Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428.

Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple associated loci, with the strongest association on chromosome 20. Herein, we report the first whole-genome sequencing study of sNCS using 63 proband-parent trios. Sequencing data for these trios were analyzed using the transmission disequilibrium test (TDT) and rare variant TDT (rvTDT) to identify high-risk rare gene variants. Sequencing data were also examined for copy number variants (CNVs) and de novo variants. TDT analysis identified a highly significant locus at 20p12.3, localized to the intergenic region between BMP2 and the noncoding RNA gene LINC01428. Three variants (rs6054763, rs6054764, rs932517) were identified as potential causal variants due to their probability of being transcription factor binding sites, deleterious combined annotation dependent depletion scores, and high minor allele enrichment in probands. Morphometric analysis of cranial vault shape in an unaffected cohort validated the effect of these three single nucleotide variants (SNVs) on dolichocephaly. No genome-wide significant rare variants, de novo loci, or CNVs were identified. Future efforts to identify risk variants for sNCS should include sequencing of larger and more diverse population samples and increased omics analyses, such as RNA-seq and ATAC-seq.

Utility of Screening for Obstructive Sleep Apnea with the Pediatric Sleep Questionnaire (PSQ) in Children with Craniofacial Anomalies.

OBJECTIVE: To determine the accuracy of the Pediatric Sleep Questionnaire (PSQ) as a screening tool for obstructive sleep apnea in children with craniofacial anomalies. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary cleft and craniofacial clinic at a tertiary care center. PATIENTS: Children with craniofacial anomalies 2 to ≤18 years of age who both completed a PSQ screen and underwent polysomnography (PSG) without interval surgery. MAIN OUTCOME MEASURES: Sensitivity and specificity of the PSQ in detecting an obstructive apnea-hypopnea index (AHI) ≥ 5 events/hour. RESULTS: Fifty children met study criteria, with 66% (n = 33) having an associated syndrome. Mean patient age at time of PSQ was 9.6 + 4.0 years. Overall, 33 (64%) screened positive on the PSQ, while 20 (40%) had an AHI ≥ 5. The sensitivity and specificity for identifying AHI ≥ 5 was 70% and 40%, respectively. With subgroup analysis, the sensitivity and specificity were higher (100% and 50%) in children with non-syndromic palatal clefting but lower (65% and 31%) in children with a syndrome or chromosomal anomaly. There was no correlation detected between PSQ score and AHI severity (p = 0.25). The mean obstructive AHI in the study population was 10.1 ± 22.7 despite 44% (n = 22) undergoing prior adenotonsillectomy. CONCLUSIONS: The PSQ was less sensitive and specific in detecting an AHI ≥ 5 in children with craniofacial anomalies than in a general population, and particularly poor in for children with syndrome-associated craniofacial conditions. Given the high prevalence of OSA in this patient population, a craniofacial-specific validated screening tool would be beneficial.

Three-Dimensional Printing in Cleft Care: A Systematic Review.

OBJECTIVE: To determine the current applications of 3-dimensional (3D) printing in the care of patients with cleft lip and palate. We also reviewed 3D printing limitations, financial analysis, and future implications. DESIGN: Retrospective systematic review. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used by 3 independent reviewers. Articles were identified from Cochrane library, Ovid Medline, and Embase. Search terms included 3D printing, 3 dimensional printing, additive manufacturing, rapid prototyping, cleft lip, and cleft palate. Exclusion criteria included articles not in English, animal studies, reviews without original data, oral presentations, abstracts, opinion pieces, and articles without relevance to 3D printing or cleft lip and palate. MAIN OUTCOME MEASURES: Primary outcome measure was the purpose of 3D printing in the care of patients with cleft lip and palate. Secondary outcome measures were cost analysis and clinical outcomes. RESULTS: Eight-four articles were identified, and 39 met inclusion/exclusion criteria. Eleven studies used 3D printing models for nasoalveolar molding. Patient-specific implants were developed via 3D printing in 6 articles. Surgical planning was conducted via 3D printing in 8 studies. Eight articles utilized 3D printing for anatomic models/educational purposes. 3-Dimensional printed models were used for surgical simulation/training in 6 articles. Bioprinting was utilized in 4 studies. Secondary outcome of cost was addressed in 8 articles. CONCLUSION: 3-Dimensional printing for the care of patients with cleft lip and palate has several applications. Potential advantages of utilizing this technology are demonstrated; however, literature is largely descriptive in nature with few clinical outcome measures. Future direction should be aimed at standardized reporting to include clinical outcomes, cost, material, printing method, and results.

