Detection and comparison of neutrophil extracellular traps in tissue samples of peri-implantitis, periodontitis, and healthy patients: A pilot study.

OBJECTIVE: The aim of this study was to detect and compare the tissular expression of neutrophil extracellular traps (NETs) in peri-implant and periodontal samples of patients with peri-implantitis, periodontitis, and controls. MATERIALS AND METHODS: An observational study was performed on patients with peri-implantitis, periodontitis, and controls. Peri-implant and/or periodontal clinical examinations were performed on each participant. Tissue samples were collected during tooth/implant extraction for clinical reasons. Electron microscopy analysis, Picro-Sirius red staining, immunohistochemical (CD15), and immunofluorescence (citrullinated H3 and myeloperoxidase) techniques were performed to detect NET-related structures and the degree of connective tissue destruction, between the study groups. RESULTS: Sixty-four patients were included in the study: 28 peri-implantitis, 26 periodontitis, and 10 controls, with a total of 51 implants, 26 periodontal teeth, and 10 control teeth. Neutrophil release of nuclear content was observed in transmission electron microscopy. Immunohistochemical analysis showed a greater CD15 expression in both peri-implantitis and periodontitis compared to controls (p < 0.001), and peri-implantitis presented lower levels of connective tissue and collagen compared to both periodontitis (p = 0.044; p < 0.001) and controls (p < 0.001). Immunofluorescence showed greater citH3 expression in peri-implantitis than the one found in both periodontitis (p = 0.003) and controls (p = 0.048). CONCLUSIONS: A greater presence and involvement of neutrophils, as well as a greater connective tissue destruction were observed in cases of peri-implantitis. A higher expression of NET-related markers was found in mucosal samples of peri-implantitis compared to periodontitis and controls.

Tooth loss during supportive periodontal care: A prospective study.

AIM: To assess periodontal stability and the association between tooth- and patient-related factors and tooth loss during supportive periodontal care (SPC). MATERIALS AND METHODS: A prospective observational study was carried out on previously treated periodontitis patients followed up for 5 years in SPC. The risk profile (low, moderate, high) of each patient based on periodontal risk assessment (PRA) scoring at baseline was evaluated, and tooth loss rates were analysed. RESULTS: Two hundred patients were included in the study, and 143 had 5-year follow-up data available for analysis. The overall annual tooth loss per patient was 0.07 ± 0.14 teeth/patient/year. Older age, smoking, staging and grading were associated with increased tooth loss rates. Most patients whose teeth were extracted belonged to the PRA high-risk group. Both PRA and a tooth prognosis system used at baseline showed high negative predictive value but low positive predictive value for tooth loss during SPC. CONCLUSIONS: Overall, the tooth loss rate of periodontitis patients in this prospective cohort study under SPC in private practice was low. Both tooth-based and patient-based prognostic systems can identify high-risk cases, but their positive predictive value should be improved.

Correlation between Inflammasomes and Microbiota in Peri-Implantitis.

The activation of inflammasomes is thought to induce the inflammatory process around dental implants. No information is available on the correlation between microbiota and inflammasomes in clinical samples from patients suffering peri-implantitis. For this cross-sectional study, 30 biofilm samples were obtained from 19 patients undergoing surgical treatment for peri-implantitis because of the presence of bleeding on probing, probing depth higher than 6 mm, and radiographic bone loss higher than 3 mm. Then, soft tissue samples from around the implant were also collected. The relative abundance of bacteria and alpha-diversity indexes were calculated after analyzing the 16S rRNA gene using next-generation sequencing. The soft-tissue samples were processed for evaluation of the inflammasomes NLRP3 and AIM2 as well as caspase-1 and IL-1ß. The relative abundance (mean (SD)) of specific species indicated that the most abundant species were Porphyromonas gingivalis (10.95 (14.17)%), Fusobacterium vincentii (10.93 (13.18)%), Porphyromonas endodontalis (5.89 (7.23)%), Prevotella oris (3.88 (4.94)%), Treponema denticola (2.91 (3.19)%), and Tannerella forsythia (2.84 (4.15)%). Several correlations were found between the species and the immunohistochemical detection of the inflammasomes NLRP3 and AIM2 as well as caspase-1 and IL-1ß, both in the epithelium and the lamina propria. A network analysis found an important cluster of variables formed by NLRP3 in the lamina propria and AIM2, caspase-1, and IL-1ß in the lamina propria and the epithelium with Prevotella dentalis, Prevotella tannerae, Tannerella forsythia, or Selenomonas timonae. Thus, it could be concluded that inflammasomes NLRP3 and AIM2 and their downstream effectors caspase-1 and interleukin-1ß can be significantly associated with specific bacteria.

