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Cemental tears are often misdiagnosed due to their scarcity. In this study, we reported the second largest cohort of cemental tears thus far. By reviewing the radiographic data and medical records of 63 cemental tear teeth, we found that periapical periodontitis was the most frequent diagnosis, followed by cracked tooth/root fracture and periodontitis. Most of the cemental tear teeth that did not have root canal treatment had vital pulp. The apical third of the root was the most prominent site of cemental tears. Cemental tears occurred more frequently in the palatal root of the maxillary molars and in the mesial root of the two-root mandibular molars. Uncontrollable bone loss and tooth mobility were the two main reasons for the extraction of teeth with cemental tears. We suggest that cemental tears should be included in the differential diagnosis of periapical periodontitis, cracked tooth, vertical root fracture and periodontitis, especially for teeth with periapical radiolucency and vital pulp. We believe our study could provide more insights into cemental tears, which will aid clinicians in the early diagnosis and proper treatment of cemental tears.

Objectives: Limited literature addresses the long-term success of complete pulpotomy in permanent molars with signs of irreversible pulpitis in young patients. The aim of this observational study was to prospectively evaluate the long-term outcomes of complete pulpotomy using mineral trioxide aggregate (MTA) over an average period exceeding 11 years., Methods: Out of 27 molars displaying signs suggestive of irreversible pulpitis which underwent MTA pulpotomy, 24 molars were followed-up for a mean duration of 11.0 ± 2.2 years (range 8.2 to 14.8 years). Clinical and radiographic assessments were periodically conducted, tailored to each patient's specific circumstances. Treatment failure criteria included clinical signs and symptoms and radiographic evidence suggesting a lack of pulpal or periapical healing., Results: 83 % of molars had signs and symptoms of symptomatic irreversible pulpitis, with 83 % displaying apical periodontitis. Clinically and radiographically, all pulpotomies (100 %) were considered successful. A hard tissue barrier was observed in 71 % of teeth, and continued root maturation was evident in all molars with open apices. Complete pulp canal obliteration (PCO) was present in 21 % of the molars. All radiographic apical radiolucencies completely resolved., Conclusions: This study demonstrates a 100 % success rate over an average 11-year follow-up for complete pulpotomy in managing permanent molars with signs and symptoms of irreversible pulpitis in young patients. It offers evidence for its long-term efficacy in promoting healing of pulp and periapical tissues., Clinical Significance: This study showed high long-term success for complete pulpotomy in young permanent molars with irreversible pulpitis, with clinical and radiographic success over 11 years. Despite initial symptoms of pulpitis and apical periodontitis, the treatment resulted in tissue healing, root maturation, and resolution of periapical radiolucencies, suggesting it as an alternative to root canal therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The primary aim of this study was to compare the radiographic changes of immature incisors with periapical radiolucency after treatment with platelet-rich fibrin (PRF) and concentrated growth factor (CGF) platelet concentrate scaffolds as well as assessment of the clinical success rate over 12 months. The secondary aim was to monitor the radiographic changes in terms of reduction of periapical lesion diameter (PALD), root dentine thickness (RDT), root length (RL), and apical foramen width (AFW). The tertiary aim was to assess and pulp responses, after 12 months., Methods: Fifty six children with seventy necrotic, single-rooted maxillary incisors with periapical radiolucency were treated with either CGF or PRF scaffolds (35 teeth per group). Two patients with 4 teeth (2 teeth in each group) failed to attain the follow-up recalls. Radiographic changes in terms of reduction of PALD, RDT, RL, and AFW were monitored using a 2-dimensional (2D) radiograph and cone-beam computed tomography (CBCT) scan. The clinical performance of teeth receiving both scaffolds was assessed after 6 and 12 months. Categorical and continuous data were analyzed using the chi-square test and the t test, respectively. The time and group effects on the means of different radiographic dimensions were tested using the general linear model. Bland-Altman plots were used to assess the level of agreement between the 2D radiographs and CBCT. The level of significance was defined at 0.05 and a 95% confidence interval., Results: The means of PALD and RL showed significant enhancement in the CGF group compared to the PRF group (P < .05). While the difference between the 2 scaffolds in terms of RDT and AFW was not significant (P > .05). The findings of the 2D radiograph and CBCT were consistent. Clinically, both scaffold success rates were similar (93.9%) over the follow-up intervals. The influence of study independent variables had no significant effect on the success of the regenerative endodontic procedures outcome (P > .05). There was no significant difference in the positive pulp responses to the thermal and electric pulp tests after one year of treatment (P > .05)., Conclusions: According to the short-term follow-up, PRF and CGF were successful in treating immature teeth with periapical radiolucency by regenerative endodontics. Both scaffold systems induced periapical healing and root lengthening with significant superiority of CGF., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Manuka oil and tea tree oil are essential oils with known antibacterial properties that are believed to be caused by one main component: terpinen-4-ol. Terpinen-4-ol has potent antibacterial activity against caries-related microorganisms. However, few studies have investigated the antimicrobial effects of terpinen-4-ol on bacteria in apical periodontitis. Thus, the objective of the present study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against Enterococcus faecalis, Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum, which have all been detected in apical periodontitis. The minimum inhibitory and minimum bactericidal concentrations of terpinen-4-ol were determined to assess its activity against biofilms. The minimum inhibitory concentration of terpinen-4-ol was 0.25% against E. faecalis and F. nucleatum, 0.05% against P. gingivalis, and 0.1% against P. intermedia. The minimum bactericidal concentration of terpinen-4-ol was 1.0% against E. faecalis, 0.2% against P. gingivalis and P. intermedia, and 0.5% against F. nucleatum. In the biofilm evaluations, all terpinen-4-ol-treated bacteria had significant reductions in biofilm viability compared with controls in experiments assessing attachment inhibitory activity. Furthermore, structural alterations and decreased bacterial cell clumping were observed under scanning electron microscopy, and significantly decreased cell survival was noted using fluorescence microscopy. Together, these results suggest that terpinen-4-ol is a potential antibacterial agent with bactericidal properties, and can also act on established biofilms., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: The present systematic review and meta-analysis aimed to evaluate the success rate of root canal retreatment filled with gutta-percha and the variables related to retreatment success., Data: The PRISMA guidelines were followed for the present