The role of acquired host immunity in periodontal diseases.

The aim of this narrative review is to relate the contribution of European researchers to the complex topic of the host immune system in periodontal disease, focusing on acquired immunity. Other chapters in this volume will address the genetics and autoantibody responses and other forms of immunity to periodontal disease. While the contribution of European authors is the focus, global literature is included in this descriptive narrative for contextual clarity, albeit many with European co-authors. The topic is relatively intense and is thus broken down into sections outlined below, tackled as descriptive narratives to enhance understanding. Any attempt at a systematic or scoping review was quickly abandoned given the descriptive nature and marked variation of approach in almost all publications. Even the most uniform area of this acquired periodontal immunology literature, antibody responses to putative pathogens in periodontal diseases, falls short of common structures and common primary outcome variables one would need and expect in clinical studies, where randomized controlled clinical trials (RCTs) abound. Addressing 'the host's role' in immunity immediately requires a discussion of host susceptibility, which necessitates consideration of genetic studies (covered elsewhere in the volume and superficially covered here).

Periodontitis and rheumatoid arthritis-Global efforts to untangle two complex diseases.

Understanding the impact of oral health on rheumatoid arthritis (RA) will inform how best to manage patients with both periodontitis and RA. This review seeks to provide an update on interventional and mechanistic investigations, including a brief summary of European Research programs investigating the link between periodontitis and RA. Recent clinical studies are described that evaluate how the treatment of one disease impacts on the other, as are studies in both humans and animal models that have sought to identify the potential mechanisms linking the two diseases.

Efficacy and safety of a novel mucoadhesive clobetasol patch for treatment of erosive oral lichen planus: A phase 2 randomized clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa. Currently there is no approved treatment for OLP. We report on the efficacy and safety of a novel mucoadhesive clobetasol patch (Rivelin® -CLO) for the treatment of OLP. METHODS: Patients with confirmed OLP and measurable symptomatic ulcer(s) participated in a randomized, double-blind, placebo-controlled, multicenter clinical trial testing a novel mucoadhesive clobetasol patch (Rivelin® -CLO) in OLP across Europe, Canada, and the United States. Patients were randomized to placebo (nonmedicated), 1, 5, 20 µg Clobetasol/patch, twice daily, for 4 weeks. The primary endpoint was change in total ulcer area compared to baseline. Secondary endpoints included improvement from baseline in pain, disease activity, and quality of life. RESULTS: Data were analyzed and expressed as mean [SD]. One hundred thirty-eight patients were included in the study; 99 females and 39 males, mean age was 61.1 [11.6] years. Statistical analyses revealed that treatment with 20-µg Rivelin® -CLO patches demonstrated significant improvement with ulcer area (p = 0.047), symptom severity (p = 0.001), disease activity (p = 0.022), pain (p = 0.012), and quality of life (p = 0.003) as compared with placebo. Improvement in OLP symptoms from beginning to the end of the study was reported as very much better (best rating) in the 20-µg group (25/32) patients compared to the placebo group (11/30), (p = 0.012). Adverse events were mild/moderate. Candidiasis incidence was low (2%). CONCLUSIONS: Rivelin® -CLO patches were superior to placebo demonstrating statistically significant, clinically relevant efficacy in objective and subjective improvement and, with a favorable safety profile.

Aerosol reduction efficacy of different intra-oral suction devices during ultrasonic scaling and high-speed handpiece use.

