Three-dimensional quantification of soft tissue changes and its relationship to skeletal changes after Le Fort III, monobloc, and facial bipartition in syndromic craniosynostosis.

To determine the effect of midface surgery on soft tissue changes and their relationship to hard tissue changes in patients with syndromic craniosynostosis. A retrospective analysis of patients who had undergone Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB) was conducted. A 3D soft tissue mesh was generated from the preoperative scan and registered to the postoperative scan, after which the advancement was visualised. A total of 68 patients were included: 28 had undergone LFIII, 27 MB, and 13 FB. The included diagnoses were Apert (n = 23), Crouzon (n = 34), and craniofrontonasal syndrome (n = 11). After LFIII, most soft tissue advancement was seen around subnasale and pronasale (mean 15.1 ± 5.9 mm and 14.7 ± 5.7 mm, at age 7-12 years). After MB, a greater hard tissue than soft tissue advancement was seen for most landmarks, showing a high positive correlation. In patients undergoing FB without distraction (n = 10), mean preoperative inter-canthal distance was 48.9 mm, this reduced by 6.9 mm postoperatively. This study provides a comprehensive overview of the outcomes after midface surgery using 3D quantification for a better understanding of the soft tissue changes and their relationship to hard tissue changes.

Self-perceived oral health and orofacial aesthetics of cleft patients.

PURPOSE: To evaluate the self-perceived oral health and aesthetics of the dentition and jaw in patients with different types of oral cleft, measured by patient-reported outcome measures (PROMs). Additionally, to compare the results of the PROMs between cleft lip and or/palate (CL/P) patients and non-affected controls. METHODS: 420 CL/P patients treated at the cleft team of the Erasmus Medical Center, Rotterdam, The Netherlands, were included, and 138 non-cleft patients were recruited as control-group. Patient's perceptions were retrospectively evaluated using the CLEFT-Q Teeth for dental aesthetics at ages 8, 12 and 22, CLEFT-Q Jaw for jaw aesthetics at ages 12 and 22, and the Child Oral Health Impact Profile-Oral Symptoms Subscale (COHIP-OSS) for oral health at ages 8 and 12. One-way ANOVA was used to compare differences in oral health and aesthetic perceptions among age-groups, cleft types, as well as between cases and controls. RESULTS: CL/P patients were significantly less satisfied than controls with their dental aesthetics (p = 0.001). CL/P patients reported significantly lower satisfaction on CLEFT-Q Teeth scores at ages 8 and 12, than at 22 years (p < 0.001). Patients with the most extensive cleft phenotype, Cleft Lip and Palate (CLAP), reported lowest satisfaction on the CLEFT-Q Teeth. No differences in perceptions of oral health nor in aesthetics of the jaw were found in the different cleft types, ages, nor in study versus control group. CONCLUSION: This study found differences in self-perceived dental aesthetics: CL/P patients are less satisfied than non-affected controls. CLAP patients are least satisfied, but satisfaction increases with age.

Skeletal changes after midface surgery in patients with craniofacial deformities: a three-dimensional quantification method.

To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB). This was a retrospective study including 75 patients: 33 treated by LFIII, 29 by MB, and 13 by FB. Twenty-five had a diagnosis of Apert, 39 Crouzon, and 11 craniofrontonasal syndrome. A three-dimensional mesh was created from the preoperative scan and registered to the postoperative scan to visualise the advancement. LFIII at age 7-12 years effectuated a higher mean advancement in the maxillary (15.5 mm) and zygomatic (7.6 mm) regions when compared to ≥13 years (10.2 mm and 5.5 mm). After MB, mean advancement of the fronto-orbital region was higher at <7 years (16.4 mm), and similarly lower at ages 7-12 (13.8 mm) and ≥13 (12.5 mm). The mean preoperative inter-dacryon distance (34.4 ± 4.4 mm) was reduced by 8.7 ± 4.2 mm after FB without distraction (n = 10). More advancement was seen when midface surgery was performed at a younger age, due to more severe cases and a desire for overcorrection. The highest mean advancement was observed in the fronto-orbital region. Antero-inferior rotational movement was seen after all three techniques.

