Platelet-rich fibrin as an apical barrier for MTA placement in the treatment of teeth with open apices: a pilot study.

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices. METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance. RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment. CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results. TRIAL REGISTRATION: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

Elevated serum hepatic transaminases in apical periodontitis individuals.

AIM: Apical periodontitis (AP) is the chronic inflammation of the periradicular tissues in response to root canal infection. Whilst AP has been linked with systemic inflammation and noncommunicable diseases, its potential association with nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as surrogate markers of hepatic injury, and the systemic inflammatory burden in otherwise healthy individuals with and without AP diagnosis. METHODOLOGY: Cross-sectional study. Individuals with AP (n = 30) and healthy controls (n = 29) were recruited. The number, mean diameter (mm) and periapical index of the apical lesions of endodontic origin (ALEO) were assessed. ALT and AST levels (pg/mL) were measured through enzyme-linked immunosorbent assays. The serum levels of TNF-α, IL-4, IL-9, IL-10, IL-17A and IL-22 were evaluated by Multiplex assay. Inferential analysis was performed using t-test or Mann-Whitney tests according to data distribution and linear regression models. Data were analysed with StataV16 (p < .05). RESULTS: ALT and AST levels were significantly higher in individuals with AP compared to controls (p < .05). Serum inflammatory biomarkers showed no significant differences between the study groups. Bivariate and multivariate analyses confirmed that AP diagnosis was independently associated with ALT and AST elevations (p < .05). Additionally, the number of ALEO positively influenced AST levels (p = .002). IL-22 on the other hand, was associated with reduced ALT levels (p = .043). CONCLUSION: AP is associated with higher serum hepatic transaminases ALT and AST, potentially contributing to NAFLD physiopathology in young adults.

TLR2 agonist prevents the progression of periapical lesions in mice by reducing osteoclast activity and regulating the frequency of Tregs.

AIM: To evaluate the role of regulatory T lymphocytes (Tregs) in the presence or absence of the synthetic ligand Pam3Cys during the progression of periapical lesion in wild-type (WT) and toll-like receptor 2 knockout (TLR2KO) mice. METHODOLOGY: A total of 130 C57BL/6 male WT and TLR2KO mice were allocated into control (n = 5) and experimental (periapical lesion induction) (n = 10) groups. In specific groups (WT+Pam3cys and TLR2KO+Pam3cys), the synthetic ligand Pam3cys was administered intraperitoneally every 7 days, according to the experimental period (14, 21 and 42 days). At the end of those periods, the animals were euthanized, and the mandible and the spleen were submitted to histotechnical processing. Mandible histological sections were analysed by haematoxylin and eosin, TRAP histoenzymology and immunohistochemistry (FOXP3, RANK, RANKL and OPG). Spleen sections were analysed by immunohistochemistry (FOXP3). RESULTS: The inflammatory infiltrate and bone resorption were more intense in the TLR2KO group compared to the WT group. The animals that received the Pam3cys had smaller periapical lesions when compared to the animals that did not receive the ligand (p < .05). TLR2KO animals showed a significant increase in the number of osteoclasts when compared to TLR2KO+Pam3cys group (p < .05). At 21 days, the WT+Pam3cys group had a lower number of osteoclasts when compared to the WT animals (p = .02). FOXP3 expression was more intense in the WT+Pam3cys groups when compared to the WT animals in the 42 days (p = .03). In the spleen analysis, the WT+Pam3cys group also had a higher expression of FOXP3 when compared to the WT animals at 14 and 42 days (p = .02). Concerning RANKL, there was a reduction in staining in the KOTLR2+Pam3cys groups at 21 and 42 days (p = .03) and a higher binding ratio between RANK/RANKL in animals that did not receive the ligand. CONCLUSION: Administration of the Pam3cys increased the proliferation of Tregs, showed by FOXP3 expression and prevented the progression of the periapical lesion in WT mice. On the other hand, in the TLR2KO animals, Treg expression was lower with larger areas of periapical lesions. Finally, systemic administration of the Pam3cys in KO animals was able to limit the deleterious effects of the absence of the TLR2 receptor.

Rev-erbα attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.

