Inter and intra-operator reliability of Lekholm and Zarb classification and proposal of a novel radiomic data-driven clustering for qualitative assessment of edentulous alveolar ridges.

OBJECTIVES: The present study was conducted to evaluate the reproducibility of Lekholm and Zarb classification system (L&Z) for bone quality assessment of edentulous alveolar ridges and to investigate the potential of a data-driven approach for bone quality classification. MATERIALS AND METHODS: Twenty-six expert clinicians were asked to classify 110 CBCT cross-sections according to L&Z classification (T0). The same evaluation was repeated after one month with the images put in a different order (T1). Intra- and inter-examiner agreement analyses were performed using Cohen's kappa coefficient (CK) and Fleiss' kappa coefficient (FK), respectively. Additionally, radiomic features extraction was performed from 3D edentulous ridge blocks derived from the same 110 CBCTs, and unsupervised clustering using 3 different clustering methods was used to identify patterns in the obtained data. RESULTS: Intra-examiner agreement between T0 and T1 was weak (CK 0.515). Inter-examiner agreement at both time points was minimal (FK at T0: 0.273; FK at T1: 0.243). The three different unsupervised clustering methods based on radiomic features aggregated the 110 CBCTs in three groups in the same way. CONCLUSIONS: The results showed low agreement among clinicians when using L&Z classification, indicating that the system may not be as reliable as previously thought. The present study suggests the possible application of a reproducible data-driven approach based on radiomics for the classification of edentulous alveolar ridges, with potential implications for improving clinical outcomes. Further research is needed to determine the clinical significance of these findings and to develop more standardized and accurate methods for assessing bone quality of edentulous alveolar ridges.

Diamond-Like Carbon Coating Reduces Connection Screw Head Stripping After Multiple Tightening Instances.

The stability of implant-abutment joint is fundamental for the long-term success of implant rehabilitation. The screw loosening, fracture, and head deformation are among the most common mechanical complications. Several surface treatments of titanium screws have been proposed to improve their resistance and stability. Diamond-like carbon (DLC) coating of the materials is widely used to increase their wear resistance and durability. The present study aimed to evaluate the effect of carbon fiber coating on the screw head on screw removal torque and screw head stripping. One hundred titanium implant screws were used, 50 without coating (Group 1) and 50 with DLC coating of the screw head (Group 2). Each screw was tightened with a torque of 25 Ncm and unscrewed 10 times. The removal torque was measured with a digital cap torque tester for each loosening. Optical 3d measurement of the screw head surface was performed by a fully automatic machine before and after multiple tightening to investigate surface modifications. The reverse torque values decreased with repeated tightening and loosening cycles in both groups without significant differences (P > .05). Optical measurements of surface dimensions revealed average changes of 0.0357 mm in Group 1 and 0.02312 mm in Group 2, which resulted to be statistically significant (P < .001). The DLC coating of the retention screw head can prevent its distortion and wear, especially after multiple tightening.

Can radiomic features extracted from intra-oral radiographs predict physiological bone remodelling around dental implants? A hypothesis-generating study.

AIM: The rate of physiological bone remodelling (PBR) occurring after implant placement has been associated with the later onset of progressive bone loss and peri-implantitis, leading to medium- and long-term implant therapy failure. It is still questionable, however, whether PBR is associated with specific bone characteristics. The aim of this study was to assess whether radiomic analysis could reveal not readily appreciable bone features useful for the prediction of PBR. MATERIALS AND METHODS: Radiomic features were extracted from the radiographs taken at implant placement (T0) using LifeX software. Because of the multi-centre design of the source study, ComBat harmonization was applied to the cohort. Different machine-learning models were trained on selected radiomic features to develop and internally validate algorithms capable of predicting high PBR. In addition, results of the algorithm were included in a multivariate analysis with other clinical variables (tissue thickness and depth of implant position) to test their independent correlation with PBR. RESULTS: Specific radiomic features extracted at T0 are associated with higher PBR around tissue-level implants after 3 months of unsubmerged healing (T1). In addition, taking advantage of machine-learning methods, a naive Bayes model was trained using radiomic features selected by fast correlation-based filter (FCBF), which showed the best performance in the prediction of PBR (AUC = 0.751, sensitivity = 66.0%, specificity = 68.4%, positive predictive value = 73.3%, negative predictive value = 60.5%). In addition, results of the whole model were included in a multivariate analysis with tissue thickness and depth of implant position, which were still found to be independently associated with PBR (p-value < .01). CONCLUSION: The combination of radiomics and machine-learning methods seems to be a promising approach for the early prediction of PBR. Such an innovative approach could be also used for the study of not readily disclosed bone characteristics, thus helping to explain not fully understood clinical phenomena. Although promising, the performance of the radiomic model should be improved in terms of specificity and sensitivity by further studies in this field.

