Use of an educational video with mobile technology for the informed consent process: A randomised controlled trial on patients undergoing surgery for an impacted lower third molar.

The purpose of this study was to determine whether audiovisual presentation of consent information would significantly improve patients' postoperative recall of risks and complications regarding surgical removal of impacted lower third molars compared to the presentation of traditional written consent information. A randomised controlled study on 59 patients undergoing third molar removal was conducted. Patients in the intervention group (n = 30) viewed an educational video on risks and complications related to surgery using mobile tablets. Control-group patients (n = 29) received written information of the risks and complications. Patients' postoperative recall of potential risks for dysesthesia of the lower lip and tongue, infection, and bleeding along with surgical complications of facial oedema, trismus, and pain were assessed using true-false tests. The effect of audiovisual information on postoperative recall of the risks and complications was determined by comparing accuracy scores between the intervention group and control group using the independent t-test. The intervention group was found to have significantly better recall scores of the potential risks and complications, due to much higher accuracy in their recall of bleeding and dysesthesia of the lower lip and/or tongue, compared to the control group [mean (SD) 4.70 (0.94) vs 3.76 (1.50), p = 0.003]. The use of an educational video played on mobile tablets rather than a written pamphlet may lead to better understanding of the informed consent process in patients.

Evaluation of dental hygiene learning outcomes through smartphone-based educational slides targeting dental hygienists: A pilot study.

OBJECTIVE: Education reflecting fundamental knowledge is required for competent health care providers, but often lectures are not available for this purpose. This study aimed to evaluate the dental hygiene learning outcomes following the presentation of web-based slides on a smartphone to dental hygienists. METHODS: A two-group nonblinded quasi-experimental design was used for this study. Forty-six dental hygienists were assigned to a study (n = 31) or control group (n = 15). The study group viewed 22 slides on fundamental oral health knowledge using smartphones. Pre and postviewing tests (score range: 1-13) and a questionnaire were conducted to evaluate knowledge acquisition and to receive feedback from participants. Differences between the study and control group and intrastudy group differences were statistically evaluated. RESULTS: The fundamental knowledge of dental hygienists improved after viewing the slides: the study group had a significantly higher mean score than the control group (10.87 vs. 6.60; p < 0.001). Study group participants also had substantially higher post-test than pretest knowledge scores (mean 10.87 vs. 6.26, p < 0.001). In the questionnaire, more than 85% of the participants answered that the content of the slides would be useful in their clinical practice. CONCLUSION: Smartphone-based educational slides were beneficial for conveying fundamental and recent oral health knowledge to dental hygienists.

Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors.

BACKGROUND: While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. METHODS: A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. RESULTS: During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P < 0.0001) and baseline eosinophil count ≥130/µL (HR, 3.01 for < 130; P = 0.012) as independent risk factors for the incidence of immune-related liver injury with grade ≥ 2. Patients who developed irAEs had a higher disease control rate (P < 0.0001) and an increased overall survival rate compared to those without irAEs (P < 0.0001). CONCLUSION: Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in higher a frequency of irAEs. Baseline absolute eosinophil count was found to be a predictive factor for immune-related liver injury. Occurrence of irAEs may be associated with higher efficacy of ICI treatment and longer survival among patients who receive ICI therapy.

Evaluation of Oral Mucosal Lesions Using the IllumiScan® Fluorescence Visualisation Device: Distinguishing Squamous Cell Carcinoma.

We evaluated whether fluorescence intensity (FI) and its coefficient of variation (CV) can be used to diagnose squamous cell carcinoma (SCC) through IllumiScan®, an oral mucosa fluorescence visualisation (FV) device. Overall, 190 patients with oral mucosal lesions (OMLs; SCC, 59; non-SCC OMLs, 131) and 49 patients with normal oral mucosa (NOM) were enrolled between January 2019 and March 2021. The FI of the images was analysed using image analysis software. After establishing regions of interest for SCC, non-SCC, and NOM, the average FI, standard deviation (SD), and CV were compared. There was a significant difference in the average FI for all pairs of comparisons. The SD was not significantly different between the SCC and NOM groups (p = 0.07). The CV differed significantly for NOM (p < 0.001) and non-SCC groups (p < 0.001) relative to the SCC group but was not different between NOM and non-SCC groups (p = 0.15). Univariate analysis of SCC and non-SCC groups showed significant differences for all factors, except age. However, multivariate analysis showed a significant intergroup difference only in the CV (p = 0.038). Therefore, analysing the CV in FV images of OML may be useful for the diagnosis of oral cancer.

Development of a radiomics and machine learning model for predicting occult cervical lymph node metastasis in patients with tongue cancer.