AIM: Rev-erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev-erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev-erbα in experimental RAP and to explore the relationship between Rev-erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments. METHODOLOGY: Enterococcus faecalis-induced RAP models were established in SD rats. Histological staining and micro-computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev-erbα and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme-linked immunosorbent assay were performed to explore the relationship between Rev-erbα and inflammatory cytokines related to macrophage polarization. RESULT: Compared to healthy periapical tissue, the expression of Rev-erbα was significantly down-regulated in macrophages from inflammatory periapical area, especially in Enterococcus faecalis-induced periapical lesions, with obvious type-1 macrophage (M1)-like dominance and the production of pro-inflammatory cytokines. In addition, Rev-erbα activation by SR9009 could induce type-2 macrophage (M2)-like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti-inflammatory cytokines IL-10 and TGF-ß. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions. CONCLUSIONS: Rev-erbα played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev-erbα might be a promising and prospective therapy method for the prevention and management of RAP.

Factors associated with the outcome of root canal treatment-A cohort study conducted in a private practice.

AIM: To investigate the association of various pre-, intra- and post-operative factors on root canal treatment outcome. METHODOLOGY: In this cohort study, primary or secondary root canal treatment of mature permanent teeth was performed by a single endodontist in a private practice over 13 years, and followed 1-4 years after treatment. Treatment details and clinical and radiographic data were collected. The proportion of successfully treated teeth and roots based on strict radiographic (periapical index (PAI) ≤2) and clinical criteria (absence of pain, swelling or sinus tract) was estimated. To evaluate joint associations of prognostic factors and treatment success probability, 44 pre, intra- and post-operative factors were investigated using bivariate associations, and a multiple logistic regression model was fitted using Generalized Estimating Equations. RESULTS: 1259 teeth (2445 roots, 3149 canals) were assessed with a recall rate of 91%. The proportion of successfully treated teeth was 79.9% [95% confidence interval 77.7-82.1]. Eleven prognostic factors were identified that significantly reduced the odds ratio (OR) for treatment success at tooth level. Six were preoperative: injury history (OR = 0.05[0.01-0.24]), root PAI (OR = 0.29[0.20-0.42], 0.21[0.13-0.34] and 0.22[0.12-0.42] for PAI = 3, 4 and 5, respectively, against PAI = 1), lesion diameter (OR = 0.30[0.21-0.43] and 0.24[0.16-0.37] for diameters of 1-5 mm and ≥6 mm, respectively, against no lesion), tooth type (OR = 0.51[0.27-0.97] and OR = 0.45[0.24-0.83] for premolars and molars, respectively, against incisors or canines), tenderness to periapical palpation (OR = 0.64[0.43-0.94]) and two canals per root (OR = 0.67[0.54-0.83]). Four factors were intraoperative: root filling of unsatisfactory quality (OR = 0.18[0.08-0.40]) or extending beyond or shorter than 2 mm from the apex (OR = 0.44[0.26-0.75] and 0.62[0.40-0.97] respectively), resin sealer (OR = 0.58[0.39-0.87] against bioceramic sealer) and single visit treatment (OR = 0.40[0.21-0.75] against multiple visits). One factor was post-operative: defective coronal restoration (OR = 0.35[0.21-0.56]). CONCLUSION: The following factors were associated with unsuccessful root canal treatment: (i) history of injury, apical periodontitis with increased severity (larger lesion, higher PAI, tenderness to periapical palpation), or complicated anatomic conditions (premolar or molar, two canals in a single root); (ii) technically suboptimal root filling (of unsatisfactory quality or not ending within 2 mm of radiographic apex) performed in a single-visit, or use of resin sealer instead of novel bioceramic sealer; (iii) suboptimal quality coronal restoration.

A comparison of radiographically determined periapical healing and tooth survival outcomes of root canal (re)treatment performed in two care pathways within the United Kingdom Armed Forces.

