Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.

Which Skeletal Factors Can Affect Lip Canting in Facial Asymmetry?: Statistical Analysis.

Lip canting, which is a noticeable factor in patients with facial asymmetry, can be influenced by the dentofacial skeleton. During orthognathic surgery, postoperative changes in facial soft tissue occur along the newly positioned hard tissue. Therefore, the evaluation of soft tissue before surgery is important. The purpose of this study was to investigate the skeletal factors that can affect lip canting by statistically comparing 2 facial horizontal planes using a three-dimensional reconstruction model. The findings of the present study showed a statistical correlation between lip canting and 3 skeletal factors: menton deviation, maxillary canting, and ramal length differences. Furthermore, a statistical correlation was identified between the Frankfort Horizontal plane and the intercanthal plane compared with the lip canting line. This result suggests that the intercanthal plane could be a standard horizontal plane in three-dimensional reconstruction model analysis.

Automatic identification of posteroanterior cephalometric landmarks using a novel deep learning algorithm: a comparative study with human experts.

This study aimed to propose a fully automatic posteroanterior (PA) cephalometric landmark identification model using deep learning algorithms and compare its accuracy and reliability with those of expert human examiners. In total, 1032 PA cephalometric images were used for model training and validation. Two human expert examiners independently and manually identified 19 landmarks on 82 test set images. Similarly, the constructed artificial intelligence (AI) algorithm automatically identified the landmarks on the images. The mean radial error (MRE) and successful detection rate (SDR) were calculated to evaluate the performance of the model. The performance of the model was comparable with that of the examiners. The MRE of the model was 1.87 ± 1.53 mm, and the SDR was 34.7%, 67.5%, and 91.5% within error ranges of < 1.0, < 2.0, and < 4.0 mm, respectively. The sphenoid points and mastoid processes had the lowest MRE and highest SDR in auto-identification; the condyle points had the highest MRE and lowest SDR. Comparable with human examiners, the fully automatic PA cephalometric landmark identification model showed promising accuracy and reliability and can help clinicians perform cephalometric analysis more efficiently while saving time and effort. Future advancements in AI could further improve the model accuracy and efficiency.

Effects of the Mandibular Functional Units and Soft Tissue on Facial Asymmetry.

Mandibular asymmetry has a variety of patterns because they are affected the position and the shape of mandible in addition to the overlying soft tissue. This study aimed to assess the factor in mandibular asymmetry, focusing on each mandibular functional units and the soft tissue thickness in the mandibular angle area. Forty patients who were diagnosed with facial asymmetry and undergone the orthognathic surgery without genioplasty were enrolled in this study. The skeletal patterns of the patients were analyzed by using cone-beam computed tomography data and 3D virtual images divided into 2 categories; the mandibular functional unit length and the soft tissue depth. All difference in bilateral mandibular functional unit lengths had a statistically significant with chin top deviation ( P <0.05). The greatest correlation was the condylar unit length compared with other functional units. The soft tissue thickness in the mandibular angle area was not statistically related to chin top deviation ( P >0.05), and the soft tissue did not change remarkably after orthognathic surgery ( P >0.05). This study suggests that the considerations of a surgical plan for treatment based on the mandibular asymmetry.

Transcriptomic Comparison Analysis between Ameloblastoma and AM-1 Cell Line.

Cancer initiation and progression are profoundly along with the crosstalk between cancer cells and the surrounding stroma. Accumulating evidence has shown that the therapy targeting the extracellular matrix (ECM) would regress tumor growth and invasion in the most common carcinomas. However, it remains largely unexplored in several rare tumors like odontogenic tumors. Ameloblastoma (AM) is the representative odontogenic epithelial tumor in the jawbone, and it usually infiltrates into adjacent bone marrow and has unlimited growth capacity and a high potential for recurrence. This study aims to investigate the role of collagen-rich ECM during the invasion of AM. Transcriptomic analysis revealed that ECM- and epithelial-to-mesenchymal transition (EMT)-related genes were up-regulated in AM compared to ameloblastoma cell line, AM-1. Tumoroid forming analysis showed that Collagen-rich ECM is indispensable for AM progression, especially for aggressive growth patterns and collective invasion.

Unraveled roles of Cav1.2 in proliferation and stemness of ameloblastoma.

