinning technique can be a safe and effective technique for treatment of pediatric mandible fractures with lateral dislocation of the condyle

Background/Purpose: After LeFort I advancement surgery, soft tissue changes are unpredictable, especially in patients with orofacial clefts, as scar tissue from primary repair can alter soft tissue responses. Therefore, this study aimed to measure and evaluate soft tissue response following LeFort I advancement in skeletally matured patients with complete cleft lip and palate (CLP). Methods/Description: The cohort of 26 patients with non-syndromic CLP who underwent Le Fort I osteotomy between 2013 and 2019 and met the inclusion criteria. Patients were included if they had lateral cephalograms or CBCT at pre-operative (T1), immediately post-operative (T2), and one-year follow-up (T3). Patients who underwent nose/lip revision surgery before T3 were excluded. Four skeletal and dental hard-tissue (ANS, point A; A-point, upper incisor most labial; U1-most, upper incisor edge; U1-tip) and 5 softtissue (tip of nose or pronasale; Prn, subnasale; Sn, superior labial sulcus; SLS, upper lip anterior or labrale superius; LS, and stomion superius; SIMS) landmarks were digitized and measured. For the outcome analyses, 5 ratios of soft- to hard-tissue changes (Prn/ANS, Sn/A-point, SLS/A-point, LS/U1-most, and SIMS/ U1-tip) were calculated for each group, and associations between hard-and-soft tissue counterparts were assessed using Pearson correlation coefficient (r).
Result(s): Sixteen patients had UCLP, and 10 patients had BCLP. At one-year follow-up (T1-T3), the mean advancement in UCLP and BCLP groups at ANS were 4.4+/-3 and 4.7+/-3.9 mm, from point A were 6.6+/-2.5, 8.8+/- 2.6 mm, respectively. The mean horizontal changes of the corresponding soft tissue anatomy, Prn, were 2.7 +/-1.7, 4.6+/-3.5 mm, from Sn, were 3.9+/-1.9, 6.2+/-2.4. mm, and from SLS were 5.2+/-2.5, 7.4+/-2.8 mm. The mean advancement in at upper incisor most labial were 7.2+/-2.7 and 8.4+/-2.4 mm, and from the upper incisal edge were 7.5+/-2.9 and 8.4+/-2.7. mm. The mean horizontal changes of the soft tissue counterpart, LS, were 5.6+/-2.9, 7.9+/- 3.7 mm, and SIMS were 6.0+/-3.2, 7.3+/- 2.7 mm. All skeletal, dental, and soft tissue advancements from T1-T3 were significant (P< 0.01) except for Sn and LS in both groups and SIMS in UCLP group. For ratio and correlation analyses in UCLP and BCLP groups, Prn/AND were 0.48 (r=0.40) and (r=0.00), Sn/A-point were 0.58 (r=0.79) and 0.70 (r=0.77), SLS/A-point were 0.79 (r=0.82) and 0.85 (r=0.80), LS/U1-most were 0.74 (r=0.92) and 0.96 (r=0.74), and SIMS/U1-tip were 0.78 (r=0.75) and 0.82(r=0.67), respectively. All associations except for Prn/ANS were statistically significant (P< 0.01).
Conclusion(s): This study demonstrated a linear relationship between soft- and hard-tissue changes in the maxillary landmarks following LeFort I advancement in patients with complete cleft lip and palate (UCLP and BCLP)