Nasal trumpet as a long-term remedy for obstructive sleep apnea syndrome in a child.

We present a case of successful long-term use of nasal trumpet for severe obstructive sleep apnea syndrome in a child with cerebral palsy and complex medical issues. Obstructive sleep apnea syndrome is frequently seen in pediatric patients with cerebral palsy due to their abnormal airway tone and pulmonary vulnerability. Identifying children with cerebral palsy who are at risk for obstructive sleep apnea syndrome is important because its treatment can improve quality of life and seizure control. Although first-line treatment for obstructive sleep apnea syndrome is adenotonsillectomy, children with cerebral palsy are more likely to have residual obstructive sleep apnea syndrome postoperatively. Other options such as positive airway pressure therapy and other upper airway surgeries may pose significant challenges and tolerance issues, as in our patient. As demonstrated in our report, the low rate of complications and ease of use make nasal trumpets a potential long-term treatment option for children with obstructive sleep apnea syndrome who fail or cannot comply with the traditional treatment options.

Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

BACKGROUND: Acetaminophen is a frequently used adjunct analgesic in pediatric patients undergoing tonsillectomy and adenoidectomy. We compared opioid administration following preoperative intravenous (IV) or oral acetaminophen in addition to a standard multimodal regimen to test the hypothesis that 1 loading dose approach would provide superior opioid sparing effects among pediatric surgical patients undergoing tonsillectomy and adenoidectomy. METHODS: This single-center, double-blind, double-dummy prospective randomized study was conducted in patients ages 3 to 15 years undergoing tonsillectomy and adenoidectomy with or without myringotomy and tube placement between September 2017 and July 2019. Subjects received 1 dose of either oral acetaminophen 30 mg/kg with IV placebo (oral group) or IV acetaminophen 15 mg/kg with oral placebo (IV group). Acetaminophen plasma levels were measured at 2 timepoints to evaluate safety and determine plasma levels attained by each dosing regimen. Intraoperative opioid administration and postoperative analgesia were standardized. Standardized postoperative multimodal analgesia included opioid if needed to control pain assessed by standardized validated pediatric pain scales. The primary outcome measure was total opioid administration in the first 24 hours after surgery. Continuous data were not normally distributed and were analyzed using the Wilcoxon rank sum test and the Hodges-Lehman estimator of the median difference. Clinical significance was defined as a 100 µg/kg IV morphine equivalents per day difference. RESULTS: Sixty-six subjects were randomized into and completed the study (29 women, 37 men; age 5.9 ± 3.0 years; percentile weight for age 49.5 ± 30.2; no differences between groups). There was no opioid dose difference between oral (median 147.6; interquartile range [IQR], 119.6-193.0 µg/kg) and IV groups (median 125.4; IQR, 102.8-150.9 µg/kg; median difference 21.3; 95% confidence interval [CI] -2.5 to 44.2 µg/kg IV morphine equivalents; P = .13). No acetaminophen levels exceeded the predefined safety threshold (40 mg/L). No difference was found in the percentage of patients with severe pain: 50.0% oral group, 47.2% IV group; relative risk of severe pain in IV 0.94; 95% CI, 0.57-1.6; P = .82. Postoperative plasma acetaminophen levels were higher in oral (22; IQR, 16-28 mg/L) than IV (20; IQR, 17-22 mg/L) group (median difference 7.0; 4.0-8.0 mg/L; P = .0001). CONCLUSIONS: Opioid-sparing effects did not differ following an oral or standard IV acetaminophen loading dose with no identified acetaminophen toxicity in pediatric patients undergoing tonsillectomy and adenoidectomy who received standardized multimodal postoperative analgesia. An oral loading dose may provide more consistent serum acetaminophen levels at lower cost compared to a standard IV dose.

