Frequency of spontaneous osteosarcomatous transformation of craniofacial fibrous dysplasia: a systematic review.

OBJECTIVE: A systematic review was undertaken to examine the spontaneous of craniofacial fibrous dysplasia (FD) into osteosarcoma (OS). STUDY DESIGN: Five databases were searched, and data were evaluated in 2 subsets: (1) frequency analysis involving only cross-sectional studies that specifically examined patients for osteosarcomatous transformation, thereby allowing a calculation of the frequency of transformation of craniofacial FD, and (2) case analysis of case reports and case series of FD that underwent osteosarcomatous transformation. Quality assessment of the studies in the frequency and case analyses was performed. RESULTS: Seven cross-sectional studies involving 779 patients in the frequency analysis documented transformation of craniofacial FD into OS in 13 patients, for a frequency of 1.67%. Of the 18 separate cases of osteosarcomatous transformation in the case analysis, 11 (61.1%) occurred in females, 11 (61.1%) developed from monostotic FD, and 7 (38.9%) arose in the mandible, with 5 in the maxilla (27.8%) and 6 (33.3%) in other craniofacial sites. The mean age of the patients at the time of malignant diagnosis was 36.4 years, with an average of 11.3 years from FD diagnosis to the appearance of OS. The quality of the articles ranged from fair to excellent. CONCLUSIONS: The risk of osteosarcomatous transformation of craniofacial FD is low, but the possibility of transformation should be taken into consideration by clinicians, as this will guide treatment and follow-up regimens.

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis-An umbrella review.

BACKGROUND: The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. OBJECTIVES: This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single-nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area and (iii) present recommendations to conduct future clinical studies and systematic reviews. METHODS: A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR)-2 tool. Two independent reviewers were involved in study selection, data extraction and appraising the included reviews; disagreements were resolved by a third reviewer. RESULTS: The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas the other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor-alpha (TNF-α) -308 G > A and interleukin 1-beta (IL-1ß) + 3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed. DISCUSSION: The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of the included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G > A and IL-1ß + 3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution. CONCLUSIONS: No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

Emerging antiresorptive medications and their potential implications for dental surgeries.

BACKGROUND: The aim of this review was to discuss the current and newly emerging antiresorptive medications and their potential implications for dental surgeries. TYPES OF STUDIES REVIEWED: The authors searched PubMed (MEDLINE), Cochrane, Embase, and other electronic databases for articles related to osteonecrosis of the jaw and medication-related osteonecrosis of the jaw (MRONJ). In addition, the authors hand searched the bibliographies of all relevant articles, the gray literature, textbooks, and guidelines in association position statements. RESULTS: The following information for MRONJ risk should be evaluated before any invasive dental procedure: metastatic carcinoma has a higher risk than osteoporosis; parenterally administered bisphosphonates and denosumab have a higher risk than orally administered bisphosphonates or antiangiogenic agents; dose and duration of medication received; adjunctive medications or combination of antiresorptive agents also may increase the risk of MRONJ; additive factors and comorbidities such as diabetes, autoimmune disease, immunosuppression, or any condition that might affect healing negatively would result in potentially higher risk of developing MRONJ; angiogenic inhibitors as part of a cancer treatment regimen, with or without antiresorptive medication, are considered high risk. PRACTICAL IMPLICATIONS: Patients who received antiresorptive therapy for malignancy were at higher risk of developing MRONJ than those who received the therapy for osteoporosis, regardless of the route of administration and type of drug. Antiangiogenic agents, bevacizumab, aflibercept, and tyrosine kinase inhibitors such as sunitinib were implicated most commonly in the development of MRONJ. Patients who are taking multiple doses of angiogenic inhibitors should be monitored closely for early diagnosis of possible MRONJ.

Perioperative Antiplatelet and Anticoagulant Management with Endodontic Microsurgical Techniques.

INTRODUCTION: The purpose of this study was to review evidence-based recommendations for the safe perioperative management of patients undergoing endodontic microsurgery who are currently taking antiplatelet or anticoagulant medications. Using the PICO (Population, Intervention, Comparison, Outcome) format, the following scientific question was asked: In patients taking anticoagulant or antiplatelet agents, what is the available evidence in the management of endodontic microsurgery? METHODS: MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov databases were searched to identify current recommendations regarding the management of antiplatelet and anticoagulant medications in the context of outpatient dental surgical procedures. Additionally, the authors hand searched the bibliographies of all relevant articles, the gray literature, and textbooks. Because of the lack of clinical studies and evidence on this subject, articles and guidelines from other organizations and association position statements were included. RESULTS: Because any minor surgery can become a major surgery, the treating doctor needs to best assess the risk of bleeding, especially if the surgery is anticipated to take longer than 45 minutes. Every patient should be stratified on a case-by-case basis. Consultation with the patient's physician is highly recommended. CONCLUSIONS: In order to maximize the effects of these medications (to prevent thrombosis) while minimizing the potential risks (procedural hemorrhage), clinicians should be aware of the best available evidence when considering continuation or discontinuation of antiplatelet and anticoagulant agents perioperatively for endodontic microsurgery. Ideally, a joint effort from an expert panel for microsurgery would be warranted.

