Single-Splint, 2-Jaw Orthognathic Surgery for Correction of Facial Asymmetry: 3-Dimensional Planning and Surgical Execution.

Three-dimensional (3D) planning of orthognathic surgery (OGS) improves the treatment of facial asymmetry and malocclusion, but no consensus exists among clinicians regarding technical details. This study verified the consistency of authors' workflow and strategies between 3D planning and surgical execution for facial asymmetry. This retrospective study recruited consecutive patients (n=54) with nonsyndromic facial asymmetry associated with malocclusion. The stepwise workflow included orthodontic treatment, 3D imaging-based evaluation, planning, and transferring the virtual of single-splint 2-jaw OGS to actual surgery in all patients. Seven landmark-based measurements were selected for postoperative assessment of facial symmetry. Fifty patients had no anesthetic/surgical-related episode and procedure-related complications. Others experienced wound infection (n=1), transient TMJ discomfort (n=1), and facial numbness (n=3). Two cases had minor residual asymmetry (cheek and chin, respectively), but did not request revisionary bone or soft tissue surgery. Comparisons between the planned and postoperative 3D images with quantitative measurement revealed acceptable outcome data. The results showed a significant increase in facial symmetry at 7 landmark-based postoperative measurements for both male and female. This 3D-assisted pathway of OGS permitted achievement of consistent satisfactory results in managing facial asymmetry, with low rate of complications and secondary management.

Bone marrow plasma level of decorin may be associated with improved treatment outcomes in a subset of multiple myeloma patients.

BACKGROUND/PURPOSE: Decorin is a small leucine-rich proteoglycan rich in extracellular matrix with potential antitumor activity. However, the role of decorin in hematological malignancies remains unclear, especially in the case of multiple myeloma (MM), a bone marrow (BM) stroma-dependent plasma cell neoplasm. METHODS: We measured decorin levels in BM plasma samples from 270 patients with newly diagnosed MM (NDMM) using enzyme-linked immunosorbent assays. RESULTS: Patients were divided into high decorin (H-DCN, > 18.99 ng/mL) and low decorin (L-DCN <9.76 ng/mL) groups. Patients in the H-DCN group had more advanced-stage disease, including more osteolysis terms of higher levels of C-terminal telopeptides of type I collagen (0.69 ± 0.55 vs. 0.49 ± 0.36 ng/mL; P = 0.028), than those in the L-DCN group. Decorin levels correlated positively with hepatocyte growth factor (HGF) levels in BM plasma samples from NDMM patients (Pearson correlation coefficient, 0.226; P < 0.001). Patients with low HGF (<0.79 ng/mL) but high decorin levels (≥12.95 ng/mL) had a higher treatment response rate (90.5% vs. 54.5%, respectively; P = 0.015) and improved overall survival (not reached vs. 53 months; P = 0.0148) than those with lower decorin levels (<12.95 ng/mL). Multivariate analysis confirmed that a high decorin level was an independent predictive factor for treatment response and survival in patients with low HGF levels. CONCLUSION: Our findings suggest that decorin may exert protective effects in this subset of MM patients.

Aesthetic Enhancement of the Vermilion Using Dermofat Graft in Patients With Cleft Lip Deformity.

BACKGROUND: There is an increasing patient expectation for better esthetics, manifesting through anatomical harmony, projection, and volume of the upper lip relative to the lower lip, in patients with cleft deformity. The aim of this study is to investigate the outcome of vermilion augmentation using autologous dermofat graft (DFG) to enhance the lip using both quantitative and qualitative assessment. METHODS: Patients with secondary cleft lip deformity who received the surgical treatment in our institution from 2015 to 2018 were recruited. Panel assessment was performed on standardized preoperative and postoperative digital photographs. A patient questionnaire was used for the reported outcome. Image processing and analyses were applied to measure the lip change. Statistical analyses were performed. RESULTS: A total of 91 patients were included. The mean age at operation was 22.7 years, and postoperative follow-up was 3.6 years. There were no complications in the study group. The panel assessment showed significant improvement (P < .00001) on upper lip vermilion in both frontal and lateral profile views. Ninety-five percent of patients reported improvement of the upper lip projection and volume. Quantitative image analysis showed an increase in the upper lip vermilion ratio in 97% of the cases in frontal views and improvement of the vermilion projection in 87% of the cases in the superimposed lateral views. CONCLUSIONS: The use of DFG is an effective and reproducible method for vermilion augmentation and aesthetic enhancement in patients presenting with upper lip insufficiency relative to the lower lip.