Evaluation and recommendations of the oral health, oral function, and orofacial aesthetics-related measures of the ICHOM Standard Set for Cleft Lip and Palate.

This study was performed to evaluate the efficacy of outcome measures for the orofacial domain included in the International Consortium for Health Outcomes Measurement Standard Set for Cleft Lip and Palate (ICHOM-SCS). In this multicentre study involving two cleft centres, suggestions to optimize the type and timing of outcome measures were made based on data and clinical experience. Patient-reported outcome measures (PROMs) (CLEFT-Q Jaw, Teeth, Eating/Drinking; Child Oral Health Impact Profile-Oral Symptoms Scale (COHIP-OSS)) and clinical outcome measures (caries experience and dental occlusion) data were collected retrospectively for age 5, 8, 10, 12, 19, and 22 years. The data were categorized by cleft type and analysed within and between age groups using Spearman correlation, the distribution of responses per item, a two-sample test for equality of proportions, and effect plots. Most correlations between PROMs and clinical outcome measures were weak (r < 0.5), suggesting PROMs and clinical outcome measures complement each other. The COHIP-OSS and CLEFT-Q Eating/Drinking barely detected problems in any patient category and are no longer recommended. A suitable alternative appears complex to find; outcomes of this study and the recent literature doubt an added value. Similar problems were found in the CLEFT-Q Jaw at time-point 12 years. Therefore, time-points 15 and 17 years are currently suggested.

Hyoid bone morphology in patients with isolated robin sequence - A case-control study utilizing 3D morphable models.

Background: Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS. Methods: Three-dimensional (3D) reconstructions of the hyoid bone were obtained from CT-imaging of children with RS and unaffected controls. A 3D morphable model was constructed using Principal Component Analysis (PCA). Partial least squares - Discriminant Analysis (PLS-DA) and multivariate analysis of variance (MANOVA) were used to characterize and compare hyoid shape differences between patients with RS and an age-matched control group. Results: The study included 23 subjects with RS (mean age 9.8 ± 10.3 months) and 46 age-matched control samples. A less voluminous hyoid was observed for the RS group with a larger lateral divergence of the greater horns compared to controls (MANOVA, p-value<0.001). The first shape variable from the PLS-DA model showed a significant correlation for the observed variance between the two groups (Spearman R = -0.56, p-value<0.001). The control samples and 151 CT-scans of subjects up to age 4 years were used to create a 3D morphable model of normal hyoid shape variation (n = 197, mean age 22.1 ± 13.1 months). For the normal 3D morphable model, a high degree of allometric shape variation was observed along the first principal component. Conclusions: The 3D morphable models provide a comprehensive and quantitative description of variation in normal hyoid bone morphology, and allow detection of distinct differences between patients with isolated RS and controls.

Effect of helmet use on maxillofacial injuries due to bicycle and scooter accidents: a systematic literature review and meta-analysis.

Maxillofacial injury is a common injury resulting from bicycle (including e-bike) and scooter accidents. With 80,000 admissions to emergency departments in 2019, bicycle accidents account for more than half of all traffic-related emergency department visits in the Netherlands. The United States reports approximately 130,000 injuries and 1000 fatalities related to cycling annually. This systematic review and meta-analysis was performed to examine the protective effect of helmets against maxillofacial injuries resulting from bicycle and scooter (including e-bike and e-scooter) accidents. After a systematic literature search, 14 studies were found to be eligible for this systematic review. Of these, 11 were included in the meta-analysis. None of the included studies focused on vehicles with motors (e-bikes and e-scooters); all focused only on non-motorized vehicles. All included studies were non-randomized, which could have led to bias in the pooled results. Data from the included studies were tested for heterogeneity using the binary random-effects model (DerSimonian-Laird method), and the odds ratio for the occurrence of maxillofacial injury in cyclists wearing a helmet versus those not wearing a helmet was calculated by random-effects meta-analysis. Patients who had worn a helmet suffered significantly fewer maxillofacial injuries than patients who had not, in bicycle accidents (odds ratio 0.682). In conclusion, wearing a helmet has a significant protective effect against maxillofacial injury, indicating the need for strict helmet legislation.