BACKGROUND: The COVID-19 pandemic led to significant changes in the provision of dental services, aimed at reducing the spread of respiratory pathogens through restrictions on aerosol generating procedures (AGPs). Evaluating the risk that AGPs pose in terms of SARS-CoV-2 transmission is complex, and measuring dental aerosols is challenging. To date, few studies focus on intra-oral suction. This study sought to assess the effectiveness of commonly used intra-oral suction devices on aerosol mitigation. METHODS: Ultrasonic scaling and high-speed handpiece procedures were undertaken to generate aerosol particles. Multiple particle sensors were positioned near the oral cavity. Sensor data were extracted using single board computers with custom in-house Bash code. Different high-volume and low-volume suction devices, both static and dynamic, were evaluated for their efficacy in preventing particle escape during procedures. RESULTS: In all AGPs the use of any suction device tested resulted in a significant reduction in particle counts compared with no suction. Low-volume and static suction devices showed spikes in particle count demonstrating moments where particles were able to escape from the oral cavity. High-volume dynamic suction devices, however, consistently reduced the particle count to background levels, appearing to eliminate particle escape. CONCLUSIONS: Dynamic high-volume suction devices that follow the path of the aerosol generating device effectively eliminate aerosol particles escaping from the oral cavity, in contrast to static devices which allow periodic escape of aerosol particles. Measuring the risk of SARS-CoV-2 transmission in a dental setting is multi-factorial; however, these data suggest that the appropriate choice of suction equipment may further reduce the risk from AGPs.

The systemic inflammatory response following hand instrumentation versus ultrasonic instrumentation-A randomized controlled trial.

OBJECTIVE: This study sought to investigate whether the immediate systemic inflammatory response following full-mouth debridement differs following use of hand compared with ultrasonic instruments. METHODS: Thirty-nine periodontitis patients were randomized to treatment with full-mouth debridement using either hand or ultrasonic instrumentation completed within 24 hr. Serum and periodontal clinical parameters were collected at baseline, day 1, day 7 and day 90 post-treatment. Differences in systemic inflammatory markers were assessed using general linear models at each timepoint, corrected for age, gender, smoking status, body mass index and baseline levels of each marker. RESULTS: Across all patients, serum C-reactive protein increased at day 1, with no differences between hand and ultrasonic groups (p(adjusted) = .22). There was no difference between groups in interleukin-6 (p(adjusted) = .29) or tumour necrosis factor α (p(adjusted) = .53) at day 1. Inflammatory markers returned to baseline levels by day 7. Treatment resulted in equal and marked improvements in clinical parameters in both groups; however, total treatment time was on average shorter for ultrasonic instruments (p(adjusted) = .002). CONCLUSIONS: Ultrasonic instrumentation resulted in shorter treatment time with comparable clinical outcomes. Levels of serum C-reactive protein at day 1 were similar following debridement with hand or ultrasonic instruments.

Revealing microbial recognition by specific antibodies.

BACKGROUND: Recognition of microorganisms by antibodies is a vital component of the human immune response. However, there is currently very limited understanding of immune recognition of 50 % of the human microbiome which is made up of as yet un-culturable bacteria. We have combined the use of flow cytometry and pyrosequencing to describe the microbial composition of human samples, and its interaction with the immune system. RESULTS: We show the power of the technique in human faecal, saliva, oral biofilm and breast milk samples, labeled with fluorescent anti-IgG or anti-IgA antibodies. Using Fluorescence-Activated Cell Sorting (FACS), bacterial cells were separated depending on whether they are coated with IgA or IgG antibodies. Each bacterial population was PCR-amplified and pyrosequenced, characterizing the microorganisms which evade the immune system and those which were recognized by each immunoglobulin. CONCLUSIONS: The application of the technique to healthy and diseased individuals may unravel the contribution of the immune response to microbial infections and polymicrobial diseases.

Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study.

BACKGROUND: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort. METHODS: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis. RESULTS: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity. CONCLUSIONS: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.

Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. OBJECTIVES: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. METHODS: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). RESULTS: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. CONCLUSIONS: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy.

The alpha 7 nicotinic receptor agonist PHA-543613 hydrochloride inhibits Porphyromonas gingivalis-induced expression of interleukin-8 by oral keratinocytes.

