The role of the host-Neutrophil biology.

Neutrophilic polymorphonuclear leukocytes (neutrophils) are myeloid cells packed with lysosomal granules (hence also called granulocytes) that contain a formidable antimicrobial arsenal. They are terminally differentiated cells that play a critical role in acute and chronic inflammation, as well as in the resolution of inflammation and wound healing. Neutrophils express a dense array of surface receptors for multiple ligands, ranging from integrins to support their egress from bone marrow into the circulation and from the circulation into tissues, to cytokine/chemokine receptors that drive their navigation to the site of infection or tissue damage and also prime them for a second stimulus, to pattern recognition receptors and immunoglobulin receptors to facilitate the destruction and removal of infective agents or debridement of damaged tissues. When afferent neutrophil signals are proportionate and coordinated they will phagocytose opsonized and unopsonized bacteria, activating the nicotinamide adenine dinucleotide phosphate oxidase (respiratory burst) to generate reactive oxygen species, which augment the proteolytic destruction of microbes secured within the phagosome. A highly orchestrated process of apoptosis follows, forming membrane-bound substructures that are removed by macrophages. Neutrophils are capable of various other forms of programmed cell death, such as NETosis and pyroptotic cell death, as well as nonprogrammed cell death by necrosis. In recent years, research has revealed that neutrophils are capable of far more subtle cell-cell interactions than previously thought possible. This includes synthesis of various inflammatory mediators and also myeloid cell training within bone marrow, where epigenetic and metabolic signals associated with returning neutrophils that undergo reverse egress from tissues into the vasculature and back to bone marrow program a hyperreactive subset of neutrophils during myelopoiesis that are capable of hypersensitive reactions to microbial aggressors. These characteristics are evident in various neutrophil subsets/subpopulations, creating broad heterogeneity in the behavior and biological repertoire of these seemingly schizophrenic immune cells. Moreover, neutrophils are critical effector cells of adaptive and innate immunity, binding to opsonized bacteria and destroying them by extracellular and intracellular methods. The former creates substantial collateral host tissue damage, as they are less specific than T-cytotoxic cell-killing mechanisms, and in conditions such as peri-implantitis, where plasma cells and neutrophils dominate the immune infiltrate, bone and tissue destruction are rapid and appear relentless. Finally, the role of neutrophils as conduits for periodontal-systemic disease connections and for oxidative damage to act as a causal link between the two has only recently been realized. In this chapter, we attempt to expand on these issues, emphasizing the contributions of European scientists throughout a detailed appraisal of the benefits and side effects of neutrophilic inflammation and immune function.

Membrane barriers for guided bone regeneration: An overview of available biomaterials.

Dental implants revolutionized the treatment options for restoring form, function, and esthetics when one or more teeth are missing. At sites of insufficient bone, guided bone regeneration (GBR) is performed either prior to or in conjunction with implant placement to achieve a three-dimensional prosthetic-driven implant position. To date, GBR is well documented, widely used, and constitutes a predictable and successful approach for lateral and vertical bone augmentation of atrophic ridges. Evidence suggests that the use of barrier membranes maintains the major biological principles of GBR. Since the material used to construct barrier membranes ultimately dictates its characteristics and its ability to maintain the biological principles of GBR, several materials have been used over time. This review, summarizes the evolution of barrier membranes, focusing on the characteristics, advantages, and disadvantages of available occlusive barrier membranes and presents results of updated meta-analyses focusing on the effects of these membranes on the overall outcome.

The efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis.