OBJECTIVE: We aimed to develop a predictive model for occult cervical lymph node metastasis in patients with tongue cancer using radiomics and machine learning from pretreatment contrast-enhanced computed tomography. STUDY DESIGN: This study included 161 patients with tongue cancer who received local treatment. Computed tomography images were transferred to a radiomics platform. The volume of interest was the total neck node level, including levels Ia, Ib, II, III, and IVa at the ipsilateral side, and each neck node level. The dimensionality of the radiomics features was reduced using least absolute shrinkage and selection operator logistic regression analysis. We compared 5 classifiers with or without the synthetic minority oversampling technique (SMOTE). RESULTS: For the analysis at the total neck node level, random forest with SMOTE was the best model, with an accuracy of 0.85 and an area under the curve score of 0.92. For the analysis at each neck node level, a support vector machine with SMOTE was the best model, with an accuracy of 0.96 and an area under the curve score of 0.98. CONCLUSIONS: Predictive models using radiomics and machine learning have potential as clinical decision support tools in the management of patients with tongue cancer for prediction of occult cervical lymph node metastasis.

Two Cases of Temporomandibular Synovial Chondromatosis Associated with Gli1 Gene Mutation.

Synovial chondromatosis (SC) is a rare benign disease involving multifocal generation of ectopic cartilage in the synovial tissue. Herein, we report two cases of SC in the temporomandibular joint: a 38-year-old woman (patient 1) and 39-year-old woman (patient 2). Both patients had trismus, jaw joint noises, and jaw-opening pain in the temporomandibular joint. Cone-beam computed tomography (CT) and magnetic resonance imaging (MRI) in patient 1 showed multiple calcified loose bodies around the right mandibular condyle. In addition, CT and MRI in patient 2 showed multiple calcified loose bodies around the left mandibular condyle and temporal bone perforation. Following establishing a diagnosis of SC, both patients underwent tumor resection via open surgery. In immunohistochemical examinations of the resected tissues, tumor cells showed intense nuclear staining with labeled anti-Gli1 antibody. Gene sequencing revealed that both patients had a homozygous mutation in the Gli1 gene (rs2228226 G>C). In conclusion, we suggest that the Gli1 gene (rs2228226 G>C) may be involved in the etiology of SC.

Effects of Tongue Pressure on Cerebral Blood Volume Dynamics: A Functional Near-Infrared Spectroscopy Study.

Tongue pressure measurement (TPM) is an indicator of oral function. However, the association between tongue pressure and cerebral activation remains unclear. We used near-infrared spectroscopy (NIRS) to examine the correlation between cerebral cortex activation and tongue pressure stimulation against the anterior palatal mucosa. We measured voluntary maximum tongue pressure (MTP) using a TPM device; a pressure value of approximately 60% of the MTP was used for the experimental tongue pressure (MTP60%). We examined the effect of oral functional tongue pressure stimulation against the anterior palatal mucosa on cerebral activation using NIRS in 13 adults. Tongue pressure stimulation caused significant changes in cerebral blood flow in some areas compared with controls (p < 0.05). We performed a correlation analysis (p < 0.05) between MTP60% and changes in oxygenated hemoglobin in all 47 NIRS channels. MTP60% triggered activation of the right somatosensory motor area and right dorsolateral prefrontal cortex and deactivation of the anterior prefrontal cortex (APFC). TPM balloon-probe insertion in the oral cavity activated the bilateral somatosensory motor area and deactivated the wide area of the APFC. Moreover, MTP60% via the TPM balloon probe activated the bilateral somatosensory and motor cortex areas. Tongue pressure stimulation changes cerebral blood flow, and NIRS is useful in investigating the relationship between oral stimulation and brain function.

Impact of Maximum Tongue Pressure in Patients with Jaw Deformities Who Underwent Orthognathic Surgery.

Malocclusion and morphological abnormalities of the jawbone often affect the stomatognathic function and long-term postoperative stability in patients with jaw deformities. There are few reports on the effect of maximum tongue pressure (MTP) in these patients. We investigated the relationship between the MTP and jawbone morphology and the effect of the MTP on surgery in 42 patients with jaw deformity who underwent surgical orthodontic treatment at Hiroshima University Hospital. The MTP was measured using a tongue pressure measurement device; the average value was considered as the MTP. Based on the MTP measured before surgery, patients were classified into the high- or the low-MTP group. The clinical findings and results of the cephalometric analysis were compared. Posterior movement of the mandible in the high-MTP group was significantly lower than that in the low-MTP group. The ANB angle, overjet, and overbite in the high-MTP group were significantly smaller than those in the low-MTP group. On the other hand, there was no difference between the two groups in the measured values, indicating a labial inclination of the anterior teeth (U1 to SN, U1 to FH, IMPA, and FMIA). MTP has been suggested to affect mandibular prognathism in patients with jaw deformities.

Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells.

Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by multiple hamartomas in various organs such as the mucosa, skin, and gastrointestinal tract. Patients with CS are at high risk for breast and thyroid cancers. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that negatively regulates the AKT pathway, and PTEN mutations are known to be the major causes of this syndrome. However, the pathogenesis of this syndrome has not been clarified. Here, we present a case of a Japanese woman with multiple oral polyps, breast cancer, and thyroid cancer who was clinically diagnosed with CS. We obtained DNA and RNA samples from the patient's peripheral blood mononuclear cells (PBMCs) and buccal mucosa tumor. Next-generation sequencing revealed novel germline mutations (c.1020delT and c.1026G > A) in exon 8 of PTEN. Sanger sequencing identified no PTEN transcript from the mutant allele. Furthermore, CS-specific induced pluripotent stem cells (CS-iPSCs) were established from PBMCs of the patient under feeder- and serum-free culture. Compared with healthy PBMCs and iPSCs, both of the CS-derived PBMCs and CS-iPSCs exhibited significantly reduced expression of the PTEN transcript. The transcriptional variant, PTENδ, was increased in CS-iPSCs, suggesting that it may be the cause of the disease.

Identification of a familial cleidocranial dysplasia with a novel RUNX2 mutation and establishment of patient-derived induced pluripotent stem cells.

Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disease associated with the gene RUNX2. Disease-specific induced pluripotent stem cells (iPSCs) have emerged as a useful resource to further study human hereditary diseases such as CCD. In this study, we identified a novel CCD-specific RUNX2 mutation and established iPSCs with this mutation. Biopsies were obtained from familial CCD patients and mutation analyses were performed through Sanger sequencing and next generation sequencing. CCD-specific human iPSCs (CCD-hiPSCs) were established and maintained under completely defined serum, feeder, and integration-free condition using a non-integrating replication-defective Sendai virus vector. We identified the novel mutation RUNX2_c.371C>G and successfully established CCD-hiPSCs. The CCD-hiPSCs inherited the same mutation, possessed pluripotency, and showed the ability to differentiate the three germ layers. We concluded that RUNX2_c.371C>G was likely pathogenic because our results, derived from next generation sequencing, are supported by actual clinical evidence, familial tracing, and genetic data. Thus, we concluded that hiPSCs with a novel CCD-specific RUNX2 mutation are viable as a resource for future studies on CCD.

MICA A5.1 homozygous genotype is associated with a risk for early-onset oral cancer.

OBJECTIVES: Genetic predisposition is reportedly involved in early-onset oral cancer, although the genetic basis of this cancer remains unclear. The major histocompatibility complex class I-related chain A (MICA) plays a crucial role in eliminating malignant tumors by activating NKG2D, the natural killer (NK) receptor. MICA polymorphism might affect its binding to NKG2D. We aimed to find whether MICA gene microsatellite polymorphism is involved in the risk of oral squamous cell carcinoma (OSCC) development in a Japanese population. MATERIALS AND METHODS: We recruited 386 patients with OSCC and 103 healthy controls. Genomic DNA was analyzed by PCR for microsatellite repeat polymorphism in the transmembrane region of the MICA gene. The groups were compared for the prevalence of various alleles and their association with disease prognosis and survival. RESULTS: We found that adolescents and young adults (AYA) with OSCC were more likely to have the MICA A5.1 homozygous genotype than healthy controls (P = 0.0001), but their survival rate was higher than with other MICA genotypes (P = 0.0185). CONCLUSION: These results suggest that cancer's immune escape is facilitated by MICA's failure to activate the NK cells. MICA A5.1 homozygosity plays a role in individual susceptibility to OSCC, increasing the risk of early-onset oral cancer. However, such patients have a better prognosis than those with other MICA genotypes.

Age-related changes in oral tactile and thermal sensation throughout adulthood.