AIMS: To compare radiographic periapical healing and tooth survival outcomes of root canal (re)treatment performed within two care pathways (Routine Dental Care and Referred Treatment Pathway), in the United Kingdom Armed Forces (UKAF), and determine the effects of endodontic complexity on outcomes. METHODOLOGY: This retrospective cohort study included 1466 teeth in 1252 personnel who received root canal (re)treatment between 2015 and 2020. General Dental Practitioners treated 661 teeth (573 patients) (Routine cohort), whilst Dentists with a Special Interest treated 805 teeth (678 patients) (Referred cohort). The latter group were graduates of an MSc programme in Endodontics with 4-8 years of postgraduation experience. Case complexity was retrospectively determined for each tooth using the endodontic component of Restorative Index of Treatment Need (RIOTN) guidelines. Periapical healing was determined using loose radiographic criteria. The data were analysed using chi-square tests, univariate logistic regression and Cox proportional hazards models. RESULTS: A significantly (p < 0.0001) larger proportion of cases of low complexity had undergone root canal treatment within the Routine versus Referred cohort. The odds of periapical healing was significantly higher within the Referred versus Routine cohort, regardless of analyses using pooled (OR = 1.17; 95% CI: 1.11, 1.22) or moderate complexity (OR = 4.71; 95% CI: 2.73, 8.11) data. Within the Routine cohort, anterior teeth had higher odds of periapical healing than posterior teeth (OR = 1.13; 95% CI: 1.04, 1.22). The 60-month cumulative tooth survival was lower (p = 0.03) in the Routine (90.5%) than the Referred (96.0%) cohort. Within the Routine cohort, the hazard of tooth loss was higher amongst posterior teeth (HR = 4.03; 95% CI: 1.92, 8.45) but lower if posterior teeth had cast restorations (HR = 0.36; 95% CI: 0.19, 0.70). For the Referred cohort, posterior teeth restored with cast restoration (vs not) had significantly lower risk of tooth loss (HR = 0.21; 95% CI: 0.08, 0.55). CONCLUSIONS: For UKAF patients, root canal (re)treatment provided within the Referred pathway was significantly more likely to achieve periapical healing and better tooth survival than those provided within the Routine pathway. Posterior teeth restored with an indirect restoration had a higher proportion of tooth survival. This study supported the utility of the endodontic component of RIOTN for assessing case complexity.

Long-term prognosis for teeth with external cervical resorption based on periapical images and cone beam CT: A clinical study.

AIM: To evaluate whether supplemental information from CBCT changed long-term prognosis for teeth with external cervical resorption (ECR) compared to periapical (PA) images. Furthermore, to assess predictive findings in PA images and evaluate which findings in CBCT affected the long-term prognosis of teeth with ECR. METHODOLOGY: One hundred and ninty-four patients, mean age 41.2, range 13-81, having 244 teeth with ECR were included. An initial long-term prognosis determined either good or poor was established based on intraoral images. Afterwards, the patients underwent CBCT, and final long-term prognosis was decided. From the PA images and CBCT, ECR using Heithersay's classification system, pulp involvement and extension of ECR was assessed. In CBCT, the number of surface lesion(s) was additionally assessed. Descriptive statistics evaluated changes in long-term prognosis after CBCT. Logistic regression analyses tested if findings in PA images and CBCT affected the long-term prognosis. RESULTS: Based on CBCT, out of 244 teeth the long-term prognosis was assessed to be poor for 173 (70.9%) teeth and good for 71 (29.1%) teeth. The long-term prognosis changed in 76 (31.1%) teeth after CBCT; 5 (2.0%) changed from poor to good, and 71 (29%) changed from good to poor long-term prognosis. In 81 (33.2%) teeth the H-class increased, and in 10 (4.1%) teeth the H-class decreased after assessing CBCT. In 70 (28.7%) teeth, there was a change from no pulp involvement to involvement of the pulp after CBCT; eight (3.3%) teeth changed in the opposite direction. H-class 2 and 4 in PA images significantly increased the probability for a change in long-term prognosis compared to an H-class 3 (p < .05). H-class 4, pulp involvement, ECR in the oral 1/3 of the root, and more than two surface lesions seen in CBCT significantly influenced a poor long-term prognosis (p < .05). CONCLUSIONS: Supplemental information from CBCT changed long-term prognosis in almost one third of teeth with ECR. In most cases, the long-term prognosis changed from good to poor. H-class 3 in PA images had a significant influence on change in long-term prognosis. Several findings in CBCT influenced a poor long-term prognosis.

Effects of apical periodontitis treatment on hyperglycaemia in diabetes: A prospective cohort study.

AIM: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. METHODOLOGY: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. RESULTS: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12-month follow-up revealed a significant difference in TL A1C (p = .022) and CG (p = .001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12-month after RCT in UTL A1c was significantly lower in comparison to CG (p = .008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157-19.816; p = .031). CONCLUSIONS: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c.

Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis.

