Metabolomics analysis in saliva from periodontally healthy, gingivitis and periodontitis patients.

OBJECTIVE: The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis. BACKGROUND: The use of metabolomics for diagnosing and monitoring periodontitis is promising. Although several metabolites have been reported to be altered by inflammation, few studies have examined metabolomics in saliva collected from patients with different periodontal phenotypes. METHODS: Saliva samples collected from a total of 63 patients were analysed by nuclear magnetic resonance (NMR) followed by ELISA for interleukin (IL)-1ß. The patient sample, well-characterised clinically, included periodontal health (n = 8), gingivitis (n = 19) and periodontitis (n = 36) cases, all non-smokers and not diabetic. RESULTS: Periodontal diagnosis (healthy/gingivitis/periodontitis) was not associated with any salivary metabolites in this exploratory study. Periodontal staging showed nominal associations with acetoin (p = .030) and citrulline (p = .047). Among other investigated variables, the use of systemic antibiotics in the previous 3 months was associated with higher values of the amino acids taurine, glycine and ornithine (p = .002, p = .05 and p = .005, respectively, at linear regression adjusted for age, gender, ethnicity, body mass index and staging). CONCLUSION: While periodontal staging was marginally associated with some salivary metabolites, other factors such as systemic antibiotic use may have a much more profound effect on the microbial metabolites in saliva. Metabolomics in periodontal disease is still an underresearched area that requires further observational studies on large cohorts of patients, aiming to obtain data to be used for clinical translation.

Molecular profiling of gingival crevicular fluid fails to distinguish between infrabony and suprabony periodontal defects.

AIM: To assess the differential molecular profiling of gingival crevicular fluid (GCF) from infrabony and suprabony periodontal defects compared with healthy sites. MATERIALS AND METHODS: Seventy-five samples from 25 patients with untreated periodontitis stage III-IV were included. Clinical and radiological parameters as well as GCF samples were collected from an infrabony defect, a suprabony defect and a periodontally healthy site per patient. A multiplex bead immunoassay was performed to assess the level of 18 biomarkers associated with inflammation, connective tissue degradation and regeneration/repair. RESULTS: GCF volume was higher in periodontal sites compared with healthy sites, with no significant difference between infrabony and suprabony defects. Fourteen biomarkers were elevated in infrabony and suprabony sites compared with healthy sites (p < .05). Only interleukin-1α levels were increased in infrabony compared with suprabony sites, whereas there was no difference in probing pocket depth. CONCLUSIONS: Although the GCF molecular profile clearly differentiates periodontally affected sites from healthy sites, the different architecture between infrabony and suprabony defects is not reflected in GCF biomarker changes.

Could dietary restrictions affect periodontal disease? A systematic review.

OBJECTIVE: This review aimed at evaluating the possible benefits that caloric restriction (CR) may provide to periodontal disease progression and response to treatment. MATERIAL AND METHODS: Electronic search on Medline, Embase and Cochrane, and manual search were performed to identify pre-clinical and on human studies reporting the consequences of CR on clinical and inflammatory parameters related to periodontitis. Newcastle Ottawa System and SYRCLE scale were used to assess the risk of bias. RESULTS: Four thousand nine hundred eighty articles were initially screened, and a total of 6 articles were finally included, consisting of 4 animal studies and 2 studies in humans. Due to the limited number of studies and heterogeneity of the data, results were presented in descriptive analyses. All studies showed that, compared to the normal (ad libitum) diet, CR might have the potential to reduce the local and systemic hyper-inflammatory state as well as disease progression in periodontal patients. CONCLUSIONS: Within the existing limitations, this review highlights that CR showed some improvements in the periodontal condition by reducing the local and systemic inflammation related to the periodontitis and by improving clinical parameters. However, the results should be interpreted with caution since robust research such as randomized clinical trials is still missing. CLINICAL RELEVANCE: This review shows that some dietary/caloric restrictions approaches may have the potential to improve periodontal conditions and, in addition, highlights a need for human studies with a robust methodology in order to draw stronger evidence-based conclusions.

Gingival phenotype changes after different periodontal plastic surgical techniques: a single-masked randomized controlled clinical trial.

ABSTRACT: OBJECTIVES: Aim of this clinical study was to evaluate the effects on gingival thickness of three surgical techniques for root coverage: the coronally advanced flap (CAF) alone, with a sub-epithelial connective tissue graft (SCTG) or with leukocyte- and platelet-rich fibrin (L-PRF) membranes. METHODS: Sixty patients with RT1 single maxillary gingival recession were treated with CAF + L-PRF (20 patients), CAF + SCTG (20 patients) or CAF alone (20 patients). At baseline and 6-month after treatment, gingival thickness (GT), keratinized tissue width (KT), gingival recession (GR), clinical attachment level (CAL), probing depth (PD), PROMs, and the aesthetic outcome were recorded. RESULTS: CAF + SCTG and CAF + L-PRF groups showed a significantly greater mean GT increase than CAF alone (0.31 ± 0.10 mm) with no significant differences between CAF + SCTG (0.99 ± 0.02 mm) and CAF + L-PRF (0.92 ± 0.52 mm) groups (p = 0.55). CAF + SCTG was associated with a significantly greater KT gain (3.85 ± 1.04 mm), while in CAF + L-PRF (2.03 ± 0.53 mm) and CAF (1.50 ± 0.69 mm) groups, KT was not significantly increased. Both GR and CAL showed a significant within groups' improvement, without among-groups differences. No significant among-groups difference for the aesthetic outcome but greater discomfort and pain-killer consumption in CAF + SCTG group was detected. CONCLUSION: All investigated surgical techniques produced significant GR reduction and CAL gain. GT was similarly augmented by CAF + L-PRF and CAF + SCTG techniques; however, the CAF + SCTG technique produced a more predictable KT and GT increase. CLINICAL RELEVANCE: The results of our study suggest that the CAF + SCTG technique represents the most predictable method for the clinician to improve the gingival phenotype, an important factor for long term gingival margin stability.

