Clinical observation using virtual reality for dental education on surgical tooth extraction: A comparative study.

BACKGROUND: Clinical observation conducted during the 3rd and 4th years of dental school is an important part of dental students' clinical education. However, conventional clinical observation is associated with several problems, including the lack of opportunity for all students to assist during surgery. Virtual reality (VR) technologies and devices can be used to demonstrate clinical processes that dental students need to learn through clinical observation. This study aimed to evaluate the effectiveness of teaching dental students the surgical tooth extraction procedure through clinical observation using VR. METHODS: We recruited third- and fourth-year dental students and divided them into a VR clinical observation group (VR group) and a conventional clinical observation group (control group). The control group visited an outpatient clinic and observed an oral and maxillofacial specialist perform surgical tooth extraction, whereas the VR group watched a 360° video of surgical tooth extraction using a head-mounted display. After observation, both groups were surveyed regarding their satisfaction with the clinical observation and their understanding of the procedure. RESULTS: Understanding of the procedure and satisfaction with the observation were significantly higher in the VR group than in the control group (p = 0.001 and p = 0.047, respectively). Compared with conventional clinical observation, VR clinical observation improved learning motivation and medical thinking and judgment skills; however, interaction between professors and students was lacking. CONCLUSIONS: VR clinical observation using 360° videos might be an effective teaching method for students. However, to allow interaction between professors and students during clinical observations, using it along with conventional clinical observation is necessary.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. MATERIALS AND METHODS: From October 2019 to April 2023, participants aged 19 years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1 min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. RESULTS: Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. CONCLUSIONS: Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. CLINICAL RELEVANCE: MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

Forced eruption in impacted teeth: analysis of failed cases and outcome of re-operation.

BACKGROUND: Forced eruption of an impacted tooth usually requires surgical and orthodontic interventions to successfully bring the tooth into the dental arch. The clinical time required for a forced eruption is difficult to predict before treatment begins and success rates are affected by several factors before and after an eruption. This study was conducted to identify factors that affect the success of forced eruption, the duration of orthodontic treatment of impacted teeth, and the reasons for re-operation and forced eruption failure in a various teeth and cases. METHODS: In this retrospective study, the records regarding the forced eruption of 468 teeth in 371 patients from June 2006 to May 2020 at the Advanced General Dentistry Department of Yonsei University Dental Hospital were initially examined. The records of 214 teeth in 178 patients who completed orthodontic treatment were included in the analysis. Data on patient demographics, tooth characteristics, orthodontic treatment duration, re-operations, and failures were collected from electronic medical records. RESULTS: There was a significant difference in age between the success and failure forced eruption. Factors significantly affecting treatment duration were apex formation, position, rotation, and re-operation. Re-operation had a 96% success rate. The average orthodontic treatment duration was 29.99 ± 16.93 months, but the average orthodontic treatment duration for teeth that undergone re-operation was 20.36 ± 11.05 months, which was approximately 9 months shorter. Additionally, there was an interaction effect between rotation and re-operation on the duration of orthodontic treatment. The causes for failure of forced eruption in 6 cases were ankyloses (3 cases), incomplete alignment with the normal dental arch (2 cases), and a significant deviation in the impacted tooth's location (1 case). CONCLUSIONS: To increase the success rate of forced eruption, age should be considered as a priority, and in order to predict the treatment period, the apex formation status, position in the arch, and rotation should be considered in addition to age. When determining re-operation, considering factors such as ankylosis, root curvature, and apex formation can help in the success of orthodontic treatment.

Preventive effect of teriparatide on medication-related osteonecrosis of the jaw in rats.

This study aimed to investigate the preventive effect of teriparatide (TPD) administration on medication-related osteonecrosis of the jaw (MRONJ) before tooth extraction due to periodontal lesions in bilaterally ovariectomized female rats treated with zoledronic acid. Thirty skeletally mature Sprague-Dawley rats were randomly divided into three groups: control (CONT, n = 10), zoledronic acid (ZA, n = 10), and zoledronic acid and teriparatide (ZA-TPD, n = 10). The rats were sacrificed 8 weeks after tooth extraction. Micro-computed tomography analysis of the tibia showed that bone mineral density was highest in the CONT, followed by that in the ZA and ZA-TPD groups (CONT/ZA, p = 0.009; CONT/ZA-TPD, p < 0.001; ZA/ZA-TPD, p < 0.001). In the trabecular bone analysis of the extraction site, significant differences in specific bone surface (CONT/ZA, p = 0.010; CONT/ZA-TPD, p = 0.007; ZA/ZA-TPD, p = 0.002) and trabecular thickness (CONT/ZA-TPD, p = 0.002; ZA/ZA-TPD, p = 0.002) were observed. Histological analyses of the extraction sites revealed characteristic MRONJ lesions in the ZA group. Osteonecrosis, inflammatory cells, and sequestrum were less frequently observed in the ZA-TPD group than in the ZA group. In conclusion, TPD administration before tooth extraction helped reduce the occurrence of MRONJ in rats treated with zoledronic acid, confirming its preventative effects.

