Salivary Diagnosis of Dental Caries: A Systematic Review.

The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.

The Association between Salivary Metabolites and Gingival Bleeding Score in Healthy Subjects: A Pilot Study.

Periodontal diseases, including gingivitis and periodontitis, are among the most prevalent diseases in humans. Gingivitis is the mildest form of periodontal disease, characterized by inflammation of the gingiva caused by the accumulation of dental plaque. Salivary diagnostics are becoming increasingly popular due to the variation in saliva composition in response to pathological processes. We used a metabolomics approach to investigate whether a specific saliva metabolic composition could indicate preclinical stage of gingivitis. 1H-NMR spectroscopy was used to obtain the salivary metabolite profiles of 20 healthy subjects. Univariate/multivariate statistical analysis evaluated the whole saliva metabolite composition, and the Full-Mouth Bleeding Score (FMBS) was employed as a classification parameter. Identifying a signature of specific salivary metabolites could distinguish the subjects with high FMBS scores but still within the normal range. This set of metabolites may be due to the enzymatic activities of oral bacteria and be associated with the early stages of gingival inflammation. Although this analysis is to be considered exploratory, it seems feasible to establish an FMBS threshold that distinguishes between the absence and presence of early inflammatory alterations at the salivary level.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Human Serum and Salivary Metabolomes: Diversity and Closeness.

Saliva, which contains molecular information that may reflect an individual's health status, has become a valuable tool for discovering biomarkers of oral and general diseases. Due to the high vascularization of the salivary glands, there is a molecular exchange between blood and saliva. However, the composition of saliva is complex and influenced by multiple factors. This study aimed to investigate the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using 1H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole-saliva samples collected concurrently from the same individuals using multivariate and univariate statistical analysis. Our results show that serum is more concentrated and less variable for most of the shared metabolites than the three saliva types. While we found moderate to strong correlations between serum and saliva concentrations of specific metabolites, saliva is not simply an ultrafiltrate of blood. The intense oral metabolism prevents very strong correlations between serum and salivary concentrations. This study contributes to a better understanding of salivary metabolic composition, which is crucial for utilizing saliva in laboratory diagnostics.

Sample optimization for saliva 1H-NMR metabolic profiling.

Nuclear Magnetic Resonance (NMR) based metabolomic analysis of whole saliva has provided potential diagnostic biomarkers for numerous human diseases contributing to a better understanding of their mechanisms. However, a comprehensive interpretation of the significance of metabolites in whole, parotid, and submandibular/sublingual saliva subtypes is still missing. Precision and reproducibility of sample preparation is an essential step. Here, we present a simple and efficient protocol for saliva 1H-NMR metabolic profiling. This procedure has been specifically designed and optimized for the identification and quantification of low concentration metabolites (as low as 1.1 µM) and is suitable for all the saliva subtypes.

Salivary Cytokines as Biomarkers for Oral Squamous Cell Carcinoma: A Systematic Review.

The prognosis of patients with oral squamous carcinoma (OSCC) largely depends on the stage at diagnosis, the 5-year survival rate being approximately 30% for advanced tumors. Early diagnosis, including the detection of lesions at risk for malignant transformation, is crucial for limiting the need for extensive surgery and for improving disease-free survival. Saliva has gained popularity as a readily available source of biomarkers (including cytokines) useful for diagnosing specific oral and systemic conditions. Particularly, the close interaction between oral dysplastic/neoplastic cells and saliva makes such fluid an ideal candidate for the development of non-invasive and highly accurate diagnostic tests. The present review has been designed to answer the question: "Is there evidence to support the role of specific salivary cytokines in the diagnosis of OSCC?" We retrieved 27 observational studies satisfying the inclusion and exclusion criteria. Among the most frequent cytokines investigated as candidates for OSCC biomarkers, IL-6, IL-8, TNF-α are present at higher concentration in the saliva of OSCC patients than in healthy controls and may therefore serve as basis for the development of rapid tests for early diagnosis of oral cancer.

Histopathological determinants of autofluorescence patterns in oral carcinoma.

Biological tissues (including oral mucosa) can absorb and re-emit specific light wavelengths, detectable through spectrophotometric devices. Such a phenomenon is known as "autofluorescence" (AF). Several devices evaluating tissue AF have been developed and commercialized in the last two decades. Among these, the VELscope® system has been proposed as a visual diagnostic aid for potentially malignant disorders and malignant lesions of the oral mucosa. In the present pilot study, we investigated which are the main histopathological features possibly related to variations in AF patterns in a set of 20 oral squamous cell verrucous carcinoma. Among all the histological features investigated, only the mean width of keratin was significantly different between hypofluorescent and hyperfluorescent carcinomas. The results of the present study demonstrate that AF features of oral malignant lesions are significantly associated with the width of their keratin layer.

