Mandibular autorotation: a critical virtual parameter in clinical decision-making regarding maxilla-first versus mandible-first sequence.

Large degrees of mandibular autorotation during intermediate splint design are prone to transfer error and decrease accuracy. The purpose of this study was to evaluate the amount of mandibular autorotation necessary to design intermediate splints for maxilla- and mandible-first sequences using virtual planning software, to help the clinical decision-making regarding the most adequate sequence for each patient. The influence of specific orthognathic movements (different vertical and sagittal changes at the Le Fort I level, cant correction) and the type of maxillofacial deformity (skeletal Class II, III, anterior open bite) were evaluated to identify those that would require higher levels of autorotation for each sequence. Three-dimensional virtual surgical planning data of 194 patients were reviewed (126 female, 68 male; mean age 26.5 ± 11.0 years; 143 skeletal Class II, 51 skeletal Class III) and subgroup analyses were conducted using the Kruskal-Wallis test and post-hoc pairwise comparisons. As an additional parameter (mandibular autorotation), maxilla-first is indicated for bimaxillary osteotomies with Le Fort I posterior intrusion, anterior open bite, and skeletal Class III, while mandible-first is recommended for Le Fort I global extrusion, especially with maxillary cant correction.

Presentation and short-term evaluation of an all-in-one patient-specific implant for cranial reconstruction: A randomized controlled trial.

Cranial reconstruction after bone graft harvesting remains a challenge. A patient-specific implant (PSI) to guide harvesting and reconstruction was evaluated and compared with the use of a free-hand procedure with calcium phosphate cement (C). Patients were randomized to either the PSI or C group. The outcome was measured clinically and radiographically as the primary endpoint. Secondary endpoints were ease of application, patient and surgeon satisfaction, and the complication rate. Twenty patients were randomized to the PSI (n=10) and C (n=10) groups. Two PSI patients were switched to the cement group due to a poor fit of the PSI. There was a non-significant trend towards more successful outcomes in the PSI group. Two PSI patients presented palpable screws, and one cement patient had a palpable dimple. Cone beam computed tomography showed a significantly lower median volume discrepancy in the PSI group (P<0.0001). The total surgical manipulation time was significantly higher in the PSI group. At 10 days postoperative, three PSI and two C patients presented with minor postoperative complications. There was no significant difference in patient or surgeon satisfaction. PSIs are a reliable alternative to cement. This PSI is novel as it also serves as a guide for harvesting the bone blocks required for reconstructive purposes.

Three-dimensional cone beam computed tomography analysis protocols for condylar remodelling following orthognathic surgery: a systematic review.

Orthognathic surgery involving the mandible can lead to remodelling of the temporomandibular joint (TMJ). Cone beam computed tomography (CBCT) provides an easily accessible three-dimensional (3D) approach to study this entity. A systematic review of the literature was performed with the aim of identifying condylar remodelling analysis protocols using CBCT-derived 3D models. The search yielded 10 eligible studies. The systematic review identified three pillars of a condylar remodelling analysis protocol that were retrievable from each of the included studies: (1) registration, (2) segmentation, and (3) analysis. The studies lacked consensus on how these pillars should be transferred to their respective protocol. Through critical assessment, criteria for a universal condylar remodelling analysis are suggested: (1) performance of a regional voxel-based registration of baseline and postoperative CBCT scans using an anatomical region not prone to postoperative changes, (2) application of a (semi-)automated 3D segmentation algorithm, (3) performance of a combination of both volumetric and surface-based 3D condylar analysis, and (4) extensive validation of each step of the protocol. The homogenization of condylar remodelling analysis protocols and their incorporation into virtual planning software suites raises the potential for the inclusion of larger numbers of patients in future prospective studies in order to gain evidence-based data.

The role of receptor MAS in microglia-driven retinal vascular development.