BACKGROUND: Transcriptome analysis has been known as a functional tool for cancer research recently. Mounting evidence indicated that calcium signaling plays several key roles in cancer progression. Despite numerous studies examining calcium signaling in cancer, calcium signaling studies in ameloblastoma are limited. RESULTS: In the present study, comparative transcriptome profiling of two representative odontogenic lesions, ameloblastoma and odontogenic keratocyst, revealed that Cav1.2 (CACNA1C, an L-type voltage-gated calcium channel) is strongly enriched in ameloblastoma. It was confirmed that the Ca2+ influx in ameloblastoma cells is mainly mediated by Cav1.2 through L-type voltage-gated calcium channel agonist and blocking reagent treatment. Overexpression and knockdown of Cav1.2 showed that Cav1.2 is directly involved in the regulation of the nuclear translocation of nuclear factor of activated T cell 1 (NFATc1), which causes cell proliferation. Furthermore, a tumoroid study indicated that Cav1.2-dependent Ca2+ entry is also associated with the maintenance of stemness of ameloblastoma cells via the enhancement of Wnt/ß-catenin signaling activity. CONCLUSION: In conclusion, Cav1.2 regulates the NFATc1 nuclear translocation to enhance ameloblastoma cell proliferation. Furthermore, Cav1.2 dependent Ca2+ influx contributes to the Wnt/ß-catenin activity for the ameloblastoma cell stemness and tumorigenicity. Our fundamental findings could have a major impact in the fields of oral maxillofacial surgery, and genetic manipulation or pharmacological approaches to Cav1.2 can be considered as new therapeutic options.

Personalized 3D-printed Titanium Cutting Guide and Prefabricated Osteosynthesis Plate for Mandibular Step Osteotomy to Treat Severe Mandibular Prognathism.

Mandibular step osteotomy, performed for mandibular prognathism, is a difficult and time-consuming procedure. Virtual computer surgery and computer-aided design & computer-aided manufacturing have demonstrated accurate results in orthognathic surgery, though not used for mandibular step osteotomy yet. In this study, the authors report the case of a 21-year-old man with severe mandibular prognathism, with a reverse overjet of 12 mm. Step osteotomy, a modified method of body osteotomy, was planned virtually and performed using 3-dimensional (3D) printed titanium surgical guides and osteosynthesis plates, using computer-aided design & computer-aided manufacturing. At the 6-month postoperative follow-up, there were no notable complications, and normal healing was observed. Each segment was stably in place with the prefabricated plates. The proximal segments were not sagged medially or laterally. With 3D-printed surgical guides and osteosynthesis plates, intraoperative complications, such as injury to adjacent teeth and nerves, could be avoided. They also showed reasonable accuracy and helped reduce operative time and improve outcomes. Unlike surgical guides made of resin/polyamide, titanium surgical guides can be made thinner, which can reduce the extent of detachment. They also did not undergo any deterioration during the operation. Cutting guides and prefabricated plates using virtual surgical planning and 3D printing have many advantages, including reduced preoperative preparation time and operative time, reduced incidence of intraoperative complications, and improved outcomes. However, limitations still exist and further studies are required.

Inhibition of L-type voltage-gated calcium channel-mediated Ca2+ influx suppresses the collective migration and invasion of ameloblastoma.

OBJECTIVES: Ameloblastoma (AM) has been known as a benign but locally invasive tumour with high recurrence rates. Invasive behaviour of the AM results in destruction of the adjacent jawbone and the non-detectable remnants during surgery, interrupting the complete elimination of cancer cells. METHODS: To explore novel targets for the tumour cell invasion, a transcriptomic analysis between AM and odontogenic keratocyst were performed through next-generation sequencing in detail. RESULTS: Enrichment of CACNA1C gene (encoding Cav1.2) in AM, a subunit of the L-type voltage-gated calcium channel (VGCC) was observed for the first time. The expression and channel activity of Cav1.2 was confirmed by immunostaining and calcium imaging in the patient samples or primary cells. Verapamil, L-type VGCC blocker revealed suppression of the Ca2+ -induced cell aggregation and collective invasion of AM cells in vitro. Furthermore, the effect of verapamil in suppressing AM invasion into the adjacent bone was confirmed through orthotopic xenograft model specifically. CONCLUSION: Taken together, Cav1.2 maybe considered to be a therapeutic candidate to decrease the collective migration and invasion of AM.

Ameloblastoma modifies tumor microenvironment for enhancing invasiveness by altering collagen alignment.