Three-Dimensional Computer-Assisted Orthognathic Surgery: Traditional Hybrid Versus Full Digital Planning Models.

PURPOSE: Three-dimensional (3D) computer-aided planning has truly revolutionized orthognathic surgery (OGS) treatment, but no study has compared the traditional hybrid and full 3D digital planning models. This study compared these virtual planning models in the treatment of asymmetric maxillomandibular disharmony. METHODS: Young adult patients with an asymmetric skeletal class III deformity who underwent 3D computer-aided 2-jaw OGS using hybrid (alginate dental impression, 2D cephalometric tracings, manual-guided stone model surgery, occlusion setup, and splint fabrication; n = 30) or full digital (laser-scanned dentition, 3D cephalometric tracings, virtual-based occlusion setup and surgery, and computer-generated surgical splint; n = 30) planning models were consecutively recruited. Preoperative and postoperative 3D cephalometric analyses (dental relation, skeletal assessments based on sagittal and frontal views, and soft tissue evaluations) were adopted for intragroup and intergroup comparisons. Postoperative patient-perceived satisfaction with facial appearance was also recorded. RESULTS: Both hybrid and full digital planning groups had significant (all P < 0.05) improvements after surgery with respect to facial convexity, incisor overjet, and frontal symmetry parameters. The full 3D digital planning-based OGS treatment had similar (all P > 0.05) 3D cephalometric-derived outcomes (preoperative, postoperative, and treatment-induced change data) and patient-perceived outcomes compared with the traditional hybrid 3D planning method. CONCLUSIONS: For the decision-making process in selecting the planning model, multidisciplinary teams could consider additional parameters such as patient comfort, storage needs, convenience for data reuse, overall planning time, availability, and costs.

Automatic Assessment of 3-Dimensional Facial Soft Tissue Symmetry Before and After Orthognathic Surgery Using a Machine Learning Model: A Preliminary Experience.

PURPOSE: An objective and quantitative assessment of facial symmetry is essential for the surgical planning and evaluation of treatment outcomes in orthognathic surgery (OGS). This study applied the transfer learning model with a convolutional neural network based on 3-dimensional (3D) contour line features to evaluate the facial symmetry before and after OGS. METHODS: A total of 158 patients were recruited in a retrospective cohort study for the assessment and comparison of facial symmetry before and after OGS from January 2018 to March 2020. Three-dimensional facial photographs were captured by the 3dMD face system in a natural head position, with eyes looking forward, relaxed facial muscles, and habitual dental occlusion before and at least 6 months after surgery. Three-dimensional contour images were extracted from 3D facial images for the subsequent Web-based automatic assessment of facial symmetry by using the transfer learning with a convolutional neural network model. RESULTS: The mean score of postoperative facial symmetry showed significant improvements from 2.74 to 3.52, and the improvement degree of facial symmetry (in percentage) after surgery was 21% using the constructed machine learning model. A Web-based system provided a user-friendly interface and quick assessment results for clinicians and was an effective doctor-patient communication tool. CONCLUSIONS: This work was the first attempt to automatically assess the facial symmetry before and after surgery in an objective and quantitative value by using a machine learning model based on the 3D contour feature map.

Outcome of full digital workflow for orthognathic surgery planning in the treatment of asymmetric skeletal class III deformity.

BACKGROUND/PURPOSE: Studies have reported the advantages of digital imaging-assisted orthognathic surgery planning, but there is scarce information about a full digital planning modality. This study evaluated the 3D cephalometric-based and patient-reported outcomes of a full digital workflow for orthognathic surgery planning in the treatment of asymmetric maxillomandibular disharmony. METHODS: A postoperative 3D image dataset of 30 Taiwanese Chinese patients with asymmetric skeletal Class III deformities who underwent full digital planning for two-jaw surgery were retrieved from the authors' database. The 3D cephalometric data (dental, skeletal, and soft tissue evaluations) were compared to the ethnicity-matched 3D cephalometric normative values. Patient-reported outcome measure tools regarding postoperative overall appearance and satisfaction with facial areas (ranging from 0 to 100 and 0 to 10, respectively) were administered. The number of needed or requested revisionary surgery was collected. RESULTS: No difference (all p > 0.05) was observed between the orthognathic-surgery-treated patients and the normative value for most of the tested 3D cephalometric parameters, with the exception (p < 0.05) of three mandible and occlusal-plane-related parameters. Both patient-reported outcome measure tools showed that patients' satisfaction with their postoperative appearance was high for overall face (89.7 ± 4.5) and specific facial regions (nose, 7.1 ± 1.3; lip, 8.3 ± 1.6; upper gum, 8.5 ± 1.2; cheek, 8.8 ± 1.1; chin, 9.2 ± 1.2; and teeth, 9.3 ± 0.8), with no need for revisionary surgery. CONCLUSION: The patients treated with a full 3D digital planning-assisted two-jaw surgery had a similar 3D dental relation, facial convexity, and symmetry compared to healthy ethnicity-matched individuals, and they reported higher satisfaction levels with their postoperative facial appearance results.