OBJECTIVE: The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia. APPROACH AND RESULTS: To assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and Mas1-/- mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced (- 24%, p < 0.0001) and vascular density decreased (- 38%, p < 0.001) in Mas1-/- compared to WT mice with no change in the junction density. The number of filopodia and filopodia bursts were decreased in Mas1-/- mice at the vascular front (- 21%, p < 0.05; - 29%, p < 0.0001, respectively). This was associated with a decreased number of vascular loops and decreased microglial density at the vascular front in Mas1-/- mice (-32%, p < 0.001; - 26%, p < 0.05, respectively). As the front of the developing vasculature is characterized by reduced oxygen levels, we determined the expression of Mas1 following hypoxia in primary microglia from 3-day-old WT mice. Hypoxia induced a 14-fold increase of Mas1 mRNA expression (p < 0.01). Moreover, stimulation of primary microglia with a MAS agonist induced expression of Notch1 (+ 57%, p < 0.05), Dll4 (+ 220%, p < 0.001) and Jag1 (+ 137%, p < 0.001), genes previously described to mediate microglia/endothelial cell interaction during angiogenesis. CONCLUSIONS: Our study demonstrates that the activation of MAS is important for microglia recruitment and vascular growth in the developing retina.

Condylar changes after orthognathic surgery for class III dentofacial deformity: a systematic review.

After orthognathic surgery for class II dentofacial deformity, remodelling of the mandibular condyle will take place. In a number of cases, this may evolve towards a phenomenon of condylar resorption. Yet, studies on the occurrence of this complication after the correction of a class III deformity are scarce. A systematic review of the literature was performed with the aim of identifying reports on condylar resorption or remodelling after orthognathic surgery for class III dentofacial deformity. A search of the international databases yielded 12 eligible studies. Eight studies reported some degree of postoperative condylar remodelling, while symptoms of condylar resorption were only described in a limited group of patients. Thus, the literature may show evidence of condylar remodelling after orthognathic treatment of class III patients, and anecdotal reports of condylar resorption exist. The small sample sizes, heterogeneity in methods and outcomes, and use of two-dimensional radiographs indicate the need for updated long-term research. In the future, the use of cone beam computed tomography data for volumetric and morphological condylar analysis in combination with three-dimensional cephalometry may provide the opportunity to further elucidate this phenomenon and better characterize its aetiology.

Bone grafting in orthognathic surgery: a systematic review.

Bone grafting has been used in orthognathic surgery to fill the gaps created by jaw repositioning, with the intention of improving healing and stability. Since the majority of orthognathic cases have a satisfactory result, the decision to graft or not is a clinical dilemma. A systematic review of the literature was performed on the use of bone grafts in orthognathic surgery. A search of PubMed, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials yielded 1927 articles published up until 2018. An additional 10 articles were retrieved through manual searching of the reference lists and citations. After title and abstract screening, 58 articles were potentially eligible; full-text screening excluded 10 of these. Thus 48 articles were included in this review. The present literature highlights the benefits of grafting bony gaps during orthognathic surgery in terms of healing, stability, and aesthetic outcomes. Generally, there was no difference between the various types of bone graft, although calcium phosphate cement and hydroxyapatite were found to increase the rate of infection. The conclusion of this review is that there remains a lack of evidence in the literature regarding the grafting of osteotomy sites in orthognathic surgery. Guidelines are proposed based on the present evidence; however, future research is needed to validate these.

Maintaining bovine satellite cells stemness through p38 pathway.

Isolating and maintaining the appropriate stem cell for large scale cell culture is essential in tissue engineering or food production. For bovine satellite cells an optimized isolation and purification protocol is lacking and there is also no detailed understanding on the factors that maintain stemness of these cells. Here, we set up a fluorescence-activated cell sorting strategy to enrich bovine satellite cells. We found that p38-MAPK signalling is activated and PAX7 expression is gradually lost during satellite cell proliferation. The p38 inhibitor (SB203580) treatment maintained PAX7 expression but inhibited the fusion of satellite cells in a concentration-dependent way in short-term incubation. The mechanism of p38 inhibition was confirmed by inhibiting canonical p38 signalling, i.e. HSP27. Long-term culture with an appropriate concentration of p38i enhanced the proliferation and PAX7 expression, while the differentiation capacity recovered and was enhanced compared to vehicle control. These studies indicate that bovine satellite cells maintenance depends on cell purity and p38 MAPK signalling. Inhibition of p38 MAPK signaling is a promising strategy to facilitate large scale cell expansion of primary cells for tissue engineering and cultured meat purposes.

Minimally invasive orthognathic surgery: a systematic review.