A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10-8): rs781716 (P = 4.71 × 10-9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10-8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10-9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10-8, OR = 0.45; P = 3.31 × 10-8, OR = 0.45; P = 1.09 × 10-8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10-8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10-6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Children with Cleft Palate: Predictors of Otologic Issues in the First 10 Years.

OBJECTIVE: To evaluate the characteristics of children with cleft palate associated with persistent otologic issues in the first 10 years of life. STUDY DESIGN: Case series with chart review. SETTING: Single academic center. SUBJECTS AND METHODS: Children born with cleft palate from 2003 to 2007 and treated by the UC Davis Cleft and Craniofacial Team between January 2003 and December 2017 were included in the study. Data from 143 patients were analyzed via Wilcoxon rank sum and Fisher exact tests for univariate analysis and logistic regression to determine adjusted odds ratios. RESULTS: The median length of follow-up was 9.9 years, and the age at last ear examination was 10.7 years. At the last evaluation, unresolved otologic issues were common, with at least 1 ear having a tympanic membrane (TM) perforation (16.1%), a tympanostomy tube (36.2%), or conductive hearing loss (23.1%). After adjusting for demographic and clinical characteristics, history of palate revision or speech surgery was associated with having a TM perforation ( P = .02). The only clinical variables associated with conductive hearing loss was the presence of a TM perforation ( P < .01) or a genetic abnormality ( P = .02). Severity of palatal clefting was not associated with specific otologic or audiologic outcomes after adjusting for other characteristics. CONCLUSION: A large proportion of children with cleft palate have persistent otologic issues at age 10 years and would benefit from continued close monitoring well after the age when most children have normalized eustachian tube function. Prolonged otologic issues were not found to be associated with cleft type.

Marginal versus segmental mandibulectomy for pediatric desmoid fibromatosis of the mandible - Two case reports and review of the literature.

Desmoid fibromatosis (DF) is a rare, benign soft tissue neoplasm with high rate of local recurrence. Surgical management of DF in the head and neck can be challenging given the desire to balance the preservation of form and function with the need to minimize local recurrence by achieving complete resection. We present two contrasting cases which highlight the advantages of marginal mandibulectomy over segmental mandibulectomy in children with DF. We favor marginal mandibulectomy even with limited bone stock given the remarkable ability of children to generate new bone.

Prevalence of Renal and Cervical Vertebral Anomalies in Patients With Isolated Microtia and/or Aural Atresia.

OBJECTIVE: The objective of this study was to determine whether patients with isolated microtia or aural atresia have an increased prevalence of renal or cervical vertebral anomalies. DESIGN: The study design was a retrospective medical record review. SETTING: The setting was the following four distinct institutions: an urban tertiary care children's hospital, two urban academic medical centers, and a staff-model health maintenance organization. PARTICIPANTS: Patients diagnosed with microtia, aural atresia, or oculoauriculovertebral spectrum were identified. Patients with facial asymmetry, craniofacial microsomia, and other craniofacial abnormalities or syndromes were excluded. MAIN OUTCOME MEASURES: Main outcome measures were the number of patients with isolated microtia or aural atresia who underwent a renal ultrasound or cervical spine X-ray, the results of those studies, and further evaluation or treatment for any abnormalities found. STATISTICAL ANALYSIS: A binomial analysis using a one-sided 95% confidence level was performed. RESULTS: A total of 514 patients with isolated microtia and/or aural atresia were identified. Of these patients, 145 (28%) had undergone a renal ultrasound and 81 (16%) had undergone cervical spine X-rays. A total of 3 patients (2%) had minimal renal pelviectasis, all of which had resolved on repeat ultrasound and required no treatment. There were no structural renal abnormalities identified, and there were no cervical spine abnormalities identified. CONCLUSIONS: The data suggest that there is no increased prevalence of structural renal or cervical vertebral anomalies in patients with isolated microtia and/or aural atresia. Therefore, these patients do not require routine screening renal ultrasound or cervical spine X-rays.