review. The study protocol was registered in the International Prospective Database of Systematic Reviews (PROSPERO CRD42021283134). Risk assessment was performed using the Newcastle-Ottawa scale. Funnel plots were used to detect publication bias and asymmetry was assessed using Egger's tests., Sources: PubMed, Scopus, ScienceDirect, Cochrane, and additional sources were searched., Study Selection: Studies published until 10 December 2022. Clinical studies evaluating the success of root canal retreatment filled with gutta-percha with at least a 1-year follow-up were selected., Results: Ten studies and one unpublished study fulfilled the inclusion criteria for quantitative analysis. The success rate of non-surgical root canal retreatment was 71% (95% CI: 66%-76%) with strict criteria and 87% (79% - 93%) with loose criteria for 1-3 years of follow-up, and 77% (66% - 86%) with strict criteria for a 4-5 years of follow-up. Endodontically retreated teeth with periapical lesions had a lower success rate under strict criteria. The tooth type, dental arch, initial periapical index (PAI) score, and the number of visits also affected the treatment success rate under strict criteria. For the loose criteria, teeth with larger periapical lesions and higher initial PAI scores had a lower success rate., Conclusions: According to the present systematic review and meta-analysis, non-surgical root canal retreatment results in favourable outcomes. The presence of a periapical radiolucency, periapical lesions >5mm, a higher initial PAI score, multiple-visit retreatments, and mandibular and molar teeth resulted in a lower success rate., Clinical Significance: Non-surgical root canal retreatment filled with gutta-percha techniques is a relatively predictable procedure with a high success rate. Several variables can affect retreatment success, mainly the presence and size of a periapical lesion and the type of tooth., Competing Interests: Declaration of competing interest The authors of this review received no financial support and declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: A 65-year-old man had nonsurgical retreatment using an iodoform and calcium hydroxide paste in a maxillary left canine with persistent apical periodontitis. An apical mineralized barrier (AMB) was observed 3-months postoperatively. Unfortunately, the tooth was extracted due to a cementum tear. This provided an opportunity to analyze the AMB histologically, as there is a lack of previous reports on its microstructure., Methods: After extraction and removal of the granulation tissue from the root surface, the canine was processed, and observed using micro-computed tomography (μCT) and light microscopy. Thereafter, the specimen was resin-embedded specimen was evaluated by scanning electron microscopy, micro-X-ray fluorescence spectroscopy and Raman spectroscopy to understand the mechanism and nature of the AMB formation during apical healing., Results: Nonsurgical retreatment was clinically successful based on the absence of clinical symptoms of apical periodontitis and the radiographic presence of an AMB. The AMB was opaque and could be readily differentiated from dentin under a light microscope. Micro-computed tomography analysis revealed that the AMB had the same mineral density as dentin. Scanning electron microscopy revealed that the AMB had two distinct layers based on the size of the calcified particles. Elemental mapping using micro-X-ray fluorescence spectroscopy showed that the localization of calcium and phosphorus differed between AMB and other areas of biomineralization. Raman spectral mapping revealed that the surface layer of the AMB consisted of collagen, calcium carbonate, and hydroxyapatite., Conclusions: This study explored new analytical methods for elucidating the apical wound-healing process and the nature of the mineralized repair. The findings provided detailed information on the AMB highlighting a bilaminar structure with high calcium components higher on the inside and a brightness similar to cementum not dentin and the presence of hydroxyapatite., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The bacteria that invade the periapical tissue of teeth can directly damage tissue cells such as periapical fibroblasts, leading to an inflammatory response in the periapical tissue and ultimately resulting in bone destruction. We investigated the role of fibroblast activation protein α (FAPα) and integrin α5 (ITGA5) in periapical bone destruction. This study found that FAPα and ITGA5 were highly expressed in human tissues from patients with chronic apical periodontitis. Osteoclast differentiation decreased when FAPα or ITGA5 was silenced and inhibited. The results of protein molecular docking showed that FAPα had good binding affinity to ITGA5, and its free energy was -14.5 kcal/mol. Immunofluorescence staining and co-immunoprecipitation showed that FAPα and ITGA5 formed protein complexes in the inflammatory microenvironment. In conclusion, this study proved that FAPα and ITGA5 participate in the regulation of osteoclast differentiation by forming protein complexes in the inflammatory microenvironment, which then regulates the occurrence and development of chronic apical periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: This study aimed to compare the postoperative pain level changes resulting from using calcium silicate- (EndoSeal MTA) and calcium hydroxide-based (Sealapex) root canal sealers in mandibular first and second molar teeth with symptomatic apical periodontitis., Methods: A total of 60 patients with symptomatic apical periodontitis in their lower molar teeth were randomly allocated into 2 groups according to sealer type (n = 30). Demographic data, including gender, age, and smoking habit, and preoperative pain measures were recorded. Root canal treatments were performed in a single visit. Postoperative pain measurements and analgesic intake were measured at 6, 12, 24, and 48 hours and after 3, 5, and 7 days using the visual analog scale. The data were statistically analyzed using a chi-squared test (to compare gender, age, smoking habit, analgesic intake, and sealer extrusion), the Mann-Whitney U test (to compare pain levels), Friedman tests (for the evaluations of the reduction in pain levels over time), and Spearman's correlation test (to analyze the relationships of age, gender, smoking habit factors with postoperative pain) (P = .05)., Results: The statistical analysis showed no significant differences between the groups in postoperative pain and analgesic intake at any of the time intervals evaluated (P > .05)., Conclusions: Patients treated with calcium silicate- and calcium hydroxide-based root canal sealers experienced similar postoperative pain and no statistically significant differences were observed in analgesic intake., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Bisphosphonates are antiresorptive drugs used worldwide to treat systemic bone pathologies. This study aimed to assess the impact of zoledronic acid on the progression of induced apical periodontitis and the expression of cytokines interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) in a mouse model., Methods: Sixteen female isogenic BALB/c mice 6 weeks of age were distributed into 2 groups: mice with induced apical periodontitis (the AP group, n = 8) and mice with induced apical periodontitis treated with zoledronic acid (the AP-ZA group, n = 8). The AP-ZA group received a dose of 125 μg/kg zoledronic acid diluted in sterile saline solution administered intraperitoneally once a week for 4 weeks before pulp exposure, whereas the AP group received only saline