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.

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.

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.

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.

Why do dentists refrain from intervention in cases of persistent asymptomatic apical periodontitis in root canal filled teeth? An interview study among general dental practitioners.

AIM: To explore the context in which general dental practitioners (GDPs) decide to refrain from further treatment, that is, ortho- or retrograde retreatment or extraction of a root canal filled tooth with persistent asymptomatic apical periodontitis (PAAP). METHODOLOGY: Fifteen GDPs were strategically selected for in-depth interviews. The informants were encouraged to describe in their own words and in as much detail as possible, the three most recent patient cases of PAAP of a root canal filled tooth, in which they decided to refrain from further treatment. The interviews were recorded digitally and transcribed verbatim. The collected material was analysed according to Qualitative Content Analysis with an inductive approach. RESULTS: A pattern of varying degrees of uncertainty associated with the decision process was identified. The motives to refrain intervention had great diversity. The result from analysis of the qualitative data was formulated in an overall theme 'Between doubt and certainty in a complex clinical context' covering the latent content. The first main category covering the manifest content was 'The continuum of confidence' with three subcategories 'Experienced uncertainty', 'Reluctant approval' and 'At ease with refraining' illustrating the feelings and attitudes experienced by the informants. The second category was 'In support of acceptance' with three subcategories 'Patient's autonomy, risks and cost-benefits', 'Emotional aspects' and 'Relieving measures' representing the reasons for refraining from intervention. CONCLUSIONS: The decision to refrain from further treatment, that is, ortho- or retrograde retreatment or extraction of a root canal filled tooth with PAAP was made with some measure of confidence, combined with compensatory strategies to support the decision, taking into account not only values beneficial to the patient and awareness of limited external resources, but also factors related to the informants' personal preferences, convenience, concerns, ambition and emotions.

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.

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.

Machine learning and deep learning models for the diagnosis of apical periodontitis: a scoping review.

OBJECTIVES: To assess the existing literature on the use of machine learning (ML) and deep learning (DL) models for diagnosing apical periodontitis (AP) in humans. MATERIALS AND METHODS: A scoping review was conducted following the Arksey and O'Malley framework. The PubMed, SCOPUS, and Web of Science databases were searched, focusing on articles using ML/DL approaches for AP diagnosis. No restrictions were applied. Two independent reviewers screened publications and charted data in predefined Excel tables for analysis. RESULTS: Nineteen publications focused on diagnosing AP by identifying periapical radiolucent lesions (PRLs) in dental radiographs were included. The average sensitivity and specificity for reviewed models were 83% and 90%, respectively. Only three studies explored the direct impact of artificial intelligence (AI) assistance on clinicians' diagnostic performance. Both consistently showed improved sensitivity without compromising specificity. Significant variability in dataset sizes, labeling techniques, and algorithm configurations was noticed. CONCLUSIONS: Findings affirm AI models' effectiveness and transformative potential in diagnosing AP by improving the accurate detection of periapical radiolucencies using dental radiographs. However, the lack of standardized reporting on crucial aspects of methodology and performance metrics prevents establishing a definitive diagnostic approach using AI. Further studies are needed to expand AI applications in AP diagnosis beyond radiographic analysis. CLINICAL RELEVANCE: AI can potentially improve diagnostic accuracy in AP diagnosis by enhancing the sensitivity of PRL detection in dental radiographs without compromising specificity.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

The association of endodontic prognostic factors with the presence of periapical lesion, its volume, and bone characteristics in endodontically treated molars: a cross-sectional study.

BACKGROUND: This study intended to evaluate the association between several endodontic prognostic factors with the presence of periapical lesions (PLs), their volume, and bone characteristics including cortical bone destruction (CBD) and buccal plate bone height (BPBH) in root-filled molar teeth using cone-beam computed tomography. METHODS: A collection of 143 scans of endodontically treated maxillary/mandibular first or second molars recorded over 8 years, were obtained from a specialized radiology center. Data on prognostic factors including tooth number, gender, jaw type, the status and number of missed canals, obturation length, restoration type, presence of a separated instrument, presence of a post or screw in the canals, and presence of perforation were collected. The assessed outcomes included PL presence, PL volume, CBD, and BPBH. The association between prognostic factors and outcomes was evaluated using multiple logistic regression models with adjusted covariates and multifactorial ANOVA at a significance level of 0.05. RESULTS: A total of 282 molars from 82 women and 50 men with a mean age of 40.6 ± 12.27 were included. Among those, 139 teeth presented PL with a mean volume of 18.68 mm3. CBD was prevalent in 137 teeth and the mean BPBH appeared to be 9.45 mm. The presence of a missed canal (OR = 10.022, P < .05), underfilled canal (OR = 3.725, P < .05), overfilled canal (OR = 15.859, P = .018), and perforation (OR = 15.261, P = .013) was significantly associated with PLs. None of the prognostic factors could considerably contribute to the CBD (P > .05). The presence of a missed canal was positively associated with the PL volume (P < .05). Similarly, missed canals (P < .05), perforation (P < .05), and separated instruments (P = .004) were associated with a significantly reduced BPBH. CONCLUSIONS: Overfillings, perforations, missed canals, and underfillings were identified as remarkable predictors of PL, arranged in descending order of their respective impact. The only factor capable of significantly increasing the PL volume was the missed canal. In brief, obturation length errors, perforations, missed canals, and separated instruments were robustly correlated with endodontic failure, which highlights the importance of mitigating the potential for errors by following the fundamentals of endodontics.

