Free buccal fat pad graft for the bone defect filling of medication-related osteonecrosis of the jaws: A novel surgical approach.

Surgical intervention for medication-related jaw osteonecrosis (MRONJ) is currently the main treatment method, offering a higher healing rate than conservative approaches. However, the management of bony defects after sequestrectomy remains a challenging issue due to poor vascularization from the drug effect. The use of pedicled buccal fat pad (PBFP) for filling bone defects has become common and effective but is limited to the posterior maxillary region. To add to the advantages of the buccal fat pad, we explored a novel treatment approach using a free buccal fat pad (FBFP) to fill bone defects other than the posterior maxilla. While the FBFP has been employed in oral defect reconstruction, currently published cases have been utilized in recipient sites with good blood supply. There has yet to be any usage in poor vascularization defects like MRONJ. This article describes that the FBFP was used to fill the surgical defects of 8 patients who were diagnosed with MRONJ and who underwent sequestrectomy and saucerization. During follow-up visits, there was excellent wound healing and no significant tissue depression. Based on successful treatment experiences, FBFP is a reliable therapeutic option for the management of poor vascularization defects like MRONJ treated through surgical intervention.

Characteristics and biological responses of selective laser melted Ti6Al4V modified by micro-arc oxidation.

Background/purpose: Additive manufacturing (AM) technology, such as selective laser melting (SLM), has been used to fabricate medical devices of Ti-6wt.% Al-4wt.%V (Ti6Al4V) alloys in dentistry. Strontium (Sr) has been shown to have the potential to treat osteoporosis. The aim of this study was to investigate the physicochemical and biological properties of strontium-containing coatings on selective laser melted Ti6Al4V (SLM-Ti6Al4V) substrate. Materials and methods: The disk of Ti6Al4V was prepared by SLM method. The strontium-containing coatings were prepared by micro-arc oxidation (MAO) in aqueous electrolytes. The surface topography, chemical composition, and phase of strontium-containing MAO (SrMAO) coatings were performed by scanning electron microscope (SEM), energy dispersive X-ray spectrometer (EDS), and thin film X-ray diffraction (TF-XRD), respectively. The apatite-forming ability of the MAO coatings was conducted in simulating body fluid (SBF), and the cell proliferation was determined by methylthiazoletetrazolium (MTT) assay. Results: The microstructure of SLM-Ti6Al4V displays acicular α-phase organization. The TF-XRD results indicated that the phase of SrMAO coating was anatase, rutile, and titanium. The calcium, phosphorus, and strontium were detected in the coatings by EDS. Using the SEM, the surface morphology of SrMAO coatings exhibited a uniform 3D porous structure. The SrMAO coatings could induce a bone-like apatite layer after immersion in SBF, and presented significantly higher cell proliferation than untreated specimens in in-vitro experiments. Conclusion: All findings in this study indicate that SrMAO coatings formed on SLM-Ti6Al4V surfaces exhibit a benefit on biological responses and thereby are suitable for biomedical applications.

Enhancing surgical outcomes of posterior iliac bone harvesting through a pivotal modification.

Traditionally, patients are positioned in the prone position to access the donor site during the posterior iliac bone graft harvesting procedure. However, this well-established method is associated with complications such as pressure injuries, displacement of the endotracheal tube and intravenous catheter, and blindness. Moreover, the process of turning patients 180° between the supine and prone positions is both laborious and time consuming. However, no updates have been made in the approaches published in the literature to counteract these problems. Therefore, to overcome these challenges and improve patient outcomes, we proposed a pivotal modification: change prone position to the lateral decubitus position. This approach allowed us to effectively avoid the aforementioned complications. In addition, this modification offered significant advantages, including ease of implementation and timesaving benefits. The article presented results of the modification and a comprehensive evaluation of clinical and anesthetic considerations comparing the two methods.

Effect of thermocycling-induced stress on properties of orthodontic NiTi wires.