Minimally invasive techniques are currently applied in many oral and maxillofacial surgical procedures, including orthognathic surgery. A systematic review on the application of potentially minimally invasive procedures in orthognathic surgery was performed to provide a clear overview of the relevant published data. Articles in English on minimally invasive orthognathic procedures, published in the scientific literature, were obtained from the PubMed, Embase, and Cochrane Library databases, and an additional manual search (revised 31 December 2016). After screening the abstracts and applying the eligibility criteria, 403 articles were identified. All articles reporting the potential for minimally invasive orthognathic surgery were included (n=44). The full papers were evaluated in detail and categorized as articles on a minimally invasive surgical approach (n=4), endoscopically assisted orthognathic procedures (n=17), or the use of a piezoelectric device in orthognathic surgery (n=25); two articles were each included in two categories. Although a small incision and minimal dissection is the basic principle of a minimally invasive technique, most articles (90.9%) reported the endoscope and piezoelectric instrument as important tools in minimally invasive orthognathic surgery. Evidence from available studies suggests that patients undergoing minimally invasive orthognathic surgery have less morbidity and make a faster recovery. Further research should aim to obtain higher levels of evidence.

Three-dimensional volumetric changes in the upper airway after maxillomandibular advancement in obstructive sleep apnoea patients and the impact on quality of life.

Obstructive sleep apnoea (OSA) is a sleep-related breathing disorder, characterized by repetitive airway obstructions, causing disruptive snoring and daytime sleepiness. Maxillomandibular advancement (MMA), which enlarges the upper airway, is a therapeutic surgical approach. However, no study has performed an upper airway sub-region analysis using validated three-dimensional (3D) anatomical and technical limits on cone beam computed tomography (CBCT). Hence, this prospective, observational trial was performed to evaluate 3D volumetric changes in the upper airway according to validated 3D cephalometric landmarks, before and after MMA, for all patients with a polysomnography diagnosis of OSA (apnoea-hypopnoea index (AHI) ≥5). The secondary objective was to evaluate the impact of MMA on the AHI and in a subjective manner with the Epworth Sleepiness Scale (ESS) and OSA questionnaire. Eleven consecutive OSA patients were included. A significant volume increase in the oropharynx (P=0.002) and hypopharynx (P=0.02) was observed, in contrast to a non-significant volume reduction in the nasopharynx (P >0.05). The median AHI (P=0.03) and ESS score (P=0.004) decreased significantly as a result of surgery. In conclusion, MMA significantly enlarges the airway volume of the oropharynx and hypopharynx and is associated with improved quality of life.

Is oestrogen associated with mandibular condylar resorption? A systematic review.

A systematic review of the literature was performed regarding the influence of oestrogen on the occurrence of mandibular condylar resorption. Search terms for oestrogen were used in combination with terms related to the effect on condylar remodelling. A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases yielded 419 articles published between October 1993 and March 2017. An additional 48 articles were retrieved through manual searching of the reference lists. After initial abstract selection, 94 eligible articles were screened in detail, resulting in a final number of 33 articles included in the review. From this review, no evidence was found that oestrogen (deficiency) contributes to mandibular condylar resorption. The conclusions are limited by the lack of studies with a high level of evidence. Further investigations on serum oestrogen concentrations in women with condylar resorption are needed. Moreover, future studies should focus on the effects of the different types of medication and diseases influencing oestrogen concentrations, the utility of oestrogen concentrations during preoperative screening, and the policies for managing orthognathic surgery patients with an oestrogen deficiency. Finally, whether the mechanisms and risk factors that lead to idiopathic condylar resorption are the same in condylar resorption following orthognathic surgery remain to be elucidated.

Application of a non-invasive reference headband and a surgical splint for intraoperative paediatric navigation.

The key to the success of surgical navigation based on computer-aided design and computer-aided manufacturing (CAD/CAM) planning is the registration process. This has to be precise and adapted to the surgical needs. However, the application of a conventional rigid skull-fixed navigation star for accurate registration is limited for use in the paediatric population, because of the risk of unstable fixation, dural perforation, and intracranial bleeding. The authors describe their experience with a non-invasive reference headband that was used in combination with a custom-made acrylic resin dental registration splint for resection of a rare infraorbital zygomatic desmoplastic fibroma in a 2-year old patient. This approach appears not to have been reported in the literature to date.

Complications of mandibular distraction osteogenesis for acquired deformities: a systematic review of the literature.