A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients.

Denosumab has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of denosumab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. The purpose of this study was to report denosumab induced MRONJ cases, and investigate the factors affecting the occurrence of MRONJ in patients who underwent denosumab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. The participants were divided into two groups: receiving only denosumab (n = 51) and receiving bisphosphonate as first treatment and denosumab as second treatment (n = 47). There was no significant difference between groups in the occurrence of MRONJ and factors affecting MRONJ. Two out of 4 patients developed MRONJ regardless of invasive treatment after denosumab administration and proceeded with extraction; one patient developed MRONJ after denosumab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and non-identified MRONJ developed after denosumab administration. MRONJ cases reported in this study show that MRONJ can develop as chronic inflammation without invasive dental treatment; therefore, implementing preventive dental treatment before initiating denosumab treatment is necessary to reduce the occurrence of MRONJ.

Development and Validation of a Visually Explainable Deep Learning Model for Classification of C-shaped Canals of the Mandibular Second Molars in Periapical and Panoramic Dental Radiographs.

INTRODUCTION: The purpose of this study was to develop and validate a visually explainable deep learning model for the classification of C-shaped canals of the mandibular second molars in dental radiographs. METHODS: The periapical and panoramic images of 1000 mandibular second molars were collected from 372 patients. The diagnostic performance of the deep learning system using periapical and panoramic radiographs was investigated in respect to its ability to determine whether the second mandibular molar showed a C-shaped canal configuration. The assessment of the canal configuration of cone-beam computed tomographic volumes from 372 patients (740 mandibular second molars) was used as a gold standard. RESULTS: The deep convolutional neural network algorithm model showed high accuracy in predicting the C-shaped canal variation among mandibular second molars in both periapical and panoramic images. The model demonstrated best results when using image patches including only the root portion of the tooth and when using both periapical and panoramic images for training (area under the curve [AUC] = 0.99). The model's diagnostic performance using only the root portion of the tooth (AUC: periapical = 0.98 and panoramic = 0.95) was similar to a specialist (AUC: periapical = 0.95 and panoramic = 0.96) and better than a novice general clinician (AUC: periapical = 0.89 and panoramic = 0.91). Both the specialist and general clinician showed better diagnostic performance when reading panoramic radiographs compared with periapical images. CONCLUSIONS: With further optimization of the test data using a larger data set and improvements made in the model, a deep learning system may be expected to effectively diagnose C-shaped canals and aid clinicians in practice and education.

Comparison of detection performance of soft tissue calcifications using artificial intelligence in panoramic radiography.

Artificial intelligence (AI) is limited to teeth and periodontal disease in the dental field, and is used for diagnosis assistance or data analysis, and there has been no research conducted in actual clinical situations. So, we created an environment similar to actual clinical practice and conducted research by selecting three of the soft tissue diseases (carotid artery calcification, lymph node calcification, and sialolith) that are difficult for general dentists to see. Therefore, in this study, the accuracy and reading time are evaluated using panoramic images and AI. A total of 20,000 panoramic images including three diseases were used to develop and train a fast R-CNN model. To compare the performance of the developed model, two oral and maxillofacial radiologists (OMRs) and two general dentists (GDs) read 352 images, excluding the panoramic images used in development for soft tissue calcification diagnosis. On the first visit, the observers read images without AI; on the second visit, the same observers used AI to read the same image. The diagnostic accuracy and specificity for soft tissue calcification of AI were high from 0.727 to 0.926 and from 0.171 to 1.000, whereas the sensitivity for lymph node calcification and sialolith were low at 0.250 and 0.188, respectively. The reading time of AI increased in the GD group (619 to 1049) and decreased in the OMR group (1347 to 1372). In addition, reading scores increased in both groups (GD from 11.4 to 39.8 and OMR from 3.4 to 10.8). Using AI, although the detection sensitivity of sialolith and lymph node calcification was lower than that of carotid artery calcification, the total reading time of the OMR specialists was reduced and the GDs reading accuracy was improved. The AI used in this study helped to improve the diagnostic accuracy of the GD group, who were not familiar with the soft tissue calcification diagnosis, but more data sets are needed to improve the detection performance of the two diseases with low sensitivity of AI.