Maintaining the space between the mandibular ramus segments during bilateral sagittal split osteotomy does not influence the stability.

BACKGROUND/PURPOSE: Three-dimensional computer-assisted orthognathic surgery allows to simulate the space between the mandibular ramus segments, i.e. intersegmental gap, for the correction of facial asymmetry. The purposes of the study were to estimate the screws- and mandible bone-related changes from the early postoperative period to the period after the debonding and to measure the association between the intersegmental gap volume and the screws- and mandible bone-related changes. METHODS: This cone-beam computed tomography (CBCT)-assisted retrospective study assessed the stability of the bicortical positional screw fixations in maintaining the space between the mandibular ramus segments after bilateral sagittal split osteotomy in correction of 31 patients with malocclusion and facial asymmetry. The primary predictor variable was the CBCT-based intersegmental gap volume at early postoperative period (T1). The primary outcome variables were CBCT-based screws- and bone-related measurement changes between the T1 and T2 (at debonding) periods. RESULTS: No significant differences were observed in screws-related linear and angular measurements between T1 and T2 virtual models. Some of mandible bone-related linear and angular measurements had significant differences (P < 0.05) between the T1 and T2 images, but with no clinical repercussion such as need of revisionary surgery. The gap volume and the screws- and bone-related changes had no significant correlations. CONCLUSION: This study contributes to the multidisciplinary-related literature by demonstrating that the bicortical positional screws-based fixation technique in maintaining the three-dimensional-simulated space between the mandibular ramus segments is a stable and clinically acceptable option for correction of facial asymmetry associated with malocclusion, regardless of intersegmental gap size.

Fat Grafting in Patients With Extensive Unilateral Facial Deficiency: Three-Dimensional Computer-Assisted Planning, Implementation, and Outcome Assessment.

PURPOSE: Autologous fat injection is a widely used, simple, and less invasive technique to correct volume deficiency. This study developed a treatment method by using a 3-dimensional (3D) simulation to plan and implement fat injection in patients with an extensive facial deficiency and then validated the accuracy of the method and treatment outcomes. METHODS: Seven patients with a large unilateral facial deficiency receiving autologous fat grafts between 2015 and 2017 were recruited. One patient received repeated treatment. Furthermore, 3D surgical simulation was used to measure the difference between the mirrored image and lesion side. An extra 20% to 30% of fat graft was added. A color map was provided, and contour lines 2 mm deep marked the location of the fat injection. Outcome assessments were then performed, and a 3D symmetry index was defined using the contour lines on the facial surface. RESULTS: No significant difference was noted between the predicted volume and postoperative fat graft retention (35.7 ± 7.4 and 31.6 ± 9.7 mL, respectively; P = 0.176). A comparison of preoperative (79.5% ± 4.3%) and postoperative (89.0% ± 3.3%) 3D symmetry indexes indicated significantly improved facial symmetry (P = 0.018). Patient-reported outcomes of satisfaction on FACE-Q questionnaires yielded an average score of 62.73, higher than the control score (59.83). CONCLUSIONS: By using the proposed method, we could predict the required fat graft volume; moreover, the contoured map aided accurate surgical implementation. Thus, this method is useful for planning and guiding fat grafting treatment in patients with major unilateral facial deficiency.

Three-dimensional cephalometry for orthognathic planning: Normative data and analyses.