Background/purpose: In orthodontic applications, NiTi wires are under continuous bending stress and exposed to fluctuations in temperature over long durations. The sensitivity of NiTi to temperature can have a considerable influence on its mechanical properties. This study investigated the effects of deflected NiTi wire, presented in stress-induced (detwinned) martensite microstructure, combined with thermal cycle on the microstructure and mechanical properties. Materials and methods: We tested four types of as-received orthodontic NiTi: (1) Nitinol Classic (3 M Unitek), (2) Sentalloy (Tomy), (3) 27 °C CuNiTi (Ormco) and (4) 40 °C CuNiTi (Ormco). Each group of specimens was subjected to three different testing conditions: (1) temperature fluctuations (5000 cycles) between 5 and 55 °C, (2) continuous three-point bending force and (3) combination of thermal cycling and bending stress. Results: The specimens that underwent thermocycling as well as loading exhibited a substantial narrowing in stress hysteresis, which may be attributed to crystallinity lower than that of as-received NiTi wires. Reduced crystallinity can manifest in a number of imperfections, such as dislocations and internal stress, as well as a less-organized structure. Micro X-ray diffraction (XRD) analysis revealed the existence of martensite phase in Sentalloy wires subject to thermal and stress conditions. Under loading conditions, stress-induced martensite of NiTi wires exposed to temperature fluctuations of 5-55 °C also induced cyclic changes in bending stress. In a simulated intra-oral environment, the stability of austenite↔martensite transformation decreased. Conclusion: This study determined that bending stress in conjunction with repeated temperature fluctuations can greatly affect the microstructure and mechanical properties of NiTi wires.

Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with Candida albicans Infection.

Oral squamous cell carcinoma (OSCC) carcinogenesis involves heterogeneous tumor cells, and the tumor microenvironment (TME) is highly complex with many different cell types. Cancer cell-TME interactions are crucial in OSCC progression. Candida albicans (C. albicans)-frequently pre-sent in the oral potentially malignant disorder (OPMD) lesions and OSCC tissues-promotes malignant transformation. The aim of the study is to verify the mechanisms underlying OSCC car-cinogenesis with C. albicans infection and identify the biomarker for the early detection of OSCC and as the treatment target. The single-cell RNA sequencing analysis (scRNA-seq) was performed to explore the cell subtypes in normal oral mucosa, OPMD, and OSCC tissues. The cell composi-tion changes and oncogenic mechanisms underlying OSCC carcinogenesis with C. albicans infec-tion were investigated. Gene Set Variation Analysis (GSVA) was used to survey the mechanisms underlying OSCC carcinogenesis with and without C. albicans infection. The results revealed spe-cific cell clusters contributing to OSCC carcinogenesis with and without C. albicans infection. The major mechanisms involved in OSCC carcinogenesis without C. albicans infection are the IL2/STAT5, TNFα/NFκB, and TGFß signaling pathways, whereas those involved in OSCC carcinogenesis with C. albicans infection are the KRAS signaling pathway and E2F target down-stream genes. Finally, stratifin (SFN) was validated to be a specific biomarker of OSCC with C. albicans infection. Thus, the detailed mechanism underlying OSCC carcinogenesis with C. albicans infection was determined and identified the treatment biomarker with potential precision medicine applications.

Investigating the association between serum human papillomavirus type 16 E7 antibodies and risk of head and neck cancer.

Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital-based case-control study conducted in Taiwan with 693 HNC cases and 1,035 controls. A positive association was observed between seropositivity to HPV16 E7 and OPC risk, whereas no significant association was found in the non-OPC cases. The increased OPC risk associated with seropositivity to HPV16 E7 was more significant among nonbetel quid or noncigarette users. Seropositivity to HPV16 E7 showed moderate agreement with P16 expression in OPC. OPC patients that were seropositive to HPV16 E7 or p16 positive were more highly educated and less likely to use alcohol, betel quids, and cigarettes compared to HPV16 E7 seronegative or p16 negative OPC patients. Furthermore, patients with p16 positive OPC were more likely to be women compared to patients with p16 negative OPC, likely owing to the low prevalence of alcohol, betel quid, and cigarette users among women. Overall, this study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan. With the declining consumption of betel quids and cigarettes in Taiwan, a higher percentage of OPC cases in Taiwan will be attributed to HPV in the future. Public health measures, including HPV vaccination, need to be implemented to prevent the occurrence of HPV-positive OPC.