OBJECTIVE: The alpha 7 nicotinic receptor (α7nAChR) is expressed by oral keratinocytes. α7nAChR activation mediates anti-inflammatory responses. The objective of this study was to determine if α7nAChR activation inhibited pathogen-induced interleukin-8 (IL-8) expression by oral keratinocytes. MATERIALS AND METHODS: Periodontal tissue expression of α7nAChR was determined by real-time PCR. OKF6/TERT-2 oral keratinocytes were exposed to Porphyromonas gingivalis in the presence and absence of a α7nAChR agonist (PHA-543613 hydrochloride) alone or after pre-exposure to a specific α7nAChR antagonist (α-bungarotoxin). Interleukin-8 (IL-8) expression was measured by ELISA and real-time PCR. Phosphorylation of the NF-κB p65 subunit was determined using an NF-κB p65 profiler assay and STAT-3 activation by STAT-3 in-cell ELISA. The release of ACh from oral keratinocytes in response to P. gingivalis lipopolysaccharide was determined using a GeneBLAzer M3 CHO-K1-bla cell reporter assay. RESULTS: Expression of α7nAChR mRNA was elevated in diseased periodontal tissue. PHA-543613 hydrochloride inhibited P. gingivalis-induced expression of IL-8 at the transcriptional level. This effect was abolished when cells were pre-exposed to a specific α7nAChR antagonist, α-bungarotoxin. PHA-543613 hydrochloride downregulated NF-κB signalling through reduced phosphorylation of the NF-κB p65-subunit. In addition, PHA-543613 hydrochloride promoted STAT-3 signalling by maintenance of phosphorylation. Furthermore, oral keratinocytes upregulated ACh release in response to P. gingivalis lipopolysaccharide. CONCLUSION: These data suggest that α7nAChR plays a role in regulating the innate immune responses of oral keratinocytes.

Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity.

OBJECTIVE: IL-17A is implicated in periodontitis pathogenesis. The roles of IL-17B-IL-17F and IL-17A/F are unknown. This study aimed to determine clinical associations between IL-17 family cytokines and periodontitis and to investigate the biological roles of IL-17A and IL-17E using in vitro model systems. MATERIALS AND METHODS: Samples from 97 patients with periodontitis and 77 healthy volunteers were used in the study. Serum, saliva and gingival crevicular fluid (GCF) levels of IL-17 family cytokines were measured by ELISA. Oral keratinocytes were stimulated with a P. gingivalis biofilm, or IL-17A, in the presence and absence of IL-17E and the expression of IL-8 and CXCL5 were investigated by ELISA and real-time-PCR. NF-κB phosphorylation in similar experiments was also measured using a cell-based ELISA. RESULTS: Serum, saliva and GCF IL-17A levels were higher in periodontitis patients and correlated positively with clinical parameters of attachment loss, pocket depth and bleeding on probing. Serum IL-17E levels were lower in periodontitis patients and the serum IL-17A:IL-17E ratio correlated positively with clinical parameters. In vitro, IL-17E inhibited Porphyromonas gingivalis and IL-17A induced expression of chemokines by reducing phosphorylation of the NF-κB p65 subunit. CONCLUSIONS: Serum IL-17A:IL-17E may be a marker of disease severity. IL-17E may have opposing roles to IL-17A in periodontitis pathogenesis. IL-17E can negatively regulate IL-17A and periodontal pathogen induced expression of chemokines by oral keratinocytes.

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules.

BACKGROUND: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties. METHODS: An in vitro multi-species biofilm containing S. mitis, F. nucleatum, P. gingivalis and A. actinomycetemcomitans was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level. RESULTS: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA. CONCLUSIONS: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.

Aberrant immunity in the oral cavity-a link with rheumatoid arthritis?

There are well established epidemiological links between rheumatoid arthritis and periodontitis. Recent data have started to shed light on the mechanisms that might underlie the relationship between these two complex diseases. Unravelling the roles of distinct pathways involved in these mechanisms has the potential to yield novel preventative and therapeutic strategies for both diseases. Perhaps most intriguingly, this represents an area where understanding the biology in the oral cavity might reveal fundamental advances in understanding immune regulation and the relationships between the host and microbiome. Here we seek to discuss aspects of the adaptive immune response that might link periodontitis and rheumatoid arthritis.