Salivary MicroRNA for Diagnosis of Cancer and Systemic Diseases: A Systematic Review.

: Background: The aberrant expression of microRNAs (miRNAs) has been associated with several diseases, including cancer, inflammatory, and autoimmune conditions. Interest in salivary miRNAs as non-invasive tools for the diagnosis of malignancies and systemic diseases is rapidly increasing. The present systematic review was developed for answering the question: "Are salivary microRNAs reliable biomarkers for diagnosis of cancer and systemic diseases?" METHODS: The application of inclusion and exclusion criteria led to the selection of 11 papers. Critical appraisals and quality assessments of the selected studies were performed through the National Institute of Health "Study Quality Assessment Tool" and the classification of the Oxford Center for Evidence-Based Medicine. RESULTS: Seven studies reported statistically significant correlations between one or more salivary miRNAs and the investigated disease. The critical analysis allowed us to classify only two studies (18.2%) as having "good" quality, the rest being scored as "intermediate" (8; 73%) and "poor" (1; 9%). Evidence exists that salivary miR-940 and miR-3679-5p are reliable markers for pancreatic cancer and that miR140-5p and miR301a are promising molecules for the salivary diagnosis of gastric cancer. CONCLUSIONS: Further studies, possibly avoiding the risk of bias highlighted here, are necessary to consolidate these findings and to identify new reliable salivary biomarkers.

Auto-Fluorescence and Histopathologic Evaluation of Medication-Related Osteonecrosis of the Jaws: Perspectives for Treatment.

Auto-fluorescence (AF) of healthy bone tissue has recently been described. Loss of AF (LAF) has, on the contrary, been reported in necrotic bone. Further, the use of LAF as a possible guidance to distinguish viable from necrotic bone during surgical treatment of osteonecrosis has been proposed. The aim of this study is to detail 8 patients of medication-related osteonecrosis of the jaws treated through an AF-guided surgical resection. The authors also provide the histopathologic description of hypo-fluorescent and hyper-fluorescent bone in each patient. After removal of necrotic bone block, Er:YAG laser was used for vaporizing further necrotic bone, up to the detection of strongly hyper-fluorescent bone. Samples of hyper-fluorescent bone were collected around areas of necrosis. Histopathologic evaluation revealed viable bone tissue in all hyper-fluorescent specimens. On the basis of these data, AF-guided surgical resection could be effective in highlighting surgical margins of necrotic bone tissue and it might have some utility in a range of applications of bone surgery.

Self-healing CD30- T-clonal proliferation of the tongue: report of an extremely rare case.

BACKGROUND: The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer. CASE PRESENTATION: Here we report a controversial case of a self-healing lesion of the tongue in a 57 year-old woman. A clonal T-cell proliferation and CD30 negative immunohistochemical (IHC) profile could be documented. DISCUSSION AND CONCLUSION: In view of the very peculiar clinical and histological features, a retrospective diagnosis of a TUGSE with scarce eosinophilic infiltrate (possibly in regression), displaying CD30- T-clonal proliferation was eventually rendered. The patient did not report signs of recurrence after a 3-year follow-up period.

Erbium Yttrium-Aluminum-Garnet Laser Versus Traditional Bur in the Extraction of Impacted Mandibular Third Molars: Analysis of Intra- and Postoperative Differences.

INTRODUCTION: Different osteotomy techniques have been proposed in order to improve postoperative course of impacted third molar extraction. The aim is to evaluate the possible advantages achieved with erbium yttrium-aluminum-garnet (Er:YAG) laser osteotomy compared with traditional burs. MATERIALS AND METHODS: Seventy-six extractions were randomly classified into 2 groups according to osteotomy instrument: group 1 (G1)-Er:YAG laser: 35 patients; group 2 (G2)-traditional bur: 41 patients. Intraoperative parameters: total time, stitches number, and patient compliance. Postoperative: pain, health-related quality of life (HR-QoL), need for analgesics, edema, trismus, intra- and extraoral hematoma, and postoperative complications. RESULTS: Mean time for G1 resulted 1069.4 seconds; for G2 1913.5 seconds (P < 0.0001). Mean number of stitches (P = 0.773) and patient compliance (P = 0.063) were not statistically different. Regarding pain, mean visual analog scale (VAS), and numeric rating scale (NRS) scores were lower in G1 than in G2. Statistically significant differences were highlighted at days 0, 1, and 3 with VAS scale and at days 0, 1, 3, and 7 with NRS scale. The HR-QoL scores resulted lower in G1 than in G2 (P < 0.0001). Mean facial swelling and trismus resulted statistically lower in G1 than in G2 at day 2 (P < 0.0001). Trismus resulted statistically lower in G1 than in G2 at days 2 (P < 0.0001) and 7 (P = 0.004). Two patients (5.71%) of subcutaneous emphysema was recorded in G1 and 2 patients (4.88%) of lip paresthesia in G2. CONCLUSION: Data confirm that the use of Er:YAG laser for osteotomy may achieve several advantages both technical and biological.