BACKGROUND/PURPOSE: The objective of this study was to create a normative database of 3D cephalometric measurements for adult Chinese in Taiwan to understand the specific features, as well as to provide information for 3-dimensional (3D) orthognathic surgery planning for patients with maxillofacial deformity. METHODS: A cross-sectional study was conducted on 30 male and 30 female adults with normal and balanced facial appearance, skeletal Class I pattern, and proper interincisal relationship with normal occlusion. Cone-beam computed tomography was performed. After standard orientation of the 3D image models, 51 landmarks were digitized and 3D cephalometric measurements of overall facial features, midface, maxilla, mandible, dentoalveolus, and soft tissue were performed and analyzed. RESULTS: Reliability and reproducibility of the 3D measurement were achieved. The data showed significant differences between males and females in facial height ratio, midface prominence, midface and maxilla width, mandible width and length for the skeleton, lower incisal inclination and interincisal angle for the dentoalveolus, and lip height, facial height and chin throat angle for the soft tissue. These dataset presented specific facial characteristics of the Chinese face as compared with other populations. CONCLUSION: The normative data helps to serve as a guide for maxillofacial treatment for globally ethnic Chinese, particularly useful for orthodontic treatment, 3D planning of orthognathic surgery and outcome assessment. Gender and ethnic differences need to be taken into consideration.

Using marker gene analysis instead of mixed lymphocyte reaction assay for identification of functional CD4+FOXP3+ regulatory T cells.

OBJECTIVE: To establish a quick analytical method using quantitative PCR for marker gene analysis to identify the functions of iTreg cells and subsequently curtail the harvest time for iTreg cells. RESULTS: The data from the marker gene analysis indicated that varying proportions of iTreg cells could reveal the various expression levels of these genes. FoxP3 expression increased to a considerable degree. By using the same iTreg population, the mixed lymphocyte reaction assay was conducted for 5 days. The suppression percentage of T-cells was dependent on the proportion of iTreg cells, indicating that gene expression levels can represent the biological functions of iTreg cells. By using human peripheral blood mononuclear cells for Treg cell induction, the marker gene expression analysis showed a difference between iTreg cells and uninduced T cells. CONCLUSION: Marker gene analysis requires only 1 day to identify the functions of human iTreg cells can save time in clinical application and might prevent graft-versus-host disease occurrence effectively.

3D printing in orthognathic surgery - A literature review.

With the recent advances in three-dimensional (3D) imaging, computer-assisted surgical planning and simulation are now regularly used for analysis of craniofacial structures and improved prediction of surgical outcomes in orthognathic surgery. A variety of patient-specific surgical guides and devices have been designed and manufactured using 3D printing technology, which rapidly gained widespread popularity to improve the outcomes. The article presents an overview of 3D printing technology for state-of-the-art application in orthognathic surgery and discusses the impacts on treatment feasibility and patient outcome. The current available literature regarding the use of 3D printing methods in orthognathic surgery including 3D computer-aided design/computer-aided manufacturing, rapid prototyping, additive manufacturing, 3D printing, 3D printed models, surgical occlusal splints, custom-made guides, templates and fixation plates is reviewed. A Medline, PubMed, ProQuest and ScienceDirect search was performed to find relevant articles over the past 10 years. A total of 318 articles were found, out of which 69 were publications addressing the topic of this study. An additional 9 hand-searched articles were added. From the review, we can conclude that the use of 3D printing methods in orthognathic surgery provide the benefit of optimal functional and aesthetic results, patient satisfaction, and precise translation of the treatment plan.

Establishment of a Reliable Horizontal Reference Plane for 3-Dimensional Facial Soft Tissue Evaluation Before and After Orthognathic Surgery.

BACKGROUND: This study aims to demonstrate the reliability of our proposed facial reference system in the horizontal axis using 3-dimensional photogrammetry and to find a correlation between this plane and the Frankfurt horizontal (FH) plane. METHODS: Forty-one patients were enrolled. Three-dimensional facial images were taken before and 6 months after orthognathic surgery. Superimposition was carried out, and differences in landmark position were evaluated. Two constant landmarks were selected to construct a reference system within a standardized reference frame. Cone-beam computed tomography and 3-dimensional facial images were superimposed. Two reference lines were identified, and the angle between these lines was calculated. RESULTS: For landmark reliability, 5 landmarks [gnathion, nasion, exocanthion (Ex), endocanthion, and tragion (T)] were constant. Two landmarks (Ex and T) were selected to construct a reference system within a standardized reference frame. For angular measurement, the mean angle between this reference plane and the skeletal FH plane was 17.6 ± 2.0 degrees. There was no statistical difference between sex, side, and preoperative/postoperative timing of photography. CONCLUSIONS: Our proposed reference plane is constructed from reliable facial Ex and T landmarks. This plane is consistent and crosses the FH plane at 17.6 degrees.

