OBJECTIVE: Although several surgical techniques have been developed for treatment of gingival recession (GR), the underlying wound healing process remains relatively unexplored. This systematic review aimed to investigate the expression of wound healing markers in gingival crevicular fluid (GCF) before and after surgical treatment of GR.
METHODS: Randomized clinical trials (RCTs) reporting changes in the expression of GCF markers following any root coverage surgical procedure were identified from 4 electronic databases and manual searches followed by data extraction and result synthesis. The risk of bias (RoB) was assessed using Cochrane RoB 2.0 tool. Overall certainty of evidence was summarized using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS: Four RCTs comprising 100 patients and investigating 15 biomarkers were included. Post-surgery, GCF levels of cytokines and inflammatory proteins were raised during the first 2-10 days of healing. MMP-8 levels increased during the first week followed by a gradual decline. RoB was found to be high for all studies and the overall certainty of evidence was very low.
CONCLUSIONS: A limited number of studies with large methodological variations precluded reliable conclusions. Well-designed studies powered for GCF markers\' levels that follow a standardized protocol for GCF sampling and processing are needed to draw conclusive evidence.

OBJECTIVE: To determine the accuracy of salivary active matrix metalloproteinase (aMMP)-8 point-of-care test (POCT) for detecting periodontitis in adults, through meta-analysis.
METHODS: Diagnostic studies evaluating the accuracy of salivary/oral rinse aMMP-8 POCT for detecting periodontitis in adults, when compared with clinical examination, were considered eligible. A comprehensive search was performed up to 31 August 2023 through five databases. Quality Assessment of Diagnostic Accuracy Studies 2 was utilized to evaluate the methodological quality of the included articles. Meta-analysis was performed using Bayesian bivariate hierarchical model and subgroup analysis.
RESULTS: From 368 screened studies, 6 studies (4 cross-sectional and 2 longitudinal studies) were included in the meta-analysis. Overall, the pooled sensitivity and specificity of salivary aMMP-8-POCT for detecting periodontitis were 0.63 (95% CI: 0.41-0.82) and 0.84 (95% CI: 0.65-0.95), respectively. Subgroup analyses revealed that the 95% CI for oral fluid types, predefined diagnostic thresholds and the POCT systems largely overlapped, indicating that the differences between them may not be significant.
CONCLUSIONS: Salivary aMMP-8 POCT shows fair accuracy for detecting periodontitis. The diagnostic accuracy cannot be significantly influenced by the types of oral fluids, predefined diagnostic thresholds or the specific POCT systems used. More research is needed to confirm the clinical utility and implementation of aMMP-8 POCT in the diagnosis of periodontitis.

BACKGROUND: Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: \"Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?\"
METHODS: The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals.
RESULTS: A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001).
CONCLUSIONS: RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.

OBJECTIVE: 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 observations.

The aim of the present systematic review is to summarize current knowledge regarding the analysis of biomarkers extracted from peri-implant crevicular fluid (PICF) as predictors of peri-implant bone loss (BL). An electronic search was conducted on three databases, PubMed/MEDLINE, Cochrane Library, and Google Scholar, to find clinical trials published until 1 December 2022 suitable to answer the following focused question: in patients with dental implants, are biomarkers harvested from PICF predictive of peri-implant BL? The initial search yielded a total of 158 entries. After a full-text review and application of the eligibility criteria, the final selection consisted of nine articles. The risk of bias in included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools (JBI). According to the present systematic review, some inflammatory biomarkers harvested from PICF (collagenase-2, collagenase-3, ALP, EA, gelatinase b, NTx, procalcitonin, IL-1β, and several miRNAs) seem to be correlated with peri-implant BL and may assist in the early diagnosis of pathological BL, that characterizes peri-implantitis. MiRNA expression demonstrated a predictive potential of peri-implant BL that could be useful for host-targeted preventive and therapeutic purposes. PICF sampling may represent a promising, noninvasive, and repeatable form of liquid biopsy in implant dentistry.

Saliva is a useful biomarker for diagnosing oral health conditions, including periodontal disease (PD). Smoking is a risk factor for PD. The aim of this systematic review was to summarize the salivary biomarkers associated with PD based on smoking status. A comprehensive search of the MEDLINE (via PubMed), EMBASE, Cochrane, SCOPUS, and Web of Sciences databases was conducted up to 1 January 2021 using key terms relevant to the topic of our research and Cochrane methodology and improved with searching a gray literature resource. The methodological quality of all included studies was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies-2. Seven studies were included. Smokers had increased levels of malondialdehyde, sialic acid, salivary cortisol, salivary interleukin 1β, albumin, tissue inhibitor of matrix metalloproteinase (TIMP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), as well as decreased levels of superoxide dismutase, activity of lactate dehydrogenase, activity of enzyme activity of β-glucuronidase, uric acid, matrix metalloproteinase-8 (MMP-8)/TIMP-1 ratio, and combinations of MMP-8 and ICTP. However, mixed results were observed some studies in detecting glutathione peroxidase, MMP-8, and MMP-14. The results were interpreted with caution because of limitations in the number of included studies and the study design. Some salivary biomarkers are potentially useful in combination or alone for diagnosing PD. Methodological and systematic studies are needed to develop more effective biomarkers.