AIM: To answer the following PICOS question: "In adult patients with peri-implantitis, what is the efficacy of surgical therapy with chemical surface decontamination of implant surfaces in comparison with surgical therapy alone or surgery with placebo decontamination, on probing pocket depth (PD) reduction and bleeding on probing (BoP)/suppuration on probing (SoP), in randomized controlled clinical trials (RCTs) and non-RCTs with at least 6 months of follow-up?" MATERIALS AND METHODS: Six databases were searched from their inception up to 20 May 2022. Data on clinical outcome variables were pooled and analysed using mean differences (MDs), risk ratios (RRs), or risk differences (RDs) as appropriate, 95% confidence intervals (CIs), and prediction intervals (PIs) in the case of significant heterogeneity. Primary outcomes were determined as changes in PD and BoP/SoP. Secondary outcomes were radiographic marginal bone loss (MBL), implant loss, and disease resolution. PROSPERO registration number: CRD42022325603. RESULTS: Six RCTs-two with moderate, three with high, and one with low risk of bias (RoB)-were included. These studies test the adjunctive effect of photodynamic therapy (PDT), chlorhexidine (CHX), and administration of local antibiotics (LAbs) during surgery on the clinical outcome. In a single 12-month study, the adjunctive use of local antibiotics showed a clinically relevant reduction of PD [MD = 1.44; 95%CI (0.40 to -2.48)] and MBL [MD = 1.21; 95%CI (0.44-1.98); one trial, 32 participants]. PDT showed a small but significant reduction in BoP [MD = 7.41%; 95%CI (0.81-14.00); p = 0.028; two trials; 42 participants]. Treatment with CHX resulted in no significant changes in PD, BoP, or MBL compared to placebo (saline solution). None of the interventions affected disease resolution and implant loss. Certainty of the evidence was very low for all outcome measures assessed. CONCLUSIONS: Within the limitations of this systematic review and the meta-analysis, adjunctive use of chemicals such as PDT, CHX, and LAbs for surface decontamination during surgery of peri-implantitis cannot be recommended as superior to standard debridement procedures (mechanical debridement with or without saline).

Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

Mechanical force application and inflammation induce osteoclastogenesis by independent pathways.

OBJECTIVE: To investigate the functional changes of PDL fibroblasts in the presence of mechanical force, inflammation, or a combination of force and inflammation. MATERIALS AND METHODS: Inflammatory supernatants were prepared by inoculating human neutrophils with Porphyromonas gingivalis. Primary human PDL fibroblasts (PDLF), gingival fibroblasts (GFs), and osteoblasts (Saos2) were then exposed to the inflammatory supernatants. Orthodontic force on the PDLFs was simulated by centrifugation. Analyses included cell proliferation, cell viability, cell cycle, and collagen expression, as well as osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression. RESULTS: Mechanical force did not affect PDLF viability, but it increased the metabolic rate compared to resting cells. Force application shifted the PDLF cell cycle to the G0/G1 phase, arresting cell proliferation and leading to elevated collagen production, mild OPG level elevation, and robust RANKL level elevation. Including an inflammatory supernatant in the presence of force did not affect PDLF viability, proliferation, or cytokine expression. By contrast, the inflammatory supernatant increased RANKL expression in GFs, but not in Saos2 cells. CONCLUSION: Applying mechanical force significantly affects PDLF function. Although inflammation had no effect on PDLF or Saos2 cells, it promoted RANKL expression in GF cells. Within the limitations of the in vitro model, the results suggest that periodontal inflammation and mechanical forces could affect bone catabolism through effects on different cell types, which may culminate in synergistic bone resorption.

Excessive inflammatory response to infection in experimental peri-implantitis: Resolution by Resolvin D2.

AIM: The aetiology and pathogenesis of peri-implantitis are currently under active research. This study aimed to dissect the pathogenesis of murine experimental peri-implantitis and assess Resolvin D2 (RvD2) as a new treatment modality. MATERIALS AND METHODS: Four weeks following titanium implant insertion, mice were infected with Porphyromonas gingivalis using single or multiple oral lavages. RvD2 was administrated following infection, and tissues were analysed using flow cytometry, quantitative RT-PCR, taxonomic profiling, and micro-computed tomography. RESULTS: Repeated infections with Pg resulted in microbial dysbiosis and a higher influx of innate and adaptive leukocytes to the peri-implant mucosa (PIM) than to gingiva surrounding the teeth. This was accompanied by increased expression levels of IFN-α, IL-1ß, and RANKL\OPG ratio. Interestingly, whereas repetitive infections resulted in bone loss around implants and teeth, a single infection induced bone loss only around implants, suggesting a higher susceptibility of the implants to infection. Treatment with RvD2 prevented Pg-driven bone loss and reduced leukocyte infiltration to the PIM. CONCLUSIONS: Murine dental implants are associated with dysregulated local immunity and increase susceptibility to pathogen-induced peri-implantitis. However, the disease can be prevented by RvD2 treatment, highlighting the promising therapeutic potential of this treatment modality.