Septorhinoplasty in the Pediatric Patient.

Pediatric septorhinoplasty has been an area of controversy because early surgical intervention can prevent normal growth. There are certain conditions where early correction of the nose is indicated, such as in cleft lip nasal deformities, severe traumatic deformities, and congenital nasal lesions. Animal and clinical studies have been helpful in elucidating certain areas of the nose that are potential growth zones that should be left undisturbed when performing nasal surgeries on pediatric patients. We discuss the timing, indications, and surgical technique in pediatric septorhinoplasty.

Revision rates and speech outcomes following pharyngeal flap surgery for velopharyngeal insufficiency.

IMPORTANCE: Velopharyngeal insufficiency in children with cleft palate (and other causes) contributes to difficulty with communication and quality of life. The pharyngeal flap is a workhorse to address hypernasality and nasal air escape. However, there is a paucity of literature on the characteristics of cases that require revision. OBJECTIVE: To measure the revision rate of pharyngeal flaps, compare the preperceptual and postperceptual speech scores, and identify the characteristics of those patients who required revision. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was completed for patients who underwent pharyngeal flap surgery from June 1, 2008, through January 31, 2013, at a tertiary academic center. MAIN OUTCOMES AND MEASURES: Perceptual speech analyses and surgical revision rates. Perceptual speech patterns before and after surgery were compared using nasal air emission and resonance scores. The association between requiring revision surgery and covariates was analyzed using multivariable mixed-effects logistic regression. RESULTS: Sixty-one patients were identified, including 24 boys (39%) and 37 girls (61%). The mean (SD) patient age at the time of pharyngeal flap surgery was 8.2 (6.8) years (range, 3-55 years). Velopharyngeal insufficiency was associated with cleft palate in 51 patients (84%), and 17 patients (28%) had a syndrome. The mean (SD) time to surgery after the speech evaluation was 225 (229) days (range, 14-1341 days). The mean (SD) nasal air emission scores decreased by -1.1 (2.0 [1.1] preoperatively to 0.8 [1.1] postoperatively). The mean (SD) resonance score decreased by -1.5 (2.4 [1.1] preoperatively to 0.9 [1.1] postoperatively; P < .001). Flaps were revised in 12 patients (20%), including port revision in 9, complete flap revision in 2, and flap takedown in 1. The only covariate that was significantly associated with revision rates was increased age at surgery, which was associated with a higher probability of revision surgery (odds ratio, 1.31; 95% CI, 1.03-1.66; P = .04). CONCLUSIONS AND RELEVANCE: Pharyngeal flap surgery, when appropriately selected, was effective at improving speech with a revision rate of 20%, which is comparable to previously published studies. Increased age at the time of the pharyngeal flap surgery was associated with an increased need for revision surgery, supporting evidence that cleft centers should encourage early childhood speech evaluations with consistent documentation and prompt treatment. LEVEL OF EVIDENCE: 3.

Neurofibromatosis of the larynx causing stridor and sleep apnea.