Effectiveness of mechanical vs. chemomechanical methods in removing intracanal calcium hydroxide medication: a randomised trial.

OBJECTIVE: To compare the mechanical and chemomechanical methods for removing calcium hydroxide medication from the root canal system. METHODS: The triple-blind, randomised clinical trial was conducted at the Department of Operative Dentistry and Endodontics, School of Dentistry, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan, from December 16, 2022, to June 15, 2023, and comprised patients having necrotic teeth and chronic apical pathosis. They were randomised into groups A and B. On the initial visit, after access opening and chemomechanical preparation, calcium hydroxide paste was placed as an intracanal medication in both groups. the patients were recalled after two weeks. In Group A, calcium hydroxide was removed from the canals using a rotary master apical file, while in Group B, an endoactivator was used to sonically agitate the endodontic irrigant. Verification of placement was done by using a periapical radiograph. Data was analysed using SPSS 26. RESULTS: Of the 98 individuals assessed initially, 60(61.22%) were included; 34(57%) females and 26(43%) males with age ranging from 19 to 57 years. There were 27(45%) incisors, 22(36.7%) premolars and 11(18.3%) canines. There were 30(50%) patients in each of the 2 groups. The intergroup difference was not statistically significant (p=0.43). Tooth arch did not significantly correlate with the removal method (p=0.79). CONCLUSIONS: Both methods were found to be equally effective in removing water-based calcium hydroxide medication from the endodontic system. Clinical Trial Number: NCT05744661.

Healing of apical periodontitis in type II diabetes mellitus patients: A prospective study.

OBJECTIVE: This study aimed to compare the healing of periapical bone between type II diabetes patients and healthy patients after root canal treatment. SUBJECTS AND METHODS: This study included 26 diabetic patients and the control group with healthy patients matching the diabetic group in age and sex. The study included only teeth with satisfactory coronal restoration. The periapical index system was used to evaluate the periapical status of treated teeth at follow-ups after 6 and 12 months. RESULTS: Analysis of the results revealed a significantly higher healing rate in the control group compared to the diabetic group only at the 6-month follow-up (66.6 vs. 33.3%; Χ2 = 4.857; p = 0.0275). Analysis of the full-scale PAI index disclosed significantly higher PAI values in the diabetic subjects at 6- and 12-month follow-up. The regression analysis showed that the risk of apical periodontitis persistence increased significantly with female gender (OR = 3.92; 95% CI = 1.04-14.79; p = 0.043), diabetes mellitus (OR = 4.27; 95% CI: 1.18-15.50; p = 0.027) and higher household income (OR = 5.39; 95% CI = 1.33-21.89; p = 0.018). CONCLUSION: Root canal treatment remains an effective means of conservative treatment in diabetic patients. While the healing is not compromised, regular follow-ups are necessary to monitor the healing process.

Effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats.

OBJECTIVE: To evaluate the effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats. METHODOLOGY: In total, 32 male Wistar rats were divided into four groups (n = 8): AP-induced apical periodontitis; S-cigarette smoke inhalation; APS-induced AP and cigarette smoke inhalation; and C (control)-neither AP nor cigarette smoke inhalation. To induce cigarette smoke inhalation, the animals were kept in a chamber filled with tobacco smoke for 8 min thrice a day for 50 days. AP was induced 20 days after inhalation initiation by exposing their coronary pulp to their oral environment for 30 days. After animals were euthanized, their right hemimaxillae were removed for histopathological, semi-quantitative and immunohistochemical (F4/80, CD206 and iNOS) analyses. RESULTS: Quantitative data showed a moderate number of inflammatory infiltrates in AP and an intense number in APS (p < .05). Comparing F4/80+ cells showed no statistically significant differences among groups, but we found more CD206+ cells in AP than in C and S (p > .05). INOS+ immunostaining showed a significant increase in AP and APS, when compared with C and S (p < .05). APS had more iNOS+ cells than AP (p < .05). CONCLUSION: Cigarette smoke inhalation worsened AP, leading to a predominantly pro- inflammatory profile in our experimental model.

