Abstract Background Porphyromonas gingivalis peptidyl‐arginine deiminase (PPAD) enzyme has been implicated in rheumatoid arthritis (RA) pathogenesis through protein citrullination and its potential contribution to neutrophil‐associated inflammatory responses and anti‐citrullinated protein antibody (ACPA) autoimmunity. However, its role in early stages of RA remains unclear. This study investigated the association of PPAD with citrullinated histone H3 (CitH3), cathelicidin (LL‐37), and ACPA in preclinical RA (preRA), early RA (eRA), and established RA (RA), with and without periodontitis (PD). Methods 108 participants were categorized into preRA, eRA, RA, and nonRA controls with and without PD. Periodontal and rheumatological parameters were assessed. ppad gene expression was quantified in subgingival plaque samples, and salivary and serum levels of CitH3, LL‐37 and ACPA were measured. Data were analyzed with SPSS version 26. Results ppad expression was elevated in all PD groups, irrespective of RA status. Among PD groups, ppad correlated with salivary CitH3 only in eRA‐PD ( r = 0.628) and with serum ACPA only in RA‐PD ( r = 0.503), while no significant associations were detected between ppad and LL‐37. CitH3 was not associated with serum ACPA in any PD group. As secondary findings, salivary CitH3 correlated with gingival bleeding index (GBI) in eRA‐PD ( r = 0.628) and RA‐PD ( r = 0.608) while serum LL‐37 correlated with serum ACPA in eRA‐PD ( r = 0.767), Conclusion Elevated ppad expression was primarily associated with PD rather than RA status. PPADs association with salivary CitH3 in eRA‐PD suggests its strong role in periodontal inflammation during early phases of RA but disproves a mechanistic link between PPAD to NETs and RA.
Abstract Background Population‐level evidence on associated factors for mid‐buccal gingival recession (GR) severity stratified by periodontitis status remains limited. This study assessed the prevalence and severity of GR in United States (US) adults and identified associated factors. Methods Data from 5891 dentate adults (≥30 years) from the National Health and Nutrition Examination 2011–2014, representing 129.6 million US adults, were analyzed. GR prevalence and severity were defined using mm‐based cutoffs (no GR, <3, <5, ≥5 mm) and the Cairo et al. classification (no GR, recession type [RT] 1/RT2, RT3). Survey‐weighted ordinal logistic regression models were stratified by periodontitis status (American Academy of Periodontology case definition) for the mm‐based outcome ( p < 0.05). Results Weighted GR prevalence was 91.1% (≥1 mm), 37.2% (≥3 mm), and 6.0% (≥5 mm), and RT1/RT2/RT3 prevalence was 7.3%, 88.2%, and 58.7%, respectively. Age was associated with GR across models, with the largest effect in participants with periodontitis (≥65 years: odds ratio [OR] = 5.0, 95% confidence interval [CI]: 3.4–7.4). Male s predicted higher GR severity across all models (OR = 1.1–1.7). Within the periodontitis stratum, current smoking (OR = 2.1; 95% CI: 1.5–2.9) and lower educational level were associated with GR. In the Cairo et al.‐based model, periodontitis (OR = 3.3; 95% CI: 2.7–3.9) and current smoking (OR = 1.6; 95% CI: 1.3–1.9) predicted more severe recession types (all p < 0.001). Conclusions Mid‐buccal GR severity in US adults shows distinct risk patterns by periodontitis status, with age and se as associated factors in both groups and current smoking as an associated factor in participants with periodontitis. Targeted prevention and risk‐based management strategies may help reduce the burden of severe GR.
Abstract Background This scoping review evaluates the recovery pattern of host responses, in terms of immune regulation and tissue remodeling, in gingival crevicular fluid (GCF) during experimental gingivitis (EG) resolution phase. Methods Electronic database and hand searches were conducted to screen the literature published from January 1960 to December 2024. The selected studies were randomized and non‐randomized controlled trials evaluating the changes of clinical parameters and host responses in GCF mediators during EG, focusing on the baseline and the resolution phase. Due to the heterogeneity of the included studies, a meta‐analysis was not conducted. Evidence quality and risk of bias were assessed. Results A total of 17 studies with 303 volunteers met the inclusion criteria, analyzing four clinical parameters and 58 biomarkers in GCF samples. Pro‐inflammatory cytokines and mediators associated with tissue remodeling, such as IL‐1α, IL‐1β, MMP‐8, and ALP increased during EG induction and decreased during EG resolution, similar to the trends in the clinical parameters. In contrast, the levels of MIP‐1β and IL‐10 were reduced during EG induction and elevated during EG resolution. In addition, the levels of IL‐1β and ALP were able to return to baseline level at the end of the resolution phase. Conclusions This scoping review showed that, following an average EG resolution period of 7 to 21 days, clinical signs of inflammation improved or restored. Notably, IL‐1β and ALP exhibited a return of levels to their pre‐disease (baseline) state, suggesting their potential as indicators for monitoring dynamic changes in inflammatory status at the molecular level during EG resolution.