A systematic review on complications in all forms of mandibular distraction osteogenesis (MDO) for acquired deformities was performed. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and the Cochrane Controlled Trials Register yielded 644 articles published between 1966 and mid October 2013. Three hundred and twenty-one eligible articles were screened in detail. Complications related to MDO in acquired deformities were reported in 105 clinical articles, involving 1332 patients. Treatments included alveolar distraction osteogenesis (ADO), mandibular lengthening, DO in bone grafts, and bi-/trifocal transport disc DO (TDDO) for segmental mandibular defects. A high incidence of complications was seen in MDO for acquired deformities (ADO 44.4%; residual group 43.9%). An index for classifying complications in MDO, based on the impact and further treatment or final results, was used. In the ADO group, soft tissue complications (8.0%), insufficient vector control (7.6%), temporary inferior alveolar nerve (IAN) neurosensory disturbances (6.5%), device-related problems (3.5%), mandible fractures (2.8%), insufficient bone formation (2.5%), and fracture of the transport disc (1.3%) were seen. In the residual group, temporary IAN neurosensory disturbances (13.4%), minor infection (5.3%), DO failure (4.0%), and device-related problems (3.8%) were reported.

Complications of mandibular distraction osteogenesis for developmental deformities: a systematic review of the literature.

A systematic review of English and non-English articles on the complications of mandibular distraction osteogenesis (MDO) for patients with developmental deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and Cochrane Controlled Trials Register yielded 644 articles published between 1966 and mid October 2013. Clinical articles that reported complications related to MDO in developmental deformities were included. Two hundred and fifty articles were eligible and were screened in detail. A total of 32 articles reporting the cases of 565 patients were finally included. Patients underwent mandibular lengthening and transverse widening. A total of 211 complications were reported (37.4%); these were classified according to an index that indicates the clinical impact. Inferior alveolar nerve (IAN) neurosensory disturbances, minor infection, device failure, anterior open bite, permanent dental damage, and skeletal relapse were most represented. Complications that resolved spontaneously (type I) were seen in 11.0%, medically or technically manageable complications, without hospitalization, were seen in 10.8% (type II), and permanent complications (type VI) were seen in 9.6%.

ADAM10 and ADAM17 have opposite roles during sprouting angiogenesis.

During angiogenesis, endothelial tip cells start sprouting and express delta-like 4 (DLL4) downstream of vascular endothelial growth factor (VEGF). DLL4 subsequently activates Notch in the adjacent stalk cells suppressing sprouting. VEGF also activates A disintegrin and metalloproteases (ADAMs) that induce Notch ectodomain shedding. Although two major ADAMs, i.e. ADAM10 and ADAM17, have been implicated in Notch-signalling activation, their apparent different roles in angiogenesis have not been fully understood yet. The objective of this study was to determine the roles of ADAM10 and ADAM17 activity in angiogenesis. In mouse retinas, ADAM10 or γ-secretase inhibition induced vascular sprouting and density in vivo, whereas attenuation of both ADAM10 and ADAM17 activity produced the opposite phenotype. Retinal blood vessel analysis in ADAM17 hypomorphic mice confirmed the requirement for ADAM17 activity in angiogenesis. However, ADAM17 inhibition did not phenocopy blood vessel increase by Notch blockage. These observations suggest that ADAM17 regulates other fundamental players during angiogenesis besides Notch, which were not affected by ADAM10. By means of an angiogenesis proteome assay, we found that ADAM17 inhibition induced the expression of a naturally occurring inhibitor of angiogenesis Thrombospondin 1 (TSP1), whereas ADAM10 inhibition did not. Accordingly, ADAM17 overexpression downregulated TSP1 expression, and the TSP1 inhibitor LSKL rescued angiogenesis in the tube formation assay downstream of VEGF in the presence of ADAM17 inhibition. Finally, genetic and pharmacological ADAM17 blockade resulted in increased TSP1 expression in mouse retina. Altogether, our results show that ADAM10 and ADAM17 have opposite effects on sprouting angiogenesis that may be unrelated to Notch signalling and involves differentially expressed anti-angiogenic proteins such as TSP1.

Complications of mandibular distraction osteogenesis for congenital deformities: a systematic review of the literature and proposal of a new classification for complications.