AIM: To assess the periapical alveolar bone pattern and the serum levels of proinflammatory cytokines, biochemical markers and metabolites in rats subjected to chronic alcohol and nicotine consumption and induced apical periodontitis. METHODOLOGY: Twenty-eight male Wistar rats were divided into four groups: Control, Alcohol, Nicotine and Alcohol+Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19 µL of nicotine/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28 days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro-computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL-1ß, IL-4, IL-6 and TNF-α), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, while one-way anova followed by Tukey's test was performed for parametric data. RESULTS: The groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL-1ß, IL-6 and TNF-α compared to the Control group (p < .05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH2 CH2 CO), n(CH2 ) and n(CH3 ). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption. CONCLUSION: Alcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.

Reduced C-reactive protein levels after root canal treatment in clinically healthy young apical periodontitis individuals at cardiovascular risk. A prospective study.

AIM: To determine the systemic inflammatory burden, including hsCRP and its monomeric forms, in patients with apical lesions of endodontic origin treated with root canal treatment (RCT). METHODOLOGY: Prospective pre-/post-study. Apical periodontitis (AP) individuals aged 16-40 were included (N = 29). Individuals received RCT and were followed at 1 and 6 months. Fasting blood samples were obtained. Apical lesions of endodontic origin (ALEO) diameter (mm), and periapical index (PAI), were recorded. The serum concentrations of total hsCRP were determined by turbidimetry. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-1ß, and soluble (s) E-selectin were assessed by Multiplex assay. Additionally, mCRP forms were determined in the serum of AP patients with a baseline moderate to high cardiovascular risk based on hsCRP stratification (hsCRP ≥1 mg/L) by immunowestern blot (n = 15). Also, CRP isoforms were explored in ALEOs from AP individuals (n = 4). Data were analysed with StataV16. RESULTS: Periapical index and ALEO sizes were reduced at both follow-up visits after RCT (p < .05). Serum levels of TNF-α, IL-6, IL-10, IL-1ß, and sE-selectin did not show significant differences. CRP was borderline reduced at 1 month (p = .04); however, in AP individuals at cardiovascular risk (hsCRP ≥ 1 mg/L), hsCRP and its monomeric isoform significantly decreased at 1 and 6 months (p < .05). CONCLUSIONS: High-sensitivity CRP and mCRP are reduced after RCT in AP individuals at cardiovascular risk.

Association between pulp and periapical disease with type 2 diabetes: A bidirectional Mendelian randomization.

AIM: This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2 diabetes mellitus (T2DM). METHODOLOGY: Summary level data of European-based population genome-wide association studies (GWASs) were employed to undertake this MR study. With the selection of single nucleotide polymorphisms (SNPs) as the instrumental variable, the radial inverse-variance weighted (radial IVW) method with modified second-order weights was applied as the primary method. Additionally, a range of sensitivity analyses were conducted to investigate pleiotropy. Results from different sources of outcome were pooled by meta-analysis with the fixed model. RESULTS: The results of this MR analysis did not suggest a significant impact of pulp and periapical disease on type 2 diabetes (combined OR = 1.04, 95% CI: 1.00-1.07, p = .033) and vice versa (OR = 1.04, 95% CI: 0.96-1.14, p = .329). No significant pleiotropy was detected in the final model after the removal of outliers, demonstrating the reliability of the results in our primary analysis. CONCLUSIONS: With the limitations inherent in the present MR study, there is no significant evidence in either direction to suggest a causal association between pulp and periapical disease and type 2 diabetes mellitus.

Outcome of single-visit root canal treatment with or without MTAD: A randomized controlled clinical trial.

AIM: This study aimed to investigate 2-year changes in periapical trabecular patterns in single-rooted teeth with apical periodontitis using fractal analysis and periapical index (PAI) after root canal treatment performed with or without BioPure MTAD solution. METHODOLOGY: In this randomized clinical trial, 100 patients were selected and randomized to either the BioPure MTAD or the control groups. Initial periapical radiographs were obtained for each participant before and 2 years after root canal treatment. The region of interest in the periapical lesion around the root apex was selected from the paired periapical radiographs, and then, the fractal dimension (FD) was calculated. With regards to the classification of periapical status, PAI was labelled as "healed" (PAI ≤ 2) or "unhealed" (PAI ≥ 3). RESULTS: After 24 months, 28 patients did not comply with the follow-up and the data of 72 patients were compared. When the initial and the follow-up PAI scores were compared, the decrease was statistically significant in 33 of 37 teeth (89.2%) and 32 of 35 teeth (91.4%) in the BioPure MTAD and control group, respectively. In both groups, statistically significant increases were observed in FD values after 2 years in all patients (p < .001). No significant difference was found between the two groups amongst decreased PAI scores and increased FD values. CONCLUSIONS: Root canal treatments with or without BioPure MTAD irrigation contributed to periapical healing in single-visit root canal treatment. Two years after root canal treatment, the extent of the periapical trabecular bone radiographically increased, as the FD and PAI data revealed.