Impact of treatment of rheumatoid arthritis on periodontal disease: A review.

BACKGROUND: Numerous studies support a bidirectional association between rheumatoid arthritis (RA), a chronic autoimmune degenerative inflammatory joint disease, and periodontitis, a chronic inflammatory disease caused by the immune reaction to bacteria organized in biofilms. RA and periodontitis are both multifactorial chronic inflammatory diseases that share common modifiable and non-modifiable risk factors. There is no cure for RA; treatment is based on lifestyle modifications and a variety of medications: nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs, e.g., conventional synthetic DMARDs [csDMARDs]; biological DMARDs [bDMARD] and targeted synthetic DMARDs). There are molecular pathways of inflammation that are common to both RA and periodontitis. Thus, there is a potential effect of RA treatments on periodontitis. This systematic review aims to assess the impact of antirheumatic agents on periodontal conditions of patients suffering from both RA and periodontitis. METHODS: PubMed/MEDLINE, Cochrane Library, and Embase online databases were systematically explored, and a manual search was performed to identify relevant studies published until January 2023. This review is registered in the PROSPERO database (CRD42023409006). RESULTS: A total of 2827 articles were identified, and 35 fulfilled the inclusion criteria. The included studies generally show a consensus that, at normal dosage, NSAID and corticosteroids have negligible impact on periodontium. Similarly, csDMARD alone or in combination with other csDMARD demonstrated no adverse effect on periodontium. Monotherapy with bDMARD had a positive effect on periodontal pocket depths and gingival inflammation in the longitudinal studies up to 6 months but showed negligible effect on the periodontium in interventional studies with a longer follow-up (9 months and 15.1 months). However, the combination of tumor necrosis factor (TNF)-α inhibitors + methotrexate (MTX) was associated with a rise in gingival inflammation. Due to the considerable heterogeneity of the study designs, a meta-analysis could not reasonably be performed. CONCLUSION: Within the limitations of the available studies, there is evidence to suggest that bDMARD monotherapy may improve the periodontal condition of RA patients with periodontal disease to a certain extent; the concomitant medication of TNF inhibitor + MTX could worsen gingival inflammation. More data are required to understand the impact of RA therapies on periodontal health.

BSP Implementation of Prevention and Treatment of Peri-implant Diseases - The EFP S3 Level Clinical Practice Guideline.

OBJECTIVES: to adapt the supranational European Federation of Periodontology (EFP) Prevention and Treatment of Peri-implant Diseases - The EFP S3 Level Clinical Practice Guideline for UK healthcare environment, taking into account a broad range of views from stakeholders and patients. SOURCES: This UK version, based on the supranational EFP guideline [1] published in the Journal of Clinical Periodontology, was developed using S3-level methodology, combining assessment of formal evidence from 13 systematic reviews with a moderated consensus process of a representative group of stakeholders, and accounts for health equality, environmental factors and clinical effectiveness. It encompasses 55 clinical recommendations for the Prevention and Treatment of Peri-implant Diseases, based on the classification for periodontal and peri-implant diseases and conditions [2]. METHODOLOGY: The UK version was developed from the source guideline using a formal process called the GRADE ADOLOPMENT framework. This framework allows for adoption (unmodified acceptance), adaptation (acceptance with modifications) and the de novo development of clinical recommendations. Using this framework, following the S3-process, the underlying evidence was updated and a representative guideline group of 111 delegates from 26 stakeholder organisations was assembled into four working groups. Following the formal S3-process, all clinical recommendations were formally assessed for their applicability to the UK and adoloped accordingly. RESULTS AND CONCLUSION: Using the ADOLOPMENT protocol, a UK version of the EFP S3-level clinical practice guideline for the Prevention and Treatment of Peri-implant Diseases was developed. This guideline delivers evidence- and consensus-based clinical recommendations of direct relevance to the UK healthcare community including the public. CLINICAL SIGNIFICANCE: The S3-level-guidelines combine evaluation of formal evidence, grading of recommendations and synthesis with clinical expertise of a broad range of stakeholders. The international S3-level-guideline was implemented for direct clinical applicability in the UK healthcare system, facilitating a consistent, interdisciplinary, evidence-based approach with public involvement for the prevention and treatment of peri-implant diseases.