Clinical Differences in Autofluorescence Between Viable and Nonvital Bone: A Case Report With Histopathologic Evaluation Performed on Medication-Related Osteonecrosis of the Jaws.

Medication-related osteonecrosis of the jaws (MRONJ) is an adverse side effect of several drug therapies, including bisphosphonates (BPs). Osteonecrosis of the jaw specifically related to BP therapy is usually referred to using the acronym BRONJ. However, no consensus has yet been reached regarding the most appropriate management of BRONJ. The greatest success rates have been recorded with surgical removal of necrotic bone. In particular, erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted surgery has shown significantly better results than conventional surgical approaches. According to a position paper reported by the American Association of Oral and Maxillofacial Surgeons in 2007, the identification of necrotic bone margins during osteonecrosis removal can be very difficult. In 2015, a review of treatment perspectives for MRONJ reported that both surgical debridement and resection cannot be standardized owing to the lack of guidance to define the necrotic margins. Recently, the use of autofluorescence (AF) of the bone as a possible suitable guide to visualize necrotic bone during surgical debridement or resection was proposed. It seems that vital bone could be highlighted by its very strong AF. In contrast, necrotic bone loses AF and, thus, appears much darker. The molecular sources of the phenomenon of AF are the specific amino acids of the collagen molecules that show AF when irradiated by ultraviolet or blue light. The use of AF as an intraoperative diagnostic tool is entirely new in the management of MRONJ, although it has been used for several years in other fields (eg, intervertebral disc surgery). The aim of the present report was to describe a case of mandibular BRONJ treated with a new surgical approach performed with an Er:YAG laser and guided by AF. The histopathologic evaluation of the removed hypofluorescent bone block and hyperfluorescent surrounding bone has also been reported in detail.

Medication-Related Osteonecrosis of the Jaw Around Dental Implants: Implant Surgery-Triggered or Implant Presence-Triggered Osteonecrosis?

INTRODUCTION: Dentoalveolar surgery including tooth extractions and dental implants placement is considered the major risk factor for developing medication-related osteonecrosis of the jaw (MRONJ).In this study, a patient series of MRONJ around dental implants were carefully analyzed to describe the findings and to assess the possible risk factors. METHODS: Fifteen patients with peri-implant bone osteonecrosis were selected out of a group of 250 patients (6%). Patients were divided into 2 groups according to the temporal relationship. Group 1 (G1)-necrosis immediately after implant placement (from 2 to 10 months) and defined as "implant surgery-triggered" MRONJ. Group 2-necrosis distant (from 1 to 15 years) from implant placement and defined as "implant presence-triggered" MRONJ. Epidemiological and pharmacological variables were recorded as well as specific data about osteonecrosis and dental implants. RESULTS: G1 included 6 patients: 5 (83.4%) treated with oral bisphosphonates (BPs) for osteoporosis and 1 (16.6%) with intravenous BPs for breast cancer. Mean duration of BP therapy (BPT) was 83.7 months. G2 included 9 patients: 8 patients (88.89%) treated with intravenous BPs for malignant disease and 1 (11.11%) with oral BPs for osteoporosis. CONCLUSIONS: Data confirms that not only surgical insertion of dental implants is a potential risk factor for the development of osteonecrosis but also the presence itself of the implant into the bone can be associated with this disease. Therefore, it is necessary to inform of the increased risk for MRONJ also the patients who have already osteointegrated implants and are going to start the BPT.The risk is lower for patients receiving oral BPs but it exists and seems to be higher if the implant is located in the posterior areas, if the duration of BPT is more than 3 years and if the patient is under corticosteroid therapy.

Different laser wavelengths comparison in the second-stage implant surgery: an ex vivo study.