BACKGROUND: Neurofibromatosis type 1 can rarely present in the larynx. Patients typically do not present with complete obstructive symptoms, but partial obstruction and stridor. We review our health centers' case series of two patients, the first of whom presented with persistent sleep apnea post tonsillectomy and adenoidectomy, and the second who presented with noisy breathing. Additionally, we will review the literature on the management and treatment options for children with this rare clinical entity. METHODS: Retrospective case review. CASE REPORT & RESULTS: A two-year old male underwent a sleep endoscopy following persistent evidence of obstructive sleep apnea on polysomnography after initial tonsillectomy and adenoidectomy. Family elicited concerns about noisy breathing at night and an accompanying video documented stridor while sleeping during the monitored polysomnography. Flexible fiberoptic laryngoscopy in the operating room revealed what appeared to be a cystic mass along the right aryepiglottic fold causing deviation of the laryngeal introitus towards the contralateral side. Subsequent direct laryngoscopy and excisional biopsy revealed pathology results consistent with a plexiform neurofibroma. A six-month-old patient with stertor and stridor was found to have a laryngeal mass, subglottic stensosis, and progressive airway obstruction due to plexiform neurofirboma in the supraglottis, subglottis, and trachea. We present a series of two patients incidentally diagnosed with neurofibromatosis type 1 by way of a laryngeal neurofibroma and review the literature on management options. Both patients were found to have accompanying café au lait spots. Both patients required tracheostomy for airway management, and one was successfully decannulated. CONCLUSION: Laryngeal neurofibroma is a rare anomaly that can manifest with airway obstruction. Both patients presented here subsequently were noted to have café au lait spots on physical examination. The Otolaryngologist should be reminded of this anomaly when evaluating a child with evidence of a submucosal laryngeal mass. We present our series including that of a patient whose diagnosis was prompted by persistent sleep apnea following adenotonsillectomy tonsillectomy and a patient with airway obstruction and subglottic stenosis due to a neurofibroma. The treatment of choice is complete excision of the neurofibroma while maintaining functionality of the larynx. This can lead to successful decannulation.

Pediatric tracheotomy: indications and decannulation outcomes.

OBJECTIVES/HYPOTHESIS: The objective of this study was to determine if there are differences in decannulation rates and duration of cannulation between pediatric patients undergoing tracheotomy for different indications. STUDY DESIGN: Retrospective chart review. METHODS: Medical records for pediatric patients (age 0-18 years) undergoing tracheotomy between January 1, 2003, and May 31, 2012, were retrospectively reviewed. Patients were assigned an indication for tracheotomy from five categories: neurological, cardiopulmonary, upper airway obstruction, craniofacial anomalies, and maxillofacial/laryngotracheal trauma. RESULTS: Initial chart review identified 124 patients, 113 for whom complete data was available. Of these patients, the indications for tracheotomy were cardiopulmonary disease in 24 (21.2%), craniofacial anomalies in 12 (10.6%), neurological impairment in 44 (38.9%), traumatic injury in 11 (9.7%), and upper airway obstruction in 22 (19.5%). The time to decannulation was shorter for trauma patients compared to cardiopulmonary (P = 0.044) and neurological patients (P = 0.001). A total of 32 (31.9%) patients were decannulated during the study period, with a higher rate in trauma patients (72.7%) and a lower rate in those with upper airway obstruction (36.4%) than would be expected under homogeneity. Of the 32 patients who were decannulated, 11 (30.6%) were decannulated during the same hospitalization in which the tracheotomy was performed. CONCLUSION: This study demonstrates a difference in overall decannulation rates and a shorter time to decannulation in children undergoing tracheotomy for maxillofacial and laryngotracheal trauma compared to cardiopulmonary and neurological indications.

A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9.

Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 × 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 × 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 × 10(-10), OR = 0.19) and rs17724206 (P = 1.50 × 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 × 10(-31) and rs10262453, P = 3.50 × 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.

Artificial muscle for reanimation of the paralyzed face: durability and biocompatibility in a gerbil model.