Antitumour activity and tolerability of an EphA2-targeted nanotherapeutic in multiple mouse models.

Antibody-mediated tumour targeting and nanoparticle-mediated encapsulation can reduce the toxicity of antitumour drugs and improve their efficacy. Here, we describe the performance of a nanotherapeutic encapsulating a hydrolytically sensitive docetaxel prodrug and conjugated to an antibody specific for EphA2-a receptor overexpressed in many tumours. Administration of the nanotherapeutic in mice led to slow and sustained release of the prodrug, reduced exposure of active docetaxel in the circulation (compared with administration of the free drug) and maintenance of optimal exposure of the drug in tumour tissue. We also show that administration of the nanotherapeutic in rats and dogs resulted in minimal haematological toxicity, as well as the absence of neutropenia and improved overall tolerability in multiple rodent models. Targeting of the nanotherapeutic to EphA2 improved tumour penetration and resulted in markedly enhanced antitumour activity (compared with administration of free docetaxel and non-targeted nanotherapeutic controls) in multiple tumour-xenografted mice. This nanomedicine could become a potent and safe therapeutic alternative for cancer patients undergoing chemotherapy.

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study.

Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m2 free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman ρ = 0.7824; P = 0.0016).Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. Clin Cancer Res; 23(14); 3638-48. ©2017 AACR.

A phase 1 trial of intravenous liposomal irinotecan in patients with recurrent high-grade glioma.

PURPOSE: Preclinical activity of irinotecan has been seen in glioma models, but only modest efficacy has been noted in clinical studies, perhaps related to drug distribution and/or pharmacokinetic limitations. In preclinical testing, irinotecan liposome injection (nal-IRI) results in prolongation of drug exposure and higher tissue levels of drug due to slower metabolism and the effect of enhanced permeability and retention. The objective of the current study was to assess the safety and pharmacokinetics (PK) of nal-IRI and to determine the maximum tolerated dose (MTD) in patients with recurrent high-grade glioma stratified based on UGT1A1 genotyping. METHODS: This phase I study stratified patients with recurrent high-grade glioma into 2 groups by UGT1A1 status: homozygous WT ("WT") vs heterozygous WT/*28 ("HT"). Patients who were homozygous *28 were ineligible. The design was a standard 3 + 3 phase I design. WT patients were started at 120 mg/m2 intravenously every 3 weeks with dose increases in 60 mg/m2 increments. HT patients were started at 60 mg/m2, with dose increases in 30 mg/m2 increments. The assessment period for dose-limiting toxicity was 1 cycle (21 days). RESULTS: In the WT cohort (n = 16), the MTD was 120 mg/m2. In the HT cohort (n = 18), the MTD was 150 mg/m2. Dose-limiting toxicity in both cohorts included diarrhea, some with associated dehydration and/or fatigue. PK results were comparable to those seen in other PK studies of nal-IRI; UGT1A1*28 genotype (WT vs. HT) did not affect PK parameters. CONCLUSIONS: Nal-IRI had no unexpected toxicities when given intravenously. Of note, UGT1A1 genotype did not correlate with toxicity or affect PK profile.

Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion.

A major challenge in the clinical use of cytotoxic chemotherapeutics is maximizing efficacy in tumors while sparing normal tissue. Irinotecan is used for colorectal cancer treatment but the extent of its use is limited by toxic side effects. Liposomal delivery systems offer tools to modify pharmacokinetic and safety profiles of cytotoxic drugs. In this study, we defined parameters that maximize the antitumor activity of a nanoliposomal formulation of irinotecan (nal-IRI). In a mouse xenograft model of human colon carcinoma, nal-IRI dosing could achieve higher intratumoral levels of the prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan. For example, nal-IRI administered at doses 5-fold lower than free irinotecan achieved similar intratumoral exposure of SN-38 but with superior antitumor activity. Tumor response and pharmacokinetic modeling identified the duration for which concentrations of SN-38 persisted above a critical intratumoral threshold of 120 nmol/L as determinant for antitumor activity. We identified tumor permeability and carboxylesterase activity needed for prodrug activation as critical factors in achieving longer duration of SN-38 in tumors. Simulations varying tumor permeability and carboxylesterase activity predicted a concave increase in tumor SN-38 duration, which was confirmed experimentally in 13 tumor xenograft models. Tumors in which higher SN-38 duration was achieved displayed more robust growth inhibition compared with tumors with lower SN-38 duration, confirming the importance of this factor in drug response. Overall, our work shows how liposomal encapsulation of irinotecan can safely improve its antitumor activity in preclinical models by enhancing accumulation of its active metabolite within the tumor microenvironment.