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability.

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20-82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.

BACKGROUND: Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. AIM: To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. METHODS: Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. RESULTS: Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p < 0.0001]. Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p < 0.05), but similar anti-CCP than non-smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p < 0.05) and anti-P. gingivalis (all participants p < 0.01). CONCLUSION: In subjects with periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis.

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

BACKGROUND: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects. METHODS: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression. RESULTS: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm. CONCLUSIONS: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.

Treatment of peri-implant diseases: a review of the literature and protocol proposal.

UNLABELLED: Over 100,000 implants were placed in the UK in 2010. As the numbers of patients with implant-retained prostheses increases, operators are encountering an increasing number of biological implant complications, most commonly peri-implant mucositis and peri-implantitis. The effective management of these complications is crucial to maintain patients' oral health. In particular, in contrast to common periodontal infections, some peri-implant infections may benefit from surgical intervention as a first line approach. CLINICAL RELEVANCE: This article reviews the literature on the treatment options for peri-implant mucositis and peri-implantitis and proposes a protocol for their treatment.

Periodontal instrumentation technique: an exploratory analysis of clinical outcomes and financial aspects.

Objective This exploratory post hoc analysis sought to investigate clinical outcomes comparing non-surgical treatment for periodontal disease using exclusively hand instruments, exclusively ultrasonic instruments or a combination approach. Differences in time efficiency and equipment use with each treatment method were evaluated.Methods In total, 55 patients with periodontitis were treated across two studies (randomised controlled trial and cohort study) with non-surgical periodontal therapy using hand instruments (HI), ultrasonic instruments (UI) or a combination approach (CI). All patients were re-evaluated 90 days after treatment. Clinical parameters, time taken and financial implications of non-surgical periodontal therapy were explored with a descriptive analysis within this post hoc analysis.Results There were no clinically relevant differences in clinical parameters across all groups at day 90. Inter-group comparisons showed no clinically relevant differences in treatment outcome between groups. UI required less time on average to complete treatment compared to HI. UI provided using a half mouth approach had fewest overall episodes of expenditure and lowest maintenance costs.Conclusions Comparison of clinical outcomes between HI, UI and CI yielded no clinically relevant differences. When comparing HI and UI, UI had a shorter treatment time on average. Full mouth treatment was associated with the least patient visits. UI was least costly on a recurring basis.

Inequalities in access to NHS primary care dental services in Scotland during the COVID-19 pandemic.

Introduction This study aimed to quantify the impact of the COVID-19 pandemic on access and inequalities in primary care dental services among children and adults in Scotland.Methods Access was measured as any NHS Scotland primary care dental contacts derived from administrative data from January 2019 to May 2022, linked to the area-based Scottish Index of Multiple Deprivation for children and adults, and related to population denominator estimates from National Record Scotland. Inequalities for pre-pandemic (January 2019-January 2020) and recent (December 2021-February 2022, and March 2022-May 2022) periods for both children and adults were calculated and compared using the slope index of inequality and relative index of inequality.Results Following the first lockdown (March 2020) there was a dramatic fall to near zero dental contacts, followed by a slow recovery to 64.8% of pre-pandemic levels by May 2022. There was initial widening of relative inequalities in dental contacts in early 2022, which, more recently, had begun to return to pre-pandemic levels.Conclusion COVID-19 had a major impact on access to NHS primary dental care, and while inequalities in access are apparent as services recover from lockdown, these inequalities are not a new phenomenon.