Predictors of periapical bone healing associated with teeth having large periapical lesions following nonsurgical root canal treatment or retreatment: A cone beam computed tomography-based retrospective study.

AIM: Several factors influence the condition of the periapical tissues associated with root filled teeth. The primary objective of this study was to retrospectively evaluate the extent and speed of bone healing of large periapical lesions associated with nonsurgical root canal treatment or retreatment. The secondary objective was to analyse the relationship between the time to complete healing when analysed using cone beam computed tomography (CBCT) and other possible predictors that affect healing. METHODOLOGY: Seventy-nine patients were treated during the years 2013-2020 with large periapical lesions of endodontic origin (10-15 mm) as observed on intraoral periapical radiographs (IOPAR) were included. IOPAR and CBCT were available before treatment and during the follow-up (IOPAR every 6 months and CBCT every 12 months). The volume of periapical lesions was calculated by OsiriX Lite software. Variables such as initial volume of the lesion, age, gender, type of treatment or type of root canal filling were compared to identify the differences between healed and unhealed lesions. Pearson's Chi-square test was used for categorical variables, the t-test for age and the Wilcoxon test for initial volume of the lesion. The association between time to healing and the variables was assessed using univariate analysis and multivariate analysis. The Wilcoxon test was used to observe the association of healing time with categorical variables and the correlation index was measured with the quantitative variables. RESULTS: Of the 79 cases analysed, 60 lesions (76%) were completely healed as verified by CBCT in a mean healing time of 19 months, of which 60% healed fully between 12 and 18 months. Increase in age of patient and larger initial volume of the lesion were associated with a significantly longer healing time (p < .001). Gender, filling material and type of treatment did not have a significant effect on the healing process (p > .05). CONCLUSIONS: Clinicians should be aware that periapical lesions in older patients and larger areas of bone loss take longer to heal. CBCT monitoring of large periapical lesions is critical and it can help clinicians in the decision-making process.

The impact of bone grafting with/without barrier membrane placement on the outcome of apical surgery: A systematic review and meta-analysis.

BACKGROUND: Regenerative techniques are increasingly being advocated in endodontic apical surgery (AS) to enhance the healing of periapical lesions. Various grafting and membrane materials are employed as adjuncts to modern AS. OBJECTIVES: This systematic review aimed to answer the following PICO question: In patients with apical periodontitis (P) what is the impact of bone grafting with/without barrier membrane materials (I) compared with surgery without grafting materials (C) on the outcome of AS evaluated clinically and radiographically (O). METHODS: A systematic search was conducted in four databases (Embase, Web of Science, PubMed and Cochrane Central Register of Controlled Trials) until 1 August 2023. Google Scholar was also manually searched. Studies with a prospective randomized design were included. Cochrane risk-of-bias (RoB) tool 2.0 assessed bias. Two independent reviewers performed the study selection, data extraction and appraisal of studies. Meta-analysis was performed using R3.5.1 software. RESULTS: From the identified 2582 studies, eight randomized clinical trials were included for meta-analysis. Two studies had low RoB, while six had some concerns. Analysis revealed significantly better outcomes when surgery involved bone regeneration techniques than conventional surgery (OR = 2.18, 95% CI: 1.32-4.31, p = .004). Subgroup analyses on individual grafts (OR = 0.22, 95% CI: -0.99 to 1.44, p = .720) (OR = -0.09, 95% CI: -1.42 to 1.23, p = .885) and membranes (OR = -1.09, 95% CI: -2.94 to 0.76, p = .247) and their combinations (OR = 0.03, 95% CI: -1.50 to 1.55, p = .970) did not yield any significant results. The type of membrane used did not significantly impact the outcome (OR = -1.09, 95% CI: -2.94 to 0.76, p = .247) nor did altering the combination of graft/membrane. DISCUSSION: This systematic review examined the effects of bone grafting with/without membrane placement on the outcome of AS. It highlights the potential advantages of regenerative techniques and the need for further research in this area. CONCLUSIONS: Based on current evidence, bone grafting with/without barrier membrane placement significantly improves healing after AS. Subgroup analysis of resorbable membranes or grafting did not significantly influence the outcome. The combination of membrane and graft was also not significant. Future well-designed, randomized controlled trials in this area are essential before these materials can be recommended for routine use to enhance healing outcomes in AS. REGISTRATION: PROSPERO (CRD42021255171).