Healthcare use and direct medical costs in a cleft lip and palate population: an analysis of observed and protocolized care and costs.

This study was performed to describe observed healthcare utilization and medical costs for patients with a cleft, compare these costs to the expected costs based on the treatment protocol, and explore the additional costs of implementing the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set for Cleft Lip and Palate (CL/P). Forty patients with unilateral CL/P between 0 and 24 years of age, treated between 2012 and 2019 at Erasmus University Medical Center, were included. Healthcare services (consultations, diagnostic and surgical procedures) were counted and costs were calculated. Expected costs based on the treatment protocol were calculated by multiplying healthcare products by the product prices. Correspondingly, the additional expected costs after implementing the ICHOM Standard Set (protocol + ICHOM) were calculated. Observed costs were compared with protocol costs, and the additional expected protocol + ICHOM costs were described. The total mean costs were highest in the first year after birth (€5596), mainly due to surgeries. The mean observed total costs (€40,859) for the complete treatment (0-24 years) were 1.6 times the expected protocol costs (€25,198) due to optional, non-protocolized procedures. Hospital admissions including surgery were the main cost drivers, accounting for 42% of observed costs and 70% of expected protocol costs. Implementing the ICHOM Standard Set increased protocol-based costs by 7%.

[Caries in cleft patients: aetiology, prevalence, prevention, and treatment]. / Cariës bij schisispatiënten: oorzaak, prevalentie, preventie en behandeling.

The caries prevalence in patients with cleft lip and/or palate is higher in both the deciduous and permanent dentition, compared to non-cleft patients. Inadequate oral hygiene is one of the main causes. Additional, individualized advice concerning diet and oral hygiene, such as the additional advice of the Ivoren Kruis (Dutch association of dental hygienists), is of great importance. During curative treatment, attention should be paid to any dental anxiety and possible reduced compliance.

Biomechanical evaluation of additively manufactured patient-specific mandibular cage implants designed with a semi-automated workflow: A cadaveric and retrospective case study.

OBJECTIVE: Mandibular reconstruction using patient-specific cage implants is a promising alternative to the vascularized free flap reconstruction for nonirradiated patients with adequate soft tissues, or for patients whose clinical condition is not conducive to microsurgical reconstruction. This study aimed to assess the biomechanical performance of 3D printed patient-specific cage implants designed with a semi-automated workflow in a combined cadaveric and retrospective case series study. METHODS: We designed cage implants for two human cadaveric mandibles using our previously developed design workflow. The biomechanical performance of the implants was assessed with the finite element analysis (FEA) and quasi-static biomechanical testing. Digital image correlation (DIC) was used to measure the full-field strains and validate the FE models by comparing the distribution of maximum principal strains within the bone. The retrospective study of a case series involved three patients, each of whom was treated with a cage implant of similar design. The biomechanical performance of these implants was evaluated using the experimentally validated FEA under the scenarios of both mandibular union and nonunion. RESULTS: No implant or screw failure was observed prior to contralateral bone fracture during the quasi-static testing of both cadaveric mandibles. The FEA and DIC strain contour plots indicated a strong linear correlation (r = 0.92) and a low standard error (SE=29.32µÎµ), with computational models yielding higher strain values by a factor of 2.7. The overall stresses acting on the case series' implants stayed well below the yield strength of additively manufactured (AM) commercially pure titanium, when simulated under highly strenuous chewing conditions. Simulating a full union between the graft and remnant mandible yielded a substantial reduction (72.7±1.5%) in local peak stresses within the implants as compared to a non-bonded graft. CONCLUSIONS: This study shows the suitability of the developed semi-automated workflow in designing patient-specific cage implants with satisfactory mechanical functioning under demanding chewing conditions. The proposed workflow can aid clinical engineers in creating reconstruction systems and streamlining pre-surgical planning. Nevertheless, more research is still needed to evaluate the osteogenic potential of bone graft insertions.

