Protraction Headgear Compliance and Orthognathic Surgery in Patients With Cleft Lip and Palate.

Assess cephalometric parameters and the need for orthognathic surgery (OS) and its relationship with compliance in protraction headgear (PHG).Retrospective case series.Hospital cleft-craniofacial center.23 patients with nonsyndromic cleft lip and palate and history of lip and palate repair.Patients received PHG and orthodontic treatment. Compliant patients were compared to patients that were not. Protraction was applied with 170-gram elastics and patients were instructed to wear for at least 12 hours daily.Cephalometric measurements at initial (T1), post-PHG (T2), and pre-surgical or post-orthodontic treatment (T3) of at least age 15 for females and 17 for males and the presence of OS were compared.83% (19) of patients reported compliance with therapy. Of those compliant, 68% (13) had OS and 32% (6) did not (P = .99). Inter-group comparisons at T1 between compliant and noncompliant showed no significant differences and the non-OS patients started with larger nasolabial angles (P < .05). At T2, there were no significant cephalometric differences between groups. At T3, compliant patients showed significantly more upper incisor proclination than noncompliant patients. Between OS and non-OS, OS patients had significantly decreased ANB, Wits, convexity, overjet, and FMA and larger nasolabial angles (P < .05).Patients compliant with PHG showed no difference in the need for OS. However, after orthodontic treatment, compliant patients showed more upper incisor proclination and OS patients with decreased ANB, Wits, convexity, overjet, FMA, and larger nasolabial angles.

The Association Between Age at Palatoplasty and Speech and Language Outcomes in Children With Cleft Palate: An Observational Chart Review Study.

OBJECTIVE: To determine whether timing of palatoplasty (early, standard, or late) is associated with speech and language outcomes in children with cleft palate. DESIGN: Retrospective case series. SETTING: Tertiary care children's hospital. PARTICIPANTS: Records from 733 children born between 2005 and 2015 and treated at the Cleft Craniofacial Clinic of a tertiary children's hospital were retrospectively reviewed. Exclusion criteria were cleft repair at an outside hospital, intact secondary palate, absence of postpalatoplasty speech evaluation, syndromes, staged palatoplasty, and introduction to clinic after 12 months of age. Data from 232 children with cleft palate ± cleft lip were analyzed. INTERVENTIONS: Palatoplasty. MAIN OUTCOME MEASURES: Speech/language delays and disorders at 20 months and 5 years of age based on formal hospital or community-based testing or screening evaluation in the Cleft Craniofacial Clinic; additional speech surgery. RESULTS: Median age at palatoplasty was 12.6 months (range: 8.8-21.9 months). Age at palatoplasty was classified as early (<11 months, n = 28), standard (11-13 months, n = 158), or late (>13 months, n = 46). Late palatoplasty was associated with increased odds of speech/language delays and speech therapy at 20 months, and language delays at 5 years, compared with standard or early palatoplasty (P < .05 for all comparisons). However, speech sound production disorders, velopharyngeal incompetence, tube replacement, and hearing loss were not significantly associated with age at palatoplasty. CONCLUSIONS: Late palatoplasty may be associated with short- and long-term delays in speech/language development. Future studies with standardized surgical technique/timing and outcome measures are required to more definitively describe the impact of age at palatoplasty on speech/language development.

Rescue of Premature Coronal Suture Fusion with TGF-ß2 Neutralizing Antibody in Rabbits with Delayed-Onset Synostosis.