Identification of keystone taxa in root canals and periapical lesions of post-treatment endodontic infections: Next generation microbiome research.

AIM: The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post-treatment infections, and to identify the presence of keystone taxa in both habitats using next-generation sequencing analysis. METHODOLOGY: Apices and periapical lesions of patients with post-treatment apical periodontitis were surgically extracted. Specimens were cryo-pulverized, bacterial DNA was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using the Illumina Miseq platform. Bioinformatic analysis was carried out with Mothur software, whilst diversity indices were obtained using operational taxonomic units (OTUs). The diversity indices were compared with the Kruskal-Wallis test, and community composition differences were explored with Permutational Multivariate Analysis of Variance (PERMANOVA). A bacterial functional study was performed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Co-occurrence network analyses were performed using the Sparse Correlations for Compositional data (SparCC). Eigencentrality, clr-based abundance and ubiquitousness were applied to infer keystone taxa. P values <.05 were considered statistically significant. RESULTS: Thirty-two apices and thirty-nine periapical lesions were sequenced and analysed. A similar alpha-diversity (p < .05) and community composition (p = .91) was observed for apices and lesion samples. The most abundant OTUs identified amongst all samples included Fusobacterium nucleatum, Prevotella loescheii, Streptococcus intermedius, Porphyromonas gingivalis, Parvimonas micra, Synergistetes bacterium, Tannerella forsythia and Peptostreptococcus stomatis. The metabolic pathways with >0.81% abundances included membrane transport, genetic information processing and metabolic pathways. F. nucleatum was identified as a keystone taxon as it showed ubiquitousness, an eigenvector centrality value of 0.83 and a clr-based abundance >4. CONCLUSIONS: The microbiome in apices and periapical lesions of post-treatment endodontic infections showed a similar diversity and taxonomic composition. Co-occurrence network analyses at OTU level identified F. nucleatum as a keystone taxon candidate in these infections.

Macrophage polarization in human periapical lesions in relation to histopathological diagnosis, clinical features and lesion volume: An ex vivo study.

AIM: To evaluate M1 and M2 macrophage polarization in radicular cysts and periapical granulomas through an immunohistochemical analysis and the correlation between macrophage polarization and histopathological diagnosis, clinical characteristics and lesion volume using cone-beam computed tomography. METHODOLOGY: Periapical biopsies diagnosed as radicular cysts (n = 52) and periapical granulomas (n = 51) were analysed by immunohistochemical method. Teeth with periapical lesion with no history of root canal treatment (primary lesion) and lesions persistent to root canal treatment (persistent lesions) were included. Pathological diagnosis, patients' age, gender and clinical characteristics were obtained from treatment records. A cone-beam computed tomographic periapical volume index (CBCTPAVI) score was assigned to each periapical lesion based on the volume of the lesion. Immuno-expressions of CD68 and CD163 were quantified. The CD68/CD163 ratio was adopted to represent M1 or M2 macrophage polarization. Mann-Whitney U test was used to determine the different CD68/CD163 ratio between groups of radicular cyst and periapical granuloma. Spearman's correlation test was performed to assess the correlation between the CD68/CD163 ratio and lesion volume and CBCTPAVI score. RESULTS: Radicular cysts and periapical granulomas had CD68/CD163 median of 2.05 (IQR = 1.33) and 1.26 (IQR = 0.81), respectively. A significantly higher CD68/CD163 ratio was observed in radicular cysts (p < .001). In contrast, periapical granulomas had significantly lower median of CD68/CD163 ratio. Larger lesions had a higher median of CD68/CD163 ratio, while smaller lesions had lower median of CD68/CD163 ratio (p = .007, rs = .262). CD68/CD163 ratio was significantly correlated with the CBCTPAVI score in the overall periapical lesions (p = .002, rs = .306). The higher CD68/CD163 ratio in larger lesions indicated a higher degree of M1 polarization compared to smaller lesions. Regarding the pathological diagnosis, there was a significant positive correlation between CBCTPAVI score and CD68/CD163 ratio in periapical granulomas (p < .001, rs = .453), whereas the negative correlation was observed for radicular cysts (p < .001, rs = -.471). CONCLUSIONS: Periapical granulomas are characterized by a M2-dominant macrophage polarization, while radicular cysts have significantly higher M1 macrophages. The higher degree of M1 macrophage polarization was significantly correlated with larger volume and higher CBCTPAVI scores of overall periapical lesion and periapical granuloma.