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Nano/Micro Hierarchical Bioceramic Coatings for Bone Implant Surface Treatments.

Bone implants with surface modifications that promote the physiological activities of osteoblasts are the first step for osseointegration in bone repair. Hydroxyapatite is the main inorganic component in mammal bones and teeth, and nanoscaled hydroxyapatite promotes the adhesion of osteoblastic cells. In this study, we created a nano/micro hierarchical structure using micro-arc oxidation coatings and hydrothermal treatments at 150 °C, 175 °C, and 200 °C for 2, 6, 12, and 24 h. After undergoing hydrothermal treatment for 24 h, CaTiO3 began forming regular-shaped crystals at the surface at 175 °C. In order to decrease the CaTiO3 formations and increase the apatite fabrication, a shorter time of hydrothermal treatment was required at 175 °C. There was still surface damage on samples treated for 6 h at 175 °C; however, the nano/micro hierarchical structures were formed in 2 h at 175 °C. The normalized alkaline phosphatase (ALP) activities of the MC3T3-E1 cells with micro-arc oxidation (MAO) coatings and nano/micro hierarchical bioceramics coatings were 4.51 ± 0.26 and 7.36 ± 0.51 µmol p-NP/mg protein (*** P value of <0.001), respectively. The MC3T3-E1 cells with coatings showed highly statistically significant results in terms of the ALP activity. This proposed nano/micro hierarchical structure promoted cell proliferation and osteogenic differentiation of the osteoblast MC3T3-E1 cells. This study realized a promising nano system for osseointegration via bone implant surface treatments, which can promote the physiological activities of osteoblasts.

Context-guided fully convolutional networks for joint craniomaxillofacial bone segmentation and landmark digitization.

Cone-beam computed tomography (CBCT) scans are commonly used in diagnosing and planning surgical or orthodontic treatment to correct craniomaxillofacial (CMF) deformities. Based on CBCT images, it is clinically essential to generate an accurate 3D model of CMF structures (e.g., midface, and mandible) and digitize anatomical landmarks. This process often involves two tasks, i.e., bone segmentation and anatomical landmark digitization. Because landmarks usually lie on the boundaries of segmented bone regions, the tasks of bone segmentation and landmark digitization could be highly associated. Also, the spatial context information (e.g., displacements from voxels to landmarks) in CBCT images is intuitively important for accurately indicating the spatial association between voxels and landmarks. However, most of the existing studies simply treat bone segmentation and landmark digitization as two standalone tasks without considering their inherent relationship, and rarely take advantage of the spatial context information contained in CBCT images. To address these issues, we propose a Joint bone Segmentation and landmark Digitization (JSD) framework via context-guided fully convolutional networks (FCNs). Specifically, we first utilize displacement maps to model the spatial context information in CBCT images, where each element in the displacement map denotes the displacement from a voxel to a particular landmark. An FCN is learned to construct the mapping from the input image to its corresponding displacement maps. Using the learned displacement maps as guidance, we further develop a multi-task FCN model to perform bone segmentation and landmark digitization jointly. We validate the proposed JSD method on 107 subjects, and the experimental results demonstrate that our method is superior to the state-of-the-art approaches in both tasks of bone segmentation and landmark digitization.

Validation of Alcohol Flushing Questionnaire to Identify ALDH2 Status in a Case-Control Study of Head and Neck Cancer.