Development and international validation of logistic regression and machine-learning models for the prediction of 10-year molar loss.

AIM: To develop and validate models based on logistic regression and artificial intelligence for prognostic prediction of molar survival in periodontally affected patients. MATERIALS AND METHODS: Clinical and radiographic data from four different centres across four continents (two in Europe, one in the United States, and one in China) including 515 patients and 3157 molars were collected and used to train and test different types of machine-learning algorithms for their prognostic ability of molar loss over 10 years. The following models were trained: logistic regression, support vector machine, K-nearest neighbours, decision tree, random forest, artificial neural network, gradient boosting, and naive Bayes. In addition, different models were aggregated by means of the ensembled stacking method. The primary outcome of the study was related to the prediction of overall molar loss (MLO) in patients after active periodontal treatment. RESULTS: The general performance in the external validation settings (aggregating three cohorts) revealed that the ensembled model, which combined neural network and logistic regression, showed the best performance among the different models for the prediction of MLO with an area under the curve (AUC) = 0.726. The neural network model showed the best AUC of 0.724 for the prediction of periodontitis-related molar loss. In addition, the ensembled model showed the best calibration performance. CONCLUSIONS: Through a multi-centre collaboration, both prognostic models for the prediction of molar loss were developed and externally validated. The ensembled model showed the best performance in terms of both discrimination and validation, and it is made freely available to clinicians for widespread use in clinical practice.

Prognostic significance of tumor budding thresholds in oral tongue squamous cell carcinoma.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. AIMS: The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. MATERIALS & METHODS: TB was evaluated on hematoxylin and eosin-stained sections in the hotspot area of the infiltrative front (×200-magnification). It was scored using a two-tier system, a three-tier system, and according to BD-model and revised-Grading system. Univariate and multivariate Cox regression analyses of disease-specific survival (DSS) and disease-free survival (DFS) were performed. A p < 0.05 was considered as statistically significant. RESULTS: The two-tier and three-tier systems resulted an independent prognostic factor of DSS. High-risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low-risk group. It is significantly increased even for intermediate-risk group. No significant differences emerged classifying patients according to BD-model and revised-Grading system. DISCUSSION: These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5-bud cutoff significantly discriminates their outcomes. CONCLUSION: Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

BACKGROUND: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. METHODS: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. RESULTS: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. CONCLUSIONS: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

Cost/effectiveness analysis of treatment options for the rehabilitation of the total edentulous mandible.

BACKGROUND: Several solutions are available for the rehabilitation of edentulous jaws. Each treatment option is characterised by specific advantages and drawbacks. OBJECTIVE: The aim of this research was to perform a cost-effectiveness (CE) analysis of the main rehabilitative solutions of totally edentulous mandibles. METHODS: Decision tree models were built using TreeAge Pro Healthcare 2021 software to compare the following strategies: Conventional Denture (CD), Overdenture retained by two implants (OD-2), Overdenture retained by a bar on two implants (ODbar), Overdenture retained by 4 mini-implants (ODmini) and Fixed denture supported by 4 implants (FD). Costs were estimated using data from public rate tables. Effectiveness measures were obtained from a meta-analysis of literature data, normalising the different scales in 0-1 range. A value of 30 000€ per 1 normalised utility points was set as threshold of willingness to pay (WTP). Probabilistic sensitivity analysis (PSA) with 1000 Monte Carlo Simulations was performed to characterise uncertainty. RESULTS: Total costs ranged between 1804,40€ for CD and 10 008,80€ for FD rehabilitations, with an effectiveness of 0,69 and 0,95 normalised points (0-1 scale) for the two solutions. The ODbar resulted to be the most CE strategy at the established WTP value, with the highest Net Monetary Benefit (22 001,20€), followed by the OD-2 rehabilitation (21 866,80€). PSA analysis confirmed the dominance of OD-2 and ODbar strategies, confirming a net separation from the other alternatives. CONCLUSION: OD stabilised by 2 implants could represent a good rehabilitative solution for patients with edentulous mandible, being a good trade-off in terms of costs and effectiveness. Nevertheless, a standardised measure of oral health-related quality of life is needed to obtain more reliable results.