The efficacy of a protective protocol for oral and maxillofacial surgery procedures in a COVID-19 pandemic area-results from 1471 patients.

OBJECTIVE: To examine the effectiveness of an empiric protection protocol during oral surgical treatments in a COVID-19 pandemic area and to evaluate the potential effect of postponed dental procedures on the frequency of facial infections during a lockdown period. METHODS: We performed a retrospective analysis of a case series of a broad-spectrum of oral surgeries in a COVID-19 pandemic area. Data collection included patient age, type of procedure performed, and COVID-19 status of staff and patients. Data were analyzed using descriptive statistics. RESULTS: Between February 21 and April 23, 2020, 1471 patients were treated in the outpatient clinic (n=1404) and under general anesthesia (n=67). All procedures were carried out under a strict empiric protective protocol that included patient screening, personal protective equipment allocation protocol, frequent staff testing, and patient testing before general anesthesia. Treatments included emergency and urgent elective procedures. Only one staff member was confirmed positive for COVID-19 during routine weekly testing, and an independent epidemiologic investigation suggested he was likely infected outside of hospital facilities. CONCLUSIONS: Our empiric protective protocol was found to be effective in preventing staff cross-infection with COVID-19 in an oral and maxillofacial surgery setting. CLINICAL RELEVANCE: To the best of our knowledge, this is the first report that provides data regarding oral surgical activity in a COVID-19 pandemic area. Our suggested protective protocol may assist oral surgeons in continuing dental services in a safe manner.

Diabetes as a risk factor for periodontal disease-plausible mechanisms.

The present narrative review examines the scientific evidence of the biological mechanisms that may link periodontitis and diabetes, as a source of comorbidity. Publications regarding periodontitis and diabetes, in human, animals, and in vitro were screened for their relevance. Periodontal microbiome studies indicate a possible association between altered glucose metabolism in prediabetes and diabetes and changes in the periodontal microbiome. Coinciding with this, hyperglycemia enhances expression of pathogen receptors, which enhance host response to the dysbiotic microbiome. Hyperglycemia also promotes pro-inflammatory response independently or via the advanced glycation end product/receptor for advanced glycation end product pathway. These processes excite cellular tissue destruction functions, which further enhance pro-inflammatory cytokines expression and alteration in the RANKL/osteoprotegerin ratio, promoting formation and activation of osteoclasts. The evidence supports the role of several pathogenic mechanisms in the path of true causal comorbidity between poorly controlled diabetes and periodontitis. However, further research is needed to better understand these mechanisms and to explore other mechanisms.

The efficacy of pocket elimination/reduction compared to access flap surgery: A systematic review and meta-analysis.

AIM: To assess the efficacy and adverse effects of resective surgery compared to access flap in patients with periodontitis. METHODS: Randomized controlled trials with a follow-up ≥6 months were identified in ten databases. Screening, data extraction, and quality assessment were conducted by two reviewers. The primary outcome was probing pocket depth, and the main secondary outcome was clinical attachment level. Data on adverse events were collected. Meta-analysis was used to synthesize the findings of trials. RESULTS: A total of 880 publications were identified. Fourteen publications from nine clinical trials met the inclusion criteria and were included for analysis. Meta-analysis was carried out using all available results. The results indicated superior pocket depth reduction following resective surgery compared to access flap after 6-12 months of follow-up (weighted mean difference 0.47 mm; confidence interval 0.7-0.24; p = .010). After 36-60 months of follow-up, no differences were found between the two treatments in pocket depth and attachment level. The prevalence of adverse effects was not different between the groups. Post-operative recession tended to be more severe for the resective approaches. CONCLUSION: Resective surgical approach was superior to access flap in reducing pocket depth 6-12 months post-surgery, while no differences between the two modalities were found at 36-60 months of follow-up.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Clinical and radiographic assessment of circular versus triangular cross-section neck Implants in the posterior maxilla: A 1-year randomized controlled trial.