BACKGROUND: Current management of permanent facial paralysis centers on nerve grafting and muscle transfer; however, limitations of those procedures call for other options. OBJECTIVES: To determine the durability and biocompatibility of implanted artificial muscle in a gerbil model and the degree of inflammation and fibrosis at the host tissue-artificial muscle interface. METHODS: Electroactive polymer artificial muscle (EPAM) devices engineered in medical-grade silicone were implanted subcutaneously in 13 gerbils. The implanted units were stimulated with 1 kV at 1 Hz, 24 h/d via a function generator. Electrical signal input/output was recorded up to 40 days after implantation. The animals were euthanized between 23 and 65 days after implantation, and the host tissue-implant interface was evaluated histologically. RESULTS: The animals tolerated implantation of the EPAM devices well, with no perioperative deaths. The muscle devices created motion for a mean of 30.3 days (range, 19-40 days), with a mean of 2.6 × 106 cycles (range, 1.6 × 106 to 3.5 × 106 cycles). Histologic examination of the explanted devices revealed the development of a minimal fibrous capsule surrounding the implants, with no evidence of bacterial infection or inflammatory infiltrate. No evidence of device compromise, corrosion, or silicone breakdown was noted. CONCLUSIONS: Artificial muscle implanted in this short-term animal model was safe and functional in this preliminary study. We believe that EPAM devices will be a safe and viable option for restoration of facial motions in patients with irreversible facial paralysis.

Unilateral and bilateral expression of a quantitative trait: asymmetry and symmetry in coronal craniosynostosis.

Bilateral symmetry in vertebrates is imperfect and mild asymmetries are found in normal growth and development. However, abnormal development is often characterized by strong asymmetries. Coronal craniosynostosis, defined here as consisting of premature suture closure and a characteristic skull shape, is a complex trait. The premature fusion of the coronal suture can occur unilaterally associated with skull asymmetry (anterior plagiocephaly) or bilaterally associated with a symmetric but brachycephalic skull. We investigated the relationship between coronal craniosynostosis and skull bilateral symmetry. Three-dimensional landmark coordinates were recorded on preoperative computed tomography images of children diagnosed with coronal nonsyndromic craniosynostosis (N = 40) and that of unaffected individuals (N = 20) and analyzed by geometric morphometrics. Our results showed that the fusion pattern of the coronal suture is similar across individuals and types of coronal craniosynostosis. Shape analysis showed that skulls of bilateral coronal craniosynostosis (BCS) and unaffected individuals display low degrees of asymmetry, whereas right and left unilateral coronal craniosynostosis (UCS) skulls are asymmetric and mirror images of one another. When premature fusion of the coronal suture (without taking into account cranial dysmorphology) is scored as a qualitative trait, the expected relationship between trait frequency and trait unilateral expression (i.e. negative correlation) is confirmed. Overall, we interpret our results as evidence that the same biological processes operate on the two sides in BCS skulls and on the affected side in UCS skulls, and that coronal craniosynostosis is a quantitative trait exhibiting a phenotypic continuum with BCS displaying more intense shape changes than UCS.

Differential growth factor adsorption to calvarial osteoblast-secreted extracellular matrices instructs osteoblastic behavior.

Craniosynostosis (CS), the premature ossification of cranial sutures, is attributed to increased osteogenic potential of resident osteoblasts, yet the contribution of the surrounding extracellular matrix (ECM) on osteogenic differentiation is unclear. The osteoblast-secreted ECM provides binding sites for cellular adhesion and regulates the transport and signaling of osteoinductive factors secreted by the underlying dura mater. The binding affinity of each osteoinductive factor for the ECM may amplify or mute its relative effect, thus contributing to the rate of suture fusion. The purpose of this paper was to examine the role of ECM composition derived from calvarial osteoblasts on protein binding and its resultant effect on cell phenotype. We hypothesized that potent osteoinductive proteins present during sutural fusion (e.g., bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-ß1)) would exhibit distinct differences in binding when exposed to ECMs generated by human calvarial osteoblasts from unaffected control individuals (CI) or CS patients. Decellularized ECMs produced by osteoblasts from CI or CS patients were incubated in the presence of BMP-2 or TGF-ß1, and the affinity of each protein was analyzed. The contribution of ECM composition to protein binding was interrogated by enzymatically modulating proteoglycan content within the ECM. BMP-2 had a similar binding affinity for each ECM, while TGF-ß1 had a greater affinity for ECMs produced by osteoblasts from CI compared to CS patients. Enzymatic treatment of ECMs reduced protein binding. CS osteoblasts cultured on enzymatically-treated ECMs secreted by osteoblasts from CI patients in the presence of BMP-2 exhibited impaired osteogenic differentiation compared to cells on untreated ECMs. These data demonstrate the importance of protein binding to cell-secreted ECMs and confirm that protein-ECM interactions have an important role in directing osteoblastic differentiation of calvarial osteoblasts.

