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Three-dimensional virtual simulation of orthognathic surgery is now a well-established method in maxillo-facial surgery. The commercial software packages are still burdened by a consistent imprecision on soft tissue predictions. In this study, the authors produced an anatomically detailed patient specific numerical model for simulation of soft tissue changes in orthognathic surgery. Eight patients were prospectively enrolled. Each patient underwent CBCT and planar x-rays prior to surgery and in addition received an MRI scan. Postoperative soft-tissue change was simulated using Finite Element Modeling (FEM) relying on a patient-specific 3D models generated combining data from preoperative CBCT (hard tissue) scans and MRI scans (muscles and skin). An initial simulation was performed assuming that all the muscles and the other soft tissue had the same material properties (Homogeneous Model). This model was compared with the postoperative CBCT 3D simulation for validation purpose. Design of experiments (DoE) was used to assess the effect of the presence of the muscles considered and of their variation in stiffness. The effect of single muscles was evaluated in specific areas of the midface. The quantitative distance error between the homogeneous model and actual patient surfaces for the midface area was 0.55 mm, standard deviation 2.9 mm. In our experience, including muscles in the numerical simulation of orthognathic surgery, brought an improvement in the quality of the simulation obtained.

Background Despite the limited number of articles dedicated to its use, augmented reality (AR) is an emerging technology that has shown to have increasing applications in multiple different medical sectors. These include, but are not limited to, the Maxillo-facial and Dentistry disciplines of medicine. In these medical specialties, the focus of AR technology is to achieve a more visible surgical field during an operation. Currently, this goal is brought about by an accurate display of either static or dynamic diagnostic images via the use of a visor or specific glasses. The objective of this study is to evaluate the feasibility of using a virtual display for dynamic navigation via AR. The secondary outcome is to evaluate if the use of this technology could affect the accuracy of dynamic navigation. Case presentation Two patients, both needing implant rehabilitation in the upper premolar area, were treated with flapless surgery. Prior to the procedure itself, the position of the implant was virtually planned and placed for each of the patients using their previous scans. This placement preparation contributed to a dynamic navigation system that was displayed on AR glasses. This, in turn, allowed for the use of a computer-aided/image-guided procedure to occur. Dedicated software for surface superimposition was then used to match the planned position of the implant and the real one obtained from the postoperative scan. Accuracies, using this procedure were evaluated by way of measuring the deviation between real and planned positions of the implants. For both surgeries it was possible to proceed using the AR technology as planned. The deviations for the first implant were 0.53 mm at the entry point and 0.50 mm at the apical point and for the second implant were 0.46 mm at the entry point and 0.48 mm at the apical point. The angular deviations were respectively 3.05° and 2.19°. Conclusions From the results of this pilot study, it seems that AR can be useful in dental implantology for displaying dynamic navigation systems. While this technology did not seem to noticeably affect the accuracy of the procedure, specific software applications should further optimize the results.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.

Background Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing. Methods With minimally invasive oral brushing, 28 consecutive OSCC, one squamous cell carcinoma with sarcomatoid features, six high-grade squamous intraepithelial lesions (HGSIL), 30 normal contralateral mucosa from the same patients, and 65 healthy donors were evaluated for DNA methylation analyzing 18 target genes by quantitative bisulfite next-generation sequencing. We further evaluated an independent cohort (validation dataset) made of 20 normal donors, one oral fibroma, 14 oral lichen planus (OLP), three proliferative verrucous leukoplakia (PVL), and two OSCC. Results Comparing OSCC with normal healthy donors and contralateral mucosa in 355 CpGs, we identified the following epigenetically altered genes: ZAP70 , ITGA4 , KIF1A , PARP15 , EPHX3 , NTM , LRRTM1 , FLI1 , MIR193 , LINC00599 , PAX1 , and MIR137HG showing hypermethylation and MIR296 , TERT , and GP1BB showing hypomethylation . The behavior of ZAP70 , GP1BB , H19 , EPHX3 , and MIR193 fluctuated among different interrogated CpGs. The gap between normal and OSCC samples remained mostly the same (Kruskal-Wallis P values < 0.05), but the absolute values changed conspicuously. ROC curve analysis identified the most informative CpGs, and we correctly stratified OSCC and HGSIL from normal donors using a multiclass linear discriminant analysis in a 13-gene panel (AUC 0.981). Only the OSCC with sarcomatoid features was negative. Three contralateral mucosa were positive, a sign of a possible field cancerization. Among imprinted genes, only MIR296 showed loss of imprinting. DNMT1 , TERC , and H19 together with the global methylation of long interspersed element 1 were unchanged. In the validation dataset, values over the threshold were detected in 2/2 OSCC, in 3/3 PVL, and in 2/14 OLP. Conclusions Our data highlight the importance of CpG location and correct estimation of DNA methylation level for highly accurate early diagnosis of OSCC.