solution. Pulp exposures were performed on the maxillary first molars for the induction of apical periodontitis, and mice were euthanized after 7 and 21 days. The jaws were collected; scanned using micro-computed tomographic imaging; and processed for polymerase chain reaction analysis of IL-1β, IL-10, IL-6, and TNF-α. The Student t test was performed for parametric data, and Mann-Whitney U tests were used for nonparametric data. The level of significance was set at 5%., Results: Micro-computed tomographic imaging revealed higher bone resorption in the AP group compared with the AP-ZA group at both time points (P < .05). Real-time polymerase chain reaction demonstrated higher TNF-α expression in the AP group at both time points and higher IL-6 and IL-1β expression in the AP group at the 7- and 21-day time points, respectively, compared with the AP-ZA group (P < .05). No differences were observed regarding IL-10 expression between the groups., Conclusions: Zoledronic acid had significant anti-inflammatory and antiresorptive effects on apical periodontitis in mice., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Bone loss is strongly associated with the immunologic milieu in apical periodontitis (AP). Tertiary lymphoid structures (TLSs) are organized lymphoid cell aggregates that form in nonlymphoid tissues under persistent inflammatory circumstances. To date, there has been no relevant report of TLSs in periapical lesions. This work aimed to investigate the formation and potential function of TLSs in AP., Methods: Tissues from human apical lesions (n = 61) and healthy oral mucosa (n = 5) were collected. Immunohistochemistry and multiplex immunofluorescence were used to detect the formation of TLSs. Correlation analyses were performed between clinical variables and TLSs. In addition, immunohistochemistry was used to evaluate the expression of interleukin-1 beta, interleukin-6, receptor activator of nuclear factor kappa-B ligand, and macrophage subsets in the apical lesions., Results: Periapical granulomas (n = 24) and cysts (n = 37) were identified by histologic evaluation. TLSs, composed of B-cell and T-cell clusters, developed in periapical granulomas and radicular cysts. The CXC-chemokine ligand 13, its receptor CXC-chemokine receptor 5, follicular dendritic cells, and high endothelial venules were localized in TLSs. The quantity and size of TLSs were positively associated with bone loss in AP. Moreover, proinflammatory cytokines and macrophage subsets were also substantially elevated in TLS regions of apical lesions., Conclusions: The formation of TLSs in periapical granulomas and cysts was closely associated with persistent immune responses and bone loss in apical lesions. TLSs provide an updated insight into the complicated immune response process in AP., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the success rate of nonsurgical root canal retreatment at the 2-3-year follow-up and identify the possible prognostic factors., Methods: Patients who underwent root canal retreatment at a university dental clinic were contacted for clinical and radiographic follow-up. The retreatment outcomes in these cases were based on clinical signs, symptoms, and radiographic criteria. Inter- and intraexaminer concordances were calculated using Cohen's kappa coefficient. The retreatment outcome was dichotomized into success or failure according to strict and loose criteria. The radiographic success criteria consisted of complete resolution or absence of a periapical lesion (strict criteria) or a reduction in the size of an existing periapical lesion at recall (loose criteria). χ 2 tests were used to evaluate possible variables associated with retreatment outcomes (age, sex, tooth type, location, contact points, periapical status, quality of previous and final root canal filling, previous and final restoration, number of visits, and complications)., Results: Overall, 129 teeth (113 patients) were included in the final evaluation. The success rate was 80.6% under strict criteria and 93% under loose criteria. Molars, teeth with an initially higher periapical index score, and teeth with >5 mm periapical radiolucency had a lower success rate according to the strict criteria model (P < .05). When the loose success criteria were used, teeth with larger (>5 mm) periapical lesions and those that had been perforated during retreatment showed a lower success rate (P < .05)., Conclusions: The present study demonstrated that nonsurgical root canal retreatment is a highly successful procedure after an observation period of 2-3 years. Treatment success is primarily affected by the presence of large periapical lesions., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Biomarkers assayed from gingival crevicular fluid (GCF) are a potential tool for endodontic diagnosis and for monitoring treatment response. This cross-sectional study measured cytokines in GCF from teeth with apical periodontitis and evaluated their relationship with preoperative pain and other clinical findings., Methods: Participants presenting for root-end resection surgery due to apical periodontitis diagnosis (n = 56) underwent standardized clinical testing and completed preoperative questionnaires. GCF from diseased and control teeth were collected, processed, and analyzed. Mann-Whitney U and Wilcoxon tests were used to examine the cytokine levels in diseased compared to healthy control teeth. We also assessed the relationship of cytokine levels with clinical findings., Results: Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, and tumor necrosis factor-⍺ (TNF-⍺) were detected in GCF. TNF-⍺ levels were significantly higher in GCF collected from diseased versus control teeth (P = .02) and increased IL-1β levels in diseased teeth were detected (P = .06). Lower IL-10 levels were observed in teeth with a sinus tract and/or swelling compared to teeth without a sinus tract and/or swelling (P = .08). Cytokine levels did not clearly relate to the presence of pain., Conclusions: Elevated levels of proinflammatory cytokines, including TNF-⍺ and IL1- β, were detected in GCF from diseased teeth compared to the healthy controls. Additional studies are needed to further investigate the utility of these biomarkers for objectively evaluating periradicular pathology., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: MicroRNAs have been shown to play a role in the pathogenesis of apical periodontitis. Upregulation of miR-10a-5p and downregulation of miR-891a-5p were previously reported in apical periodontitis samples. This study aims to perform a functional characterization of miR-10a-5p, investigating its capacity to regulate the expression of inflammatory cytokines and growth factors, as well as a possible co-regulation mechanism with miR-891a-5p in the development of apical periodontitis., Methods: miR-10a-5p mimics/controls and miR-891a-5p inhibitors/controls were introduced to human K-562 cells in the presence or absence of lipopolysaccharide. Total RNA was extracted from cell lysates, and target genes were examined via quantitative reverse transcription-polymerase chain reaction. Cell lysates were also subjected to proteomics analysis. Furthermore, mimics of miR-10a-5p and inhibitors of miR-891a-5p were co-transfected into K-562 cells. RNA sequencing and quantitative reverse transcription-polymerase chain reaction were carried out to examine their target genes., Results: Overexpression of miR-10a-5p led to downregulation of tumor necrosis factor-alpha and interleukin-1 beta mRNA and upregulation of transforming growth factor-beta 1 (TGFB1) mRNA expression, whereas interleukin 3 and TGF-β1 