Evaluation of Research Diagnostic Criteria in Craniofacial Microsomia.

Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on standardized clinical diagnostic criteria is available. The use of diagnostic criteria could improve research and communication among patients and healthcare professionals. Two sets of phenotypic criteria for research were independently developed and based on multidisciplinary consensus: the FACIAL and ICHOM criteria. This study aimed to assess the sensitivity of both criteria with an existing global multicenter database of patients with CFM and study the characteristics of patients that do not meet the criteria. A total of 730 patients with CFM from were included. Characteristics of the patients were extracted, and severity was graded using the O.M.E.N.S. and Pruzansky-Kaban classification. The sensitivity of the FACIAL and ICHOM was respectively 99.6% and 94.4%. The Cohen's kappa of 0.38 indicated a fair agreement between both criteria. Patients that did not fulfill the FACIAL criteria had facial asymmetry without additional features. It can be concluded that the FACIAL and ICHOM criteria are accurate criteria to describe patients with CFM. Both criteria could be useful for future studies on CFM to create comparable and reproducible outcomes.

Association between prenatal alcohol exposure and children's facial shape: a prospective population-based cohort study.

STUDY QUESTION: Is there an association between low-to-moderate levels of prenatal alcohol exposure (PAE) and children's facial shape? SUMMARY ANSWER: PAE before and during pregnancy, even at low level (<12 g of alcohol per week), was found associated with the facial shape of children, and these associations were found attenuated as children grow older. WHAT IS KNOWN ALREADY: High levels of PAE during pregnancy can have significant adverse associations with a child's health development resulting in recognizably abnormal facial development. STUDY DESIGN, SIZE, DURATION: This study was based on the Generation R Study, a prospective cohort from fetal life onwards with maternal and offspring data. We analyzed children 3-dimensional (3D) facial images taken at ages 9 (n = 3149) and 13 years (n = 2477) together with the data of maternal alcohol consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined six levels of PAE based on the frequency and dose of alcohol consumption and defined three tiers based on the timing of alcohol exposure of the unborn child. For the image analysis, we used 3D graph convolutional networks for non-linear dimensionality reduction, which compressed the high-dimensional images into 200 traits representing facial morphology. These 200 traits were used for statistical analysis to search for associations with PAE. Finally, we generated heatmaps to display the facial phenotypes associated with PAE. MAIN RESULTS AND THE ROLE OF CHANCE: The results of the linear regression in the 9-year-old children survived correction for multiple testing with false discovery rate (FDR). In Tier 1 where we examined PAE only before pregnancy (exposed N = 278, unexposed N = 760), we found three traits survived FDR correction. The lowest FDR-P is 1.7e-05 (beta = 0.021, SE = 0.0040) in Trait #29; In Tier 2b where we examine any PAE during first trimester (exposed N = 756; unexposed N = 760), we found eight traits survived FDR correction. The lowest FDR-P is 9.0e-03 (beta = -0.013, SE = 0.0033) in Trait #139. Moreover, more statistically significant facial traits were found in higher levels of PAE. No FDR-significant results were found in the 13-year-old children. We map these significant traits back to the face, and found the most common detected facial phenotypes included turned-up nose tip, shortened nose, turned-out chin, and turned-in lower-eyelid-related regions. LIMITATIONS, REASONS FOR CAUTION: We had no data for alcohol consumption more than three months prior to pregnancy and thus do not know if maternal drinking had chronic effects. The self-reported questionnaire might not reflect accurate alcohol measurements because mothers may have denied their alcohol consumption. WIDER IMPLICATIONS OF THE FINDINGS: Our results imply that facial morphology, such as quantified by the approach we proposed here, can be used as a biomarker in further investigations. Furthermore, our study suggests that for women who are pregnant or want to become pregnant soon, should quit alcohol consumption several months before conception and completely during pregnancy to avoid adverse health outcomes in the offspring. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam, and the Netherlands Organization for Health Research. V.W.V.J. reports receipt of funding from the Netherlands Organization for Health Research (ZonMw 90700303). W.J.N. is a founder, a scientific lead, and a shareholder of Quantib BV. TRIAL REGISTRATION NUMBER: N/A.