OBJECTIVES: Implants with a triangular neck were recently introduced to limit peri-implant bone loss. The primary objective of this randomized controlled trial was to compare peri-implant bone changes of circular versus triangular cross-section neck implants 1 year after loading. The secondary objectives were to assess buccal hard tissue thickness changes, Pink Esthetic Score (PES), and patient satisfaction. MATERIAL AND METHODS: Thirty four patients requiring replacement of the single, intercalated missing tooth of healed site for at least 4 months in the posterior maxilla were randomized into 2 groups according to the type of implant. Immediately after surgery and 1 year after final restoration, a cone beam CT (CBCT) was performed to assess proximal bone remodeling and buccal bone thickness. Peri-implant soft tissue health, PES, and patient-reported outcome measures (PROMs) were recorded. RESULTS: No implant loss occurred within the follow-up period. The mean ± SD peri-implant proximal bone loss 1 year after loading was 0.22 ± 0.30 mm for triangular and 0.42 ± 0.67 mm for circular implants necks (p = .25). Peri-implant bone loss exceeding 2 mm was observed in a single implant in the circular neck group. Buccal bone thickness remained stable and did not differ different between the 2 groups. The peri-implant soft tissue health, PES, and patient satisfaction were also comparable. CONCLUSIONS: Within the limitations of the present study, patient clinical and radiographic outcomes did not differ between triangular and circular cross-section neck implants in the posterior maxilla.

Myd88 plays a major role in the keratinocyte response to infection with Porphyromonas gingivalis.

AIM: To explore the role of keratinocyte myeloid differentiation primary response 88 (MyD88) expression in the adhesion of Porphyromonas gingivalis to the cells and its subsequent invasion and intracellular survival. MATERIALS AND METHODS: Primary mouse keratinocytes from wild-type (WT) or Myd88-/- mice were infected with P gingivalis alone or co-infected with Fusobacterium nucleatum. Bacterial adhesion and invasion were measured using fluorescent microscopy and flow cytometry, and intracellular survival in keratinocytes was quantified by an antibiotic protection assay. Keratinocyte expression of antimicrobial peptides was measured by real-time PCR. RESULTS: In the absence of MyD88, P gingivalis adherence, invasion, and intracellular survival were enhanced compared with WT keratinocytes. The presence of F nucleatum during infection increased the adhesion of P gingivalis to WT keratinocytes but reduced the adhesion to Myd88-/- keratinocytes. Fusobacterium nucleatum improved mildly the invasion and survival of P gingivalis in both cell types. Baseline expression of beta-defensin 2, 3, 4 and RegIII-γ was elevated in Myd88-/- keratinocytes compared to WT cells; however, following infection beta-defensin expression was strongly induced in WT cells but decreased dramatically in the MyD88 deficient cells. CONCLUSION: In the absence of MyD88 expression, P gingivalis adhesion to keratinocytes is improved, and invasion and intracellular survival are increased. Furthermore, keratinocyte infection by P gingivalis induces antimicrobial peptide expression in a MyD88-dependent manner. Thus, MyD88 plays a key role in the interaction between P gingivalis and keratinocytes.

Incorporating antibiotics into platelet-rich fibrin: A novel antibiotics slow-release biological device.