proteins were upregulated. Simultaneous overexpression of miR-10a-5p and inhibition of miR-891a-5p further increased TGFB1 mRNA transcript levels. RNA sequencing revealed that genes co-regulated by miR-10a-5p and miR-891a-5p may be involved in apical periodontitis-related pathways such as tumor necrosis factor, transient receptor potential, and vascular endothelial growth factor signaling pathways., Conclusions: miR-10a-5p may modulate the expression of multiple inflammatory cytokines and growth factors such as tumor necrosis factor-alpha, IL-1β, interleukin 3, and TGF-β1. In addition, miR-10a-5p and miR-891a-5p cooperatively regulate TGFB1 gene expression, and the gene network of this co-regulation is integrated with many pathways in apical periodontitis., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The study aimed at determining antibacterial efficiency of adjuvant photodynamic therapy (PDT) and high-power diode laser (DL) in the treatment of chronic periapical periodontitis (CPP) in young permanent teeth., Methods: Forty-four young permanent teeth with CPP were randomly divided into three groups (PDT, DL and control). Each tooth underwent standard chemo-mechanical treatment, while within tested groups was additionally treated by PDT or DL. Bacterial identification and quantification were provided by MALDI-TOF spectrometry and plate counting assay, performed after accessing the canal, following chemo-mechanical preparation, and after PDT or DL procedure where applicable., Results: Thirty-nine young permanent teeth with CCP (patients age 9.77 ± 1.43) completed the study. Before the treatments, 202 isolates belonging to 13 genera/species, including Streptococcus (36), Actinomyces (34), Peptostreptococcus micros (27), Veillonella (25) and Enterococcus faecalis (22), were recovered. Chemo-mechanical treatment reduced CFU count in the all three groups (p < 0.001), but complete eradication was not observed for any of isolated species. Adjuvant PDT and DL completely eradicated isolates of 8 and 6 bacterial genera/species, resulting in complete bacterial elimination from 53.8% and 30.8% of root canals, respectively. In the rest canals, total Δlog CFUs were 4.71 and 4.58., Conclusion: The results indicated that both PDT and DL could be performed as adjuvants to standard endodontic treatment of the young permanent teeth with CPP., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in the present study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Smoking can be considered a risk factor for chronic apical periodontitis (CAP). This study compared the immunoexpression of biomarkers receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), osteopontin (OPN), and tumor necrosis factor alpha (TNF-α) in CAP in smokers and nonsmokers., Methods: Twelve smokers and 12 nonsmokers diagnosed with CAP and indicated for tooth extraction were selected. Exclusion factors were teeth with a diagnosis of root fracture, previous endodontic treatment, or endoperiodontal injury, in addition to individuals with systemic diseases, under 18 years of age, users of anti-inflammatory and/or antibiotics in the last 3 months, and drug users. Specimens were processed for histopathologic and immunohistochemical analysis., Results: Qualitative analysis of RANKL expression showed 66.66% weak/moderate and 33.33% strong in smokers and 100% weak/moderate in nonsmokers. OPG and OPN expressions were 100% negative to focal in the smoker group and 50% negative to focal and 50% weak/moderate in the nonsmoker group. TNF-α was 25% negative to focal and 75% weak/moderate in the smoker group and 33.33% negative to focal and 66.66% weak/moderate in the nonsmoker group. Quantitative analysis of the data using the Mann-Whitney U test showed that there was a significant difference in the immunoexpression of RANKL (P < .05), OPG (P < .05), and OPN (P < .05), but there was no statistical difference in the immunoexpression of TNF-α (P > .05) between the 2 groups., Conclusions: These findings suggest that smoking is capable of altering the inflammatory response, influencing the evolution of CAP., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Periapical periodontitis develops due to the interplay between root canal microorganisms and host defenses. The mechanism underlying the pathogenesis of periapical periodontitis remains unclear. Regulator of G protein signaling protein 10 (RGS10) has been suggested to play a role in regulating inflammation. This study explored the potential regulatory effects of RGS10 on periapical periodontitis and the proinflammatory pathway of nuclear factor (NF)-κB., Methods: Disease models of periapical inflammation in mice were established, and adenovirus-associated virus (AAV) was used to inhibit RGS10 expression. Periapical lesions were detected using micro-computed tomography. Quantitative reverse transcriptase PCR (qRT-PCR), western blotting (WB), enzyme-linked immunosorbent assay (ELISA), enzyme activity staining of tartrate-resistant acid phosphatase, and immunohistochemistry were conducted to assess the role of RGS10 expression on NF-κB proinflammatory signaling, OPG, RANKL, and osteoclasts in the periapical regions of each group. TNFα was used to stimulate L929 cells alone or with small interfering RNA (siRNA). To assess the expression of associated molecules, WB, immunofluorescence, qRT-PCR, and ELISA were performed., Results: RGS10 inhibition increased alveolar bone destruction in periapical periodontitis lesions and substantially enhanced the NF-κB proinflammatory signaling pathway activation level. Furthermore, RGS10 inhibition upregulated the ratio of OPG/RANKL and the maturation of osteoclasts during alveolar bone resorption. L929 cell TNFα stimulation and siRNA transfection confirmed these in vivo results., Conclusion: RGS10 negatively regulates NF-κB proinflammatory signaling in periapical periodontitis and participates in bone remodeling. Therefore, RGS10 is a promising treatment option for long-term chronic periapical inflammation and may be a new target for the artificial regulation of inflammation., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Interferon regulatory factor 5 (IRF5) is critical for the regulation of immune and inflammatory responses in health and diseases. However, the presence of IRF5 in human apical periodontitis remains unknown. This study aimed to explore the expression and colocalization of IRF5 with tumor necrosis factor receptor-associated factor 6 (TRAF6) and AKT2 in human apical periodontitis., Methods: A total of 39 human periapical tissues, including healthy gingival tissues (n = 12), periapical granulomas (PGs, n = 13), and radicular cysts (RCs, n = 14), were used in this study. The inflammatory infiltrates of lesions were evaluated by hematoxylin-eosin staining. The expression of IRF5 was detected by immunohistochemistry. Double immunofluorescence assessment was performed to colocalize IRF5 with CD68, TRAF6, and AKT2, respectively. Data were analyzed using the Kruskal-Wallis test., Results: Immunohistochemistry revealed significantly higher expressions of IRF5 in PGs and RCs than the healthy control group. IRF5-CD68 double-positive cells were more predominant in RCs and PGs than the healthy control group. Significant differences of the IRF5-TRAF6 and IRF5-AKT2 double-positive cells were detected in periapical lesions compared with the healthy control tissues., Conclusions: IRF5 was highly expressed in macrophages of human periapical tissues and was colocalized with TRAF6 or AKT2 in human periapical tissues. These findings may provide new clues for understanding the pathogenesis of periapical