Artificial Intelligence in Endodontics: Current Applications and Future Directions.

INTRODUCTION: Artificial intelligence (AI) has the potential to replicate human intelligence to perform prediction and complex decision making in health care and has significantly increased its presence and relevance in various tasks and applications in dentistry, especially endodontics. The aim of this review was to discuss the current endodontic applications of AI and potential future directions. METHODS: Articles that have addressed the applications of AI in endodontics were evaluated for information pertinent to include in this narrative review. RESULTS: AI models (eg, convolutional neural networks and/or artificial neural networks) have demonstrated various applications in endodontics such as studying root canal system anatomy, detecting periapical lesions and root fractures, determining working length measurements, predicting the viability of dental pulp stem cells, and predicting the success of retreatment procedures. The future of this technology was discussed in light of helping with scheduling, treating patients, drug-drug interactions, diagnosis with prognostic values, and robotic-assisted endodontic surgery. CONCLUSIONS: AI demonstrated accuracy and precision in terms of detection, determination, and disease prediction in endodontics. AI can contribute to the improvement of diagnosis and treatment that can lead to an increase in the success of endodontic treatment outcomes. However, it is still necessary to further verify the reliability, applicability, and cost-effectiveness of AI models before transferring these models into day-to-day clinical practice.

Tumor Necrosis Factor Alpha -308 G/A Single-Nucleotide Polymorphism and Apical Periodontitis: An Updated Systematic Review and Meta-analysis.

INTRODUCTION: This study aimed to perform a more precise estimation of the association between tumor necrosis factor alpha (TNF-α) -308 G/A single-nucleotide polymorphism (SNP) and the risk of development of apical periodontitis (AP) and its phenotypes based on all available published studies. METHODS: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered in PROSPERO (CRD42020176190). The literature search was conducted via Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases from inception to December 2020 with no language restrictions. Two reviewers were involved independently in the study selection, data extraction, and appraising the studies that were included. The quality of the included studies was evaluated using the Strengthening the Reporting of Genetic Association and the Grading of Recommendations Assessment, Development and Evaluation system. The frequencies of the genotypes and alleles of the TNF-α (G>A 308, rs1800629) gene with 95% odds ratio were used. RESULTS: Four studies met the inclusion criteria with moderate risk of bias. This study revealed no significant association between TNF-α -308 G/A SNP and AP and the risk of AP development. Moreover, there was no significant association between genotype or allele frequency distribution and clinical manifestations (acute vs chronic) of AP. The certainty of evidence per the Grading of Recommendations Assessment, Development and Evaluation system was very low. CONCLUSIONS: Because of very low certainty of evidence, whether there is an association between TNF-α -308 G/A SNP and AP warrants further well-designed multicentric studies to adjudicate a better understanding of the role of genetic factors in the etiopathogenesis of AP.

Preclinical Assessment of the Effectiveness of Magnetic Resonance Molecular Imaging of Extradomain-B Fibronectin for Detection and Characterization of Oral Cancer.

PURPOSE: Oral squamous cell carcinoma (OSCC) has not seen a substantial improvement in patient survival despite therapeutic advances, making accurate detection and characterization of the disease a clinical priority. Here, we aim to demonstrate the effectiveness of magnetic resonance imaging (MRI) with the targeted MRI contrast agent MT218 specific to extradomain-B fibronectin (EDB-FN) in the tumor microenvironment for detection and characterization of aggressive OSCC tumors. PROCEDURES: EDB-FN expression was evaluated in human normal tongue and OSCC specimens with immunohistochemistry. Invasiveness of human CAL27, HSC3, and SCC4 OSCC cells was analyzed with spheroid formation and transwell assays. EDB-FN expression in the cells was analyzed with semiquantitative real-time PCR, western blotting, and a peptide binding study with confocal microscopy. Contrast-enhanced MRI with MT218 was performed on subcutaneous OSCC mouse models at a dose of 0.04 mmol/kg, using gadoteridol (0.1 mmol/kg) as a control. RESULTS: Strong EDB-FN expression was observed in human untreated primary and metastatic OSCC, reduced expression in treated OSCC, and little expression in normal tongue tissue. SCC4 and HSC3 cell lines demonstrated high invasive potential with high and moderate-EDB-FN expression, respectively, while CAL27 showed little invasive potential and low-EDB-FN expression. In T1-weighted MRI, MT218 produced differential contrast enhancement in the subcutaneous tumor models in correlation with EDB-FN expression in the cancer cells. Enhancement in the high-EDB-FN tumors was greater with MT218 at 0.04 mmol/kg than gadoteridol at 0.1 mmol/kg. CONCLUSIONS: The results suggest EDB-FN has strong potential as an imageable biomarker for aggressive OSCC. MRMI results demonstrate the effectiveness of MT218 and the potential for differential diagnostic imaging of oral cancer for improving the management of the disease.