Higher Dose of Dexamethasone Does Not Further Reduce Facial Swelling After Orthognathic Surgery: A Randomized Controlled Trial Using 3-Dimensional Photogrammetry.

PURPOSE: The objective of this prospective, double-blind, randomized clinical trial was to compare the effect of 2 dexamethasone dosages on reducing facial swelling after orthognathic surgery through 3-dimensional (3D) photogrammetry. PATIENTS AND METHODS: Patients were classified into group 1 (control group) and group 2 (study group), depending on the administered dexamethasone dosage (5 and 15 mg, respectively). Three-dimensional images were recorded at 5 time points: preoperative (T0) and postoperative at 48 ± 6 hours (T1), 1 week (T2), 1 month (T3), and 6 months (T4). A preliminary study was performed on 5 patients, in whom 3D images were captured at 24, 36, 48, and 60 hours postoperatively to record serial changes in facial swelling. Facial swelling at T1, T2, and T3 and the reduction in swelling at T2 and T3 compared with that at the baseline (T4) were calculated. Possible complications, namely, adrenal suppression, wound dehiscence, wound infection, and postoperative nausea and vomiting were evaluated. RESULTS: In total, 68 patients were enrolled, of whom 25 patients in group 1 and 31 patients in group 2 were eligible for final evaluation. No significant differences were found between the 2 groups at any period. On average, the swelling subsided by 86% at 1 month after the orthognathic surgery. Facial swelling peaked approximately 48 hours after the surgery. The incidence of nausea and vomiting did not differ significantly between the groups. CONCLUSIONS: The effect of 5 and 15 mg of dexamethasone on facial swelling reduction as well as on nausea and vomiting after orthognathic surgery was not significantly different.

A Modified Technique of Mandibular Ramus Sagittal Split Osteotomy for Prevention of Inferior Alveolar Nerve Injury: A Prospective Cohort Study and Outcome Assessment.

BACKGROUND: Postoperative functional impairment of the inferior alveolar nerve (IAN) has been a common and well-recognized complication. Our study introduced a modified Obwegeser-Dal Pont bilateral sagittal split osteotomy (BSSO) technique and evaluated the subsequent incidence of postoperative neurosensory disturbance of IAN. METHODS: In this prospective cohort study, 57 patients receiving our modified BSSO during orthognathic surgery were enrolled. The technique contained opening the 2 ramus cortices and inserting the osteotome bypassing the IAN to avoid nerve injury. A 5-point scale self-assessment questionnaire was used to evaluate IAN neurosensory disturbance one week, six months and 12 months postoperatively. Differences between groups were analyzed using χ test for categorical and Wilcoxon signed-rank test for pairwise categorical data. RESULTS: Complete ramus splitting could be achieved in 109 (95.6%) sides. Lower lip or chin neurosensory disturbances presented in 72 (63.2%) sides 1 week postoperatively and gradually reduced to 9 (7.9%), and 4 (3.5%) at postoperative months 6 and 12, respectively. CONCLUSIONS: This BSSO technique could be safely performed with low rates of IAN exposure and injury and a low incidence of persistent neurosensory disturbance in 3.5% of patients 12 months postoperatively.

Three-dimensional computer-assisted orthognathic surgery: experience of 37 patients.

PURPOSE: Three-dimensional computer-assisted orthognathic surgery has been applied to improve planning and outcome. This study presents our experience with this promising modality for simulation of surgery, prefabrication of positioning guides, and navigation of the surgery. METHODS: Thirty-seven patients who received surgical simulation and intraoperative navigation for 2-jaw orthognathic surgery were recruited. Preoperative 3-dimensional cone-beam computed tomographic images were used for surgical simulation and design of intraoperative guidance. An initial surgical plan was developed and transferred for 3-dimensional virtual surgery. Modification of the surgical plan was made if facial symmetry and skeletal harmony or collision of ramus segments were concerned. The result of virtual surgery was used to design and manufacture positioning guides and perform preoperative navigation planning. During the operation, the positioning guides were used to transfer the virtual planning to actual surgery, and a real-time navigation system was used to confirm the predetermined position of the maxillomandibular complex. For assessment of the computer-assisted surgical system, the simulation image was superimposed to the postoperative image for comparison. RESULTS: The computer-assisted orthognathic surgery was successfully carried out in all patients. The initial surgical plan was modified in 17 patients in whom the position of maxillomandibular complex was changed. The positioning guides were helpful in controlling the spatial position of the maxillomandibular complex. The BrainLabTR navigation system was useful to further confirm the position of the facial bone. Superimposition of the simulation and postoperative images revealed satisfactory result with acceptable errors. The difference ranged from 0.05 to 1.46 mm, with a mean value of 0.66 mm, for patients using the positioning guides; and the difference ranged from 0.07 to 2.30 mm, with a mean value of 1.20 mm, for patients using the navigation system. Overall, patient and doctor satisfaction was high. CONCLUSION: This computer-assisted orthognathic surgery system helps to improve surgical planning, reduce surgical difficulty, facilitate positioning and fixation of the maxillomandibular complex, and improve outcome.