The implant surgery consists of two distinct techniques, the transmucosal, also known as "one-stage" and the "two-stage" technique. Lasers represent a possible aid in implant dentistry, especially in the two-stage technique and its main characteristics are represented by a decreased trauma to bone and soft tissues, a reduction of pain as well as a reduction of the risk of postoperative infections. The aim of this study was to analyze in an animal model the thermal elevation induced by four different laser wavelengths (diode, Nd:YAG, Er:YAG, KTP) during the implant uncovering. Four pig jaws were used to carry out this study. Five implants were placed in each anatomical specimen for a total of 20 fixtures. Four wavelengths (532, 810, 1,064 and 2,940 nm) were used to uncover the implants. Two thermocouples were used to measure temperature changes during laser irradiation at bone level, peri-implant tissues and on the fixture surface The thermocouples were connected with two probes of 1.5 mm in diameter, in order to simultaneously recording two temperature variations. Surface temperature was also checked during all procedures with a thermal camera (Thermovision A 800, Flyr Systems, Stockolm, Sweden) connected to a PC. The mean temperatures of each specimen (five fixtures) were calculated (TM1, mean temperature at the beginning; TM2, mean peak temperature). Furthermore, a record of the temperature at 1 min after the end of the surgical procedure was taken (mean: TM3). All the recorded values were statistically evaluated by one-way analysis of variance (ANOVA). The thermocouples recorded a lower increase in temperature for Er:YAG and KTP laser; Nd:YAG and diode laser produced similar increases characterized by higher values. The thermo-camera pointed out the lower increase for Er:YAG and higher for diode laser. KTP laser resulted faster in uncovering implants and diode laser was the one that needed more time. This ex vivo study showed that laser utilization with the recommended parameters gives no risks of dangerous thermal elevation to the tissues and implants.

Tooth extractions in high-risk patients under bisphosphonate therapy and previously affected with osteonecrosis of the jaws: surgical protocol supported by low-level laser therapy.

Trauma during dental surgery is a predisposing factor for medication-related osteonecrosis of the jaws (MRONJ). There are no specific guidelines for the management of dental extractions in patients under bisphosphonate therapy (BPT). The authors proposed in 2013 a successful protocol for tooth extractions in patients under BPT supported by Nd:YAG low-level laser therapy (LLLT). The aim of this study was to validate the safety and efficacy of this protocol reporting the data related to its application in a particular category of patients under BPT at high risk for MRONJ and who were previously affected with MRONJ. Eighty-two tooth extractions were performed in 36 patients previously affected with MRONJ. Antibiotic treatment was administered 3 days before and 2 weeks after tooth extractions. Patients were additionally treated with Nd:YAG LLLT, 5 applications of 1 minute each. Patients were evaluated 3 days and once a week for 2 months after the extractions and every time they received LLLT. In a total of 82 extractions, minimal bone exposure was observed in 2 cases, treated with Er:YAG laser vaporization and then completely healed. The data confirmed that laser biostimulation is a reliable technique that can be considered in the surgical protocol for patients under BPT.

Odontogenic myxofibroma: a concise review of the literature with emphasis on the surgical approach.

PURPOSE: The aim of this work is to report a review of the literature concerning epidemiology, clinical and radiographic features as well as treatment of odontogenic myxofibroma (MF). METHODS: The PubMed database was searched using the following keywords: "odontogenic myxofibroma", "odontogenic fibromyxoma", "myxofibroma of the jaw" and "fibromyxoma of the jaw". RESULTS: Fifteen articles reporting the experience with 24 patients were identified. Male/female ratio was 1:1.4 and the average age 29.5 years. The most frequent location was the mandible. In 66.7% of the cases the radiographic appearance was a multilocular radiolucency. Swelling was observed in 13 patients (92.86%), varying degrees of pain in 5 (35.71%) and paresthesia in only one patient (7.14%). Six out of 24 patients (26.09%) were treated with radical surgery and 17 out of 24 (73.91%) with a conservative approach. In two out of 21 cases (9.52%) a recurrence was reported. CONCLUSIONS: MF is an extremely rare tumour and no agreement exist on the causes of its development. According to the present review, the choice of treatment should depend on variables such as localization, presence of a primary or of a recurrent lesion, age, general medical conditions and aesthetic needs of the patient.

Laser welded versus resistance spot welded bone implants: analysis of the thermal increase and strength.

INTRODUCTION: The first aim of this "ex vivo split mouth" study was to compare the thermal elevation during the welding process of titanium bars to titanium implants inserted in pig jaws by a thermal camera and two thermocouples. The second aim was to compare the strength of the joints by a traction test with a dynamometer. MATERIALS AND METHODS: Six pigs' jaws were used and three implants were placed on each side of them for a total of 36 fixtures. Twelve bars were connected to the abutments (each bar on three implants) by using, on one side, laser welding and, on the other, resistance spot welding. Temperature variations were recorded by thermocouples and by thermal camera while the strength of the welded joint was analyzed by a traction test. RESULTS: For increasing temperature, means were 36.83 and 37.06, standard deviations 1.234 and 1.187, and P value 0.5763 (not significant). For traction test, means were 195.5 and 159.4, standard deviations 2.00 and 2.254, and P value 0.0001 (very significant). CONCLUSION: Laser welding was demonstrated to be able to connect titanium implant abutments without the risk of thermal increase into the bone and with good results in terms of mechanical strength.