The Effect of Lunasin on Receptor Activator of Nuclear Factor Kappa-B Ligand-mediated Osteoclast Formation from RAW 264.7 Cells.

INTRODUCTION: To date, no study has investigated the antiresorptive property of lunasin. Hence, the present study aimed to assess the ability of lunasin to inhibit the osteoclast formation using RAW 264.7 cells. We hypothesized that lunasin is able to inhibit osteoclast formation. METHODS: In the present study, the murine monocytic cell line RAW 264.7 was induced to differentiate into mature osteoclasts in the presence of recombinant receptor activator of nuclear factor kappa-B ligand. Tartrate-resistant acid phosphatase, a marker of osteoclasts, was used to identify osteoclasts. Cell lines were divided into different groups and exposed to different concentrations of 50 µmol/L, 75 µmol/L, and 100 µmol/L active and inactive lunasin. The control group was RAW 264.7 cells with receptor activator of nuclear factor kappa-B ligand. Tartrate-resistant acid phosphatase-positive cells of 3 or more nuclei, indicative of mature osteoclasts, were counted by 3 observers. The mean number of the data collected was analyzed using 1-way analysis of variance and the multiple comparison post hoc Bonferroni correction. RESULTS: There was a significant difference in the reduction of osteoclast formation in all the active lunasin groups (P < .001) compared with the control group and the inactive lunasin group (P < .001). CONCLUSIONS: Considering the suppressive effect of lunasin on osteoclastogenesis, the use of lunasin as a potential antiresorptive agent can be evaluated in future studies.

Comparison of IL-1ß, TNF-α, hBD-2, and hBD-3 Expression in the Dental Pulp of Smokers Versus Nonsmokers.

INTRODUCTION: To date, the endodontic literature lacks research on the effect of smoking on cytokine and defensin expression in the dental pulp. Therefore, the aim of this study was to investigate the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2 and hBD-3 in the dental pulp of smokers and compare them with nonsmokers. We hypothesized that cytokine and defensin expression would be reduced in smokers as compared with nonsmokers. METHODS: Thirty-two smokers and 37 nonsmokers with endodontic pulpal diagnoses of normal, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis were included in this cross-sectional study. Samples from pulp chambers were collected and stored in phosphate-buffered saline at -80°C. Luminex was used to measure IL-1ß and TNF-α levels. The levels of hBD-2 and hBD-3 were measured using enzyme-linked immunosorbent assay. Marker levels were normalized to protein concentrations and data were analyzed using Kruskal-Wallis test, Mann-Whitney U test, and 2-way analysis of variance (α = 0.05). RESULTS: Pulpal concentrations of TNF-α and hBD-2 were significantly lower among smokers (P < .01), whereas no significant difference was observed for IL-1ß, or hBD-3. Two-way analysis of covariance revealed that smoking status (P < .001), not endodontic diagnosis (pulpal status), significantly affected TNF-α and hBD-2 levels. CONCLUSIONS: This study reported that smokers are immunologically deficient in TNF-α and hBD-2, suggesting that dental pulps of smokers possess limited defense mechanisms, affecting their endodontic prognosis and indicating a cause for their reported inferior outcome.

The Influence of Periodontal Status on Endodontically Treated Teeth: 9-year Survival Analysis.