Evaluation of postoperative pain and healing following regenerative endodontics using platelet-rich plasma versus conventional endodontic treatment in necrotic mature mandibular molars with chronic periapical periodontitis. A randomized clinical trial.

AIM: To evaluate the post-operative pain and the healing of necrotic mature permanent mandibular molar teeth with peri-apical periodontitis after conventional endodontic treatment versus after platelet-rich plasma (PRP) revascularization. METHODOLOGY: The protocol of this randomized clinical trial was registered at www. CLINICALTRIALS: gov with identification number NCT03350841. Twenty-eight patients were included in the study after confirming the diagnosis clinically and radiographically. In the first visit, mandibular molar teeth of both groups were mechanically prepared. Double antibiotic paste was prepared and injected then the cavity that was sealed with glass ionomer. At the second visit, the patients were randomized either to control group where standard endodontic treatment was completed by lateral condensation technique or assigned to intervention group where PRP revascularization technique. The degree of spontaneous pain was assessed using numerical rating scale (NRS) pre-operatively, then post-operatively after 6, 12 h and daily for 5 days. Patients were given a placebo to be administrated in case of pain. An analgesic (ibuprofen 400mg) was prescribed in case of persistent pain. Clinical and radiographic healing was assessed after 6 and 12 months. All demographic, baseline and outcome data were collected and statistically analysed. RESULTS: Regarding the post revascularization/obturation pain, there was no statistically significant difference between severity of pain in the two groups at all time intervals except after 12 h, revascularization group showed statistically significantly higher prevalence of no pain than endodontic treatment group. Regarding the healing; the periapical lesions decrease in size significantly from the pre-operative lesion size in both groups without significant difference between the both groups. CONCLUSION: Within the limitation of this study, PRP revascularization could be an alternative treatment to root canal treatment but further randomized clinical trials with standardized techniques and long follow up periods are recommended for more reliable results.

Effectiveness of endodontic tissue engineering in treatment of apical periodontitis: A systematic review.

BACKGROUND: Regenerative endodontics has evolved in recent years with tissue engineering concepts in particular appearing promising. Endodontic tissue engineering (ETE) describes the various approaches based on the orthograde introduction of scaffolds or biomaterials (with or without cells) into the root canal to achieve pulp tissue regeneration. There are currently no systematic reviews investigating whether ETE is a suitable method for the treatment of endodontic disease in both mature and immature permanent teeth. OBJECTIVES: The purpose of this systematic review was to determine the effectiveness of ETE in permanent teeth with pulp necrosis in comparison with conventional endodontic treatment. METHODS: We searched MEDLINE, Embase and the Cochrane Library for published reports as well as Google Scholar for grey literature up to November 2021. Included were studies of patients with permanent immature or mature teeth and pulp necrosis with or without signs of apical periodontitis (P) comparing ETE (I) with calcium hydroxide apexification, apical plug and root canal treatment (C) in terms of tooth survival, pain, tenderness, swelling, need for medication (analgesics and antibiotics), radiographic evidence of reduction in apical lesion size, radiographic evidence of normal periodontal ligament space, function (fracture and restoration longevity), the need for further intervention, adverse effects (including exacerbation, restoration integrity, allergy and discolouration), oral health-related quality of life (OHRQoL), presence of sinus tract and response to sensibility testing (O). An observation period of at least 12 months was mandatory (T) and the number of patients in human experimental studies or longitudinal observational studies had to be at least 20 (10 in each arm) at the end (S). Risk of bias was appraised using the Cochrane risk-of-bias (RoB 2) tool. Two authors independently screened the records, assessed full texts for eligibility and evaluated risk of bias. Heterogeneity of outcomes and limited body of evidence did not allow for meta-analysis. RESULTS: Two randomized clinical trials investigating cell transplantation approaches with a total of 76 participants (40 treated immature teeth and 36 treated mature teeth) were included for qualitative analysis. Both studies had moderate concerns in terms of risk of bias. Due to the lack of homogeneity a meta-analysis was not possible. Tooth survival for ETE, root canal treatment and apexification was 100% after 12 months. Teeth treated with ETE showed a higher number of cases with positive pulpal responses to sensitivity tests and with blood perfusion compared with root canal treatment or apexification. DISCUSSION: This systematic review highlights that there is limited evidence for ETE approaches. Even though the results of this review suggest a high survival with ETE in mature and immature teeth, there is a moderate risk of bias due to methodological limitations in the included studies, so the overall results should be interpreted with caution. Lack of a robust control group was a common problem during literature screening, and outcomes besides dental survival were reported inconsistently. Future clinical trials need to address methodical as well as assessment concerns and report long-term results. CONCLUSION: The benefits and high survival rates reported for ETE techniques suggest that this procedure might be an alternative to conventional procedures for permanent teeth with pulpal necrosis. However, more appropriate studies are needed to derive clinical recommendations. REGISTRATION: PROSPERO (CRD42021266350).