Impact of Circulating Cell-Free DNA (cfDNA) as a Biomarker of the Development and Evolution of Periodontitis.

In the last few decades, circulating cell-free DNA (cfDNA) has been shown to have an important role in cell apoptosis or necrosis, including in the development and evolution of several tumors and inflammatory diseases in humans. In this regard, periodontitis, a chronic inflammatory disease that can induce the destruction of supporting components of the teeth, could represent a chronic inflammatory stimulus linked to a various range of systemic inflammatory diseases. Recently, a possible correlation between periodontal disease and cfDNA has been shown, representing new important diagnostic-therapeutic perspectives. During the development of periodontitis, cfDNA is released in biological fluids such as blood, saliva, urine and other body fluids and represents an important index of inflammation. Due to the possibility of withdrawing some of these liquids in a non-invasive way, cfDNA could be used as a possible biomarker for periodontal disease. In addition, discovering a proportional relationship between cfDNA levels and the severity of periodontitis, expressed through the disease extent, could open the prospect of using cfDNA as a possible therapeutic target. The aim of this article is to report what researchers have discovered in recent years about circulating cfDNA in the development, evolution and therapy of periodontitis. The analyzed literature review shows that cfDNA has considerable potential as a diagnostic, therapeutic biomarker and therapeutic target in periodontal disease; however, further studies are needed for cfDNA to be used in clinical practice.

Intaglio surface trueness of milled and 3D-printed digital maxillary and mandibular dentures: A clinical study.

STATEMENT OF PROBLEM: While the dimensional accuracy of the intaglio surface of a removable complete denture is key to its adaptation, comfort, and clinical performance, information on the ability of milling and 3D-printing workflows to accurately reproduce this surface is lacking. PURPOSE: The purpose of this clinical study was to compare the trueness of the intaglio surface of milled and 3D-printed removable complete digital dentures. MATERIAL AND METHODS: Intraoral scans were obtained from 14 participants for a total of 20 edentulous arches. Ten maxillary and 10 mandibular denture bases were then designed and fabricated with a completely digital workflow, both with milling and 3D-printing. Fabricated dentures were digitized with the same intraoral scanner used to obtain intraoral digital scans of the edentulous arches. Standard tessellation language (STL) files of the printed and milled denture bases were used for 3D analysis and comparisons with the STL file of the corresponding designed denture base. Specifically, a reverse engineering software program was used to trim and extract intaglio surfaces, align them, and measure their global mean 3D distance. In order to evaluate the homogeneity of production accuracy of each manufacturing process, the intaglio surfaces were also divided into several regions of interest and the corresponding 3D distances measured. Within- and between-group differences and maxillary and mandibular dentures differences were assessed with parametric and nonparametric tests (α=.05). RESULTS: Milling showed a global better trueness of the entire intaglio surface (-0.002 mm) than 3D-printing (0.018 mm), both for the whole data set (P<.001) and for maxillary (P=.032) or mandibular (P=.049) denture base subgroups. Within each fabrication technology, maxillary (P<.11) and mandibular dentures (P=.2) showed no significant difference in trueness. Measured deviations were significantly different from zero for the 3D-printed dentures (P<.001), but not for the milled dentures (P=.487). Additionally, for milled dentures, no significant difference in trueness was found among the 11 regions of interest identified for the maxillary dentures (P=.085) and the 13 regions of interest for the mandibular dentures (P=.211). Conversely, 3D-printing showed significant variations in trueness among the same zones of interest, both in maxillary (P<.001) and mandibular (P=.004) dentures. CONCLUSIONS: Within the limits of the manufacturing methodologies used for complete dentures, milling can provide a slightly better trueness of the intaglio surface than 3D-printing, with less variation across several zones of interest. However, given the magnitude of such differences, they may be reasonably considered to be of limited, if any, clinical significance.