Force requirements for artificial muscle to create an eyelid blink with eyelid sling.

OBJECTIVE: To determine the force requirements, optimal vector, and appropriate materials of a novel eyelid sling device that will be used to rehabilitate eyelid closure (blink) in congenital or acquired permanent facial paralysis with an artificial muscle. METHODS: The force required to close the eyelids in human cadavers (n = 6) were measured using a load cell system. The eyelid sling using either expanded polytetrafluoroethylene (ePTFE) or temporalis muscle fascia was implanted. The ideal vector of force and placement within the eyelid for a natural eyelid closure were compared. RESULTS: The eyelid sling concept was successful at creating eyelid closure in a cadaver model using an upper eyelid sling attached to the distal tarsal plate. Less force was necessary to create eyelid closure using a temporalis muscle fascia sling (627 +/- 128 mN) than for the ePTFE eyelid sling (1347 +/- 318 mN). CONCLUSIONS: The force and stroke required to close an eyelid with the eyelid sling are well within the attainable range of the electroactive polymer artificial muscle (EPAM). This may allow the creation of a realistic and functional eyelid blink that is symmetric and synchronous with the contralateral, normally functioning blink. Future aims include consideration of different sling materials and development of both the EPAM device and an articulation between the EPAM and sling. The biocompatibility and durability studies of EPAM in a gerbil model are under way. The successful application of artificial muscle technology to create an eyelid blink would be the first of many potential applications.

Mandibular distraction osteogenesis used to treat upper airway obstruction.

OBJECTIVE: To evaluate whether mandibular distraction osteogenesis relieves tongue-based airway obstruction in patients with severe micrognathia. DESIGN: Retrospective medical review spanning a 7-year period in a tertiary care hospital. The inclusion criterion was defined as micrognathia associated with a severe tongue-based obstruction. The patients included 11 neonates and infants (mean age, 4.3 months) and 2 pediatric patients (mean age, 5.4 years). Two patients had already received tracheotomies, 11 had not. The intervention was bilateral mandibular osteotomies with distraction osteogenesis. The outcome measures were avoidance of tracheotomy and decannulation. RESULTS: Ten of 11 patients avoided tracheotomy. Two of 2 patients who had already undergone tracheotomies were successfully decannulated. CONCLUSION: Mandibular distraction osteogenesis is an acceptable treatment alternative to tracheotomy in select pediatric patients with micrognathia and severe tongue-based obstruction.

Children's tonsillectomy experiences: influencing factors.

The aim of this study was to explore factors influencing children's (7-13 years) tonsillectomy experiences and outcomes. A prospective, repeated measures, design was used to investigate the effect of age, gender, ethnicity, time, and previous pain, hospitalization and surgery on children's (N = 60) perceptions of anxiety, pain intensity, quality of pain and sleep, and oral intake. The relationship between postoperative pain and anxiety was also examined. Using a diary, three days of data were collected. Descriptive statistics, Pearson correlation coefficient, and a mixed linear regression model were used for analysis. Children's tonsillectomy experiences and outcomes were affected by time, previous experience, age, and anxiety. Moderate correlations were found between level of anxiety and pain intensity. These findings provide clinicians with additional knowledge to guide their perioperative practice and care of children.