Accidental implant screwdriver aspiration: A case series report with literature review and proposed action protocol.

This article presents the first reported case series of three cases of aspiration of a dental implant screwdriver, which was successfully removed by flexible bronchoscopy. The report highlights preventive measures that can be taken in the dental office and the clinical signs and symptoms of the presence of a dental implant screwdriver in the bronchial tree. The nine reports published to date on this phenomenon are reviewed and compared, and an action protocol for dental practitioners, anaesthetists and pulmonologists is proposed to address this emergency. Some early and late complications are also described.

Randomized clinical trial on the clinical effects of a toothpaste containing extra virgin olive oil, xylitol, and betaine in gingivitis.

To determine the effects on gingival bleeding, dental biofilm, and salivary flow and pH in patients with gingivitis of using toothpaste with extra-virgin olive oil (EVOO), xylitol, and betaine in comparison to a placebo or commercial toothpaste. This controlled, double blinded, and multicenter randomized clinical trial included patients with gingivitis randomly assigned to one of three groups: test group (EVOO, xylitol, and betaine toothpaste), control group 1 (placebo toothpaste), or control group 2 (commercial toothpaste). Percentage supragingival biofilm and gingival bleeding were evaluated at baseline (T0), 2 months (T2), and 4 months (T4), measuring non-stimulated salivary flow and salivary pH. Comparisons were performed between and within groups. The final study sample comprised 20 in the test group, 21 in control group 1, and 20 in control group 2. In comparison to control group 1, the test group showed significantly greater decreases in gingival bleeding between T4 and T0 (p = 0.02) and in biofilm between T2 and T0 (p = 0.02) and between T4 and T0 (p = 0.01). In the test group, salivary flow significantly increased between T2 and T0 (p = 0.01), while pH alkalization was significantly greater between T4 and T0 versus control group 2 (p = 0.01) and close-to-significantly greater versus control group 1 (p = 0.06). The toothpaste with EVOO, xylitol, and betaine obtained the best outcomes in patients with gingivitis, who showed reductions in gingival bleeding and supragingival biofilm and an increase in pH at 4 months in comparison to a commercial toothpaste.

A Nutraceutical Containing Chlorogenic Acid and Luteolin Improves Cardiometabolic Parameters in Subjects with Pre-Obesity: A 6-Month Randomized, Double-Blind, Placebo-Controlled Study.

Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement's effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-ß), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and < 30 kg/m2. All subjects received the Altilix® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects.

Managing the Systemic Impact of Periodontitis.

Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone. It is associated with elevation of systemic inflammatory markers and with the presence of systemic co-morbidities. Furthermore, periodontal treatment leads to a 24-48 h-long acute local and systemic inflammatory response. This systemic response might increase the burden of patients with compromised medical history and/or uncontrolled systemic diseases. The correlation between periodontitis and systemic diseases, the impact of periodontitis on the quality of life and public health, the effects of periodontal treatment on systemic health and disease, and the available methods to manage systemic inflammation after periodontal therapy are discussed. The main focus then shifts to a description of the existing evidence regarding the impact of periodontitis and periodontal treatment on systemic health and to the identification of approaches aiming to reduce the effect of periodontitis on systemic inflammation.

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer.

There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pathogenic mechanisms of this relationship in a comprehensive manner. Finally, the main questions and further research perspectives are presented.

Prevention of Occupational Hazards Due to Asbestos Exposure in Dentistry. A Proposal from a Panel of Experts.

Asbestos in all its forms is a Group 1 material agent with proven carcinogenic effects in the human being since 1977. Exposure to asbestos can be considered unsafe. The use of asbestos in the field of dentistry had a common use in the manufacture of dental prostheses in the 1960s and 1970s. Taking into account the long induction period of this agent and the plausibility for being a risk factor in dentistry, the objective of this study is to propose a plan for the prevention of occupational risks due to asbestos exposure in dentistry by means of the contribution of a panel of experts. An Expert Panel (EP) approach was used in which a group of nine experts identified and documented the use of asbestos in the dental profession. EP was created and followed the protocol in accordance with the EuropeAid Assessment Guidelines. As a result of this study, EP documented the common use and sources of asbestos in dentistry in prosthetic materials, dental dressings, and in the coating of casting cylinders. EP also created a consensus document on the priority measures for the Plan for the Prevention of Risks from Asbestos in Dentistry, based on previous reports from the European Commission Senior Labour Inspectors' Committee. The document concluded that obtainment of information, receiving specific training on the subject and performing epidemiological studies, and the proper risk assessments were the priority measures to adopt.