Adjuvant therapy with a 980-nm diode laser in root canal retreatment: randomized clinical trial with 1-year follow-up.

The purpose of this study is to assess the laser effect in root canal disinfection and periapical healing of endodontically treated teeth from patients with asymptomatic apical periodontitis. This study was performed as a randomized clinical trial. Thirty patients were selected according to the inclusion/exclusion criteria. Fifteen patients received the root canal retreatment (RCR) combined with 980-nm diode laser irradiation (LI). The canals were irrigated with saline solution and gently dried with paper points, keeping the dentin partially moist. The irradiation was performed using a 320-µm-diameter fiber in helicoidal movements (pulsed mode, power output of 1.5 W, 100 Hz for 20 s). The other 15 patients received the RCR with placebo irradiation (PI). Microbiological samples were taken in three periods: S1, after the filling material removal (baseline); S2, after laser or placebo irradiation (LI or PI); and S3, after the RCR followed by laser or placebo. The samples were submitted to the total microbial and E. faecalis counting. The periapical radiographic healing was analyzed after 3, 6, 9, and 12 months. Microbiological data (CFU/mg) were analyzed by ANOVA and Tukey's test (P < 0.05), and the repair by Mann-Whitney test (P < 0.05). In S2, the laser provided 42.44% microbial reduction and 53.14% of E. faecalis, different from the placebo that had no reduction, and 4.85% for Enterococcus (P < 0.05). In S3, the bacterial counts decreased without differences between groups. No differences in healing were found at 3 months. However, diode laser facilitated the repair from 3- to 12-month follow-up (P < 0.05) and had 45% more healed cases than placebo. Diode laser provided an antimicrobial effect before the biomechanical preparation but was not synergistic in RCR. It improved the periapical healing during follow-up.

Differential expression of circular RNAs in interleukin 6-promoted osteogenic differentiation of human stem cells from apical papilla.

INTRODUCTION: Studies have shown that interleukin 6 (IL-6) can regulate stem cell osteogenic differentiation; however, the exact mechanism is not clear. Circular RNAs (circRNAs) are closed circular non-coding RNAs that are involved in the process of stem cell osteogenic differentiation. Therefore, the purpose of this present study was to investigate the effect of IL-6 treatment on osteogenic differentiation of human apical tooth papillae stem cells (hSCAPs), and to detect the difference in circRNA expression using gene microarray technology. METHODS: After extraction and identification of hSCAPs, alkaline phosphatase (ALP) activity, alizarin red staining, and calcium ion quantitative assay were used to determine the changes of ALP enzyme, mineralized nodules, and matrix calcium levels before and after IL-6 treatment of hSCAPs gene microarray technology was used to analyze the changes in circRNA expression levels before and after IL-6 induction of mineralization. The four selected circRNAs were validated by qRT-PCR. Moreover, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the potential functions and biological signaling pathways of circRNAs. Finally, these data are integrated and analyzed to construct circRNA-microRNA-mRNA networks. RESULTS: Alp and Alizarin red staining confirmed that IL-6 promoted the osteogenic differentiation of hSCAPs. The gene microarray results identified 132 differentially expressed circRNAs, of which 117 were upregulated and 15 were downregulated. Bioinformatic analysis predicted that the circRNA-406620/miR-103a-3p/FAT atypical cadherin 4 (FAT4) pathway might be involved in regulating IL-6 to promote osteogenic differentiation of hSCAPs. CONCLUSION: Differentially expressed circRNAs might be closely involved in regulating IL-6 to promote osteogenic differentiation of hSCAPs.

Clinical efficacy of endodontic protocols on reducing cultivable bacteria and endotoxin in infected root canal in patients submitted to head and neck radiotherapy: a randomised clinical trial.