diseases., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Circulating blood is a readily available scaffold when enough bleeding cannot be induced from periapical tissues during regenerative endodontic treatments (RETs). The aim of this investigation was to compare the radiographic outcome (ie, linear and 3-dimensional volumetric) of RET using periapical blood or circulating blood as scaffolds in sheep immature mandibular incisors., Methods: Thirty-two immature sheep mandibular central incisors were randomly assigned to the following groups (n = 8): the positive control groups, the pulps were removed without any treatment; the periapical blood group, RET was performed using periapical blood as the scaffold; the circulating blood group, RET was performed using circulating blood as the scaffold; and the negative control group, intact teeth without any treatment. After 8 months, micro-computed tomographic images of mandibular blocks were taken to assess the following: root length, root thickness at the midroot and cementoenamel junction levels, and the incidence of apical closure. Root structures were segmented, and root volumes were calculated and analyzed statistically., Results: RET using periapical blood and circulating blood resulted in increases in root length and root wall thickness at the midroot and cementoenamel junction levels, the incidence of apical closure, and root volume (P < .05). There were no significant differences between the RET groups and the negative control group regarding linear measurements (ie, root length, root thickness, and apical closure) (P > .05). The root volumes of the 2 RET groups were similar (P > .05) and were less than those observed in the negative control group (P < .05)., Conclusions: There were no significant radiographic differences between the RET groups using periapical blood and circulating blood as scaffolds. RET resulted in less root volume compared with normal root development., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: This retrospective study compared changes in periapical trabecular patterns using fractal analysis and the periapical index (PAI) on the periapical radiographs of patients who underwent multivisit nonsurgical endodontic retreatment of persistent periapical disease., Study Design: In total, 50 participants were included in the study. For each patient, baseline periapical radiographs were acquired just before retreatment and postoperative radiographs were acquired 1 year later. The region of interest, located in the abnormal tissue around the root apex, was selected from each of the paired radiographs and the fractal dimension (FD) was calculated. Periapical status was classified using the PAI as "healed" (PAI <3) or "unhealed" (PAI ≥3)., Results: According to the PAI scores, retreatment after 1 year had a healing rate of 70%. In healed cases, the FD values increased significantly (P < .001), whereas FD decreased significantly in unhealed cases (P = .021). Change in FD was significantly different between healed and unhealed cases (P < .001). However, change in FD did not have a significant correlation with PAI in either healed or unhealed cases (P > .05). There was no significant effect of sex on the change in FD values in either healed or unhealed cases (P ≥ .690)., Conclusions: The significant differences in FD suggest that this parameter may be useful in detecting increased trabeculation and estimating retreatment prognosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to monitor the effects of chemomechanical preparation (CMP) performed with 6% sodium hypochlorite and calcium hydroxide-based intracanal medication (ICM) on the levels and diversity of bacteria, endotoxins (lipopolysaccharides [LPS]), and lipoteichoic acid (LTA) in root canals of teeth with symptomatic irreversible pulpitis., Methods: Samples were collected from 10 teeth with symptomatic irreversible pulpitis before CMP (S1), after CMP (S2), and after ICM (S3). The levels of bacteria, LPS, and LTA were assessed by using checkerboard DNA-DNA hybridization, LAL Pyrogent 5000, and enzyme-linked immunosorbent assay, respectively. Wilcoxon test, repeated-measures analysis of variance, and Tukey post hoc test were used for statistical analysis at a significance level of 5%., Results: Forty species were detected at S1. Two species were eliminated after CMP and 5 after ICM. Resistant and pain-related species were detected in the root canals. Higher levels of culturable bacteria were detected at S1. However, CMP and ICM effectively reduced the microbial load in the root canals. Higher levels of LPS and LTA were detected at S1. CMP was effective in reducing both LPS and LTA (P < .05). ICM produced additional reduction in the levels of LPS (P > .05) and LTA (P < .05)., Conclusions: Chemomechanical preparation using 6% sodium hypochlorite and calcium hydroxide-based intracanal medication were effective in reducing the levels of bacteria, LPS, and LTA in teeth with vital pulp and irreversibly inflamed pulp., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This randomized clinical trial aimed to compare the effectiveness of endodontic retreatment of teeth with posttreatment apical periodontitis (PTAP) performed in 1 visit versus 2 visits on the reduction of cultivable bacteria (colony-forming units [CFUs]), lipopolysaccharides (LPSs), lipoteichoic acid (LTA), and the periapical lesion volume (mm 3 ) after 18 months of follow-up., Methods: Forty patients diagnosed with PTAP were selected and randomly divided into the following 2 groups: 1-visit retreatment and 2-visit retreatment with the placement of calcium hydroxide medication for 14 days. Cone-beam computed tomographic scans were performed at 2 stages: preoperatively and after 18 months of follow-up. Samples were collected before and after root canal procedures. A chromogenic limulus amebocyte lysate assay test was used to quantify endotoxins (EU/mL). LTA levels were measured using the enzyme-linked immunosorbent assay (pg/mL). Culture techniques were used to determine cultivable bacteria by counting the CFU (CFU/mL). The volume of the periapical lesions at the onset of the trial and at the 18-month posttreatment follow-up was obtained by the ITK-SNAP program (Cognitica, Philadelphia, PA)., Results: All samples showed baseline values greater than those collected after the retreatment protocol for all investigated parameters. A higher bacterial load and lower LTA level were found in the 2-visit group after the retreatment protocol (P < .05), with no statistical differences between the groups regarding endotoxin levels and periapical lesion volume (mm³) at the 18-month follow-up analyzed by cone-beam computed tomographic imaging (P > .05)., Conclusions: Endodontic retreatment in 1 or 2 visits exhibited equally favorable periapical healing at 18 months, with no statistically significant differences between groups., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Although epigallocatechin-3-gallate (EGCG) from green tea has been successfully used in the prevention and treatment of several infectious and immunoinflammatory diseases because of its proven anti-inflammatory, antioxidant, antimicrobial, and antiresorptive role, its use as an intracanal dressing has not been proposed. The aim of this study was to develop a formulation based on EGCG for endodontic use by assessing its physicochemical and biological properties., Methods: Initially, physicochemical characterization of EGCG was performed by ultraviolet-visible and fluorescence spectroscopy to evaluate if the properties were maintained in acidic pH and time (1-6, 24, and 27 hours). After that, biological studies evaluated