Tumor progression is profoundly affected by crosstalk between cancer cells and their stroma. In the past decades, the development of bioinformatics and the establishment of organoid model systems have allowed extensive investigation of the relationship between tumor cells and the tumor microenvironment (TME). However, the interaction between tumor cells and the extracellular matrix (ECM) in odontogenic epithelial neoplasms and the ECM remodeling mechanism remain unclear. In the present study, transcriptomic comparison and histopathologic analysis revealed that TME-related genes were upregulated in ameloblastoma compared to in odontogenic keratocysts. Tumoroid analysis indicated that type I collagen is required for ameloblastoma progression. Furthermore, ameloblastoma shows the capacity to remodel the ECM independently of cancer-associated fibroblasts. In conclusion, ameloblastoma-mediated ECM remodeling contributes to the formation of an invasive collagen architecture during tumor progression.

Reliability of Anterior Nasal Spine as a Reference Point After LeFort I Surgery Using Three-Dimensional Analysis.

ABSTRACT: To evaluate the stability of maxilla following orthognathic surgery, it is necessary to consider the positional change of various landmarks according to bone remodeling of the maxilla. This study aimed to evaluate the stability of the anterior nasal spine (ANS) as a reliable landmark after orthognathic surgery. Forty-seven patients with skeletal class III malocclusion who underwent bimaxillary orthognathic surgery were included. Skeletal changes were measured using cone-beam computerized tomography at 3 time points: preoperative (T0), 1-month postoperative (T1), and 12-month postoperative (T2). Linear changes of the 6 landmark points of the maxilla were measured in 3 directions: anteroposterior, vertical, and transverse. The data were analyzed with paired t tests, independent t tests, and multiple regression analysis. At 12-month postoperatively, the ANS showed mean (standard deviation) 1.23 (1.07) mm posterior movement ( P = 0.00), while other landmarks did not show positional changes, implying bony resorption of ANS. Multiple regression test showed surgical forward movements of ANS (T1-0) affect the postoperative backward changes (ß = -0.05, P < 0.05). There was a negative correlation between the surgical movement and postoperative change of ANS by Pearson correlation test ( r = -0.38, P < 0.05). The ANS is not a reliable measurement point in three-dimensional superimposition after orthognathic surgery. Therefore, in studying the stability and positional change pattern after LeFort I surgery, it is not recommended to use ANS as a reference point, as changes can occur in the measurement point itself.

Predictors of Blood Loss During Orthognathic Surgery and the Need for Pre-Deposit Autologous Blood Donation.

ABSTRACT: The aim of this study was to identify the clinicolaboratory predictors of relative blood loss (RBL) during orthognathic surgery and determine the need for predeposit autologous blood donation (PABD) for the surgery. Using a retrospective study design, 297 patients who underwent bimaxillary orthognathic surgery between 2016 and 2020 were enrolled. To investigate patient-specific risk factors, we calculated the allowable blood loss (ABL) for each patient and RBL as the ratio of estimated intraoperative blood loss (EiBL) to ABL. The correlations between the clinico-laboratory variables and EiBL and RBL were analyzed using stepwise multivariate regression analysis, and independent t test and one-way ANOVA were performed.There was no significant difference in transfusion rate between the PABD group (N = 202/279) and non-PABD group (N = 77/279) ( P   =  0.052). Sex ( P   <  0.001), body mass index class ( P   =  0.001), operative time ( P  < 0.001), and baseline hematocrit ( P  < 0.001) were significant predictors of EIBL and RBL. EIBL exceeded ABL in only 2 patients. The significant factors of RBL in orthognathic surgery were hematocrit, body mass index, and operative time. Clinicians should be more careful about bleeding in patients with low baseline hematocrit level or high body mass index, or those expected to undergo prolonged surgeries owing to a complicated surgical plan. The need for PABD before orthognathic surgery is low.

Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma.

OBJECTIVES: The treatment of ameloblastoma, an odontogenic epithelial tumour destroying jawbone, mainly depends on radical destructive resections. Other therapeutic options are limited by the characteristics of ameloblastoma, such as high recurrence rates and resistance to radiation and chemotherapy, which implies possible existence of cancer stem cells (CSCs) in ameloblastoma. Here, we identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population. METHODS: We investigated subpopulations of AM-1 cell line and human ameloblastoma cells using immunocytochemistry and flow cytometry and the effects of Wnt signalling activators on the 2- and 3-dimensional cultured ameloblastoma cells using molecular biological analyses. RESULT: Among heterogenous ameloblastoma cells, small-sized and round-shaped cells were found to be proliferative and expressed a marker of dental epithelial stem cells, SRY-box 2 (Sox2). Exogenous activation of Wnt signalling using glycogen synthase kinase 3ß inhibitors, lithium chloride (LiCl) and valproic acid (VPA), increased the cell size and decreased proliferation of cells and expression of Sox2 in 2 dimensionally cultured AM-1 and human primary ameloblastoma cells. Furthermore, the growth of 3 dimensionally cultured AM-1 cells as suspended or embedded in gel was suppressed by treatment with Wnt signalling activators, VPA and CHIR99021, or antibodies to sclerostin, an antagonist of Wnt signalling. CONCLUSION: We suggest that Wnt signalling activators are potential drug candidates to suppress CSCs in ameloblastoma.

