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Frontiers in Immunology 2021Periodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This... (Meta-Analysis)
Meta-Analysis
AIM
Periodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This systematic review explored multiple cytokine gene polymorphisms in the pathogenesis of periodontitis.
MATERIAL AND METHODS
A systematic search was performed using the databases from previous publications, which indicated the association between cytokine polymorphisms and periodontitis pathogenesis. Meta-analysis was conducted using fixed or randomized models to calculate the significance of multiple cytokine polymorphisms. A total of 147 articles were analyzed with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β)]. Doi plot was used to probe the occurrence of publication bias.
RESULTS
The polymorphisms of IL-2 and TNF-α of Th1 cytokine family may be associated with the pathogenesis or the prevention of periodontitis risk, while the polymorphism of IFN-γ is not related to periodontitis risk. The polymorphisms for IL-4 and IL-13 of Th2 cytokine family are not found to be associated with the pathogenesis of periodontitis. For the polymorphisms of the members of Th17 cytokine family, different IL-1α polymorphisms may have inverse actions in the pathogenesis of periodontitis. IL-1β is a noteworthy cytokine biomarker in periodontitis development and progression. IL-6 may have a protective function in the inflammatory responses of periodontitis, and IL-17 has a weak relationship the inflammatory responses. The polymorphisms for the members of Treg cell cytokines may have a protective function against periodontitis risk. LFK indexes show the major asymmetry due to publication bias.
CONCLUSION
IL-1β is a notable cytokine biomarker in periodontitis risk. Treg cytokines favor an anti-inflammatory and protective environment. Further data are needed to confirm the present conclusion due to publication bias.
Topics: Animals; Cytokines; Humans; Periodontitis; Polymorphism, Genetic
PubMed: 35046930
DOI: 10.3389/fimmu.2021.713198 -
International Journal of Molecular... Dec 2023Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This... (Review)
Review
Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This systematic review aims to evaluate the effects of non-surgical periodontal treatment (NSPT) on RA and, conversely, the impact of disease-modifying anti-rheumatic drugs (DMARDs) on periodontitis. PubMed, Embase, and Web of Science were searched using the MESH terms "periodontitis" and "rheumatoid arthritis" from January 2012 to September 2023. A total of 49 articles was included in the final analysis, 10 of which were randomized controlled trials. A total of 31 records concerns the effect of NSPT on parameters of RA disease activity, including a 28-joint disease activity score, anti-citrullinated protein antibodies, rheumatoid factor, C reactive protein, erythrocyte sedimentation rate, pro-inflammatory cytokines and acute phase proteins in serum, saliva, gingival crevicular fluid, and synovial fluid. A total of 18 articles investigated the effect of DMARDs on periodontal indexes and on specific cytokine levels. A quality assessment and risk-of-bias of the studies were also performed. Despite some conflicting results, there is evidence that RA patients and periodontitis patients benefit from NSPT and DMARDs, respectively. The limitations of the studies examined are the small samples and the short follow-up (usually 6 months). Further research is mandatory to evaluate if screening and treatment of periodontitis should be performed systematically in RA patients, and if the administration of DMARDs is useful in reducing the production of cytokines in the periodontium.
Topics: Humans; Antirheumatic Agents; Periodontitis; Arthritis, Rheumatoid; Rheumatoid Factor; Cytokines
PubMed: 38139057
DOI: 10.3390/ijms242417228 -
Healthcare (Basel, Switzerland) Sep 2023A high detection rate of diabetes among dental visitors has been reported recently. This systematic review aimed to evaluate the association between periodontitis and... (Review)
Review
BACKGROUND
A high detection rate of diabetes among dental visitors has been reported recently. This systematic review aimed to evaluate the association between periodontitis and glycated hemoglobin (HbA1c) levels among non-diabetic individuals.
METHODS
The EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed, and Open GREY databases were searched, and observational studies published until 1st June 2023 were identified. A methodological quality assessment was conducted based on the original and modified versions of the Newcastle-Ottawa scale. Cohort, case-control, and cross-sectional studies that performed clinical periodontal examinations and measured HbA1c levels in non-diabetic adults were included. A meta-analysis was conducted to estimate the weighted mean difference (WMD) between individuals with and without periodontitis.
RESULTS
In total, 29 case-control and 5 cross-sectional studies were selected from 2583 potentially eligible articles. Among them, sixteen case-control and three cross-sectional studies with moderate to high quality were selected for the meta-analyses. The HbA1c levels in periodontitis patients were significantly higher than those in individuals with healthy periodontal conditions (WMD = 0.16; < 0.001) among the non-diabetic populations.