the developed formulation of EGCG at different concentrations (1.25, 5, 10, and 20 mg/mL). The tissue compatibility with subcutaneous tissue of mice was evaluated by plasma leakage after 24 hours and the examination of macroscopic and microscopic features at 7, 21, and 63 days after the insertion of polyethylene tubes containing the formulations. The repair of experimentally induced periapical lesions in dog's teeth by radiographic and histopathologic analysis was also evaluated. The scores were statistically analyzed by the chi-square and Fisher exact test. Analysis of variance followed by the Tukey posttest were used for the quantitative analysis. The significance level was 5%., Results: The physicochemical characterization performed under ultraviolet-visible spectrophotometry showed that the EGCG properties remained unaltered in acid pH and function of time, keeping its wavelength to 274 nm. Macroscopic parameters evaluated at 7, 21, and 63 days showed that all concentrations presented no epithelial ulceration or presence of mild superficial tissue necrosis, edema, or vascularization with no significant difference in the control group. During all periods of microscopic examination, all groups presented the absence of abscess foci and edema and the presence of fibrous capsule and neovascularization. The presence of reparative tissue with a gentle presence of neutrophilic inflammatory cells was also observed for all groups, except for the calcium hydroxide paste group, which presented a more pronounced inflammation and tissue necrosis at days 7 and 21 (P < .001). At day 63, all groups presented an absence of inflammatory infiltrate and necrosis. The evaluation of dog teeth showed that treatment with the EGCG formulation provided a reduction of the periapical radiolucent area and allowed the repair of apical and periapical tissues (P > .05)., Conclusions: The developed formulation based on EGCG from green tea presented physicochemical stability and tissue compatibility and provided the repair of periapical lesions when used as an intracanal dressing., (Copyright © 2021 American Association of Endodontists. All rights reserved.)

Introduction: Semaphorin 7A (SEMA7A) is a membrane-bound or secretory protein exerting multiple functions in the regulation of inflammation, neural degradation, and cancer progression. Human periapical lesions are chronic and infectious diseases mainly caused by bacteria. However, the involvement of SEMA7A in human periapical lesions is still unclear. This study aimed to explore the expression of SEMA7A in human periapical lesions accompanied by the potential association of SEMA7A with matrix metalloproteinase (MMP)-1 and MMP-3 during the progression of apical periodontitis., Methods: Samples of periapical lesions and healthy controls were collected. Total RNA and protein were extracted respectively for quantitative real-time polymerase chain reaction and Western blot analysis. Additionally, 6 healthy samples and 27 periapical lesion samples were fixed, dehydrated, and embedded for further histologic and immunochemical analysis. The expression of SEMA7A was quantified by average integrated optical density. Immunofluorescence analysis was conducted to explore the colocalization of SEMA7A/MMP-1 and SEMA7A/MMP-3., Results: Compared with healthy controls, the messenger RNA and protein expression of SEMA7A was markedly up-regulated in periapical lesions. A stronger expression of MMP-1, MMP-3, and inflammatory cytokines was exhibited in periapical lesions than in healthy groups. An increasing expression of SEMA7A can be observed in both the periapical granuloma group and the radicular cyst group compared with the normal group (P < .01). Immunofluorescence results showed the colocalization of SEMA7A with both MMP-1 and MMP-3 in vascular vessels and extracellular matrix., Conclusions: SEMA7A was up-regulated in periapical periodontitis and might be involved in the tissue destruction and infiltration of immune cells in periapical lesions., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The aim of this case series was to describe the endodontic management of 3 immature permanent teeth that sustained traumatic injuries and subsequently presented with complete ingrowth of mineralized tissue into the canal space. Ingrowth of bone/mineralized tissue into the canal has been considered a poor long-term outcome with an inherent risk of ankylosis. In cases 1 and 2, no endodontic treatment was undertaken, except for emergency management requiring splinting. The cases were followed for 36 and 23 months, respectively. No ankylosis was evident over the review period, and normal teeth eruption was apparent. In case 1, the tooth was treated orthodontically and was responsive to pulp sensibility testing. In both cases, there was an appearance of an internal periodontal ligament-like space on the inner root wall of the canal. In case 3, 2 years postinjury, pulp necrosis and apical periodontitis occurred, and the tooth was managed with regenerative endodontic treatment consistent with the European Society of Endodontology and the American Association of Endodontists guidelines/recommendations for a regenerative procedure. The case was followed for 8 years after regenerative endodontic treatment. No ankylosis was noted with normal eruption of the teeth. The tooth was responsive to pulp sensibility testing despite the ingrowth of mineralized tissue, which was confirmed clinically., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: We verified the association between selected bacterial profiles and levels of cytokines, chemokines, and the expression of signs and symptoms of primary endodontic infection with apical periodontitis., Methods: Samples were collected from 21 root canals, and macrophages were stimulated for 24 hours. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-10, IL-12p70, interferon gamma, and chemokine (C-C motif) ligand 2 (CCL2) were measured using cytometric bead array. We investigated the overlapping networks between cytokines and chemokines with regression analysis. Checkerboard DNA-DNA hybridization was used to assess 40 target bacteria species. Using factor analysis, bacterial species aggregated in 2 factors. The association of bacteria species-based factors on cytokine and chemokine levels and clinical features was estimated with regression analysis., Results: A negative relationship between IL-10 (anti-inflammatory cytokine) and CCL2, TNF-α, and IFN-γ (proinflammatory cytokines) (all P < .05) was observed. CCL2 was positively correlated with TNF-α (P < .01). Thirty-eight bacteria species were detected in primary endodontic infection with apical periodontitis. The first bacteria species-based factor was associated with the size of the radiolucent area (coefficient = 15.42) and tenderness to percussion/pain on palpation (coefficient = 20.79). The second factor was associated with CCL2 levels (coefficient = 1.28)., Conclusions: Different bacterial profiles can be differentially related to the expression of inflammatory proteins and the experience of clinical features., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Human-derived composite amnion-chorion membrane (ACM) has been used for various regenerative treatments. The aim of this pilot study was to investigate the effectiveness of the ACM as a scaffold for pulp regeneration in mature canine teeth., Methods: A total of 24 roots from mature premolars in dogs were included for regenerative procedures using blood clots (BC) (group 1, n = 8), collagen membrane (CM) (group 2, n = 8), and ACM (group 3, n = 8). Each tooth was left open through a buccal access to