Derivation and Validation of the Periodontal and Tooth Profile Classification System for Patient Stratification

BACKGROUND: The goal of this study is to use bioinformatics tools to explore identification and definition of distinct periodontal and tooth profile classes (PPCs/TPCs) among a cohort of individuals by using detailed clinical measures at the tooth level, including both periodontal measurements and tooth loss. METHODS: Full-mouth clinical periodontal measurements (seven clinical parameters) from 6,793 individuals from the Dental Atherosclerosis Risk in Communities Study (DARIC) were used to identify PPC. A custom latent class analysis (LCA) procedure was developed to identify clinically distinct PPCs and TPCs. Three validation cohorts were used: NHANES (2009 to 2010 and 2011 to 2012) and the Piedmont Study population (7,785 individuals). RESULTS: The LCA method identified seven distinct periodontal profile classes (PPCs A to G) and seven distinct tooth profile classes (TPCs A to G) ranging from health to severe periodontal disease status. The method enabled identification of classes with common clinical manifestations that are hidden under the current periodontal classification schemas. Class assignment was robust with small misclassification error in the presence of missing data. The PPC algorithm was applied and confirmed in three distinct cohorts. CONCLUSIONS: The findings suggest PPC and TPC using LCA can provide robust periodontal clinical definitions that reflect disease patterns in the population at an individual and tooth level. These classifications can potentially be used for patient stratification and thus provide tools for integrating multiple datasets to assess risk for periodontitis progression and tooth loss in dental patients

Maternal Periodontal Disease is Associated with Oxidative Stress during Pregnancy

We sought to determine if maternal periodontal disease is associated with oxidative stress as measured by serum 8-isoprostane. A secondary analysis was conducted using prospective data from the Oral Conditions and Pregnancy Study. Healthy women enrolled at <26 weeks’ gestational age underwent oral examination and serum sampling. Maternal periodontal disease status was categorized as healthy, mild, or moderate to severe by clinical criteria. Maternal serum was analyzed for 8-isoprostane using ultrasensitive enzyme-linked immunosorbent assay. Elevated 8-isoprostane level was defined as ≥75th percentile. Maternal factors associated with elevated 8-isoprostane were determined using chi-square or t test. Multivariable logistic regression was used to assess association between elevated 8-isoprostane and maternal factors. Seven hundred ninety-one women had complete data. Median (interquartile) 8-isoprostane serum level was 1806 (16 to 81,870) pg/dL. Using bivariate analysis, maternal age, race, marital status, utilization of public assistance, and mild or moderate to severe periodontal disease were associated with elevated serum 8-isoprostane. Using logistic regression, moderate to severe periodontal disease (adjusted odds ratio 2.9, 95% confidence interval: 1.7 to 5.0) remained significantly associated with an elevated serum 8-isoprostane level. Maternal periodontal disease is associated with oxidative stress during pregnancy. Further study is needed to determine the role of maternal oxidative stress in periodontal disease-associated adverse pregnancy outcomes

Periodontal Disease and Recurrent Vascular Events in Stroke/Transient Ischemic Attack Patients

Periodontal disease has been shown to be associated with incident stroke. We investigated whether periodontal disease is independently associated with recurrent vascular events and certain inflammatory markers in stroke/TIA patients. In this prospective longitudinal hospital-based cohort study, periodontal disease was assessed in stroke/TIA patients. High periodontal disease was defined as the highest tertile of extent (% of sites) with attachment loss ≥ 5 mm. Serum interleukin-6, high sensitivity C-reactive protein and soluble intracellular adhesion molecule-1 were measured. The patients were followed for recurrent vascular events-stroke, TIA, myocardial infarction and vascular death. In the 106 patients that were evaluated, 40 (38%) showed high periodontal disease and 27 (26%) had recurrent vascular events over a median of 24 months (range 12–24 months). High periodontal disease patients had higher levels of interleukin-6 (p=0.01) and soluble intracellular adhesion molecule-1 (p=0.03). High periodontal disease was associated with recurrent vascular events before (Log rank p=0.01, hazard ratio 2.6, 95% CI, 1.2–5.7) and after adjustment for significant confounders -age and stroke status (Hazard Ratio 2.5, 95% confidence interval, 1.1 to 5.5, p=0.03); adjustment for possible confounders age, males, years of education and cardioembolic strokes (hazard ratio 2.8, 95% confidence interval, 1.2–6.5, p=0.02); and adjustment for propensity score that accounted for all potential measured confounders (hazard ratio 2.8, 95% confidence interval,1.2–6.5, p=0.02). There is an independent association between high periodontal disease and recurrent vascular events in stroke/TIA patients. High periodontal disease is also associated with higher serum levels of interleukin-6 and soluble intracellular adhesion molecule-1

Periodontal Disease, Oxidative Stress, and Risk for Preeclampsia

Maternal periodontal infection is associated with an increased risk for preeclampsia. Periodontal infection is also associatedwith increased oxidative stress. Our objective was to determine the relationship among maternal periodontal disease, maternal oxidative stress, and the development of preeclampsia

Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease

Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of eight periodontal pathogens) and local inflammatory response (gingival crevicular fluid IL-1β) and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.5 million markers) to identify PCT-associated loci among 975 European American adult participants of the Dental ARIC study. We sought to validate these findings for CP in the larger ARIC cohort (n = 821 participants with severe CP, 2031—moderate CP, 1914—healthy/mild disease) and an independent German sample including 717 aggressive periodontitis cases and 4210 controls. We identified six PCTs with distinct microbial community/IL-1β structures, although with overlapping clinical presentations. PCT1 was characterized by a uniformly high pathogen load, whereas PCT3 and PCT5 were dominated by Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, respectively. We detected genome-wide significant signals for PCT1 (CLEC19A, TRA, GGTA2P, TM9SF2, IFI16, RBMS3), PCT4 (HPVC1) and PCT5 (SLC15A4, PKP2, SNRPN). Overall, the highlighted loci included genes associated with immune response and epithelial barrier function. With the exception of associations of BEGAIN with severe and UBE3D with moderate CP, no other loci were associated with CP in ARIC or aggressive periodontitis in the German sample. Although not associated with current clinically determined periodontal disease taxonomies, upon replication and mechanistic validation these candidate loci may highlight dysbiotic microbial community structures and altered inflammatory/immune responses underlying biological sub-types of CP

Racial differences in C-reactive protein levels during normal pregnancy

Characterization of serum C-Reactive Protein (CRP) levels in a diverse population of healthy pregnant women using a high sensitivity assay

Third Molars and Periodontal Pathology in Middle Aged and Older Americans

Assess the association between the visible presence of 3rd molars and the severity of periodontal pathology on teeth more anterior in the mouth

Periodontal Disease Early in Pregnancy Is Associated With Maternal Systemic Inflammation Among African American Women

Maternal periodontal disease is a chronic oral infection with local and systemic inflammatory responses and may be associated with adverse pregnancy outcomes. This study determined whether maternal periodontal disease in early pregnancy is associated with elevated serum C-reactive protein (CRP) levels and whether maternal race influences the relationship between maternal periodontal disease and systemic inflammatory responses

Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.

Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products, which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed nonribosomal peptide/polyketide origin, to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows minimal inhibition of major drug transporters, and has a high barrier to generation of both HCV and HIV-1 resistance

A Randomized Controlled Trial of Intensive Periodontal Therapy on Metabolic and Inflammatory Markers in Patients With ESRD: Results of an Exploratory Study

Periodontitis is a novel risk factor for inflammation and cardiovascular disease in the dialysis population. Limited information about the impact of periodontal therapy in patients receiving dialysis exists