Two- and three-dimensional healing assessment after endodontic microsurgery in through-and-through periapical lesions: 5-year follow-up from a randomized controlled trial.

AIM: To evaluate clinical and radiographic outcome of endodontic microsurgery in through-and-through periapical lesions at 1-year and 5-year follow-up with adjunct use of platelet-rich plasma (PRP). METHODOLOGY: Thirty-two patients with large through-and-through periapical lesions were randomized in platelet-rich plasma (PRP) group and control group. Two-dimensional (2D) healing was evaluated with Molven's criteria and three-dimensional (3D) healing with modified PENN 3D criteria. Healing at resection plane (R), apical area (A), buccal cortex (BC), palatal cortex (PC) and overall bone healing (B) was assessed using CBCT scans. The volume of lesion was measured using ITK-Snap software. The analysis included comparison of 1- to 5-year intragroup (Friedman test/McNemar test) and intergroup scoring (Chi-square/ Mann-Whitney test). Logistic regression analysis was performed to determine the effect of various factors on healing at 5 years. RESULTS: Out of 32 patients/59 teeth evaluated after 1-year of endodontic microsurgery, 24 patients/44 teeth reported at 5 - year follow-up. Healing assessment with modified PENN 3D criteria revealed improvement in overall success rate of 66.7% at 1 year to 83.3% at 5 years, with no deterioration in any healing category. PRP group exhibited significantly better 3D healing than control group; both at 1 year (84.6% vs. 45.5%) and 5 years (100% vs. 63.6%). A significantly higher number of completely healed teeth were observed in PRP group than the control group at 5 years with respect to R, BC and B parameters. A volume reduction of 88% (91.4% PRP, 84% control) was depicted at 1 year and 94% (97.1% PRP, 91.1% control) at 5 years. None of the recorded factors including age, gender, size of lesion, preoperative swelling and sinus, histology of lesion, use of PRP, tooth location, preoperative buccal bone had significant effect on 3D healing at 5 years. CONCLUSIONS: This 5-year study suggested improvement in 3D radiographic healing of large through-and-through periapical lesions from 1 to 5 years with no deterioration in any healing parameter in both control and PRP groups. The additional use of PRP led to significantly better healing in such lesions. RACB index using CBCT allows better estimation of healing at resected, apical and cortical plane over modified PENN 3D or Molven's criteria.

Simultaneous management of chronic maxillary sinusitis from dental origin and the relevance of nasal septal deviation: A retrospective evaluation of 65 cases.

PURPOSE: Dental origin constitutes most chronic unilateral maxillary sinusitis (CMS) and is referred to as dental chronic maxillary sinusitis (DCMS). Recently, dental implants and related surgical procedures have become more prevalent. We present an evaluation of the simultaneous treatment of DCMS. MATERIALS AND METHODS: A retrospective review of records from 395 patients with CMS treated at our medical center from 2015 to 2020 found 65 patients diagnosed with DCMS. Statistical analyses were performed using the records data. RESULTS: Four patients were excluded. The final study population included 35 males and 26 females with a mean age of 55. 29 % were post-dental implant placement or related pre-prosthetic procedures. Presenting symptoms included middle meatus edema (72 %), pus in the middle meatus (70 %), and nasal secretion (39 %). Clinical findings included septal deviation (39 %), among them 87 % deviated toward the diseased sinus, OAF (49 %), and nasal polyposis (16 %). In 32 patients, the OAF was closed in one layer using a local mucoperiosteal flap. In 29 patients, the closure was done in two layers, including a buccal fat pad (BFP) regional flap. One patient had a reopened OAF, and five patients required revision surgery. 92 % of patients in this study had complete clinical and radiological resolution of the DCMS. CONCLUSIONS: Relevance of nasal septal deviation in association with DCMS is present. There is no distinct difference in the manner of OAF closure if it is done in a simultaneous procedure. One stage combined multidisciplinary surgical procedure is sufficient to treat DCMS.