Accuracy of trial complete dentures fabricated by using fused deposition modeling 3-dimensional printing: An in vitro study.

STATEMENT OF PROBLEM: Three-dimensional (3D) printing technologies commonly used for trial complete dentures use photopolymerizing resins. Although effective, some clinical, process-related, and practical issues associated with them are still unclear. The option of using alternative printing technologies may help in overcoming limitations. PURPOSE: The purpose of this in vitro study was to evaluate the trueness of trial dentures fabricated by using 3D-printing fused deposition modeling (FDM). MATERIAL AND METHODS: Ten maxillary and 10 mandibular digital complete trial dentures designed from intraoral scans were fabricated from polylactic acid by using a FDM 3D-printer. Each denture was scanned, and the scans were compared with the digital file of the designed denture by means of a surface-matching software program. The mean distance (both signed and absolute) was measured and recorded for the intaglio surface, as well as for the entire denture surface. Statistical analysis was performed to investigate the significance of the extent of measured distances, as well as differences between intaglio and global deviations; subgroup analysis for arch type was also performed (α=.05). RESULTS: Mean values of the intaglio distance were not significantly different from zero (P=.223). The manufacturing accuracy of the intaglio surface was higher than that measured for the entire denture (P<.001), confirmed both by the averaged signed (0 mm and -0.028 mm, respectively) and the absolute mean deviations (0.06 mm and 0.08 mm, respectively). No significant differences were found between maxillary and mandibular trial dentures. CONCLUSIONS: 3D-printing may constitute a valid and practical option for accurate and affordable digital trial dentures.

Three Dimensional Printed Surgical Guides: Effect of Time on Dimensional Stability.

PURPOSE: To analyze, in vitro, the dimensional stability over time of 3D-printed surgical guides. MATERIALS AND METHODS: Ten surgical guides, manufactured by digital light processing 3D-printing technology, were scanned immediately after post-processing and then after 5, 10, 15, and 20 days. The corresponding standard tessellation language (STL) files were used for comparison with the reference CAD project. Mean absolute deviation (MAD) of the intaglio surface, axial, and linear deviations of the sleeves' housings were measured. Generalized estimated equations models (α = 0.05) were used to investigate the effect of time. RESULTS: MAD of the teeth intaglio surface showed less variation (minimum: 0.002, maximum: 0.014 mm) than that of the mucosa (minimum: 0.026, maximum: 0.074 mm). Axial variations of the sleeves' housings on the sagittal (minimum: -0.008°, maximum: -0.577°) and frontal plane (minimum: -0.193°, maximum: 0.525°) changed with similar patterns, but opposite trends (decreasing for the former). Linear deviations of center points of the sleeves' housings had a shifting (minimum: -0.074, maximum: 0.02 mm) pattern with a decreasing tendency. Time after processing had a significant effect, either alone or nested with guides volume, on all outcomes of interest, except for MAD of the mucosa intaglio surface (p < 0.001), which was significantly affected only by the time-volume nested effect (p = 0.012). CONCLUSIONS: Within the limitations of the experimental design, postmanufacturing dimensional variations of surgical guides were statistically significant. Although limited, they are an additional source of variability affecting the overall accuracy of computer-guided surgery. As such, they should be addressed by further research.

Adjunctive use of locally delivered host-modulators in intra-bony defects as part of step 2 periodontal therapy: systematic review, meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review and meta-analysis aimed at investigate the role of locally delivered host-modulators in combination with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level and reducing bone defect depth in intra-bony defects. HIGHLIGHT: RCT with at least 6 months follow-up were included in this study. Risk of bias assessment was performed with Cochrane collaboration tool and Grade GRADEpro. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence. 22 studies met the inclusion criteria and were included in this systematic review. At 6 months locally delivered host-modulators significantly improved PD and CAL and bone defect depth. CONCLUSION: Considering the emerging role of host-inflammatory response in the treatment of periodontitis, several studies are exploring the role of locally delivered host modulators as an adjunct to step 2 of periodontal therapy.

Effects of Fermented Wheat Germ Extract on Oral Cancer Cells: An In Vitro Study.