Although the life expectancy of women is over 80 years in many countries, oral sensation has scarcely been compared between adults ≥ 80 years and younger age groups. The purpose of this study was to clarify age-related changes in oral sensation throughout adulthood. After exclusion of individuals with factors that might have confounded somatosensory performance, 123 female participants were divided into four age groups: 20-39 years, 40-59 years, 60-79 years, and 80-96 years. Perceptions of tactile and thermal sensations were examined at points on the anterior and posterior palate, anterior and posterior tongue, lower labial-attached gingiva, lower lip, and buccal mucosa; two-point discrimination was examined only on the tongue. The tactile and two-point discrimination thresholds for the anterior and posterior tongue were significantly higher in the 80-96-year-old group than in any other age group (p < 0.05). The tactile threshold for the buccal mucosa was significantly higher in the 80-96-year-old group than in the 60-79-year-old group (p < 0.05). The percentage of participants able to perceive a warm stimulus (50 °C) in the buccal mucosa was significantly lower in the 80-96-year-old group than in the 20-39-year-old group (p < 0.05). Only the topography of the warm sensation perception changed with age. This cross-sectional study suggests that oral tactile and thermal sensation for warm stimuli deteriorates with age in a site-specific manner, especially after the age of 80 years, but the same does not occur with cool stimuli.

Enhanced KRT13 gene expression bestows radiation resistance in squamous cell carcinoma cells.

Cancer metastasis and recurrence are potentially lethal. A small number of cancer cell groups called cancer stem cells (CSCs) have both stem cell capacity and cancer-forming ability and are reported to play important roles in cancer metastasis and recurrence. These CSCs are considered to be radiation-resistant (RR). Therefore, understanding the biological effects of radiation on squamous cell carcinoma (SCC) cell lines in vitro and in vivo might be worthwhile to circumvent radiation resistance. Currently, there are no reports on the establishment of RR-SCC cells in serum-free defined culture, which mimics biological mechanisms and prevents instability of using serum in the culture medium. We isolated radiation-resistant strains, designated A431-LDR and A431-HDR, from A431 cells derived from vulval SCC and irradiated them with a total dose of 60 Gy at a low-dose rate (2.2 Gy/d) (RM1000) and a high-dose rate (5 Gy/5.75min) in serum-free defined culture. These cells exhibited high sphere-forming and migration ability in vitro and high tumor-forming ability in nude mice xenografts. Overexpression of KRT13 in A431-RR cells might play a role in its radiation-resistant characteristics. These cells might be useful not only to study cancer stem cells but also to study the circumvention of radiation resistance by novel cancer treatment modalities.

Bosutinib-induced osteonecrosis of the jaw in a patient with chronic myeloid leukemia: a case report.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon adverse drug reaction that can be induced by certain therapeutic drugs, including antiresorptive and antiangiogenic agents. Here, we describe the first case of ONJ induced by bosutinib, a tyrosine kinase inhibitor, in a patient with chronic myeloid leukemia (CML) who was not taking an antiresorptive agent. A 65-year-old male with no history of either antiresorptive treatment or dental surgery but diagnosed with CML had been undergoing treatment with bosutinib for 2 years. He developed right mandibular stage 2 osteonecrosis. The patient eventually underwent extensive surgery consisting of removal of the necrotic bone and infected soft tissue in combination with nasolabial flap reconstruction. He obtained complete resolution of MRONJ at 12 months postoperatively. As new cancer therapies become available, it is important that clinicians are aware of this novel case of bosutinib-induced ONJ in a patient undergoing CML treatment.

Development of Kikuchi-Fujimoto disease after a cervical lymph node metastasis of mucoepidermoid carcinoma: a case report.

Kikuchi-Fujimoto disease (KFD) was first reported by Kikuchi and Fujimoto in 1972 as a rare disease with lymphadenitis of unknown etiology. KFD is characterized by the main symptoms of fever and enlarged cervical lymph nodes (LNs), which are similar to the features of other LN-associated diseases. Therefore, it is difficult to diagnose this condition. We report the case of a 24-year-old woman who presented with KFD after surgery to treat a mucoepidermoid carcinoma of the palate and dissection of the left neck. The patient presented with a fever and right cervical lymphadenopathy when she visited our department for a regular follow-up related to the mucoepidermoid carcinoma. The results of computed tomography and ultrasonography evaluations led to a clinical diagnosis of lymph node metastasis, and a right neck dissection was performed. However, the pathological tissue analysis did not suggest malignancy but showed necrosis and various cellular infiltrates. We made a diagnosis of KFD from these clinical and pathological features. KFD may be misdiagnosed as a LN-associated disease such as metastasis. Clinically, KFD should be considered in patients with head and neck cancer who present with cervical lymphadenopathy.

Novel PTCH1 mutations in Japanese familial nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is inherited in an autosomal dominant manner and is characterized by a combination of developmental abnormalities and a predisposition to tumor formation. Hedgehog receptor Patched 1 (PTCH1) has been identified as the mutated gene in NBCCS. We identified the PTCH1_c.3298_3299insAAG_p.1099_1100insE mutation in the transmembrane region, which comprises a sterol transporter whose abnormal function is reportedly related to pathogenicity.