BACKGROUND: Carriers of the ALDH2*2 allele have impaired alcohol metabolism and are more susceptible to the development of alcohol-related cancers, including head and neck cancer (HNC). Screening for ALDH2*2 allele may identify high-risk individuals for alcohol health education. Although genotyping of ALDH2 is the most accurate way to identify ALDH2 deficiency, it may not be practical due to the cost and requirement for genotyping service. METHODS: This study evaluated the accuracy of the alcohol flushing questionnaire to identify ALDH2 deficiency in a case-control study of HNC conducted in Taiwan using data collected from 904 patients with HNC and 1,078 controls. RESULTS: Overall, alcohol flushing questionnaire had a high sensitivity (89%) of identifying ALDH2*2 carriers among the control subjects and a good sensitivity (79%) among the patients with HNC. The sensitivity of the alcohol flushing questionnaire in identifying ALDH2*2 carriers was affected by alcohol use, with a lower sensitivity among individuals who consumed alcohol, particularly among current regular (drinking alcohol once per week or more) alcohol drinkers. CONCLUSIONS: The current validation study showed that the alcohol flushing questionnaire may be a reasonable method to identify ALDH2-deficient individuals. However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.

Oral hygiene and the overall survival of head and neck cancer patients.

Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03-1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41-3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65-1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.

Unusual Supernumerary Teeth and Treatment Outcomes Analyzed for Developing Improved Diagnosis and Management Plans.

PURPOSE: Supernumerary teeth (SNTs) are teeth or tooth-like structures that have erupted or might erupt in addition to the 20 primary or 32 permanent teeth. The simultaneous presentation of multiple SNTs, syndrome-related multiple SNTs, SNTs inside the maxillary sinus and treatment outcomes were analyzed to develop improved diagnosis and management plans. PATIENTS AND METHODS: This retrospective study reviewed the medical records of National Cheng Kung University Hospital patients who had undergone surgical intervention with general anesthesia between February 2014 and September 2018; analyzed panoramic radiographs and cone beam computed tomography scans of their multiple SNTs; and used descriptive statistics to discuss treatments and relative complications, especially of unusual SNTs. RESULTS: The records of 165 patients (127 male and 38 female patients; mean age, 12.4 years) with 241 SNTs (120 patients had 1 SNT, 35 had 2 SNTs, 3 had 3 SNTs, 2 had 4 SNTs, 2 had 5 SNTs, 2 had 6 SNTs, and 1 had 12 SNTs) were reviewed. There were 185 SNTs in the maxilla and 56 in the mandible; 153 were mesiodens and 115 were inverted; 142 were asymptomatic and 137 were conical; and 228 were fully impacted and 210 were partial roots. Two patients had SNTs inside the maxillary sinus, and one had 5 SNTs and Marfan syndrome. Two patients had postoperative lip or chin paresthesia, and two had postoperative sinusitis. CONCLUSIONS: Patient demographic variables provided useful epidemiologic information. We recommend panoramic radiographs or cone beam computed tomography for managing patients with possible multiple SNTs and for extracting SNTs.

The Influence of Prediagnosis Alcohol Consumption and the Polymorphisms of Ethanol-Metabolizing Genes on the Survival of Head and Neck Cancer Patients.

BACKGROUND: Although alcohol drinking is an established risk factor of head and neck cancer (HNC), less is known about its role in the prognosis of HNC. The current study investigated the association between pretreatment alcohol consumption and the overall survival (OS) of HNC patients. METHODS: Cox proportional hazards models were performed to evaluate the association between prediagnosis alcohol drinking and the OS of HNC patients. In addition, the influence of the polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on this relationship was also evaluated. RESULTS: The results showed a significant positive dose-response relationship between prediagnosis alcohol use and worse OS of HNC patients. This association was more significant for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral cancer. The association between alcohol use and the poorer OS of HNC patients was mainly through its association with a higher stage of HNC at diagnosis. The worst OS associated with alcohol use was observed among HNC patients with the fast ADH1B and the slow/nonfunctional ALDH2 genotype combination. CONCLUSIONS: Our analysis showed a significant positive dose-response relationship between prediagnosis alcohol use and a worse OS of HNC. This association was mainly due to the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of the ethanol-metabolizing genes, ADH1B and ALDH2, modified the relationship between prediagnosis alcohol use and the OS of HNC patients. IMPACT: Prediagnosis alcohol use may be a prognostic indicator of HNC.

Two-channel autofluorescence analysis for oral cancer.

We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.

The interplay between oral microbiome, lifestyle factors and genetic polymorphisms in the risk of oral squamous cell carcinoma.

Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1ß, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.