Oral carcinoma is one of the most aggressive cancers, and despite the advances in the therapy, its mortality is still high. An attention in cancer treatment has focused on natural compounds due to their potential beneficial effects on human health. In this study, the effects of dietary supplement Fermented Wheat Germ Extract (FWGE) on oral tongue squamous cell carcinoma (OTSCC) cells were investigated In Vitro using three cell lines (HSC-3, SAS, SCC-25) with variable aggressiveness. The cell viability was significantly decreased by the treatment with high concentration of FWGE in every cell line. Regarding migration and invasion, HSC-3 and SCC-25 cells were most sensitive to FWGE since their movement was significantly reduced with 5 and 10 mg/ml FWGE, while SAS was inhibited only with 10 mg/ml FWGE. Chemotherapeutic compounds (cisplatin and 5-fluorouracil) significantly reduced all OTSCC cells viability. Importantly, combination of these drugs with 10 mg/ml FWGE significantly decreased the cell viability compared to the treatment with the chemotherapeutics or FWGE alone. Based on these In Vitro experiments, the use of FWGE seems to improve the anticancer effects on OTSCC cells. Further In Vivo and clinical studies should be conducted to verify the positive effects of FWGE for OTSCC patients.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer.

BACKGROUND: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. METHODS: Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. RESULTS: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . CONCLUSION: The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

Antibiotic prophylaxis at the time of dental implant placement: a cost-effectiveness analysis.

BACKGROUND: Antibiotic prophylaxis during implant placement may improve implant short term survival. Nevertheless, use of antibiotics carries risks of adverse effects and antibiotic resistance. The aim of the present study is to compare the use of antibiotics in dental implant procedures in terms of costs and effectiveness. METHODS: A decision-tree model was developed using TreeAge Pro Healthcare software. Two strategies were compared: Antibiotics and No antibiotics in implant placement procedures. The costs were calculated considering direct costs for implant placement, antibiotic costs, and costs for implant replacement in case of failure. Effectiveness was defined in terms of General Oral Health Assessment Index. Outcomes were evaluated as Incremental Cost Effectiveness Ratio (ICER). One-way sensitivity analysis and Probabilistic Sensitivity Analysis were performed for the most influential variables to test parameter uncertainty. Patient and healthcare perspectives were considered. RESULTS: Antibiotic prophylaxis resulted to be cost-effective compared to no use of antibiotics (ICER = 14,692,64 and ICER = 3841,18, respectively for patient's and healthcare perspective). The cost of antibiotics, cost of implant replacement in case of failure and probability of adverse effects significantly influenced the results. CONCLUSIONS: From an individual patient perspective, antibiotic strategy can be considered cost-effective, even when the cost of antibiotic therapy increases. We can conclude that the administration of antibiotics in association with implant placement is recommended in clinical practice, as it increases the success rate and makes the treatment more effective. However, attention should be placed when healthcare perspective is considered, particularly in terms of antibiotic resistance that may impact public health and associated costs.

Comparative cost-analysis for removable complete dentures fabricated with conventional, partial, and complete digital workflows.