CONCLUSIONS
This study reveals a significant association between periodontitis and HbA1c levels in non-diabetic populations. Thus, HbA1c screening may be recommended to detect potential hyperglycemia in non-diabetic periodontitis patients.
PubMed: 37830686
DOI: 10.3390/healthcare11192649 -
BMC Oral Health Jun 2017This study aimed to assess the difference in serum levels of leptin and adiponectin in patients with periodontitis and in periodontally healthy individuals and evaluate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to assess the difference in serum levels of leptin and adiponectin in patients with periodontitis and in periodontally healthy individuals and evaluate the changes in circulating leptin and adiponectin after periodontal therapy. Leptin and adiponectin are the most generally studied adipokines that function as inflammatory cytokines. Although the association between periodontitis and serum levels of leptin and adiponectin has been studied extensively, the results were not consistent.
METHODS
A systematic search of the Pubmed, Embase, Web of Science, and Cochrane Library up to September 2016 was conducted. The studies were screened and selected by two writers according to the specific eligibility criteria. The quality of included cross-sectional studies was assessed using the quality assessment form recommended by the Agency for Healthcare Research and Quality and Methodological Index for Nonrandomized Studies. The meta-analyses were conducted using the STATA 12.0 software.
RESULTS
A total of 399 manuscripts were yielded and 25 studies were included in the present meta-analysis. Significantly elevated serum levels of leptin and decreased serum levels of adiponectin in patients with periodontitis were observed in the subgroup analysis of body mass index (BMI) <30. The overall and subgroup analyses showed no significant change in the serum levels of leptin in patients with periodontitis after periodontal treatment. The subgroup analysis of systemically healthy patients showed no significant change in serum levels of adiponectin in patients with periodontitis after periodontal treatment.
CONCLUSIONS
The present meta-analysis supported elevated serum levels of leptin and decreased serum levels of adiponectin in patients with periodontitis compared with controls in the BMI <30 population. In systemically healthy patients with periodontitis, serum levels of leptin and adiponectin do not significantly change after periodontal treatment.
Topics: Adiponectin; Humans; Leptin; Periodontitis
PubMed: 28662701
DOI: 10.1186/s12903-017-0395-0 -
Vascular Health and Risk Management 2019This systematic review and meta-analysis investigate the association between periodontitis and stroke. This review followed the methods established by the Preferred... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis investigate the association between periodontitis and stroke. This review followed the methods established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Searches were conducted in five databases and two sources of grey literature. After the selection of the articles, a risk of bias evaluation was performed. Three meta-analyzes were performed: Assessing the overall association between stroke and periodontitis in case-control studies; Ischemic stroke and periodontitis in case-control studies; The association between stroke and periodontitis in cohort studies. Heterogeneity was assessed using the I index and the odds ratio was also calculated (p < 0.05). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to evaluate the level of evidence. 2193 potentially relevant studies were identified, with 10 studies included in qualitative and quantitative analysis. All the articles were considered with low risk of bias and a low level of certainty. The results demonstrated a positive association between both disorders and increased risk for stroke among cohort studies (RR 1.88 [1.55, 2.29], p<0.00001, I=0%) and for ischemic stroke events in case-control studies (RR 2.72 [2.00, 3.71], p<0.00001, I= 4%). Periodontitis may represent a risk factor for stroke, especially in ischemic events. However, new studies with a robust design are necessary for a reliable conclusion.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Periodontitis; Prognosis; Risk Assessment; Risk Factors; Stroke; Young Adult
PubMed: 31806984
DOI: 10.2147/VHRM.S204097 -
Heliyon Jun 2020Quantitative proteomic workflow based on mass spectrometry (MS) is recently developed by the researchers to screen for biomarkers in periodontal diseases comprising... (Review)
Review
Quantitative proteomic workflow based on mass spectrometry (MS) is recently developed by the researchers to screen for biomarkers in periodontal diseases comprising periodontitis. Periodontitis is known for chronic inflammatory disease characterized by progressive destruction of the tooth-supporting apparatus, yet has a lack of clear pathobiology based on a discrepancy between specified categories and diagnostic vagueness. The objective of this review was to outlined the accessible information related to proteomics studies on periodontitis. The Preferred Reporting Items for Systematical Reviews and Meta-Analysis (PRISMA) statement guides to acquaint proteomic analysis on periodontal diseases was applied. Three databases were used in this study, such as Pubmed, ScienceDirect and Biomed Central from 2009 up to November 2019. Proteomics analysis platforms that used in the studies were outlined. Upregulated and downregulated proteins findings data were found, in which could be suitable as candidate biomarkers for this disease.