induce root canal infection and inflammation. The root canals were disinfected with 1.5% NaOCl and calcium hydroxide intracanal medicament. After 2 weeks, bleeding was evoked to induce blood clot formation (group 1) or before the placement of the membranes (groups 2 and 3). After 12 weeks, the animals were euthanized for histologic assessment. The histologic data including intracanal fibrous connective tissue, odontoblast-like cell lining, intracanal mineralized tissue, periapical inflammation, and apical closure were qualitatively and quantitively analyzed., Results: Histologic analysis revealed that intracanal fibrous connective tissue was identified in all groups, but a higher volume of the fibrous tissues was formed in the ACM group. Odontoblast-like cells were only observed in the ACM group. The intracanal mineralized tissue was observed only in the BC and CM groups. The BC group showed more periapical inflammation than the ACM group (P < .05). Apical closure was more often found in the CM group than the BC group (P < .05)., Conclusions: More intracanal fibrous tissue and odontoblast-like cell lining, and less periapical inflammation were observed after regenerative endodontic treatment in mature teeth using the ACM than blood clot alone or blood clot with collagen membrane. The use of the ACM may be useful for a cell-homing-based pulp regeneration in mature teeth., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to evaluate the accuracy of low-dose multidetector computed tomographic (LD-MDCT) imaging for the volumetric measurement of simulated periapical lesions., Methods: Eighteen monoradicular teeth were introduced in bone blocks, and periapical lesions were simulated at the periapical region of each tooth. All teeth were imaged using 4 acquisition protocols: large (dentoalveolar) field of view (FOV) cone-beam computed tomographic (CBCT) imaging (120 kV, 5 mA, and 0.2-mm voxel), small (dental) FOV CBCT imaging (90 kV, 10 mA, and 0.2-mm voxel), standard multidetector computed tomographic imaging (120 kV, 50 mA, and 0.62-mm voxel), and LD-MDCT imaging (120 kV, 10 mA, and 0.62-mm voxel). Tomographic images were evaluated by a single trained and calibrated examiner (intraclass correlation coefficient = 0.991) using ITK-SNAP segmentation software (University of Pennsylvania, Philadelphia, PA). The gold standard was obtained by the impressions of the lesions with regular fluid addition silicone and individual weighing using a precision analytical scale. Data were evaluated by the repeated measures analysis of variance test; the significance level was defined as P < .05., Results: No statistical differences (P > .05) were found among the groups regardless of the device, milliamperage, FOV, or voxel size., Conclusions: LD-MDCT shows performance comparable with other standard reference methods for measuring the volume of periapical lesions and can be a useful and safe protocol in clinical situations in which CBCT imaging is not available, such as in cases of patients admitted to hospitals., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Aim: To elucidate the presence of apical periodontitis in the root canal of teeth with secondary/persistent infection, including composition of microbiota, levels of endotoxins and lipoteichoic acid (LTA), and clinical implications of these findings., Method: Samples were collected from root canals of 50 patients who needed endodontic retreatment and had radiographic evidence of apical periodontitis. Microorganisms were identified by using the culture technique and biochemical tests. Nested-polymerase chain reaction (nested-PCR) was used to identify 17 species of specific bacteria. Lipopolysaccharides (LPS) and LTAs were quantified by using, respectively, limulus amebocyte lysate and enzyme-linked immunosorbent assay tests., Results: Bacteria were detected in all samples by culture and molecular methods. A total of 154 gram-positive strains, of 188 strains isolated, were found in the root canals by culture. Enterococcus faecalis and Gemella morbillorum were the most prevalent species identified by the biochemical tests, whereas molecular analyses (nested-PCR) showed a high frequency of P. gingivalis, E. faecalis, and Fusobacterium nucleatum. LPS and LTA were detected in all samples, with mean values being 3.52 EU/mL and 597.83 pg/mL, respectively. Significant statistical correlations were found between levels of LTA and clinical features., Conclusion: Despite the prevalence of gram-positives, the microbiota present in secondary/persistent infections showed a large variety of species. Within this diversity, associations were found between specific bacteria and clinical features. In addition, higher levels of LTA were statistically associated with larger periapical radiolucent areas, but no correlation between this feature and LPS was found., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Maternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP., Methods: Fifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05)., Results: Maternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring., Conclusions: Maternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice., Methods: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis., Results: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods., Conclusions: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to compare the immunoexpression of biomarkers interleukin (IL)-17, IL-6, and IL-1β in primary chronic apical periodontitis in smokers and nonsmokers., Methods: Teeth with primary chronic apical periodontitis indicated for extraction in 16 cigarette smokers and 16 nonsmokers were selected. Silanized sections of tissue were used for immunohistochemical analysis after being stained with hematoxylin-eosin for histopathologic categorization. Subsequently, the images were analyzed with an optical microscope, and each slide was subdivided into 5 high-magnification fields, with scores (0-2) being assigned according to the amount of staining for each antibody., Results: The qualitative analysis of IL-17 cytokine expression showed no focal expression in 5.8%, weak to moderate expression in 17.6%, and strong expression in 76.4% of the smokers and no focal expression in 78.5% and weak to moderate expression in 21.4% of the nonsmokers. IL-6 expression was negative to focal in 13.3%, weak to moderate in 53.3%, and strong in 33.3% of the smokers and negative to focal in 33.3%, weak to moderate in 25%, and strong in 41.6% of the nonsmokers. IL-1β expression was weak to moderate in 87.5% and negative to focal expression in 12.5% of the smokers and negative to focal expression in 100% of the nonsmokers. Quantitative evaluation of the data using the Mann-Whitney U test showed a significant difference in the immunoexpression of IL-17 (P < .0001) and IL-1β (P < .0001) and no significant difference in the immunoexpression of IL-6 (P = .46) between the 2 groups (P < .05)., Conclusions: The cytokines IL-17 and IL-1β were more highly expressed in smokers than nonsmokers, whereas IL-6 expression was similar in the 2 groups., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Dental pulp is a specialized tissue able to respond to infectious processes. Nevertheless, infection progress and root canal colonization trigger an immune-inflammatory response in tooth-surrounding tissues, leading to apical periodontitis and bone tissue destruction, further contributing to tooth loss. In order to shed some light on the effects of IL-4 on periradicular pathology development modulation, microtomographic, histological and proteomic analyses were performed using 60 mice, 30 wild type