OBJECTIVE: This integrative literature review provides an overview of current best research evidence on the screening and diagnosis of women for chorioamnionitis, as no current review has been conducted. An overview of best practices on screening and diagnosis of women for chorioamnionitis can assist midwives with an accurate diagnosis, allowing for early referral and adequate management of this infection.
METHODS: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost (CINAHL with Full Text, e-Book Collection, Health Source: Nursing/Academic Edition, MEDLINE, Open Dissertations and PsycINFO), Cochrane Online, PubMed, Scopus, followed by a manual search for grey literature using Google and a citation search. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study.
RESULTS: After critical appraisal, using the Joanna Briggs Institution\'s checklists, Evaluation Tool for Quantitative Research Studies\' tool and the Appraisal of Guidelines for Research & Evaluation instrument, 31 articles were included. More than half (64%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening and diagnosis of women for chorioamnionitis was synthesised into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis.
CONCLUSIONS: Screening and recording of any risk factors will assist midwives in providing tailored health education to possibly prevent causative factors that could lead to chorioamnionitis. Although matrix-metalloproteinase-8 (MMP-8) seems the most suitable test to use for screening, an accurate diagnosis of chorioamnionitis requires a combination of screening methods and tests, such as clinical signs and symptoms, maternal biomarkers, amniotic fluid testing and histology. Screening for chorioamnionitis, particularly the parameters for maternal fever as a clinical symptom of chorioamnionitis, contributing factors and microbes responsible for chorioamnionitis, the usability of MMP-8 and the development of rapid, inexpensive, easy-to-use techniques for screening and diagnosis of chorioamnionitis, warrants further research.
CONCLUSIONS: Findings can be used by midwives in the screening and diagnosis of women for chorioamnionitis which allows for early referral and adequate management before maternal and neonatal complications arise.

Purpose: To explore whether baseline matrix metalloproteinase (MMP)-8 level in gingival crevicular fluid (GCF) (exposure) can predict the outcome (reduction in probing pocket depth (PPD) (outcome)) of nonsurgical periodontal therapy (NSPT) (manual or ultrasonic or both) in patients with periodontitis (population/problem) after 3 months. Methods: Six databases (PubMed, Cochrane library, ProQuest, Ovid, Scopus, EBSCO) were searched for relevant articles published until 30 July 2021. Retrieved articles were passed through a three-phase filtration process on the basis of the eligibility criteria. The primary outcome was the change in PPD after 3 months. Quality of the selected articles was assessed using Cochrane Risk of Bias tool (RoB2) and Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tools. Results: From 1306 articles, five were selected for analysis. The results showed high variations in the level of GCF MMP-8 level at baseline. The average amount of reduction in PPD was 1.20 and 2.30 mm for pockets with initial depth of 4−6 mm and >6 mm, respectively. Conclusion: On the basis of available evidence, it was not possible to reach a consensus on the ability of baseline GCF MMP-8 to forecast the outcome of NSPT. This could have been due to variation in clinical and laboratory techniques used. However, consistency in mean PPD reduction after 3 months was shown.

To determine the diagnostic value of inflammatory cytokines in periodontal disease, we performed a systematic review of the changes in inflammatory cytokines after non-surgical periodontal therapy and a meta-analysis of the utility of interleukin (IL)-1β and matrix metalloproteinase (MMP)-8 as salivary biomarkers. All available papers published in English until 20 August 2020, were searched in the MEDLINE and EMBASE databases. Population, intervention, comparison, and outcome data were extracted from the selected studies, and the roles of IL-1β and MMP-8 were assessed in a meta-analysis. Eleven studies, including two meta-analyses, were assessed in the systematic review. Biomarkers showing high levels in periodontal disease were salivary IL-1β, IL-4, IL-6, MMP-8, and tissue inhibitor of matrix metalloproteinases (TIMP)-2, and those in the controls were tumor necrosis factor (TNF)-α, IL-10, IL-17, and IL-32. Biomarkers that decreased after scaling and root planning (SRP) and oral hygiene instruction (OHI) in periodontitis patients were IL-1β, MMP-8, MMP-9, prostaglandin E2 (PGE2), and TIMP-2. The pooled standardized mean difference of IL-1β and MMP-8 was -1.04 and 35.90, respectively, but the differences between periodontitis patients and healthy controls were not significant. Although the changes in salivary IL-1β and MMP-8 levels after non-surgical periodontal therapy were not significant, salivary cytokines could be used to confirm the effect of periodontal therapy or diagnose periodontal disease.

Matrix metalloproteinases (MMPs) have traditionally been considered as tumor promoting enzymes as they degrade extracellular matrix components, thus increasing the invasion of cancer cells. It has become evident, however, that MMPs can also cleave and alter the function of various non-matrix bioactive molecules, leading to both tumor promoting and suppressive effects. We applied systematic review guidelines to study MMP8 in cancer including the use of MMP8 as a prognostic factor or as a target/anti-target in cancer treatment, and its molecular mechanisms. A total of 171 articles met the inclusion criteria. The collective evidence reveals that in breast, skin and oral tongue cancer, MMP8 inhibits cancer cell invasion and proliferation, and protects patients from metastasis via cleavage of non-structural substrates. Conversely, in liver and gastric cancers, high levels of MMP8 worsen the prognosis. Expression and genetic alterations of MMP8 can be used as a prognostic factor by examination of the tumor and serum/plasma. We conclude, that MMP8 has differing effects on cancers depending on their tissue of origin. The use of MMP8 as a prognostic factor alone, or with other factors, seems to have potential. The molecular mechanisms of MMP8 in cancer further emphasize its role as an important regulator of bioactive molecules.