Associations between host genetic variants and Herpes Simplex Labialis in the TwinsUK cohort.

OBJECTIVE: Previous literature supports controversial results about the role of host genetic factors in the reactivation of Herpes Simplex Labialis (HSL). The objective of this study is to explore the association between different putative single nucleotide polymorphisms (SNPs) and self-reported HSL reactivation in the TwinsUK cohort. DESIGN: 1761 participant were recruited for this study from the TwinsUK register. Blood collection and HSL questionnaire were completed for a subset of 595 participants (age 61.9, dizygotic twins 62.8%). Blood was stored at -80 °C and DNA analysed from all samples. The potential associations between candidate SNPs and HSL were assessed using a set of 40 SNPs, including SNPs previously correlated with HSL disease and other SNPs previously associated with the oral microbiota. RESULTS: 235 participants reported to have experienced 'cold sores' at least once in their lives, and 160 reported reinfection episodes. No association was detected between rs243588, rs1047978, rs1062202 genotypes and both occurrence of cold sores (p = 0.172, p = 0.360, p = 0.742) and their recurrence (p = 0.160, p = 0.105,p = 0.746). Among other investigated SNPs, a nominal significant association was detected between Vitamin D Receptor (VDR) Fok I (rs2228570) and both history of HSL (p = .001) and its recurrence (p = .007). CONCLUSIONS: A single nucleotide polymorphism in the VDR gene may be correlated with cold sores and their recurrence.

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.

Added benefit of L-PRF to autogenous bone grafts in the treatment of degree II furcation involvement in mandibular molars.

BACKGROUND: Tissue regeneration within the periodontally involved furcation area is one of the most challenging aspects of periodontal surgery. The aim of this study was to evaluate the additional benefit of leukocyte and platelet-rich fibrin (L-PRF) to autogenous bone grafts (ABGs) in the treatment of mandibular molar degree II furcation involvement, comparing the clinical outcomes with those from open flap debridement (OFD)+ABG and OFD alone treatments. METHODS: Fifty-four patients, exhibiting one buccal or lingual mandibular molar furcation defect, were randomly assigned to three treatment groups: OFD+ABG+L-PRF (n = 18); OFD+ABG (n = 18); and OFD (n = 18). Clinical (probing depth [PD], horizontal clinical attachment level [HCAL], vertical clinical attachment level [VCAL], gingival recession [GR]) and radiographic (vertical bone level [VBL]) parameters were evaluated at baseline and 6 months after treatment. HCAL change was the primary outcome. RESULTS: No significant differences within each group were reported for GR changes, but statistically significant improvements in HCAL, VCAL, PD, and VBL were observed in all groups, except for VBL in the OFD group. At 6 months, the mean HCAL gain was 2.29 ± 0.18 mm in the OFD+ABG+L-PRF group, which was significantly greater than that in the OFD+ABG (1.61 ± 0.18 mm) and OFD (0.86 ± 0.18 mm) groups. Both OFD+ABG+L-PRF and OFD+ABG therapies produced a significantly greater clinical and radiographic improvement than OFD. CONCLUSION: The addition of L-PRF to ABG produces a significantly greater HCAL gain and PD reduction as compared with OFD+ABG treatment in mandibular degree II furcation involvements.

Efficacy of inorganic bovine bone combined with leukocyte and platelet-rich fibrin or collagen membranes for treating unfavorable periodontal infrabony defects: Randomized non-inferiority trial.

BACKGROUND: Growing evidence shows the efficacy of platelet concentrates in periodontal therapy. This study aimed to demonstrate that an inorganic bovine bone graft (IBB) in combination with a leukocyte and platelet rich fibrin (L-PRF) is non-inferior to a combination with a collagen membrane (CM) when managing unfavorable infrabony defects (IBDs). METHODS: All patients exhibited at least one unfavorable IBD; they were randomly assigned to two groups, 31 treated with L-PRF+IBB and 31 with CM+IBB. A clinical and radiographic examination was performed at baseline and 12 months later. Clinical attachment level (CAL), gingival recession (GR), probing depth (PD), and radiographic defect bone level (DBL) post-therapy changes were compared between the two treatments. A non-inferiority margin = 1 mm was set to determine the efficacy of the test treatment (-1 mm for GR); a second non-inferiority margin = 0.5 mm (-0.5 mm for GR) was chosen for clinical relevance. RESULTS: Twelve months after surgery a significant improvement of clinical and radiographic parameters was observed at both experimental sites. The 90% confidence intervals of the CM+IBB-L-PRF+IBB mean difference for CAL gain (-0.810 mm [-1.300 to -0.319]) and DBL gain (-0.648 mm [-1.244 to -0.052]) were below the 0.5 mm non-inferiority margin; GR increase (1.284 mm [0.764 to 1.804]) remained above the -0.5 mm, while PD reduction (0.499 mm [0.145 to 0.853]) crossed its 0.5-mm margin. CONCLUSIONS: The L-PRF+IBB treatment of unfavorable IBDs offers non-inferior efficacy for CAL gain, showing less GR and more DBL gain too, while for PD reduction it is inferior to the CM+IBB treatment.