Three-dimensional computer-assisted surgical simulation and intraoperative navigation in orthognathic surgery: a literature review.

By incorporating three-dimensional (3D) imaging and computer-aided design and manufacturing techniques, 3D computer-assisted technology has been applied widely to provide accurate guidance for assessment and treatment planning in clinical practice. This technology has recently been used in orthognathic surgery to improve surgical planning and outcome. The modality will gradually become popular. This study reviewed the literature concerning the use of computer-assisted techniques in orthognathic surgery including surgical planning, simulation, intraoperative translation of the virtual surgery, and postoperative evaluation. A Medline, PubMed, ProQuest, and ScienceDirect search was performed to find relevant articles with regard to 3D computer-assisted orthognathic surgery in the past 10 years. A total of 460 articles were revealed, out of which 174 were publications addressed the topic of this study. The purpose of this article is to present an overview of the state-of-art methods for 3D computer-assisted technology in orthognathic surgery. From the review we can conclude that the use of computer-assisted technique in orthognathic surgery provides the benefit of optimal functional and aesthetic results, patient satisfaction, precise translation of the treatment plan, and facilitating intraoperative manipulation.

Nasal changes after orthognathic surgery for patients with prognathism and Class III malocclusion: analysis using three-dimensional photogrammetry.

BACKGROUND/PURPOSE: Orthognathic surgery alters the position of maxilla and mandible, and consequently changes the nasal shape. The nasal change remains a concern to Asian patients. The aim of this study was to measure the nasal changes using a novel three-dimensional photographic imaging method. METHODS: A total of 38 patients with Class III malocclusion and prognathism were enrolled. All patients underwent two-jaw surgery with the standard technique. A nasal alar cinching suture was included at the end of procedure. Facial landmarks and nasal morphology were defined and measured from pre- and postoperative three-dimensional photographic images. Intra-rater errors on landmark identification were controlled. Patient's reports of perceptual nasal changes were recorded. RESULTS: The average width of the alar base and subalare remained similar after surgery. Alar width was increased by 0.74 mm. Nasal height and length remained the same. Nasolabial angle increased significantly. The area of nostril show revealed a significant increase and was correlated with a decrease of columella inclination. Nasal tip projection decreased significantly, by 1.99 mm. Preoperative nasal morphology was different between patients with and without cleft lip/palate, but most nasal changes were concordant. In the self-perception, 37% of patients reported improved nasal appearance, 58% reported no change, and 5% were not satisfied with the nasal changes. CONCLUSION: After the surgery, characteristic nasal changes occurred with an increase of nasolabial angle and nostril show, but a preserved nasal width. The majority of patients did not perceive adverse nasal changes.

Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma.

Cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide. However, the clinical implications of CRBN in MM patients are unclear. Using immunohistochemical (IHC) staining on paraffin-embedded bone marrow sections, the expression of CRBN protein in myeloma cells (MCs) was assessed in 40 relapsed/refractory MM (RRMM) patients who received lenalidomide/dexamethasone (LD) and 45 and 22 newly diagnosed MM (NDMM) patients who received thalidomide/dexamethasone (TD) and melphalan/bortezomib/prednisolone (MVP), respectively. IHC staining were scored on a scale representing the diffuseness and intensity of positive-staining MCs (range, 0-8) and a score ≥4.5 was used for CRBN positivity (CRBN(+)) on a cut-point analysis of all possible scores and response of TD and LD. Compared to CRBN(+) NDMM patients, CRBN(-) NDMM patients had more international staging system (ISS) III (26 vs. 61 %, respectively; P = 0.006). In the LD and TD cohorts, the response rate (RR) was higher in CRBN(+) patients than CRBN(-) patients (LD 79 vs. 33 %, respectively; P = 0.005) (TD 75 vs. 29 %, respectively; P = 0.005); however, this trend was not observed in the MVP cohort. In the LD and TD cohorts, the positive and negative prediction value of CRBN(+) for treatment response was 79 and 67 % and 75 and 71 %, respectively. Multivariate analysis showed that CRBN(+) was a significant factor associated with superior RR for LD and TD. The data suggest that expression of CRBN protein in MCs assessed using the IHC is a feasible approach to predict the response of IMiDs in MM patients.