Background/Purpose: The relative value unit (RVU) is a metric established by Medicare to quantify physician time and intensity required to furnish a surgical service, and is broadly used for the purposes of billing and physician compensation. Despite widespread use since the 1990s, the accuracy of RVU assignments has not been scientifically evaluated for cleft and craniofacial surgery. We hypothesize that unbalanced RVU allocation creates inappropriate disparities in value amongst procedures performed by cleft and craniofacial surgeons. Methods/Description: The American College of Surgeons Pediatric National Surgical Quality Improvement Program (NSQIP) database was queried to identify all cleft and craniofacial surgery cases performed by plastic surgeons from 2012-2019 based on Current Procedural Terminology (CPT) code. Microsurgical cases and CPT codes with a case count of fewer than 10 were excluded. Total RVUs per case were calculated based on the sum of work RVUs for the principal procedure, and any other procedure that was performed during the case. Efficiency was defined as total RVUs divided by total operative time (i.e. RVUs/hour), based on previously published methodology. Mean efficiency per CPT code was ranked and compared by quartile using Student's t-tests.
Result(s): The sample consisted of 69 CPT codes with a total of 50,450 cases. The most common procedure was cleft palate repair of the soft and/or hard palate (CPT 42200). The mean efficiency for the top quartile of CPT codes was 15.65+/-4.22 (range 12.05-26.56) RVUs/hour, compared to 7.39+/-0.98 (range 5.57-8.69) RVUs/hour for the bottom quartile (p<0.001). The mean operative time for the top quartile of CPT codes was 167.14+/-90.29 minutes, compared to 107.79 +/-55.17 minutes for the lowest quartile (p=0.029). In the top quartile, the majority of CPT codes were craniofacial procedures including frontofacial procedures (23.53%) and craniectomies for craniosynostosis or bony lesions (35.29%). The lowest quartile was comprised mainly of CPT codes for cleft procedures including surgeries for velopharyngeal insufficiency (17.65%), cleft palate repair (23.53%), and cleft septoplasty (5.88%). It was 2.5 times more efficient for a cleft and craniofacial surgeon to perform a local skin flap (15.18 RVUs/ hour, CPT 14040) than a secondary palatal lengthening for cleft palate (6.09 RVUs/hour, CPT 42200).
Conclusion(s): The current RVU allocation to cleft and craniofacial procedures creates arbitrary disparities in physician efficiency, with cleft procedures disproportionately negatively affected despite being among the most common procedures. RVU assignments should be reevaluated to avoid disincentivizing cleft surgical care

Background/Purpose: Nasoalveolar molding (NAM) in combination with primary gingivoperiosteoplasty (GPP) may obviate the need for a secondary alveolar bone graft. While the long-term facial growth following GPP has been well documented, no study has evaluated the transverse growth of the cleft-maxilla following NAM and GPP. Here we report the effects of NAM and GPP on the maxillary transverse dimension in patients with complete unilateral cleft lip and palate (UCLP). Methods/Description: A retrospective single-institution review of nonsyndromic patients with complete unilateral cleft lip and palate born between 2005 and 2010 was completed. Patients were divided into four groups based on their interventions: 1) NAM-GPP with adequate bone formation 2) NAM-GPP without adequate bone formation (requiring ABG) 3) NAM-no GPP (requiring ABG), and 4) No NAM-no GPP control (patients who received primary surgeries outside of our institution). Cone-beam computed tomographic scans (CBCTs) taken at the early-mixed dentition stage, prior to orthodontic intervention, were used to assess the anterior and posterior maxillary transverse dimensions. The transverse discrepancy at the affected and non-affected sides was measured at the level of the primary canines (anterior dimension) and the permanent first molars (posterior dimension) to the maxillary midline. Wilcoxon signed-rank tests were used to compare the transverse dimension of the affected versus non-affected sides within each group. Mann-Whitney U tests were used to compare each NAM group with the no NAM-no GPP control group.
Result(s): A total of 85 patients were included in this study (mean age = 8.7). Male patients (50.6%) and the left side (64.7%) were most affected. Of the 85 patients, 26 (30.6%) underwent NAM-GPP with adequate bone formation, 22 (25.9%) underwent NAM-GPP but required ABG, 16 (18.8%) underwent NAM without GPP, and 21 (24.7%) underwent no NAM-no GPP. Median values were significantly different in the anterior maxilla between the affected and nonaffected sides across all four groups (p = 0.001). The transverse dimension at the affected side also revealed a significant difference in both the NAM-GPP (with adequate bone formation) and the NAM-GPP (requiring ABG) groups compared to the no NAM-no GPP group (p= 0.022 and p= 0.001, respectively). There was no significant difference between the NAM-no GPP group compared to the control (p = 0.059). Distances to the molars of the affected and nonaffected sides were not statistically significant within or across any of the groups (p > 0.05).
Conclusion(s): In patients with UCLP, the maxillary primary canine transverse dimension on the affected side is significantly reduced in patients undergoing NAM and GPP compared to the control. However, the position of the maxillary first molars appear to be unaffected by NAM and GPP