Novel Genetic Determinants of Dental Maturation in Children.

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10-8), 14q13.3 (PAX9: P = 1.9 × 10-8), and 16q12.2 (IRX5: P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

Caries Preventive Interventions and Oral Health Inequalities: A Scoping Review.

INTRODUCTION: Dental caries remains one of the most prevalent but preventable diseases among children worldwide and especially affects children with a lower socioeconomic status or ethnic minority background. It is important that all groups of children are reached by preventive interventions to reduce oral health inequalities. So far, it is unknown whether children from different social and ethnic groups benefit equally from potentially effective oral health interventions. OBJECTIVES: This scoping review aimed to identify European public health interventions that report their effect on dental caries across different social groups. METHODS: Four databases were searched for studies evaluating the effect of oral health interventions on dental caries among children from 0 to 12 y, and studies were included when results were presented by children of different social groups separately. RESULTS: A total of 14 studies were included, representing 4 different countries: 3 randomized and 11 nonrandomized studies. Most studies were performed at schools. Six studies showed results indicative of a reduction in oral health inequalities, 4 studies showed results that potentially widen oral health inequalities, and 5 studies showed results that were indicative of no impact on oral health inequalities. Interventions that contain early approaches, with a high frequency, approaching multiple levels of influence, and including at least the broader organizational or public policy level, may have the potential to reduce oral health inequalities among children from birth to young adolescence. CONCLUSION: We recommend researchers to perform high-quality intervention studies and to evaluate the effectiveness of oral health intervention always in different socioeconomic or ethnic groups separately, to better understand their contribution toward oral health (in)equalities. KNOWLEDGE TRANSFER STATEMENT: This review offers insight in the differential effects that oral health interventions might have across different social groups. Its results can be used to develop interventions that might reduce oral health inequalities among children. Also, we recommend future researchers to always evaluate the effects of any preventive oral health measure in different social groups separately.

Semi-automated digital workflow to design and evaluate patient-specific mandibular reconstruction implants.

The reconstruction of large mandibular defects with optimal aesthetic and functional outcomes remains a major challenge for maxillofacial surgeons. The aim of this study was to design patient-specific mandibular reconstruction implants through a semi-automated digital workflow and to assess the effects of topology optimization on the biomechanical performance of the designed implants. By using the proposed workflow, a fully porous implant (LA-implant) and a topology-optimized implant (TO-implant) both made of Ti-6Al-4V ELI were designed and additively manufactured using selective laser melting. The mechanical performance of the implants was predicted by performing finite element analysis (FEA) and was experimentally assessed by conducting quasi-static and cyclic biomechanical tests. Digital image correlation (DIC) was used to validate the FE model by comparing the principal strains predicted by the FEM model with the measured distribution of the same type of strain. The numerical predictions were in good agreement with the DIC measurements and the predicted locations of specimen failure matched the actual ones. No statistically significant differences (p < 0.05) in the mean stiffness, mean ultimate load, or mean ultimate displacement were detected between the LA- and TO-implant groups. No implant failures were observed during quasi-static or cyclic testing under masticatory loads that were substantially higher (>1000 N) than the average maximum biting force of healthy individuals. Given its relatively lower weight (16.5%), higher porosity (17.4%), and much shorter design time (633.3%), the LA-implant is preferred for clinical application. This study clearly demonstrates the capability of the proposed workflow to develop patient-specific implants with high precision and superior mechanical performance, which will greatly facilitate cost- and time-effective pre-surgical planning and is expected to improve the surgical outcome.

The Association of Helmet Use with the Occurrence of Maxillofacial Injuries Following Bicycle or Scooter Accidents: A Retrospective Cohort Study.