The efficacy of 2780 nm Er,Cr;YSGG and 940 nm Diode Laser in root canal disinfection: A randomized clinical trial.

OBJECTIVES: Effective disinfection of the root canals is the cornerstone of successful endodontic treatment. Diminishing the microbial load within the root canal system is crucial for healing in endodontically treated teeth. The aim of this study was to evaluate the effect of 2780 nm Er,Cr:YSGG and 940 nm diode lasers on the eradication of microorganisms from single-rooted teeth with asymptomatic apical periodontitis. MATERIALS AND METHODS: Thirty participants conforming to the inclusion criteria were randomly divided into 3 groups according to the disinfection protocol used; Conventional group: 2.5% Sodium Hypochlorite (NaOCl) and 17% EDTA solution NaOCl/EDTA, Dual laser group: 2780 nm Erbium, chromium: yttrium scandium-gallium-garnet (Er,Cr:YSGG) laser and 940 nm diode laser Er,CrYSGG/Diode, and Combined group: 17% EDTA and 940 nm diode laser EDTA/Diode. Bacterial samples were collected before and after intervention. The collected data were statistically analyzed using Friedman's test and Kruskal-Wallis test (P ≤ 0.05). RESULTS: The results of the study showed that both dual laser Er,CrYSGG/Diode and combined laser EDTA/Diode groups showed significantly less mean Log10 CFU/ml of aerobic and anaerobic bacterial counts than the conventional NaOCl/EDTA group. CONCLUSIONS: In this study we evaluated in vivo the bactericidal efficacy of three disinfection protocols for endodontic treatment of single-rooted teeth with apical periodontitis. The results indicated that both dual laser Er,CrYSGG/Diode and combined laser EDTA/Diode groups provide superior bactericidal effect compared to the conventional NaOCl/EDTA group. CLINICAL RELEVANCE: The integration of lasers into root canal disinfection protocols has demonstrated significant bacterial reduction which might promote healing and long-term success.

Association between the irrigation-agitation techniques and Periapical Healing of large periapical lesions: a Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to evaluate the effects of manual dynamic activation (MDA), passive ultrasonic irrigation (PUI), and laser-activated irrigation (shock wave-enhanced emission photoacoustic streaming (SWEEPS)) on the periapical healing of large periapical lesions following nonsurgical root canal treatment. MATERIALS AND METHODS: A total of fifty-six systemically healthy patients with a mandibular single-rooted tooth with periapical lesions of endodontic origin and a periapical index score of 3 or higher were included in the study. Before the treatment procedures, lesion volumes were determined volumetrically using cone-beam computed tomography (CBCT). Patients were randomized into treatment (MDA, PUI, SWEEPS) and control groups (n = 14). Root canal treatment and irrigation procedures were performed by a calibrated postgraduate operator and completed at one visit. For routine follow-up, clinical and radiographic evaluations were performed by a blinded evaluator using periapical (PA) radiographs according to Molven's criteria at 3, 6, and 9 months. At 12 months, lesion volumes were quantified volumetrically using CBCT (ITK-SNAP). The data were statistically analyzed with the Wilcoxon test. The significance level was set at p < 0.05. RESULTS: In all groups, the mean lesion volume after treatment was significantly smaller than the mean volume before treatment (p = 0.001). Among the 56 teeth, 11 teeth were 'totally healed', and 39 teeth were 'reduced' on PA radiographs. No 'enlargement' was detected in any group. On CBCT, the lesion volume decreased in the following order: LAI-SWEEPS (86.9%) > PUI (85.4%) > MDA (80.4%) > control (74.5%), with no statistically significant difference (p > 0.05). CONCLUSIONS: Despite the limitations of the present study, although a greater percentage of healing was observed in the LAI-SWEEPS and PUI groups, irrigation procedures had no statistically significant effect on the healing of periapical lesions with a single root canal at the 12-month follow-up. On the other hand, the outcome may change in multirooted teeth with curved and complex root canal systems. CLINICAL RELEVANCE: In the short term and in single-canal teeth, advanced irrigation agitation methods such as laser and ultrasonic did not make a difference in healing other than manual irrigation agitation.