A systematic review of English and non-English language articles on the complications of mandibular distraction osteogenesis (MDO) for patients with congenital deformities was performed, in accordance with the PRISMA statement. Search terms expressing distraction osteogenesis were used in 'AND' combination with search terms comprising 'mandible' and terms for complication, failure, and morbidity. A search using PubMed (National Library of Medicine, NCBI), EMBASE, and the Cochrane Central Register of Controlled Trials yielded 644 articles published between 1966 and mid October 2013. Clinical articles that reported complications related to MDO were included. Finally 81 articles on MDO in congenital deformities were eligible and were screened in detail. Complications including minor infection (6.0%), device-related problems (7.3%), skeletal open bite (2.4%), hypertrophic scar formation (2.1%), facial nerve palsy (1.8%), neurosensory disturbances of the inferior alveolar nerve (1.9%), and (fibrous) non-union (0.7%) were seen. A new index for more detailed classification of complications in MDO is proposed based on six categories that indicate the impact of the complication and its further treatment or final results. The proposed complication index may be a useful tool to classify complications related to MDO.

Three-dimensional cone beam computed tomography definition of the anatomical subregions of the upper airway: a validation study.

The exact boundaries of the upper airway subregions remain undefined. Consequently, anatomical limits vary greatly among different research groups and impede unbiased comparisons. The aim of this study was to provide clinical three-dimensional anatomical limits for the upper airway subregions, translate them into accurate and reliable cephalometric landmarks in cone beam computed tomography (CBCT) data, and validate the proposed measuring protocol. The upper airway of 40 normative individuals aged 23-35 years was evaluated with Dolphin Imaging(®) software. An appropriate grey-scale threshold value was pre-calculated. After adapting specific head positioning and virtual orientation protocols, the volume and minimum cross-sectional area of the nasopharynx, oropharynx, and hypopharynx, as previously defined by the authors, were calculated. Intra- and inter-observer reliability was excellent for volumes and moderate for areas. The sexual dimorphism analysis revealed a significantly greater oropharyngeal volume, hypopharyngeal volume, and minimum cross-sectional oropharyngeal area in males than in females. In conclusion, the proposed subregion definition showed technical feasibility and statistical reliability, especially for three-dimensional calculations. The reliability of two-dimensional calculations may be increased with improved head positioning during CBCT scanning and subsequent virtual head orientation. Standardization of the proposed anatomical limits has the potential to homogenize upper airway subregion analysis and permit comparisons among future studies.

Validation of a novel semi-automated method for three-dimensional surface rendering of condyles using cone beam computed tomography data.

Morphological changes of the condyles are often observed following orthognathic surgery. In addition to clinical assessment, radiographic evaluation of the condyles is required to distinguish the physiological condylar remodelling from pathological condylar resorption. The low contrast resolution and distortion of greyscale values in cone beam computed tomography (CBCT) scans have impeded an accurate three-dimensional (3D) rendering of the condyles. The current study proposes a novel semi-automated method for 3D rendering of condyles using CBCT datasets, and provides a clinical validation of this method. Ten patients were scanned using a standard CBCT scanning protocol. After defining the volume of interest, a greyscale cut-off value was selected to allow an automatic reconstruction of the condylar outline. The condylar contour was further enhanced manually by two independent observers to correct for the under- and over-contoured voxels. Volumetric measurements and surface distance maps of the condyles were computed. The mean within-observer and between-observer differences in condylar volume were 8.62 mm(3) and 6.13 mm(3), respectively. The mean discrepancy between intra- and inter-observer distance maps of the condylar surface was 0.22 mm and 0.13 mm, respectively. This novel method provides a reproducible tool for the 3D rendering of condyles, allowing longitudinal follow-up and quantitative analysis of condylar changes following orthognathic surgery.

Cone beam CT: non-dental applications.

Initially cone beam CT was almost exclusively used to perform dental radiology. However, the first generation CBCT systems were later increasingly used to study sinuses, facial and nose fractures, temporomandibular joints etc. 3D-cephalometric head and neck studies became possible once CBCT systems were available that allowed scanning of the complete head. For this purpose a double rotation technique with stitching of the resulting two data sets was needed. CBCT systems on which the rotation could be stopped were needed to perform dynamic swallow or pharyngography studies. The advent of more powerful high-end CBCT systems led the way to temporal bone and skull base imaging. Finally, high-end "supine" CBCT systems using a "gantry" made small joint musculoskeletal imaging possible. These non-dental CBCT studies gradually replaced conventional X-rays and CT/MDCT studies because they allowed imaging with higher resolution, lower radiation dose and less metal artifacts. In this paper the most important non-dental CBCT indications will be discussed.