Surgical-orthodontic treatment for severe malocclusion in a patient with osteopetrosis and bilateral cleft lip and palate.

Orthognathic surgery in patients with craniofacial osteopetrosis, a condition associated with osteoclast dysfunction, is usually avoided because of the risk of osteomyelitis. A 19-year-old woman presented with the chief complaint of severe malocclusion and anterior crossbite. After radiographic evaluation, craniofacial osteopetrosis was diagnosed. Surgical-orthodontic treatment was performed after meticulous history taking and verification of normal bone turnover using bone-metabolism markers for endocrine evaluation. Favorable esthetic and functional outcomes were achieved.

The best options in superior capsular reconstruction.

Irreparable massive rotator cuff tears cause pain, loss of function, and a decrease in range of motion, which cause serious disturbances in daily life. Young patients, in particular, are active and have relatively high functional requirements, and their surgical options are limited. Superior capsular reconstruction (SCR) was first proposed for irreparable massive rotator cuff tears, good clinical results have been reported in short-term follow up. Since then, SCR has been used increasingly worldwide for irreparable massive rotator cuff tears, and various studies have been published on clinical outcomes, biomechanical outcomes, surgical techniques, and graft types. This article reviews the optimal graft and surgical options for improving clinical outcomes in SCR.

Changes in Cellular Regulatory Factors before and after Decompression of Odontogenic Keratocysts.

Decompression followed by enucleation, which is one of the treatments used for odontogenic keratocysts (OKCs), is frequently used in OKC lesions of large sizes. This method offers the advantage of minimizing the possibility of sensory impairment without creating a wide-range bone defect; moreover, the recurrence rate can be significantly lower than following simple enucleation. This study aimed to assess the changes in histology and expression of proliferation markers in OKCs before and after decompression treatment. A total of 38 OKC tissue samples from 19 patients who had undergone decompression therapy were examined morphologically and immunohistochemically to observe changes in proliferative activity before and after decompression. The markers used for immunohistochemistry (IHC) staining were Bcl-2, epidermal growth factor receptor (EGFR), Ki-67, P53, PCNA, and SMO. The immunohistochemistry positivity of the 6 markers was scored by using software ImageJ, version 1.49, by quantifying the intensity and internal density of IHC-stained epithelium. The values of Bcl-2, Ki-67, P53, proliferating cell nuclear antigen (PCNA), and SMO in OKCs before and after decompression showed no significant change. No correlation between clinical shrinkage and morphologic changes or expression of proliferation and growth markers could be found. There was no statistical evidence that decompression treatment reduces potentially aggressive behavior of OKC within the epithelial cyst lining itself. This might indicate that decompression does not change the biological behavior of the epithelial cyst lining or the recurrence rate.

Retained Foreign Body Which Should be Suspected as a Cause of Retractable Chronic Hand Inflammation and Diagnostic Capacity of Ultrasonography.

Background: Foreign bodies in the hand are common but easily and often missed in the initial evaluation of injury. Diagnosing retained foreign bodies is difficult due to radiolucent foreign bodies. Purpose of this study is to emphasize the need of consideration of foreign bodies in patients with chronic synovitis in hand. Methods: Twenty-five patients who had retained foreign body in soft tissue of hand with chronic inflammation symptoms were included. Ultrasonography was conducted in all of the patients. Patient age, sex, localization of foreign body, duration of symptom, history of injury, follow up period, complication, and biopsy results were recorded and reviewed. Also, patients' demographics and clinical results were retrospectively reviewed. Results: Nine of the 25 patients diagnosed with a foreign body in the hand did not remember the initial presentation of injury. The average symptom duration (from injury to hospitalization) was 10.5 months (range 1-96 months). The middle finger and the proximal interphalangeal joint were the most common site of a retained foreign body (10 patients). All patients were diagnosed via ultrasonography and underwent surgery. Biopsy results showed mainly chronic inflammation, fibrosis, granuloma, and foreign bodies. Conclusions: Patient with symptoms of cellulitis, osteomyelitis, and palpable mass in hand for over a month without a diagnosis should be suspected of retained FBs.

Stability of bimaxillary surgery involving intraoral vertical ramus osteotomy with or without presurgical miniscrew-assisted rapid palatal expansion in adult patients with skeletal Class III malocclusion.