Study Design: Retrospective Cohort Study. Objective: Yearly, bicycle and scooter accidents in the Netherlands amount to 90 thousand emergency department visits. Maxillofacial injuries are common after cycling or scooter accidents. To prevent these injuries, helmet use might be beneficial. However, the effect of helmet use on maxillofacial injuries remains unclear. The aim of this retrospective study is to assess the effect of helmet use on maxillofacial injuries in patients who had a bicycle or scooter accident. Methods: We collected data from the emergency department of the Erasmus Medical Center in the period from October 2017 to October 2019. Patients that were involved in a bicycle or scooter accident and subsequently received a CT scan of the head were included. We compared the incidence of maxillofacial injuries in helmeted cyclists and scooter users to non-helmeted users. Descriptive and analytic statistics were computed. Level of statistical significance was set at p < 0.05. Results: Helmet use among scooter users was associated with a significant reduction in maxillofacial fractures (p < 0.001) and soft tissue injuries (p < 0.001). Helmet use among cyclists was not associated with a reduction in maxillofacial fractures (p = 0.17) or soft tissue injuries (p = 0.30). Helmet use was not associated with a reduction in soft tissue injuries of the lower face in both cyclists (p = 0.47) and scooter users (p = 0.24). Conclusions: Helmet use should be considered among cyclists and scooter users to prevent maxillofacial injuries. Especially unhelmeted scooter users might benefit from helmet use as this is associated with a lower incidence of maxillofacial injuries.

Craniofacial morphology and growth in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis.

OBJECTIVES: To determine whether the midface of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is hypoplastic compared to skeletal facial proportions of a Dutch control group. MATERIAL AND METHODS: We included seventy-four patients (43 patients with Muenke syndrome, 22 patients with Saethre-Chotzen syndrome, and 9 patients with TCF12-related craniosynostosis) who were referred between 1990 and 2020 (age range 4.84 to 16.83 years) and were treated at the Department of Oral Maxillofacial Surgery, Special Dental Care and Orthodontics, Children's Hospital Erasmus University Medical Center, Sophia, Rotterdam, the Netherlands. The control group consisted of 208 healthy children. RESULTS: Cephalometric values comprising the midface were decreased in Muenke syndrome (ANB: ß = -1.87, p = 0.001; and PC1: p < 0,001), Saethre-Chotzen syndrome (ANB: ß = -1.76, p = 0.001; and PC1: p < 0.001), and TCF12-related craniosynostosis (ANB: ß = -1.70, p = 0.015; and PC1: p < 0.033). CONCLUSIONS: In this study, we showed that the midface is hypoplastic in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis compared to the Dutch control group. Furthermore, the rotation of the maxilla and the typical craniofacial buildup is significantly different in these three craniosynostosis syndromes compared to the controls. CLINICAL RELEVANCE: The maxillary growth in patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis is impaired, leading to a deviant dental development. Therefore, timely orthodontic follow-up is recommended. In order to increase expertise and support treatment planning by medical and dental specialists for these patients, and also because of the specific differences between the syndromes, we recommend the management of patients with Muenke syndrome, Saethre-Chotzen syndrome, or TCF12-related craniosynostosis in specialized multidisciplinary teams.

Feeding and swallowing outcomes following mandibular distraction osteogenesis: an analysis of 22 non-isolated paediatric cases.

Patients with mandibular hypoplasia and upper airway obstruction are at an increased risk of feeding and swallowing difficulties. Little has been described regarding these outcomes following mandibular distraction. The aim of this study was to evaluate the effect of mandibular distraction on feeding and swallowing function. A retrospective study was performed on 22 patients with non-isolated mandibular hypoplasia and severe upper airway obstruction treated with mandibular distraction. Median age at first mandibular distraction was 3.1 years (interquartile range 2.3-6.0 years) and the median follow-up time was 3.5 years (interquartile range 2.0-9.4 years). Prior to mandibular distraction, feeding difficulties were present in 18 patients. Swallowing difficulties were present in 20 patients, all of whom had problems in the oral phase of swallowing, while 11 patients had additional problems in the pharyngeal phase. Following mandibular distraction, at the time of follow-up, feeding difficulties persisted in 13 patients. Swallowing difficulties in the oral phase remained present in all 20 patients, while pharyngeal phase problems persisted in seven patients. In conclusion, feeding and swallowing difficulties are highly prevalent in non-isolated patients and often persist following mandibular distraction. Moreover, these can be the reason that decannulation cannot be accomplished. Hence, awareness and close follow-up by a specialized speech therapist is of paramount importance.