BACKGROUND: The aim of the present in vitro study was to explore the possibility of using platelet-rich fibrin (PRF) as a local sustained released device for antibiotics. MATERIALS AND METHODS: Platelet-rich fibrin was prepared with the addition of antibiotics (5 mg/ml metronidazole; 150 mg/ml clindamycin; 1 mU/ml penicillin) or saline prior to centrifugation, while collagen sponges served as control. PRFs anti-bacterial properties were examined in an anti-biogram assay with Staphylococcus aureus or Fusobacterium nucleatum at different time intervals after PRF preparation. RESULTS: The addition of antibiotic solutions at volumes of 2 or 1 ml led to significant changes in PRF's physical properties, while the addition of 0.5 ml solution did not. PRF with saline showed minor anti-bacterial activity, while all PRFs with antibiotics showed significant anti-bacterial activity (p < 0.05). No differences were observed between raw (clot) and pressed (membrane) forms of PRF. Collagen sponges with and without antibiotics showed similar results to PRF. PRF and collagen sponges with antibiotics preserved their anti-bacterial properties 4 days after preparation. CONCLUSIONS: Platelet-rich fibrin incorporated with antibiotics showed long-term anti-bacterial effect against F. nucleatum and S. aureus. This modified PRF preparation may be used to reduce the risk of post-operative infection in addition to the beneficial healing properties of PRF.

Nupharidine enhances Aggregatibacter actinomycetemcomitans clearance by priming neutrophils and augmenting their effector functions.

OBJECTIVES: Nupharidine (6,6'-Dihydroxythiobinupharidine), purified from the aquatic plant Nuphar lutea leaves (Water lily) prompts antimicrobial activity of immune cells. The aim of the study was to test the effect of Nupharidine on neutrophil function against Aggregatibacter actinomycetemcomitans, JP2 clone (Aa-JP2). METHODS: Neutrophils derived from the human cell line HL60 and human peripheral blood derived from aggressive periodontitis and periodontally healthy subjects were incubated with Nupharidine or vehicle and inoculated with JP2. Bacterial survival was tested using viable counts on blood agar (CFU's). Neutrophils' necrosis/apoptosis, reactive oxygen species (ROS) production, phagocytosis and neutrophil extracellular traps (NET) production following infection were tested, as well as markers of neutrophil priming. RESULTS: Nupharidine had no direct bactericidal effect on JP2, but it enhanced Aa-JP2 clearance by neutrophils. Nupharidine enhanced neutrophil phagocytosis, ROS production and NET formation during JP2 infection. Furthermore, Nupharidine enhanced the expression of certain markers of neutrophils priming, specifically iCAM1, DECTIN-2 and intracellular IL-1ß. CONCLUSION: Nupharidine was shown to promote neutrophil effector bactericidal functions, boosting Aa-JP2 clearance. The results point to the potential of Nupharidine as an adjunctive agent in the treatment of Aa-JP2 periodontitis, but this should be tested initially using pre-clinical and clinical studies.

Biological factors involved in alveolar bone regeneration: Consensus report of Working Group 1 of the 15th European Workshop on Periodontology on Bone Regeneration.

BACKGROUND AND AIMS: To describe the biology of alveolar bone regeneration. MATERIAL AND METHODS: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self-regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop. RESULTS AND CONCLUSIONS: This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research.

Effect of implant neck design on primary and secondary implant stability in the posterior maxilla: A prospective randomized controlled study.