OBJECTIVES: An overexpression of Tgf-ß2 leads to calvarial hyperostosis and suture fusion in individuals with craniosynostosis. Inhibition of Tgf-ß2 may help rescue fusing sutures and restore normal growth. The present study was designed to test this hypothesis. DESIGN: Twenty-eight New Zealand White rabbits with delayed-onset coronal synostosis had radiopaque markers placed on either side of the coronal sutures at 10 days of age. The rabbits were randomly assigned to: (1) sham control rabbits (n = 10), (2) rabbits with control IgG (100 µg/suture) delivered in a collagen vehicle (n = 9), and (3) rabbits with Tgf-ß2 neutralizing antibody (100 µg/suture) delivered in a collagen vehicle (n = 9). Longitudinal growth data were collected at 10, 25, 42, and 84 days of age. Sutures were harvested at 84 days of age for histomorphometry. RESULTS: Radiographic analysis showed significantly greater ( P < .05) coronal suture marker separation, craniofacial length, cranial vault length, height, shape indices, cranial base length, and more lordotic cranial base angles in rabbits treated with anti-Tgf-ß2 antibody than in controls at 42 and 84 days of age. Histologically, rabbits treated with anti-Tgf-ß2 antibody at 84 days of age had patent and significantly ( P < .05) wider coronal sutures and greater sutural area compared to controls. CONCLUSIONS: These data support our hypothesis that antagonism of Tgf-ß2 may rescue fusing coronal sutures and facilitate craniofacial growth in this rabbit model. These findings also suggest that cytokine therapy may have clinical significance in infants with progressive postgestational craniosynostosis.

Biophysical characterization of laforin-carbohydrate interaction.

Laforin is a human dual-specificity phosphatase (DSP) involved in glycogen metabolism regulation containing a carbohydrate-binding module (CBM). Mutations in the gene coding for laforin are responsible for the development of Lafora disease, a progressive fatal myoclonus epilepsy with early onset, characterized by the intracellular deposition of abnormally branched, hyperphosphorylated insoluble glycogen-like polymers, called Lafora bodies. Despite the known importance of the CBM domain of laforin in the regulation of glycogen metabolism, the molecular mechanism of laforin-glycogen interaction is still poorly understood. Recently, the structure of laforin with bound maltohexaose was determined and despite the importance of such breakthrough, some molecular interaction details remained missing. We herein report a thorough biophysical characterization of laforin-carbohydrate interaction using soluble glycans. We demonstrated an increased preference of laforin for the interaction with glycans with higher order of polymerization and confirmed the importance of tryptophan residues for glycan interaction. Moreover, and in line with what has been described for other CBMs and lectins, our results confirmed that laforin-glycan interactions occur with a favourable enthalpic contribution counter-balanced by an unfavourable entropic contribution. The analysis of laforin-glycan interaction through the glycan side by saturation transfer difference (STD)-NMR has shown that the CBM-binding site can accommodate between 5 and 6 sugar units, which is in line with the recently obtained crystal structure of laforin. Overall, the work in the present study complements the structural characterization of laforin and sheds light on the molecular mechanism of laforin-glycan interaction, which is a pivotal requisite to understand the physiological and pathological roles of laforin.

Circularly Polarized Luminescence from Helically Chiral N,N,O,O-Boron-Chelated Dipyrromethenes.

Helically chiral N,N,O,O-boron chelated dipyrromethenes showed solution-phase circularly polarized luminescence (CPL) in the red region of the visible spectrum (λem (max) from 621 to 663 nm). The parent dipyrromethene is desymmetrised through O chelation of boron by the 3,5-ortho-phenolic substituents, inducing a helical chirality in the fluorophore. The combination of high luminescence dissymmetry factors (|glum | up to 4.7 ×10(-3) ) and fluorescence quantum yields (ΦF up to 0.73) gave exceptionally efficient circularly polarized red emission from these simple small organic fluorophores, enabling future application in CPL-based bioimaging.

Fracture healing using degradable magnesium fixation plates and screws.

PURPOSE: Internal bone fixation devices made with permanent metals are associated with numerous long-term complications and may require removal. We hypothesized that fixation devices made with degradable magnesium alloys could provide an ideal combination of strength and degradation, facilitating fracture fixation and healing while eliminating the need for implant removal surgery. MATERIALS AND METHODS: Fixation plates and screws were machined from 99.9% pure magnesium and compared with titanium devices in a rabbit ulnar fracture model. Magnesium device degradation and the effect on fracture healing and bone formation were assessed after 4 weeks. Fracture healing with magnesium device fixation was compared with that of titanium devices using qualitative histologic analysis and quantitative histomorphometry. RESULTS: Micro-computed tomography showed device degradation after 4 weeks in vivo. In addition, 2-dimensional micro-computed tomography slices and histologic staining showed that magnesium degradation did not inhibit fracture healing or bone formation. Histomorphology showed no difference in bone-bridging fractures fixed with magnesium and titanium devices. Interestingly, abundant new bone was formed around magnesium devices, suggesting a connection between magnesium degradation and bone formation. CONCLUSION: Our results show potential for magnesium fixation devices in a loaded fracture environment. Furthermore, these results suggest that magnesium fixation devices may enhance fracture healing by encouraging localized new bone formation.