A new semi-orthotopic bone defect model for cell and biomaterial testing in regenerative medicine.

In recent decades, an increasing number of tissue engineered bone grafts have been developed. However, expensive and laborious screenings in vivo are necessary to assess the safety and efficacy of their formulations. Rodents are the first choice for initial in vivo screens but their size limits the dimensions and number of the bone grafts that can be tested in orthotopic locations. Here, we report the development of a refined murine subcutaneous model for semi-orthotopic bone formation that allows the testing of up to four grafts per mouse one order of magnitude greater in volume than currently possible in mice. Crucially, these defects are also "critical size" and unable to heal within the timeframe of the study without intervention. The model is based on four bovine bone implants, ring-shaped, where the bone healing potential of distinct grafts can be evaluated in vivo. In this study we demonstrate that promotion and prevention of ossification can be assessed in our model. For this, we used a semi-automatic algorithm for longitudinal micro-CT image registration followed by histological analyses. Taken together, our data supports that this model is suitable as a platform for the real-time screening of bone formation, and provides the possibility to study bone resorption, osseointegration and vascularisation.

Registration of magnetic resonance and computed tomography images in patients with oral squamous cell carcinoma for three-dimensional virtual planning of mandibular resection and reconstruction.

The aim of this study was to evaluate and present an automated method for registration of magnetic resonance imaging (MRI) and computed tomography (CT) or cone beam CT (CBCT) images of the mandibular region for patients with oral squamous cell carcinoma (OSCC). Registered MRI and (CB)CT could facilitate the three-dimensional virtual planning of surgical guides employed for resection and reconstruction in patients with OSCC with mandibular invasion. MRI and (CB)CT images were collected retrospectively from 19 patients. MRI images were aligned with (CB)CT images employing a rigid registration approach (stage 1), a rigid registration approach using a mandibular mask (stage 2), and two non-rigid registration approaches (stage 3). Registration accuracy was quantified by the mean target registration error (mTRE), calculated over a set of landmarks annotated by two observers. Stage 2 achieved the best registration result, with an mTRE of 2.5±0.7mm, which was comparable to the inter- and intra-observer variabilities of landmark placement in MRI. Stage 2 was significantly better aligned compared to all approaches in stage 3. In conclusion, this study demonstrated that rigid registration with the use of a mask is an appropriate image registration method for aligning MRI and (CB)CT images of the mandibular region in patients with OSCC.

Functional outcomes in patients with facial dysostosis and severe upper airway obstruction.

An increased risk of upper airway obstruction (UAO) is seen in up to 95% of patients with facial dysostosis. Secondary to respiratory problems are feeding difficulties and increased nutritional requirements. Little has been described regarding these outcomes in this patient population. Hence, a retrospective cohort study was performed to gather data on functional outcomes. Eighteen patients with facial dysostosis and severe UAO were included. The median follow-up time was 3.42 years. A tracheostomy tube was placed in 13 patients, of whom 10 subsequently underwent mandibular distraction. Three of the five patients without a tracheostomy underwent mandibular distraction as the primary surgical treatment; the remaining two patients were treated conservatively with oxygen supplementation. At presentation, 13 patients had feeding difficulties. Overall malnutrition was present in 16 patients during follow-up. At the end of follow-up, severe UAO was present in 12 patients, feeding difficulties in seven patients, and malnutrition in four patients, while two patients died. In conclusion, patients with facial dysostosis have a high prevalence of severe UAO, feeding difficulties, and malnutrition. Importantly, mandibular distraction has limited success in treating severe UAO in these patients. Close follow-up by a specialized craniofacial team is of paramount importance to manage the long-term consequences.