INTRODUCTION: The aim of this study was to investigate the effect of periodontal status at the time of nonsurgical root canal treatment (NSRCT) on the survival rate of endodontically treated teeth (ETT). METHODS: In this retrospective investigation, molars that received NSRCT in an advanced specialty education program in endodontics from 2009 through 2017 were initially recruited. After the application of inclusion and exclusion criteria, 315 teeth were included in the study. Inclusion criteria were ETT with an acceptable quality of NSRCT; ETT that received an adequate crown within 3 months after NSRCT; and ETT with complete periodontal charting before NSRCT including pocket depths, clinical attachment loss, and bone loss. The periodontal status of all included teeth was assessed based on American Academy of Periodontology guidelines. All included ETT were divided into 3 groups as follows: healthy group, mild periodontitis, and moderate periodontitis. The survival rate of ETT was analyzed using univariate Kaplan-Meier and log-rank tests for differences between groups (P < .05). A Cox regression model was used to assess the effect of independent variables on the survival rate. RESULTS: Teeth that were diagnosed with mild periodontitis were almost 2 times more likely to be extracted compared with ETT diagnosed with normal periodontium at the time of NSRCT (odds ratio [OR] = 1.9, P < .05). This increased risk of tooth loss was 3.1 (OR = 3.1, P < .05) for ETT diagnosed with moderate periodontitis. Smokers were twice as likely to have tooth loss compared with nonsmokers (OR = 2.2, P < .05). CONCLUSIONS: Patients' periodontal health, being 1 of the prognostic determinants of the outcome of NSRCT, requires attention before and subsequent to NSRCT. This may improve the survival of ETT and help patients maintain their natural dentition.

Determination of mutagenicity of the precipitate formed by sodium hypochlorite and chlorhexidine using the Ames test.

The aim of this study was to determine the direct mutagenic potential of any precipitate formed by combining sodium hypochlorite (NaOCl) and chlorhexidine (CHX). The precipitates formed by NaOCl and CHX were dissolved in 100% dimethyl sulfoxide and cultured with mutant Salmonella Typhimurium strains. The cells were observed for reverse mutation. The numbers of positive/mutated wells were statistically compared with those in the background plates using the two-sample proportion independent t-test. The precipitates were not found to be significantly more mutagenic than the background plates. Within the limitations of this study, the results suggest that the precipitates formed when sodium hypochlorite and chlorhexidine contact did not show mutagenic (and are therefore carcinogenic) potential.

Association of Functional Gene Polymorphism with Apical Periodontitis.

INTRODUCTION: To date, only a few studies have searched for relationships between genetic polymorphism and periapical microbial infection. Thus, the purpose of this systematic review was to evaluate the relationship between host modifying factors and their association with apical periodontitis. METHODS: Two reviewers independently conducted a comprehensive literature search. The MEDLINE, Embase, Cochrane, and PubMed databases were searched. Additionally, the bibliographies of all relevant articles and textbooks were manually searched. RESULTS: Eight articles were identified and included in this review. The results of the present review suggest that although some authors have reported that some biologic markers may play a role in apical periodontitis, others have not supported this association. Limitations were noted in the current studies by not judiciously matching selected case/control groups, balancing or adjusting for confounders (such as smoking, diabetes, and body mass index), using the Hardy-Weinberg Equilibrium, providing power calculation for a given sample size, correcting for false-positive (type I) error, or providing odds ratios with confidence intervals. The results of this review suggest polymorphism and biological modifiers, by which some individuals, if challenged by bacterial accumulations, may exhibit a more vigorous immunoinflammatory response, leading to apical periodontitis. CONCLUSIONS: More research in this area is warranted to determine greater specificity in these possible interactions.

An analysis of moderate sedation protocols used in dental specialty programs: a retrospective observational study.

INTRODUCTION: Pain and anxiety control is critical in dental practice. Moderate sedation is a useful adjunct in managing a variety of conditions that make it difficult or impossible for some people to undergo certain dental procedures. The purpose of this study was to analyze the sedation protocols used in 3 dental specialty programs at the Case Western Reserve University School of Dental Medicine, Cleveland, OH. METHODS: A retrospective analysis was performed using dental school records of patients receiving moderate sedation in the graduate endodontic, periodontic, and oral surgery programs from January 1, 2010, to December 31, 2012. Information was gathered and the data compiled regarding the reasons for sedation, age, sex, pertinent medical conditions, American Society of Anesthesiologists physical status classifications, routes of administration, drugs, dosages, failures, complications, and other information that was recorded. RESULTS: The reasons for the use of moderate sedation were anxiety (54%), local anesthesia failures (15%), fear of needles (15%), severe gag reflex (8%), and claustrophobia with the rubber dam (8%). The most common medical conditions were hypertension (17%), asthma (15%), and bipolar disorder (8%). Most patients were classified as American Society of Anesthesiologists class II. More women (63.1%) were treated than men (36.9%). The mean age was 45 years. Monitoring and drugs varied among the programs. The most common tooth treated in the endodontic program was the mandibular molar. CONCLUSIONS: There are differences in the moderate sedation protocols used in the endodontic, periodontic, and oral surgery programs regarding monitoring, drugs used, and record keeping.