STATEMENT OF PROBLEM: Comparative cost-analysis related to different manufacturing workflows for removable complete denture fabrication is seldom performed before the adoption of a new technology. PURPOSE: The purpose of this study was to compare the clinical and laboratory costs of removable complete dentures fabricated with a conventional (workflow C), a partial digital (workflow M), and a complete digital (workflow D) workflow and to calculate the break-even points for the implementation of digital technologies in complete denture fabrication. MATERIAL AND METHODS: Clinical and laboratory costs for each of the investigated workflows and the manufacturing options related to denture base and denture teeth fabrication were collected from 10 private Italian dental laboratories and clinics. The selected variables included the clinical and laboratory manufacturing time needed to complete each workflow (opportunity cost); costs for materials, labor, packaging, and shipping; and capital and fixed costs for software and hardware, including maintenance fees. The effect of manufacturing workflows and their options on the outcomes of interest was investigated by using generalized estimated equations models (α=.05). Cost minimization and sensitivity analysis were also performed, and break-even points were calculated for the equipment capital costs related to the implementation of workflows M and D. RESULTS: From a laboratory standpoint, workflows M and D and related manufacturing options significantly (P<.001) reduced manufacturing time (5.90 to 6.95 hours and 6.30 to 7.35 hours, respectively), and therefore the opportunity cost of each denture compared with workflow C. Workflow M allowed variable costs savings between 81 and 169 USD, while workflow D allowed for an additional saving of 34 USD. The sensitivity analysis showed that the break-even point related to the capital investment for the equipment needed to implement workflows M and D could be reached, depending on the manufacturing options adopted, between 170 and 933 dentures for workflow M and between 73 and 534 dentures for workflow D. From a clinical standpoint, workflows C and M were almost identical. Conversely, workflow D, which included intraoral scanning, required 1 fewer appointment, saving 0.6 hours of chairside time and about 14 USD for materials compared with M. CONCLUSIONS: Digital workflows (partial and complete digital workflows) were more efficient and cost-effective than the conventional method of fabricating removable complete dentures, with workflow D showing the lowest opportunity and variable costs and break-even point. Savings increased when stock denture teeth were replaced with milled denture teeth and still further with the adoption of 3-dimensionally (3D) printed denture teeth. Milling equipment and materials for denture base fabrication were more expensive than those for 3D-printing. Milling monobloc dentures reduced opportunity and labor costs but increased material cost.

Added effect of 1% topical alendronate in intra-bony and inter-radicular defects as part of step II periodontal therapy: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level, and reducing bone defect depth in intra-bony and inter-radicular defects. METHODS: RCTs with more than 6 months follow-up were included in this study. Risk of bias assessment was performed using the Cochrane collaboration tool. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence. RESULTS: Seven studies met the inclusion criteria and were included in the systematic review. Topical application of alendronate during second step of periodontal therapy significantly improved PD and CAL. CONCLUSION: Local application of alendronate may confer a beneficial effect when applied during step II of periodontal therapy even if long term studies are needed to confirm these results. CLINICAL RELEVANCE: Considering the emerging role of host-inflammatory response in treatment of periodontitis and the antiresorptive and osteostimulative properties of bisphosphonates, several studies are focusing on the role of alendronate as an addition to non-surgical periodontal therapy.

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer.

BACKGROUND: Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. METHODS: A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome-genome-transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients' overall survival. RESULTS: TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. CONCLUSIONS: The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.

Addition of the tumour-stroma ratio to the 8th edition American Joint Committee on Cancer staging system improves survival prediction for patients with oral tongue squamous cell carcinoma.

AIMS: One of the objectives of current research is to customise the treatment of cancer patients. The achievement of this objective requires stratification of patients based on the most significant prognostic factors. The aims of this study were to evaluate the prognostic value of the tumour-stroma ratio (TSR), defined as the proportion of tumour cells relative to surrounding stroma, in patients with oral tongue squamous cell carcinoma (OTSCC), and to develop a prognostic nomogram based on the most significant clinicopathological features. METHODS AND RESULTS: Clinicopathological data of 211 patients treated at 'Ospedali Riuniti' General Hospital (Ancona, Italy) for OTSCC were collected. One hundred and thirty-nine patients were restaged according to the 8th edition American Joint Committee on Cancer (AJCC) staging system. Evaluation of the TSR was performed on haematoxylin and eosin-stained slides, and correlation with survival outcomes was evaluated. In addition, with the aim of integrating the independent value of the TSR with the 8th edition AJCC staging system, a prognostic nomogram for OTSCC has been developed. OTSCC with a low TSR (i.e. a high proportion of stroma and a low proportion of tumour cells) was shown to have negative prognostic value in terms of disease-specific survival, with a hazard ratio (HR) of 1.883 and a 95% confidence interval (CI) of 1.033-3.432 (P = 0.039), and overall survival (HR = 1.747, 95% CI 0.967-3.154; P = 0.044), independently of other histological and clinical parameters. For the cohort of 139 patients restaged according to the 8th edition AJCC staging system, variables correlating with a poor prognosis were: the TSR, perineural invasion, and sex. The nomogram built on these parameters showed good predictive capacity, outperforming the 8th edition AJCC staging system in stratifying disease-specific survival in OTSCC patients. CONCLUSIONS: Including the TSR in the predictive model could improve risk stratification of OTSCC patients and aid in making treatment decisions.