OBJECTIVE: The aim of this study was to evaluate the stability of bimaxillary surgery involving bilateral intraoral vertical ramus osteotomy performed with or without presurgical miniscrew-assisted rapid palatal expansion (MARPE) in adult patients with skeletal Class III malocclusion. METHODS: A total of 40 adult patients with skeletal Class III malocclusion were retrospectively divided into two groups (n = 20 each) according to the use of MARPE for the correction of transverse maxillomandibular discrepancy during presurgical orthodontic treatment. Serial lateral cephalograms and dental casts were analyzed until 6 months after surgery. RESULTS: Before presurgical orthodontic treatment, there was no significant differences in terms of sex and age between groups. However, the difference of approximately 3.1 mm in the maxillomandibular intermolar width was statistically significant (p < 0.001). Two days after surgery, the mandible had moved backward and upward without any significant intergroup difference. Six months after surgery, the maxillary intercanine (2.7 ± 2.1 mm), interpremolar (3.6 ± 2.4 mm), and intermolar (2.0 ± 1.3 mm) arch widths were significantly increased (p < 0.001) relative to the values before presurgical orthodontic treatment in the MARPE group; these widths were maintained or decreased in the control group. However, there was no significant difference in surgical changes and the postsurgical stability between the two groups. No significant correlations existed between the amount of maxillary expansion and postsurgical mandibular movement. CONCLUSIONS: MARPE is useful for stable and nonsurgical expansion of the maxilla in adult patients with skeletal Class III malocclusion who are scheduled for bimaxillary surgery.

Positional changes in the mandibular proximal segment after intraoral vertical ramus osteotomy: Surgery-first approach versus conventional approach.

OBJECTIVE: To compare postoperative positional changes in the mandibular proximal segment between the conventional orthognathic surgery (CS) and the surgery-first approach (SF) using intraoral vertical ramus osteotomy (IVRO) in patients with Class III malocclusion. METHODS: Thirty-eight patients with skeletal Class III malocclusion who underwent bimaxillary surgery were divided into two groups according to the use of preoperative orthodontic treatment: CS group (n = 18) and SF group (n = 20). Skeletal changes in both groups were measured using computed tomography before (T0), 2 days after (T1), and 1 year after (T2) the surgery. Three-dimensional (3D) angular changes in the mandibular proximal segment, condylar position, and maxillomandibular landmarks were assessed. RESULTS: The mean amounts of mandibular setback and maxillary posterior impaction were similar in both groups. At T2, the posterior portion of the mandible moved upward in both groups. In the SF group, the anterior portion of the mandible moved upward by a mean distance of 0.9 ± 1.0 mm, which was statistically significant (p < 0.001). There were significant between-group differences in occlusal changes (p < 0.001) as well as in overjet and overbite. However, there were no significant between-group differences in proximal segment variables. CONCLUSIONS: Despite postoperative occlusal changes, positional changes in the mandibular proximal segment and the position of the condyles were similar between CS and SF, which suggested that SF using IVRO achieved satisfactory postoperative stability. If active physiotherapy is conducted, the proximal segment can be adapted in the physiological position regardless of the occlusal changes.

A randomised trial evaluating the effect of intraoperative iron administration.

Perioperative anaemia increases postoperative morbidity and mortality, and iron deficiency is anaemia's most common cause in surgical patients. Preoperative intravenous iron increases postoperative haemoglobin; however, data regarding intraoperative intravenous iron's effectiveness are inadequate. This study examined intraoperative intravenous iron's effects on postoperative haemoglobin levels in adults. Fifty-seven healthy subjects (aged 19-40 years) scheduled for bimaxillary orthognathic surgery were assigned randomly to the iron (n = 28) or control (n = 29) groups. The iron group received intravenous ferric derisomaltose (1,000 mg) after anaesthetic induction. The control group received an identical volume of intravenous normal saline. The primary outcome was postoperative haemoglobin level. Secondary outcomes included other postoperative haematologic and iron parameters. Laboratory data were obtained preoperatively and at 1 day, 2 weeks, and 4 weeks postoperatively. Haemoglobin was higher in the iron group 2 weeks postoperatively (12.9 g/dL vs. 12.2 g/dL), but the between-group difference was not significant after adjustment for multiple testing. However, the reticulocyte production index was significantly higher in the iron group 2 weeks postoperatively. Intraoperative intravenous iron maintains postoperative haemoglobin values in patients undergoing bimaxillary orthognathic surgery by increasing haematopoietic function and iron bioavailability and therefore appears to be a useful strategy for blood management.