IntroductionTemporomandibular disorders (TMDs) are considered a collection of musculoskeletal conditions involving the masticatory muscles, the temporomandibular joint and associated structures. The myogenous group appears to represent the most frequently diagnosed category. In the context of a multimodal approach, splint therapy and musculoskeletal physiotherapy are often considered as a preferred therapy. The purpose of this study will be to investigate the effects of musculoskeletal physiotherapy combined with occlusal splint and education versus occlusal splint and education alone in the treatment of chronic myogenous TMD on pain and mandibular range of motion.Methods and analysisAll consecutive adults complaining of TMDs presented to the Department of Biomedical and Neuromotor Sciences of the University of Bologna will be considered eligible. Inclusion criteria shall be based on the presence of myogenous TMDs, as diagnosed through clinical examination in reference to the international diagnostic criteria of TMDs. Randomisation, concealed allocation, blinded assessment and intention-to-treat analysis will be employed. The splint therapy will consist of the use of the splint every night and concurrent delivery of an educational programme; the protocol shall have a duration of three consecutive months. The combined musculoskeletal physiotherapy, splint therapy and education will additionally consist of manual therapy techniques and exercise; such protocol shall consist of a duration of three consecutive months, inclusive of 10 sessions for the enhanced elements. All outcome measures will be collected at baseline, after treatment and at a 6 months follow-up.Ethics and disseminationEthical approval has been obtained from the Independent Ethic Committee in Clinical Research of AUSL Bologna-Italy (47/2018/SPER/AUSLBO). Pursuant to applicable rules,we will obtain informed consent from each participant and collect data anonymously to maintain privacy. Results will be disseminated to clinicians and researchers through peer-reviewed publications and conferences.Trial registration numberNCT03726060

Background: The aim is to assess the current evidence-based knowledge about treatment decisions for skeletal malocclusion in adult borderline patients. Methods: A literature search was conducted through three databases. Inclusion criteria were restricted to systematic reviews, prospective, retrospective, and control studies. Only articles comparing orthodontic camouflage and orthognathic surgical treatment for Class II and Class III malocclusions in adult patients were selected to be reviewed. Results: Seven articles concerning Class II and nine concerning Class III met the inclusion criteria. Scientific evidence was poor due to low methodological quality. Conclusions: Surgical treatment was found to better improve skeletal and soft-tissue cephalometric values, whereas camouflage treatment mainly involved dentoalveolar movements. Aesthetic changes, as perceived by the patient, were not significantly different in the two groups. Recently improved surgical techniques, differing from those described in the analyzed articles, may provide similar or more stable outcomes compared with orthodontic-only treatment. Although some cephalometric variables can be helpful, the most important parameters for treatment selection are the patient’s presenting complaint and their self-image perception. Further studies with larger sample sizes and similar pretreatment conditions, and considering patient self-evaluation of esthetics and function, should be undertaken.

ObjectivesThe aim of this study is to introduce a novel 3D cephalometric analysis (3DCA) and to validate its use in evaluating the reproducibility of virtual orthodontic-surgical planning (VOSP) in surgery-first approach (SF) comparing VOSP and post-operative outcome (PostOp). MethodsThe cohort of nineteen patients underwent bimaxillary orthognathic surgery following the VOSP designed in SimPlant O&O software by processing cone-beam computed tomography (CBCT) scans and intraoral digital scanning of the dental arches. Said records were re-acquired once the post-operative orthodontic treatment was completed. The 3DCA was performed by three expert operators on VOSP and PostOp 3D models. Descriptive statistics of 3DCA measures were evaluated, and outcomes were compared via Wilcoxon test. ResultsIn the comparison between cephalometric outcomes against planned ones, the following values showed significant differences: Wits Index, which suggests a tendency towards skeletal class III in PostOp (p = 0.033); decreased PFH/AFH ratio (p = 0.010); decreased upper incisors inclination (p < 0.001); and increased OVJ (p = 0.001). However not significant (p = 0.053), a tendency towards maxillary retroposition was found in PostOp (A/McNamara VOSP: 5.05 ± 2.64 mm; PostOp: 4.1 ± 2.6 mm). On average, however, when McNamara’s plane was considered as reference, a tendency to biprotrusion was found. Upper incisal protrusion was greater in PostOp as an orthodontic compensation for residual maxillary retrusion (VOSP: 5.68 ± 2.56 mm; PostOp: 6.53 ± 2.63 mm; p = 0.084). Finally, the frontal symmetry in relation to the median sagittal plane decreased in craniocaudal direction.LimitationsA potential limit of studies making use of closest point distance analysis is represented by the complexity that surgeons and orthodontists face in applying this three-dimensional evaluation of SF accuracy/predictability to everyday clinical practice and diagnosis. Also, heterogeneity and limited sample size may impact the results of the study comparison.ConclusionsThe presented 3DCA offers a valid aid in performing VOSP and analysing orthognathic surgery outcomes, especially in SF. Thanks to the cephalometric analysis, we found that surgery-first approach outcome unpredictability is mainly tied to the sagittal positioning of the maxilla and that the transverse symmetry is progressively less predictable in a craniocaudal direction.

Gnathodiaphyseal dysplasia (GDD) is an autosomal dominant syndrome characterized by frequent bone fractures at a young age, bowing of tubular bones and cemento-osseus lesions of the jawbones. Anoctamin 5 (ANO5) belongs to the anoctamin protein family that includes calcium-activated chloride channels. However, recent data together with our own experiments reported here add weight to the hypothesis that ANO5 may not function as calcium-activated chloride channel. By sequencing the entire ANO5 gene coding region and untranslated regions in a large Italian GDD family, we found a novel missense mutation causing the p.Thr513Ile substitution. The mutation segregates with the disease in the family and has never been described in any database as a polymorphism. To date, only two mutations on the same cysteine residue at position 356 of ANO5 amino-acid sequence have been described in GDD families. As ANO5 has also been found to be mutated in two different forms of muscular dystrophy, the finding of this third mutation in GDD adds clues to the role of ANO5 in these disorders.

Background Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. Methods A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. Results HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p  = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p  = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p  = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. Conclusions An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.