Determination of the location of the mental foramen: a critical review.

INTRODUCTION: The mental foramen (MF) is an important landmark to consider during surgical endodontic procedures. The purpose of this review article was to discuss the variety of techniques that have been developed to determine the location of the MF, to make recommendations for the current best technique available, and to discuss upcoming technologies. METHODS: Articles that have addressed the location of the MF were evaluated for information pertinent to include in this review. RESULTS: Different technologies have been used to help operators determine the clinical location of the MF. Most of the techniques have shortcomings such as magnification, radiation, and cost. Cone-beam computed tomographic imaging is the best current available imaging technology to determine the accurate location of the MF, but it has shortcomings such as radiation, cost, and not being real time, which means the data must be interpreted at a later time than when the information was computed. CONCLUSIONS: In the future, magnetic resonance imaging and ultrasound technologies seem to provide promising noninvasive imaging techniques.

The effect of docosahexaenoic acid (DHA) on expression of IL-1ß, IL-6, IL-8, and TNF-α in normal and lipopolysaccharide (LPS)-stimulated macrophages.

OBJECTIVE: Differentiated macrophages (MØ) are the resident tissue phagocytes and sentinel cells of the innate immune response. These cells are major constituents of periapical granulomas. Current studies indicate these activated cells as the source of bone-resorbing cytokines in the periapical granuloma. Periapical inflammation can be mediated by proinflammatory cytokines like interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), IL-6, and IL-8. Reducing the production of these cytokines may be beneficial for the treatment of periapical lesions. Oils rich in omega-3 fatty acids like docosahexaenoic acid (DHA) have been linked with anti-resorptive and bone-protective effects. The purpose of this investigation was to study the effect of DHA on the expression of these cytokines by normal and lipopolysaccharide (LPS)-treated MØ. We hypothesized that pretreatment of MØ with DHA decreases the expression of pro-inflammatory cytokines induced by LPS-treated MØ. METHOD AND MATERIALS: THP-1 monocytes were cultured and differentiated into MØ. DHA was added to MØ in a dose-dependent manner. MØ samples were added to the following groups: Group 1, ethanol alone as a solvent control; Group 2, 10 µg/ml of DHA (D1); Group 3, 20 µg/ml of DHA (D2); Group 4, 10 µg/ml of DHA + LPS (DL1); Group 5, 20 µg/ml of DHA + LPS (DL2); Group 6, LPS alone. Reverse transcriptase-PCR (RT-PCR) followed by ImageJ analysis was used to measure cytokine expression. RESULTS: The results show that IL-1ß and TNF-α levels for DL and DHA (basal) were significantly lower than the levels in LPS alone. IL-6 was increased in the DL groups. There was no significant change for IL-8. CONCLUSION: DHA at higher concentrations may selectively decrease proinflammatory cytokine production of IL-1ß and TNF-α. More studies are needed to verify the anti-inflammatory therapeutic action of agents like DHA omega-3 fatty acids.

A comparison of the cytotoxicity and proinflammatory cytokine production of EndoSequence root repair material and ProRoot mineral trioxide aggregate in human osteoblast cell culture using reverse-transcriptase polymerase chain reaction.

INTRODUCTION: The purpose of this study was to compare the cytotoxicity and cytokine expression profiles of EndoSequence Root Repair Material (ERRM; Brasseler, Savannah, GA) putty, ERRM flowable, and ProRoot mineral trioxide aggregate (MTA; Dentsply Tulsa Dental, Johnson City, TN) using osteoblast cells (MG-63). METHODS: Four millimeters in diameter of each material was placed in the center of a 6-well culture plate, and a 2-mL suspension (10(5) cells/mL) of human osteoblasts was seeded in each well. Photomicrograph images were used to evaluate cytotoxicity as evidenced by the lack of osteoblast cell growth in relation to the materials with AH-26 (Dentsply Tulsa Dental) as the positive control. In addition, reverse-transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the expression of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Cytokine expression of MG-63 cells upon lipopolysaccharide treatment was used as controls. RT-PCR results were normalized by the expression of the housekeeping gene ß-actin and were used to measure cytokine expression. Statistical analysis was performed using analysis of variance. RESULTS: Results showed that ERRM putty and MTA exhibited minimal levels of cytotoxicity; however, ERRM was slightly more cytotoxic although not statistically significant. The expression of IL-1ß, IL-6, and IL-8 was detected in all samples with minimal TNF-α expression. CONCLUSIONS: We concluded that ERRM and MTA showed similar cytotoxicity and cytokine expressions.