Is Computed Tomography an Adequate Imaging Modality for the Evaluation of Juvenile Ossifying Fibroma? A Comparison of 2 Imaging Modalities (Computed Tomography and Magnetic Resonance Imaging).

PURPOSE: Given the problems of overuse of medical technology and the current burden of health care cost in the United States, it is important to establish clear imaging guidelines to diagnose conditions such as juvenile ossifying fibroma (JOF). This study compared the efficacy of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of JOF and thus could aid establishing such guidelines. MATERIALS AND METHODS: Radiologic criteria were established by 2 radiologists to compare the efficacy of CT and MRI in the evaluation of JOF. The following parameters were compared: presence of a well-defined corticated border, presence of a well-delineated internal calcified component, fluid-to-fluid levels, and anatomic extent of the lesion. Six patients diagnosed with JOF of the craniofacial bones from 2002 to 2013 had preoperative CT and MRI studies available for review. RESULTS: After review of CT and MRI images, fluid-to-fluid levels and anatomic extent of the lesions were comparable on CT and MRI. However, the corticated borders and the internal calcified component were better defined on CT images, which also enabled for distinction between the 2 subtypes of JOF. No MRI characteristics were identified that allowed for this distinction. CONCLUSION: Based on these findings, CT is an adequate and preferable imaging modality in the evaluation of JOF.

Regeneration of periosteum by human bone marrow stromal cell sheets.

PURPOSE: The presence of a functional periosteum accelerates healing in bone defects by providing a source of progenitor cells that aid in repair. We hypothesized that bone marrow stromal cell (BMSC) sheets could be used to engineer functional periosteal tissues. MATERIALS AND METHODS: BMSCs were cultured to hyperconfluence and produced sufficient extracellular matrix to form robust tissue sheets. The sheets were wrapped around calcium phosphate pellets and implanted subcutaneously in mice for 8 weeks. Histologic comparisons were made between calcium phosphate samples with and without BMSC sheet wraps. Bone and periosteum formation were analyzed through tissue morphology and tissue-specific protein expression. RESULTS: Calcium phosphate pellets wrapped in BMSC sheets regenerated a bone-like tissue, but pellets lacking the cell sheet wrap did not. The bone-like tissue seen on the calcium phosphate scaffolds wrapped with the BMSC sheets was enclosed within a periosteum-like tissue characterized morphologically and through expression of periostin. CONCLUSIONS: These data indicate that cell sheet technology has potential for regenerating a functional periosteum-like tissue that could aid in future orthopedic therapy.

Revisiting the recurrence risk of nonsyndromic cleft lip with or without cleft palate.

Sub-epithelial defects (i.e., discontinuities) of the superior orbicularis oris (OO) muscle appear to be a part of the phenotypic spectrum of cleft lip with or without cleft palate (CL ± P). Analysis of the OO phenotype as a clinical tool is hypothesized to improve familial recurrence risk estimates of CL ± P. Study subjects (n = 3,912) were drawn from 835 families. Occurrences of CL ± P were compared in families with and without members with an OO defect. Empiric recurrence risks were calculated for CL ± P and OO defects among first-degree relatives (FDRs). Risks were compared to published data and/or to other outcomes of this study using chi-square or Fisher's exact tests. In our cohort, the occurrence of CL ± P was significantly increased in families with OO defects versus those without (P < 0.01, OR = 1.74). The total FDR recurrence of isolated OO defects in this cohort is 16.4%; the sibling recurrence is 17.2%. The chance for one or more FDRs of a CL ± P proband to have an OO defect is 11.4%; or 14.7% for a sibling. Conversely, the chance for any FDR of an individual with an OO defect to have CL ± P is 7.3%; or for a sibling, 3.3%; similar to published recurrence risk estimates of nonsyndromic (NS) CL ± P. This study supports sub-epithelial OO muscle defects as being part of the CL ± P spectrum and suggests a modification to recurrence risk estimates of CL ± P by utilizing OO defect information.