Periodontitis is associated with higher subclinical atherosclerosis in patients with systemic lupus erythematosus.

AIM: To determine periodontitis prevalence in patients with systemic lupus erythematosus (SLE) and to assess whether periodontitis in SLE patients is associated with a greater subclinical atherosclerosis. METHODS: An observational case-control study was conducted in SLE (cases) and patients without any rheumatic diseases (controls), matched for sex. Sociodemographic and cardiometabolic variables were gathered, and SLE activity was assessed through several indexes. Periodontal examination registered probing pocket depth, clinical attachment level, bleeding on probing, plaque index, and tooth loss. Subclinical atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry, homocysteine levels, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Bivariate analyses and logistic regression were used to assess the association of any of the studied variables with SLE. RESULTS: Seventy-one cases and 72 controls were included in the study. Thirty-nine SLE patients (54.9%) were diagnosed with periodontitis, compared with 16 controls (22.2%). High levels of PWV (≥7.7 m/s, 75th percentile) were shown by 44.3% of the cases vs. 22.4% of the controls (p = .011). Among SLE patients, those with periodontitis showed higher PWV values (8.1 ± 1.52 vs. 7.16 ± 1.11 m/s, p = .006) and higher homeostasis model assessment index (indicative of insulin resistance) (1.7 ± 0.73 vs. 2.92 ± 3.05, p = .028) compared to those with periodontal health. Logistic regression showed that waist circumference (OR 1.06, 95% CI 1.01-1.12, p = .015); ESR (OR 1.09, 95% CI 1.03-1.16, p = .003); and bleeding on probing (OR 1.1, 95% CI 1.01-1.19, p = .018) were associated with the risk of SLE. CONCLUSION: Systemic lupus erythematosus patients showed a higher periodontitis percentage than controls. Higher PWV values were found in SLE patients with periodontitis, indicating a higher prevalence of subclinical atherosclerosis. Patients with higher gingival bleeding showed a higher risk of SLE.

Liraglutide Improved Cardiometabolic Parameters More in Obese than in Non-obese Patients with Type 2 Diabetes: A Real-World 18-Month Prospective Study.

INTRODUCTION: The glucagon-like peptide-1 agonist (GLP1-RA) liraglutide is currently approved for the treatment of both obesity and type 2 diabetes (T2DM). We investigated whether the effect of this agent on cardiometabolic parameters in subjects with T2DM varied in relation to the concomitant presence of obesity. METHODS: One hundred thirty-five subjects (78 men and 57 women; age: 62 ± 10 years) naïve to incretin-based therapies were treated with low-dose liraglutide (1.2 mg/day) as an add-on to metformin for 18 months. Patients were divided into two subgroups based on their body-mass index (BMI): (a) obese (BMI ≥ 30) and (b) non-obese (BMI < 30). Clinical and laboratory analyses were assessed at baseline and every 6 months. RESULTS: During follow-up, significant improvements were seen in both groups in fasting glycemia, glycated hemoglobin, waist circumference, and carotid intima-media thickness (cIMT), while body weight, BMI, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in obese subjects only. Correlation analysis revealed that changes in subclinical atherosclerosis (assessed by cIMT) were associated with changes in triglycerides (r = 0.488, p < 0.0001) in the obese group only. CONCLUSION: Liraglutide had beneficial actions on glycemic parameters and cardiometabolic risk factors in both non-obese and obese patients with T2DM, with a greater efficacy in the latter. These findings reinforce the benefits of liraglutide for the cardiometabolic outcomes of obese patients with T2DM in the real-world setting. This has critical importance during the current pandemic, since patients with diabetes and obesity are exposed globally to the most severe forms of COVID-19, related complications, and death. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01715428.

Patients with periodontitis and erectile dysfunction suffer a greater incidence of major adverse cardiovascular events: A prospective study in a Spanish population.