Abstract Background Observational evidence suggests that periodontitis is associated with the progression of chronic kidney disease (CKD) in Chinese adults, and that periodontal care may be associated with a lower risk of end‐stage renal disease (ESRD). Because this evidence is observational rather than causal, whether comprehensive periodontal management is a cost‐effective use of resources in CKD remains uncertain and has not been formally evaluated within the Chinese healthcare system. Methods We developed a seven‐state Markov cohort model (CKD stages G1–G5/ESRD + Death) for a Chinese adult cohort aged 50 years at entry. Three strategies were compared: usual care (UC), scaling and root planing plus periodontal maintenance (SRP), and comprehensive intensive management (CIM). Clinical parameters were derived from verified published sources. Costs (CNY 2024) and health utility values (EQ‐5D‐5L, Chinese tariff) were extracted from peer‐reviewed literature. Model outcomes included discounted lifetime costs and quality‐adjusted life years (QALYs) over a 40‐year horizon with a 3.5% annual discount rate. The willingness‐to‐pay (WTP) threshold was CNY 90,000/QALY (approximately 1× Chinese GDP per capita, 2024). Sensitivity analyses included one‐way deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA; n = 10,000 Monte Carlo simulations), expected value of perfect information (EVPI), budget impact analysis (BIA), and a break‐even time‐horizon analysis. In addition, the CKD transition probabilities were re‐derived from published longitudinal cohort data (C‐STRIDE; a 10‐year Taiwanese integrated kidney‐care cohort) and cross‐checked against an externally validated Asian multi‐state Markov model; multi‐factor scenario, threshold and value‐of‐information analyses were added; and the comprehensive‐management strategy was decomposed against the EFP S3‐level guideline, including a conservative scaling‐and‐root‐planing‐only floor. Results In the early CKD subgroup (G1–G2 dominant), SRP and CIM produced incremental cost‐utility ratios (ICURs) of CNY 217,600/QALY and CNY 109,700/QALY, respectively, both exceeding the WTP threshold (not cost‐effective). In the advanced CKD subgroup (G3–G4 dominant), both SRP and CIM were dominant strategies (lower lifetime costs and higher QALYs vs UC), driven by substantial cost savings from avoided dialysis (SRP: −CNY 21,100; CIM: −CNY 40,300 per patient over 40 years). The probability of cost‐effectiveness at WTP = CNY 90,000/QALY was 27%–32% (early CKD) versus ≥ 97% (advanced CKD). For advanced CKD, the break‐even time horizon was 5 years. The EVPI was CNY 1190/patient for early CKD, indicating that further research is economically justified. Under the literature‐anchored parameters, the advanced‐CKD result remained robustly dominant across scenarios, probabilistic (probability of cost‐effectiveness ≈ 99.9%) and conservative scaling‐only analyses, whereas the early‐CKD result was sensitive to the contested assumptions (probability of cost‐effectiveness ≈ 50%) and is therefore reported as exploratory. Conclusions Under a set of exploratory assumptions—and conditional on the observational (non‐causal) association between periodontal scaling and reduced ESRD risk—comprehensive periodontal management may be economically attractive in patients with advanced CKD (G3–G4), where the result was robust to literature‐anchored transition probabilities and to scenario, probabilistic and conservative scaling‐only analyses. In early CKD, the cost‐effectiveness is uncertain (probability of cost‐effectiveness ≈ 50%). These exploratory scenario analyses identify early CKD as a high‐value target for a future randomized controlled trial rather than a basis for immediate policy mandates. Plain Language Summary Gum disease (periodontitis) and kidney disease (chronic kidney disease, CKD) are both very common in China and are linked: people with severe gum disease progress to kidney failure faster. This study used a computer model to ask whether treating gum disease is worth the cost for the Chinese health system. We compared three approaches—no extra gum care, standard deep cleaning, and intensive gum treatment—in patients with different stages of CKD. For patients with moderate‐to‐advanced CKD (stages G3–G4), intensive gum treatment saved money and improved health at the same time, mainly because it delayed the need for dialysis, which costs around CNY 95,000 per year. The savings paid for the treatment within 5 years. For patients with early CKD (stages G1–G2), gum treatment was not cost‐effective under cautious assumptions, but became cost‐effective when realistic upper‐end estimates were used. The uncertainty around the early‐CKD result is large enough to justify a clinical trial in China. These exploratory findings suggest that comprehensive periodontal care may be economically attractive in advanced CKD and warrant confirmation in a prospective study before any change to China's national health‐insurance (NHSA) policy; because the underlying evidence is observational, they do not by themselves establish that periodontal treatment slows kidney disease progression.
Abstract Background This study aimed to evaluate clinical and patient‐centered outcomes of palatal donor sites protected with epithelialized fragments (EF) of the free gingival graft (FGG) or a hemostatic sponge (HEM). Methods Forty‐four patients with deep single gingival recessions in lower incisors were treated using subepithelial connective tissue graft (SCTG) of standardized size (17 × 6 mm). Patients were randomized to HEM (n = 22) or EF (n = 22), both stabilized with sutures and a palatal stent. Remaining wound area of healing was assessed through standardized photographs by a blinded, calibrated examiner over 28 days. Results Significant effects were observed for group ( p = 0.031) and time ( p < 0.001), with no group×time interaction ( p = 0.132). EF showed lower values than HEM (β = −7.02; 95% confidence interval [CI]: −13.2, −0.80). A significant reduction in wound area occurred at 7, 14, and 28 days (p < 0.001). Between‐group differences were significant only at day 14 (β = −12.26; 95% CI: −23.4, −1.17), with no statistically significant differences at days 7 and 28. Between‐subject variability was low‐to‐moderate (intraclass correlation coefficient [ICC] = 0.276). Pain scores and analgesic consumption decreased significantly over time in both groups, with no differences between interventions or interactions. Conclusions EF demonstrated improved palatal healing compared to HEM at day 14, while pain levels and analgesic consumption were similar between groups, indicating comparable postoperative discomfort. Trial Registration Plataforma Brasil, 52609021.0.1001.5318