Fetal diagnosis and treatment of craniomaxillofacial anomalies.

So many advances in health care are built on the evolution of technology. In the case of fetal medicine, technology has availed an entirely new patient. Advances in prenatal imaging allow us to see and diagnose disease not previously appreciated. Armed with this information, clinicians can better plan for the delivery of the neonate such that any identified anomalies are optimally managed, and the impact on the neonate's health minimized. The oral and maxillofacial surgeon can be a key member in this team by offering expertise in the management of craniomaxillofacial anomalies including congenital tumors, facial clefts, craniosynostosis, micrognathia, and other congenital abnormalities. The techniques for perinatal care of the patient with craniofacial abnormalities continue to evolve as the technology improves. The review of the cases presented at the University of Pittsburgh Fetal Diagnosis and Treatment Team during the past 6 years has shown many opportunities for craniomaxillofacial prenatal evaluation. We describe our recent experience and some of the more common abnormalities with their management considerations that may be encountered by the oral and maxillofacial surgeon on the fetal diagnosis and treatment team.

Chronic Recurrent Multifocal Osteomyelitis of the Mandible: A Diagnostic Challenge.

Chronic recurrent multifocal osteomyelitis is a rare autoinflammatory bone disorder of children and adolescents characterized by monofocal or multifocal inflammatory bone lesions that are culture-negative on biopsy, associated with periods of exacerbation and resolution that can last over several months to years. Although it is predominantly a disease of long bones and the spine, craniofacial involvement is not uncommon, affecting the mandible in up to one-fifth of cases. Similarities with other causes of osteitis in clinical presentation and imaging, and the lack of specific symptoms or laboratory tests, make chronic recurrent multifocal osteomyelitis mainly a diagnosis of exclusion. An accurate diagnosis is required for appropriate treatment to induce remission. This article highlights the challenges faced by plastic and oral surgeons in diagnosing mandibular chronic recurrent multifocal osteomyelitis, and describes two pediatric patients affected with the disease. Both cases were initially confused with other entities, leading to unnecessary initial treatments and a delayed diagnosis. A review aimed at surgeons summarizes the major aspects of this condition so that it is considered as a differential diagnosis in young patients presenting with a facial bony mass. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Noggin inhibits postoperative resynostosis in craniosynostotic rabbits.

UNLABELLED: Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis. INTRODUCTION: Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, which causes secondary deformations of the cranial vault, cranial base, and brain. Current surgical intervention involves extirpation of the fused suture to allow unrestricted brain growth. However, resynostosis of the extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well-described inducers of ossification, are involved in bone healing. This study tested the hypothesis that a postoperative treatment with Noggin, an extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human familial nonsyndromic craniosynostosis. MATERIALS AND METHODS: Thirty-one New Zealand white rabbits with bilateral coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a slow-resorbing collagen vehicle (n = 10). At 10 days of age, a 3 x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan reconstructions of the defects and standard radiographs were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histological analysis. RESULTS: Radiographic analysis revealed that Noggin-treated animals had significantly greater coronal suture marker separation by 25 days and significantly greater craniofacial length at 84 days of age compared with controls. 3D-CT analysis revealed that Noggin treatment led to significantly greater defect areas through 84 days and to increased intracranial volumes at 84 days of age compared with other groups. Histological analysis supported CT data, showing that the untreated and BSA-treated groups had significant healing of the suturectomy site, whereas the Noggin-treated group had incomplete wound healing. CONCLUSIONS: These data support our hypothesis that inhibition of BMP activity using Noggin may prevent postoperative resynostosis in this rabbit model. These findings also suggest that Noggin therapy may have potential clinical use to prevent postoperative resynostosis in infants with craniosynostosis.

Soft Tissue Regeneration Incorporating 3-Dimensional Biomimetic Scaffolds.