BACKGROUND: Periodontitis and erectile dysfunction (ED) have been linked with cardiovascular disease. The association of periodontitis and ED with the occurrence of major adverse cardiovascular events has not been previously assessed. The aim of this study was to determine if the presence of periodontitis and ED has any effect on the incidence of major adverse cardiovascular events. METHODS: Male patients that attended the Urology service were enrolled in a prospective study. Erectile dysfunction was diagnosed according to the International Index of Erectile Function. Sociodemographic data and periodontal clinical parameters were gathered (pocket probing depth, clinical attachment loss, bleeding on probing (BoP), plaque index and number of teeth) at baseline. Major adverse cardiovascular events occurred both before and during the follow-up time were registered. Bivariate analyses, as well as a multivariate analysis were performed, adjusting for potential confounders. RESULTS: A total of 158 patients were included, with a mean follow-up of 4.2 years. A greater number of major adverse cardiovascular events occurred in the group that presented periodontitis and ED (P = 0.038). After adjusting by age and previous cardiovascular disease in the multivariate analysis, the annual major adverse cardiovascular event rate was estimated to be 3.7 times higher in the same group (P = 0.049). Other periodontal clinical variables together with ED supported these results and were close to statistical significance. CONCLUSIONS: Patients with periodontitis and ED, adjusted by age and a cardiovascular disease, showed 3.7 times more risk of suffering major adverse cardiovascular events after mean follow-up of 4.2 years.

Periodontal Treatment by Dental Undergraduate Students: Assessment of the Patient's Oral Quality of Life - A Prospective Pilot Study.

PURPOSE: To assess the impact of nonsurgical periodontal treatment, performed by undergraduate dental students, on oral health-related quality of life of patients with periodontitis. MATERIALS AND METHODS: An observational, prospective, single-arm cohort study with pre­post test involving 31 undergraduate dental students was performed. A complete periodontal examination was performed before and after receiving nonsurgical periodontal treatment. The main independent clinical variables assessed were the degree of periodontal inflammation and the number of teeth with periodontitis. Oral health-related quality of life was assessed before and after treatment through the Oral Impacts on Daily Performances (OIDP) questionnaire. The association between the extent of periodontal treatment (measured as number of treated teeth) and final OIDP score was assessed, adjusting for age, sex, and baseline OIDP, in a multiple regression model. RESULTS: Thirty-four patients were enrolled and treated by the undergraduate students. The mean OIDP value (global absolute score), representing the severity and frequency of the impacts, decreased from 26.2 to 12 after treatment. The mean percentage of impact, representing the number dimensions affected by oral health (global percent score), was reduced from 13% to 6%. However, no association between the number of treated teeth and post-treatment OIDP score was observed after adjusting for age, sex, and baseline OIDP score. CONCLUSION: Nonsurgical periodontal treatment performed by undergraduate dental students improved the oral health-related quality of life of periodontal patients, although no statistically significant association was found between the extent of periodontal treatment and the final OIDP score.

Hyaluronic acid reduces inflammation and crevicular fluid IL-1ß concentrations in peri-implantitis: a randomized controlled clinical trial.

PURPOSE: This study investigated the effects of hyaluronic acid (HA) on peri-implant clinical variables and crevicular concentrations of the proinflammatory biomarkers interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in patients with peri-implantitis. METHODS: A randomized controlled trial was conducted in peri-implantitis patients. Patients were randomized to receive a 0.8% HA gel (test group), an excipient-based gel (control group 1), or no gel (control group 2). Clinical periodontal variables and marginal bone loss after 0, 45, and 90 days of treatment were assessed. IL-1ß and TNF-α levels in crevicular fluid were measured by enzyme-linked immunosorbent assays at baseline and after 45 days of treatment. Clustering analysis was performed, considering the possibility of multiple implants in a single patient. RESULTS: Sixty-one patients with 100 dental implants were assigned to the test group, control group 1, or control group 2. Probing pocket depth (PPD) was significantly lower in the test group than in both control groups at 45 days (control 1: 95% CI, -1.66, -0.40 mm; control 2: 95% CI, -1.07, -0.01 mm) and 90 days (control 1: 95% CI, -1.72, -0.54 mm; control 2: 95% CI, -1.13, -0.15 mm). There was a trend towards less bleeding on probing in the test group than in control group 2 at 90 days (P=0.07). Implants with a PPD ≥5 mm showed higher levels of IL-1ß in the control group 2 at 45 days than in the test group (P=0.04). CONCLUSIONS: This study demonstrates for the first time that the topical application of a HA gel in the peri-implant pocket and around implants with peri-implantitis may reduce inflammation and crevicular fluid IL-1ß levels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03157193.

CORRIGENDUM TO: "Preterm birth and/or low birth weight are associated with periodontal disease and the increased placental immunohistochemical expression of inflammatory markers".

This correct the article DOI: 10.14670/HH-11-671.

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect.

Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide's benefits and may represent useful targets for cardiometabolic management.

Correction to: Relationship between periodontal parameters and plasma cytokine profiles in pregnant woman with preterm birth or low birth weight.

The authors are correcting this article because they accidentally included some wrong data in the analysis.

Neutrophil Extracellular Traps in Periodontitis.

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.