OBJECTIVES: Assess the efficacy of biomechanical preparation using a reciprocating system followed by final irrigation protocols, then intracanal medication, on reducing endotoxins and cultivable bacteria of infected teeth in irradiated patients. MATERIALS AND METHODS: Twenty-two infected single-rooted canals in patients submitted to head and neck radiotherapy were prepared by reciprocating motion and 2.5% NaOCl. Patients were randomly divided into two groups of 11 patients before the final irrigation protocol: apical positive pressure (APP) or passive ultrasonic activation (PUA). Both groups were treated in two sessions, using Ca(OH)2 as intracanal medication for 14 days. Root canal content sampling was performed after canal access (S1), after biomechanical preparation plus the irrigation protocol (S2), and after intracanal medication (S3). Chromogenic limulus amoebocyte lysate assay measured endotoxin levels (EU/mL), and bacterial load was determined by culture techniques (CFU/mL). RESULTS: Treatment protocols reduced bacterial counts after S2 in both groups (p = 0.01). S3 differed from S1 (p = 0.01), but not from S2 (p = 0.4). Endotoxin levels were reduced in both groups after S2 (P = 0.03) and were lower in S3 than in S2, with significant differences in the APP group (p = 0.03). CONCLUSIONS: Biomechanical preparation using a reciprocating system and 2.5% NaOCl in irradiated teeth, followed by the irrigation protocol (APP or PUA), demonstrated efficacy in reducing endodontic contaminants. Ca(OH)2 as intracanal medication should be performed in irradiated patients with infected root canals. CLINICAL RELEVANCE: This clinical study demonstrated that endodontic treatment in irradiated patients is efficacious at reducing bacterial load and endotoxin levels.

Effect of endodontic treatment on endothelial dysfunction and subclinical atherosclerosis-a prospective intervention study.

OBJECTIVE: The objective of this study is to investigate the effect of endodontic treatment on flow-mediated dilatation (FMD) and carotid intima-media thickness (c-IMT) in patients with apical periodontitis (AP). MATERIAL AND METHOD: The study includes 32 young men having AP with a mean age of 25.78 years free from cardiovascular disease (CVD) and its risk factors, including periodontitis. All subjects underwent complete physical and dental examination, echocardiography, and ultrasound assessment of FMD on the brachial artery and c-IMT on the carotid artery at baseline and 12 months after the endodontic treatment. Data were analyzed using paired Student's t-test and Pearson's correlation coefficient (r) test using SPSS 26 version. RESULTS: Endodontic treatment leads to the improvement of FMD significantly from a pooled baseline value of 4.84 ± 1.55% to 7.68 ± 2.08% (p < 0.05). The study also depicts a statistically significant difference between c-IMT (mean = 0.62 ± 0.11 mm) before treatment as compared to 12 months after treatment (mean = 0.59 ± 0.11 mm) (p < 0.05). CONCLUSION: Endodontic treatment leads to improved FMD and decreased c-IMT suggesting that treating AP can be help revert the early stages of CVD. CLINICAL RELEVANCE: AP could be a potential etiological factor of future CVD and should be treated as soon as diagnosed.

The effect of periapical bone defects on stress distribution in teeth with periapical periodontitis: a finite element analysis.

BACKGROUND: Apical periodontitis directly affects the stress state of the affected tooth owing to the destruction of the periapical bone. Understanding the mechanical of periapical bone defects/tooth is clinically meaningful. In this study, we evaluate the effect of periapical bone defects on the stress distribution in teeth with periapical periodontitis using finite element analysis. METHODS: Finite element models of normal mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using a digital model design software. The edges of the mandible were fixed and the masticatory cycle was simplified as oblique loading (a 400 N force loaded obliquely at 45° to the long axis of the tooth body) to simulate the tooth stress state in occlusion and analyze the von Mises stress distribution and tooth displacement distribution in each model. RESULTS: Overall analysis of the models: Compared to that in the normal model, the maximum von Mises stresses in all the different periapical bone defect size models were slightly lower. In contrast, the maximum tooth displacement in the periapical bone defect model increased as the size of the periapical bone defect increased (2.11-120.1% of increase). Internal analysis of tooth: As the size of the periapical bone defect increased, the maximum von Mises stress in the coronal cervix of the tooth gradually increased (2.23-37.22% of increase). while the von Mises stress in the root apical region of the tooth showed a decreasing trend (41.48-99.70% of decrease). The maximum tooth displacement in all parts of the tooth showed an increasing trend as the size of the periapical bone defect increased. CONCLUSIONS: The presence of periapical bone defects was found to significantly affect the biomechanical response of the tooth, the effects of which became more pronounced as the size of the bone defect increased.