Soft tissue replacement and repair is crucial to the ever-developing field of reconstructive surgery as trauma, pathology, and congenital deficits cannot be adequately restored if soft tissue regeneration is deficient. Predominant approaches were sometimes limited to harvesting autografts, but through regenerative medicine and tissue engineering, the hope of fabricating custom constructs is now a feasible and fast-approaching reality. The breadth of this field includes tissues ranging from skin, mucosa, muscle, and fat and hopes to not only provide construct to replace a tissue but also to replace its function.

Preemptive rofecoxib and dexamethasone for prevention of pain and trismus following third molar surgery *.

Objective The goal of this preliminary randomized prospective clinical trial was to compare the analgesic efficacy and the reduction in trismus of preoperative rofecoxib, intraoperative dexamethasone, and both rofecoxib and dexamethasone following third molar extraction surgery. Study design Thirty-five subjects requiring surgical removal of at least 1 partial bony impacted mandibular third molar were invited to participate in this double-blind and double-dummy placebo-controlled clinical trial. Subjects were randomly assigned into 1 of 4 treatment groups: (1) placebo po preoperatively and placebo IV intraoperatively; (2) rofecoxib 50 mg po preoperatively and placebo IV intraoperatively; (3) placebo po preoperatively and dexamethasone10 mg IV intraoperatively; and (4) rofecoxib 50 mg po preoperatively and dexamethasone 10 mg IV intraoperatively. Subjects completed a diary assessing postoperative pain onset and intensity using categorical and visual analogue scales. Interincisal opening was assessed 1, 2, 3, and 7 days postoperatively using a Therabite ruler. Results This randomized controlled clinical trial enrolled 35 subjects. Two subjects did not meet the inclusion criteria and 4 did not return completed diaries. The mean age of the remaining 29 subjects (11 males, 18 females) was 22.8 years (+/- 0.6 year). The active treatments tended to delay the need for initial pain medication. When compared to other active treatments and to placebo, the combination of preoperative rofecoxib and intraoperative dexamethasone significantly reduced initial pain intensity ( P < .05). Baseline interincisal opening was 52.6 mm (+/- 6.2). The greatest decrease in interincisal opening was 43.3% for the placebo group at 24 hours. Preoperative rofecoxib alone showed a decrease in interincisal opening of 42.3% ( P = ns) at 24 hours. Intraoperative dexamethasone alone showed a decrease in the interincisal opening of 24.1% of baseline ( P < .05 vs placebo). The group receiving the combination of rofecoxib and dexamethasone showed a decrease in interincisal opening of 23.7% of baseline ( P < .05 vs placebo). Conclusions The results of this trial indicate that the use of intraoperative dexamethasone is an effective therapeutic strategy for limiting trismus following surgical removal of impacted third molars. The combination of preoperative rofecoxib 50 mg and intraoperative dexamethasone 10 mg was most effective in minimizing pain and trismus following third molar surgery.

Pediatric mandibular hypomobility: current management and controversies.

Limited range of motion of the pediatric mandible (eg, mandibular hypomobility) presents many challenges. Untreated or recurrent hypomobility can cause problems with mastication, oral hygiene, speech, growth, and the airway. Treatments for ankylosis or adhesions include coronoidectomy, gap arthroplasty, costochondral rib reconstruction, prosthetic joint replacement, and transport distraction osteogenesis. There are many different causes of mandibular hypomobility in young patients, including idiopathic (congenital), posttraumatic, infectious, inflammatory, neoplastic, and iatrogenic. A detailed evaluation and diagnosis of the limited range of motion are critical to developing an appropriate treatment strategy. This article outlines evaluation, differential diagnosis, and the current operative approaches for treating hypomobility in young patients. Controversies related to timing of various procedures and the uses of various treatment options are discussed.

Mandibular distraction osteogenesis in children.

Distraction osteogenesis is currently considered a useful treatment option for the correction of specific facial skeletal deformities. Although it is apparent that distraction may have significant potential and broader application in the management of maxillofacial problems, very few comprehensive scientific data exist, making it difficult to describe its exact role in the reconstructive oral and maxillofacial surgeon's armamentarium. This article reviews the biological basis for distraction osteogenesis, potential applications, and current surgical approaches for mandibular distraction in children.