Background/Purpose: Traditional palatoplasty techniques rely on repositioning of soft palate muscle and mucosa to restore velopharyngeal closure. In the case of the wide cleft palate (10 mm or greater), we hypothesize that soft palate nasal mucosa closure can result in vertical shortening of the palate. Furthermore, horizontal release of the reconstructed soft palate nasal mucosa from the hard palate will result in significant lengthening of the soft palate, identifying a potential loss of domain of palatal length in patients with a wide cleft palate. This study characterizes this potential loss of vertical length of the nasal soft palate mucosa in patients with a wide cleft. Methods/Description: A retrospective review of all patients who underwent a primary cleft palate repair with a buccal flap prior to 18 months of age by a single plastic surgeon over a 2-year period. Inclusion criteria was defined as patients with cleft palate at least 10 mm in length at the area of the posterior nasal spine. All patients who met inclusion criteria underwent primary cleft palate repair with horizontal transection of the nasal mucosa during palatoplasty. This transection was performed after nasal mucosa repair, but prior to muscular reconstruction. The resulting mucosal defect was measured and reconstructed with a buccal flap. Patient demographics, intra-operative palatal measurements, and post-operative outcomes were analyzed.
Result(s): Twenty-two patients met inclusion criteria. Mean age at surgery was 10.68+/-1.04 months, mean gestational age at birth was 38.14+/-1.75 weeks, and mean weight at surgery was 8.75+/-1.22 kg. Three (13.6%) had a history of Pierre Robin sequence and 5 (22.7%) had an associated syndrome. Notably, 13 (59.1%) had a history of nasoalveolar molding, and 15 (68.2%) had previously had a cleft lip repair. No patients had a Veau I cleft, 7 (31.8%) had a Veau II, 12 (54.5%) had a Veau III, and 3 (13.6%) had a Veau IV cleft. Regarding palate repair techniques employed, 12 (54.5%) had a Bardach, 7 (31.8%) had a Von Langenbeck, 3 (13.6%) had an Oxford, and all had a concomitant radical intravelar veloplasty. All 22 (100%) patients had a right buccal flap during primary palatoplasty. The mean cleft width or horizontal separation of the palate at the posterior nasal spine was 10.6+/-2.82 mm, and the mean lengthening of the palate was measured as 10.5+/-2.23 mm. For complications, there were 2 (9.1%) fistulas, 1 (4.5%) wound dehiscence, 1 (4.5%) 30-day readmission (for RSV bronchiolitis), and no bleeding complications.
Conclusion(s): Patients with a wide cleft palate have a potential loss of vertical length of approximately 1 cm. Considering that patients with a wide palatal cleft are predisposed to developing VPI, these data provide supportive evidence that acute palatal lengthening during palatoplasty should be considered for this patient population. The buccal flap can mitigate the loss of domain in palatal length, and potentially improve palatal excursion

Background/Purpose: Gingivoperiosteoplasty (GPP) is a procedure performed at the time of primary cleft lip or palate repair in which the alveolus is repaired without the need for bone graft. Although the success of GPP is reported up to 70%, the associated disparities with regards to access or receipt of GPP has not been studied. This study reports on patient access to GPP reconstruction. Methods/Description: The American College of Surgeons National Surgical Quality Improvement Program Pediatric (ACS NSQIP Peds) was queried from 2014 to 2019. Patients were selected using the Current Procedural Terminology (CPT) codes (Table 1). Patient race, gender, age at time of surgery, 30 day readmission, comorbidities and complications were recorded. Postoperative complications included surgical site infections (SSI), dehiscence and transfusion. Receipt of GPP was analyzed using binary logistic regression to control for variables that could potentially affect access to/ receipt of GPP. For multivariable analysis, Bonferroni correction was used.
Result(s): 23408 patients with a cleft were included in our analysis. 12590 were White, 1732 were Black/African American, 3914 were Hispanic, 2267 were Asian/other Pacific Islander, and 2905 did not have a reported Race. Amongst this cohort, 709 patients underwent GPP (2.25%). Patients who did not report/of unknown Race were less likely to undergo GPP (p = 0.001), while there was no statistically significant difference amongst access to GPP for Black/African American, Hispanic, or Asian/ other Pacific Islander patients. The average age of all patients was 2411 days. White patients had primary cleft repair at a younger age (p = 0.000) than non-White patients. There was no difference in gender or co-morbidities (cardiac risk factors and congenital/chronic lung disease, respectively) amongst all Races (p = 0.291, p = 0.276, p = 0.547). There was no statistically significant difference in unplanned 30-day readmission and 30-day postoperative complication (p = 0.326, 0.934, respectively). Patients with ASA class 3 or 4 and minor or major cardiac risk factors had a statistically significant higher chance of 30-day readmission (p = 0.000, 0.000, 0.000, 0.001, respectively).
Conclusion(s): Amongst reported Races there was no statistically significant difference with regards to access/receipt of GPP, but patients without a reported Race were less likely to undergo GPP. Undergoing GPP did not appear to increase the likelihood of 30-day readmission or postoperative complication. We did find that White patients received cleft lip/palate repair at a statistically significant younger age and Hispanic patients at a later age, which is similar to previous studies. Although there was no difference in access to GPP amongst Races, further studies to evaluate disparities in outcomes for children undergoing GPP needs to be elucidated