PubMed: 32529063
DOI: 10.1016/j.heliyon.2020.e04022 -
Maedica Dec 2019The association between chronic periodontitis and cardiovascular disease is still controversial, despite the plethora of research on this topic. The objective of this...
The association between chronic periodontitis and cardiovascular disease is still controversial, despite the plethora of research on this topic. The objective of this systematic review is to update the level of evidence on connection between periodontal and cardiovascular disease. The review question is: could a link between periodontal disease and ischemic cardiac disease be established? A PubMed, Science Direct and Scopus systematic search was performed, which was restricted only to articles published in English or French during the last five years. This study followed PRISMA statement guidelines. A significant relationship between the periodontal and cardiovascular pathology in 17 selected studies was observed, although there was a huge methodological heterogeneity and no randomized study was found. It can be concluded that there is a connection between periodontal and cardiovascular disease, but the link mechanism is still not strongly proved. The scientific evidence level of the future research must be improved.
PubMed: 32153670
DOI: 10.26574/maedica.2019.14.4.384 -
The Cochrane Database of Systematic... Nov 2020Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing (SRP)) as a non-surgical treatment approach to manage... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing (SRP)) as a non-surgical treatment approach to manage periodontitis. A range of antibiotics with different dosage and combinations are documented in the literature. The review follows the previous classification of periodontitis as all included studies used this classification.
OBJECTIVES
To assess the effects of systemic antimicrobials as an adjunct to SRP for the non-surgical treatment of patients with periodontitis.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases to 9 March 2020: Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, and Embase. The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) which involved individuals with clinically diagnosed untreated periodontitis. Trials compared SRP with systemic antibiotics versus SRP alone/placebo, or with other systemic antibiotics.
DATA COLLECTION AND ANALYSIS
We selected trials, extracted data, and assessed risk of bias in duplicate. We estimated mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 45 trials conducted worldwide involving 2664 adult participants. 14 studies were at low, 8 at high, and the remaining 23 at unclear overall risk of bias. Seven trials did not contribute data to the analysis. We assessed the certainty of the evidence for the 10 comparisons which reported long-term follow-up (≥ 1 year). None of the studies reported data on antimicrobial resistance and patient-reported quality of life changes. Amoxicillin + metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -16.20%, 95% CI -25.87 to -6.53; 1 study, 44 participants); clinical attachment level (CAL) (MD -0.47 mm, 95% CI -0.90 to -0.05; 2 studies, 389 participants); probing pocket depth (PD) (MD -0.30 mm, 95% CI -0.42 to -0.18; 2 studies, 389 participants); and percentage of bleeding on probing (BOP) (MD -8.06%, 95% CI -14.26 to -1.85; 2 studies, 389 participants) was of very low certainty. Only the results for closed pockets and BOP showed a minimally important clinical difference (MICD) favouring amoxicillin + metronidazole + SRP. Metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -12.20%, 95% CI -29.23 to 4.83; 1 study, 22 participants); CAL (MD -1.12 mm, 95% CI -2.24 to 0; 3 studies, 71 participants); PD (MD -1.11 mm, 95% CI -2.84 to 0.61; 2 studies, 47 participants); and percentage of BOP (MD -6.90%, 95% CI -22.10 to 8.30; 1 study, 22 participants) was of very low certainty. Only the results for CAL and PD showed an MICD favouring the MTZ + SRP group. Azithromycin + SRP versus SRP for chronic/aggressive periodontitis: we found no evidence of a difference in percentage of closed pockets (MD 2.50%, 95% CI -10.19 to 15.19; 1 study, 40 participants); CAL (MD -0.59 mm, 95% CI -1.27 to 0.08; 2 studies, 110 participants); PD (MD -0.77 mm, 95% CI -2.33 to 0.79; 2 studies, 110 participants); and percentage of BOP (MD -1.28%, 95% CI -4.32 to 1.76; 2 studies, 110 participants) (very low-certainty evidence for all outcomes). Amoxicillin + clavulanate + SRP versus SRP for chronic periodontitis: the evidence from 1 study, 21 participants