Average Three-Dimensional Skeletofacial Model as a Template for Bone Repositioning during Virtual Orthognathic Surgery.

BACKGROUND: Virtual planning has revolutionized orthognathic surgery. This study presents a computer-assisted method for constructing average three-dimensional skeletofacial models that can be applied as templates for surgical planning for maxillomandibular repositioning. METHODS: The authors used the images of 60 individuals (30 women and 30 men) who had never undergone orthognathic surgery to construct an average three-dimensional skeletofacial model for male participants and one for female participants. The authors validated the accuracy of the newly developed skeletofacial models by comparing their images with 30 surgical simulation images (ie, skulls) that had been created using three-dimensional cephalometric normative data. The comparison was conducted by superimposing surgical simulation images created using the authors' models with the previously created images to analyze their differences, particularly differences in the jawbone position. RESULTS: For all participants, the authors compared the jaw position in the surgical simulation images created using the authors' average three-dimensional skeletofacial models with that in the images created using three-dimensional cephalometric normative data. The results revealed that the planned maxillary and mandibular positions were similar in both images and that the differences between all facial landmarks were less than 1 mm, except for one dental position. Most studies have reported less than 2 mm to be the success criterion for the distance difference between planned and outcome images; thus, the authors' data indicate high consistency between the images in terms of jawbone position. CONCLUSION: The authors' average three-dimensional skeletofacial models provide an innovative template-assisted orthognathic surgery planning modality that can enhance the fully digital workflow for virtual orthognathic surgical planning. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Artifact-resistant superimposition of digital dental models and cone-beam computed tomography images.

PURPOSE: Combining the maxillofacial cone-beam computed tomography (CBCT) model with its corresponding digital dental model enables an integrated 3-dimensional (3D) representation of skeletal structures, teeth, and occlusions. Undesired artifacts, however, introduce difficulties in the superimposition of both models. We have proposed an artifact-resistant surface-based registration method that is robust and clinically applicable and that does not require markers. MATERIALS AND METHODS: A CBCT bone model and a laser-scanned dental model obtained from the same patient were used in developing the method and examining the accuracy of the superimposition. Our method included 4 phases. The first phase was to segment the maxilla from the mandible in the CBCT model. The second phase was to conduct an initial registration to bring the digital dental model and the maxilla and mandible sufficiently close to each other. Third, we manually selected at least 3 corresponding regions on both models by smearing patches on the 3D surfaces. The last phase was to superimpose the digital dental model into the maxillofacial model. Each superimposition process was performed twice by 2 operators with the same object to investigate the intra- and interoperator differences. All collected objects were divided into 3 groups with various degrees of artifacts: artifact-free, critical artifacts, and severe artifacts. The mean errors and root-mean-square (RMS) errors were used to evaluate the accuracy of the superimposition results. Repeated measures analysis of variance and the Wilcoxon rank sum test were used to calculate the intraoperator reproducibility and interoperator reliability. RESULTS: Twenty-four maxilla and mandible objects for evaluation were obtained from 14 patients. The experimental results showed that the mean errors between the 2 original models in the residing fused model ranged from 0.10 to 0.43 mm and that the RMS errors ranged from 0.13 to 0.53 mm. These data were consistent with previously used methods and were clinically acceptable. All measurements of the proposed study exhibited desirable intraoperator reproducibility and interoperator reliability. Regarding the intra- and interoperator mean errors and RMS errors in the nonartifact or critical artifact group, no significant difference between the repeated trials or between operators (P < .05) was observed. CONCLUSIONS: The results of the present study have shown that the proposed regional surface-based registration can robustly and accurately superimpose a digital dental model into its corresponding CBCT model.