Accuracy of periodontitis diagnosis obtained using multiple molecular biomarkers in oral fluids: A systematic review and meta‐analysis

Aim To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. Methods Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). Results Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1β with IL-6 (83.0%/83.7%); IL-1β with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1β, IL-6 and MMP-8 (81.8%/84.3%); and IL-1β, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). Conclusions Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1β, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observationsThis study was funded by the Instituto de Salud Carlos III (ISCIII) through the project PI21/00588 and co-funded by the European UnionS

Accuracy of single molecular biomarkers in gingival crevicular fluid for the diagnosis of periodontitis: A systematic review and meta-analysis

This is the peer reviewed version of the following article: Arias‐Bujanda, N, Regueira‐Iglesias, A, Balsa‐Castro, C, Nibali, L, Donos, N, Tomás, I. Accuracy of single molecular biomarkers in gingival crevicular fluid for the diagnosis of periodontitis: A systematic review and meta‐analysis. J Clin Periodontol. 2019; 46: 1166– 1182. https://doi.org/10.1111/jcpe.13188, which has been published in final form at https://doi.org/10.1111/jcpe.13188. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsAbstract Aim To analyse, by means of a meta‐analytical approach, the diagnostic accuracy of molecular biomarkers in gingival crevicular fluid (GCF) for the detection of periodontitis in systemically healthy subjects. Material and Methods Studies on GCF molecular biomarkers providing a binary classification table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. The search was performed using six electronic databases. The methodological quality of studies was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic, which adjusts classification data using random effects logistic regression. Results The included papers identified 36 potential biomarkers for the detection of periodontitis and for four of them meta‐analyses were performed. The median sensitivity and specificity were for MMP8, 76.7% and 92.0%; for elastase, 74.6% and 81.1%; for cathepsin, 72.8% and 67.3%, respectively. The worst estimates of sensitivity and specificity were for trypsin (71.3% and 66.1%, respectively). Conclusions MMP8 showed good sensitivity and excellent specificity, which resulted in this biomarker being clinically the most useful or effective for the diagnosis of periodontitis in systemically healthy subjects, regardless of smoking conditionInstituto de Salud Carlos III FEDER. Grant Number: ISCIII/PI17/01722 Consellería de Cultura, Educación e Ordenación Universitaria da Xunta de Galicia. Grant Numbers: ED431B 2017/029, ED481A‐201

Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta-analysis

This is the peer reviewed version of the following article: Arias‐Bujanda, N, Regueira‐Iglesias, A, Balsa‐Castro, C, Nibali, L, Donos, N, Tomás, I. Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta‐analysis. J Clin Periodontol. 2020; 47: 2– 18. https://doi.org/10.1111/jcpe.13202, which has been published in final form at https://doi.org/10.1111/jcpe.13202. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsAim To analyse, using a meta‐analytical approach, the diagnostic accuracy of single molecular biomarkers in saliva for the detection of periodontitis in systemically healthy subjects. Materials and Methods Articles on molecular biomarkers in saliva providing a binary contingency table (or sensitivity and specificity values and group sample sizes) in individuals with clinically diagnosed periodontitis were considered eligible. Searches for candidate articles were conducted in six electronic databases. The methodological quality was assessed through the tool Quality Assessment of Diagnostic Studies. Meta‐analyses were performed using the Hierarchical Summary Receiver Operating Characteristic model. Results Meta‐analysis was possible for 5 of the 32 biomarkers studied. The highest values of sensitivity for the diagnosis of periodontitis were obtained for IL1beta (78.7%), followed by MMP8 (72.5%), IL6 and haemoglobin (72.0% for both molecules); the lowest sensitivity value was for MMP9 (70.3%). In terms of specificity estimates, MMP9 had the best result (81.5%), followed by IL1beta (78.0%) and haemoglobin (75.2%); MMP8 had the lowest specificity (70.5%). Conclusions MMP8, MMP9, IL1beta, IL6 and Hb were salivary biomarkers with good capability to detect periodontitis in systemically healthy subjects. MMP8 and IL1beta are the most researched biomarkers in the field, both showing clinically fair effectiveness for the diagnosis of periodontitis.the Instituto de Salud Carlos III (General Division of Evaluation and Research Promotion, Madrid, Spain) and co‐financed by FEDER. Grant Number: Grant ISCIII/PI17/01722 the Consellería de Cultura, Educación e Ordenación Universitaria da Xunta de Galicia (Spain). Grant Number: Grant ED431B 2017/02

Short-term anti-plaque effect of a cymenol mouthwash analysed using the DenTiUS Deep Plaque software: a randomised clinical trial

Abstract Background The effect of cymenol mouthwashes on levels of dental plaque has not been evaluated thus far. Objective To analyse the short-term, in situ, anti-plaque effect of a 0.1% cymenol mouthwash using the DenTiUS Deep Plaque software. Methods Fifty orally healthy participants were distributed randomly into two groups: 24 received a cymenol mouthwash for eight days (test group A) and 26 a placebo mouthwash for four days and a cymenol mouthwash for a further four days thereafter (test group B). They were instructed not to perform other oral hygiene measures. On days 0, 4, and 8 of the experiment, a rinsing protocol for staining the dental plaque with sodium fluorescein was performed. Three intraoral photographs were taken per subject under ultraviolet light. The 504 images were analysed using the DenTiUS Deep Plaque software, and visible and total plaque indices were calculated (ClinicalTrials ID NCT05521230). Results On day 4, the percentage area of visible plaque was significantly lower in test group A than in test group B (absolute = 35.31 ± 14.93% vs. 46.57 ± 18.92%, p = 0.023; relative = 29.80 ± 13.97% vs. 40.53 ± 18.48%, p = 0.024). In comparison with the placebo, the cymenol mouthwash was found to have reduced the growth rate of the area of visible plaque in the first four days by 26% (absolute) to 28% (relative). On day 8, the percentage areas of both the visible and total plaque were significantly lower in test group A than in test group B (visible absolute = 44.79 ± 15.77% vs. 65.12 ± 16.37%, p < 0.001; visible relative = 39.27 ± 14.33% vs. 59.24 ± 16.90%, p < 0.001; total = 65.17 ± 9.73% vs. 74.52 ± 13.55%, p = 0.007). Accounting for the growth rate with the placebo mouthwash on day 4, the above results imply that the cymenol mouthwash in the last four days of the trial reduced the growth rate of the area of visible plaque (absolute and relative) by 53% (test group A) and 29% (test group B), and of the area of total plaque by 48% (test group A) and 41% (test group B). Conclusions The 0.1% cymenol mouthwash has a short-term anti-plaque effect in situ, strongly conditioning the rate of plaque growth, even in clinical situations with high levels of dental plaque accumulation