for CAL (MD 0.10 mm, 95% CI -0.51 to 0.71); PD (MD 0.10 mm, 95% CI -0.17 to 0.37); and BOP (MD 0%, 95% CI -0.09 to 0.09) was of very low certainty and did not show a difference between the groups. Doxycycline + SRP versus SRP in aggressive periodontitis: the evidence from 1 study, 22 participants for CAL (MD -0.80 mm, 95% CI -1.49 to -0.11); and PD (MD -1.00 mm, 95% CI -1.78 to -0.22) was of very low certainty, with the doxycycline + SRP group showing an MICD in PD only. Tetracycline + SRP versus SRP for aggressive periodontitis: we found very low-certainty evidence of a difference in long-term improvement in CAL for the tetracycline group (MD -2.30 mm, 95% CI -2.50 to -2.10; 1 study, 26 participants). Clindamycin + SRP versus SRP in aggressive periodontitis: we found very low-certainty evidence from 1 study, 21 participants of a difference in long-term improvement in CAL (MD -1.70 mm, 95% CI -2.40 to -1.00); and PD (MD -1.80 mm, 95% CI -2.47 to -1.13) favouring clindamycin + SRP. Doxycycline + SRP versus metronidazole + SRP for aggressive periodontitis: there was very low-certainty evidence from 1 study, 27 participants of a difference in long-term CAL (MD 1.10 mm, 95% CI 0.36 to 1.84); and PD (MD 1.00 mm, 95% CI 0.30 to 1.70) favouring metronidazole + SRP. Clindamycin + SRP versus metronidazole + SRP for aggressive periodontitis: the evidence from 1 study, 26 participants for CAL (MD 0.20 mm, 95% CI -0.55 to 0.95); and PD (MD 0.20 mm, 95% CI -0.38 to 0.78) was of very low certainty and did not show a difference between the groups. Clindamycin + SRP versus doxycycline + SRP for aggressive periodontitis: the evidence from 1 study, 23 participants for CAL (MD -0.90 mm, 95% CI -1.62 to -0.18); and PD (MD -0.80 mm, 95% CI -1.58 to -0.02) was of very low certainty and did not show a difference between the groups. Most trials testing amoxicillin, metronidazole, and azithromycin reported adverse events such as nausea, vomiting, diarrhoea, mild gastrointestinal disturbances, and metallic taste. No serious adverse events were reported.
AUTHORS' CONCLUSIONS
There is very low-certainty evidence (for long-term follow-up) to inform clinicians and patients if adjunctive systemic antimicrobials are of any help for the non-surgical treatment of periodontitis. There is insufficient evidence to decide whether some antibiotics are better than others when used alongside SRP. None of the trials reported serious adverse events but patients should be made aware of the common adverse events related to these drugs. Well-planned RCTs need to be conducted clearly defining the minimally important clinical difference for the outcomes closed pockets, CAL, PD, and BOP.
Topics: Adult; Aggressive Periodontitis; Anti-Bacterial Agents; Bias; Chemotherapy, Adjuvant; Chronic Periodontitis; Confidence Intervals; Dental Prophylaxis; Humans; Randomized Controlled Trials as Topic
PubMed: 33197289
DOI: 10.1002/14651858.CD012568.pub2 -
PeerJ 2023The aim of this systematic review is to determine microRNAs (miRs) that are differently expressed between diseased pulpal and periapical tissues.
BACKGROUND
The aim of this systematic review is to determine microRNAs (miRs) that are differently expressed between diseased pulpal and periapical tissues.
DESIGN
This systematic review used PubMed, Scopus, EBSCO, ProQuest, Cochrane database as well as manual searching to extract studies from January 2012 up to February 2022.
RESULTS
A total of 12 studies met the eligibility criteria were included. All selected studies were of case-control type. Twenty-four miRNAs associated with apical periodontitis, 11 were found to be upregulatedand 13 were downregulated. Four out of the 44 miRs associated with pulpal inflammation were upregulated, whereas forty were downregulated. Six miRs, namely hsa-miR-181b, hsa-miR-181c,hsa-miR-455-3p,hsa-miR-128-3p, hsa-miR199a-5p, and hsa-miR-95, exhibited considerable downregulation in both periapical and pulp tissues.
CONCLUSION
MiRs have been investigated for their role in pulpal and periapical biology and may be utilised in diagnostic and therapeutic purposes. Further investigations are required to determine why certain irreversible pulpitis situations progress to apical periodontitis and others do not, based on the various miR expressions. Moreover, clinical and laboratory trials are needed to support this theory.
Topics: Humans; Gene Expression Profiling; MicroRNAs; Down-Regulation; Inflammation; Periapical Periodontitis
PubMed: 36890871
DOI: 10.7717/peerj.14949 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042