OBJECTIVE: To compare the early changes in implant stability of implants with different neck design during the first 3 months of healing in the posterior maxilla. MATERIALS AND METHODS: Patients were randomized to receive triangular neck implant (test), or round neck implant (control). Resonance frequency analysis (ISQ) measurements were obtained at surgery and at 2, 4, 7, 14, 21, 28, 45, 60, and 90 days following implant placement. Non-parametric statistic was used for data analysis. RESULTS: Thirty-two patients were included (17 test and 15 controls). Initial ISQ values of the test implants were high (mean: 68.4, SD = 8.4) and increased over time (mean: 74.4, SD = 6.0). Control implants presented a statistically significant higher initial ISQ value at implant placement (mean: 76.9, SD = 8.7), which was maintained over the healing period (mean: 77.6, SD = 3.6) with no significant changes between time intervals. After 6 weeks of healing, both implants displayed comparable ISQ values with no differences between the groups. All implants exhibited a decrease in stability on days 2 and 21 post-placement. All roundneck implants used, and 82% of the triangularneck implants showed initial ISQ values above the suggested threshold for immediate loading (>60). CONCLUSIONS: Implant neck design plays a role in implant primary stability in the posterior maxilla. Both implants show high primary stability, with significantly higher values for the round neck. However, these differences disappeared after 6 weeks of healing. While primary implant stability is partially governed by implant neck design, the role of this result is negligible for the achievement of secondary stability.

Microbial accumulation on different suture materials following oral surgery: a randomized controlled study.

BACKGROUND: The aim of the study was to compare bacterial accumulation on different suture materials following oral surgery. METHODS: Patients scheduled for implant or periodontal surgery were included in the study. Upon flap closure, four different sutures were placed in a randomized sequence-silk, coated polyglactin, nylon, and polyester. Ten days following surgery, the sutures were removed and incubated in aerobic as well as anaerobic conditions for 7 days and colony-forming units (CFUs) were calculated. Association between bacterial accumulation and periodontal diagnosis, type of surgery, and antibiotic treatment were also tested. RESULTS: All sutures in all patients were found to contain bacteria. Overall, nylon sutures showed significantly lower CFU levels compared to silk, coated polyglactin, and polyester sutures. The type of surgery (implant vs. periodontal surgery) did not significantly influence bacterial accumulation. Also, periodontal diagnosis had little impact on CFU counts. Interestingly, post-surgical antibiotic treatment also had only a minor effect on bacterial accumulation on the various sutures. DISCUSSION: The results indicate that the monofilamentous nylon sutures showed less microbial accumulation than the other tested materials that were all braided. This effect may be due to material qualities as well as suture macrostructure. Type of surgery, periodontal diagnosis, and antibiotic consumption have little effect on bacterial accumulation of sutures. CLINICAL RELEVANCE: The study provides the microbial profile of commonly used sutures and may assist in suture selection during clinical procedures.

An update on the evidence for pathogenic mechanisms that may link periodontitis and diabetes.

AIM: To provide an update of the review by Taylor (Journal of Clinical Periodontology, 2013, 40, S113) regarding the scientific evidence of the biological association between periodontitis and diabetes. METHODS: Literature searches were performed using MeSH terms, keywords and title words and were published between 2012 and November 2016. All publications were screened for their relevance. The data from the articles were extracted and summarized in tables and a narrative review. RESULTS: Small-scale molecular periodontal microbiome studies indicate a possible association between altered glucose metabolism in pre-diabetes and diabetes and changes in the periodontal microbiome, with no evidence for casual relationships. Clinical and animal studies found elevated gingival levels of IL1-ß, TNF-α, IL-6, RANKL/OPG and oxygen metabolites in poorly controlled diabetes. In addition, individuals with diabetes and periodontitis exhibit high levels of circulating TNF-α, CRP and mediators of oxidative stress, and successful periodontal treatment reduces their levels. CONCLUSIONS: The elevated pro-inflammatory factors in the gingiva of patients with poorly controlled diabetes suggest a biological pathway that may aggravate periodontitis. Some evidence suggests that the systemic inflammatory burden in periodontitis has the potential to affect diabetes control, but no studies addressed the impact of successful periodontal therapy on the pathophysiological mechanisms involved in systemic complications of diabetes.

Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology.

BACKGROUND: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship. AIMS: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C). EPIDEMIOLOGY: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes. MECHANISMS: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-ß, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression. INTERVENTIONS: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months, although studies involving longer-term follow-up are inconclusive. CONCLUSIONS: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis.

Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.