and 30 IL-4 - / - . For that, 5 animals were used for microtomographic and histological analysis, and another 5 for proteomic analysis for 0, 7 and 21 days with/without pulp exposure. The periapical lesions were established in WT and IL-4 - / - mice without statistical differences in their volume, and the value of p < 0.05 was adopted as significant in microtomographic and histological analyses. Regarding histological analysis, IL-4 - / - mice show aggravation of pulp inflammation compared to WT. By using proteomic analysis, we have identified 32 proteins with increased abundance and 218 proteins with decreased abundance in WT animals after 21 days of pulp exposure, compared to IL-4 - / - animals. However, IL-4 - / - mice demonstrated faster development of apical periodontitis. These animals developed a compensatory mechanism to overcome IL-4 absence, putatively based on the identification of upregulated proteins related to immune system signaling pathways. Significance: IL-4 might play a protective role in diseases involving bone destruction and its activity may contribute to host protection, mainly due to its antiosteoclastogenic action., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This case report describes the resolution of a 20-year misdiagnosed nasal sinus tract after root canal therapy with multiple sessions of calcium hydroxide (Ca[OH] 2 ) intracanal medication. Clinical evaluation, including diagnostic testing and sinus tract tracing, was performed followed by a cone-beam computed tomographic scan and 3-dimensional reconstruction of the apical lesion. Bacteria and endotoxin analyses were performed from the nasal sinus tract and paired root canal infection before (s1) and after instrumentation (s2) and after 7 (s3), 14 (s4), and 21 (s5) days of Ca(OH) 2 medication. The bacteria analysis was performed using the checkerboard DNA-DNA hybridization method and endotoxin quantified by the limulus amebocyte lysate method. A similar microbiota profile was found in the sinus tract and paired root canal infection. No target bacterial species were detected in the root canal at s2, s3, and s5. In contrast, Actinomyces israellii and Eubacterium nodatum were detected at s4. Differences in bacterial detection were found between s1 × s2, s3 × s4, and s4 × s5 (all P < .05). Endotoxin was detected in the root canal at all sampling times. Differences in the levels of endotoxin were found between s1 × s2, s2 × s3, and s3 × s4 (all P < .05).The bacterial analysis revealed similar microbiota profiles present in the nasal sinus tract and paired root canal infection with the participation of a wide variety of gram-positive and -negative species. Additionally, root canal therapy with multiple sessions of Ca(OH) 2 intracanal medication for 21 days was effective in disinfecting the root canal system and resolving the nasal sinus tract., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the effects of a high-fat diet (HFD) on the progression of apical periodontitis (AP), local inflammation, systemic antioxidant status, and blood lipid profile in rats., Main Methods: Sixteen male Wistar rats were fed a standard diet (SD) or a HFD. At the sixth experimental week, the pulp chambers of the mandibular first molars were exposed to develop AP. A glucose tolerance test was performed the week before euthanasia. At the tenth experimental week, the animals were euthanized and the livers were collected to estimate catalase (CAT) and reduced glutathione (GSH) levels. Blood was acquired for biochemical analysis. The size of AP was estimated from radiographs and described as AP size-to-body weight ratio; inflammatory grade of AP was determined by histological analysis., Key Findings: At the end of the experimental period, the rats fed the HFD had 30% less weight (P < 0.0001) and higher blood glucose levels after 30 min of sucrose intake (P < 0.05) than those fed the SD. Animals from the HFD group had lower levels of CAT (P < 0.01), but the same was not observed in the GSH levels. Plasma insulin and total cholesterol were not affected by the diet. The rats fed the HFD presented greater AP than those fed the SD (P < 0.05). However, the local inflammatory infiltrate was similar in both groups., Significance: The alterations promoted by the consumption of a HFD were not only observed systemically, but also locally, producing greater AP in rats than a SD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Guided endodontics has been used for the treatment of anterior teeth with a successful outcome. This approach is not only limited to anterior teeth because it can also be used for the treatment of premolars and molars. However, in such cases, space may be a limitation because a long bur has to be used in addition to the guide being placed on top of the teeth. The aim of this case report was to present a novel guided endodontics technique using a sleeveless 3-dimensional-printed guide. This design can reduce vertical space, allowing an open view of the tooth and irrigation during drilling. A 46-year-old female patient consulted the endodontic department with intermittent pain around tooth #5. Tooth #5 presented pain upon percussion and responded negative to a cold test. The initial periapical radiograph revealed an apical radiolucency with pulp canal obliteration. Clinically, there was no sinus tract. The tooth was diagnosed with pulp necrosis and symptomatic apical periodontitis. Guided endodontic treatment was performed with a sleeveless 3-dimensional-printed guide and long neck carbide bur with a head diameter of 1 mm to drill a minimally invasive access cavity up to the root canal. A completely healed apical area of tooth #5 was visible after 1 year on periapical radiographs. This technique seems to be a promising alternative in comparison with the conventional guided endodontic guide design for the negotiation of pulp canal obliteration in cases in which vertical space is limited., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients seeking endodontic treatment commonly present with reduced mechanical pain thresholds (ie, mechanical allodynia [MA]) in the offending teeth. In patients with moderate to severe pain, MA may manifest in the teeth contralateral to the offending teeth because of the onset of central sensitization (CS). We hypothesize that there are quantitative differences in MA and CS in patients with different pulp and periradicular diagnoses., Methods: Patients (n = 70) receiving endodontic treatment in the graduate endodontic clinic at the University of Texas Health Science Center at San Antonio and healthy volunteers (n = 10) were included in this cross-sectional study. The mechanical pain threshold from molar teeth was measured by a digital bite force transducer on the offending tooth (ipsilateral) and the contralateral tooth. Ipsi- and contralateral MA among different endodontic diagnoses were analyzed using the Kruskal-Wallis with Dunn post hoc test and the Student t test for differences between sexes. Multivariate regression models analyzed predictors for MA and CS., Results: Periradicular diagnoses of asymptomatic apical periodontitis, symptomatic apical periodontitis, and chronic apical abscess cases were significantly associated with MA. CS, seen as contralateral MA, was only detected in pulpal diagnosis of symptomatic irreversible pulpitis, previously initiated treatment, symptomatic apical periodontitis, and chronic apical abscess. Females experienced significantly lower pain thresholds than males on both sides. MA and CS were significantly correlated in both sexes. The preoperative pain level and duration were significant predictors for MA and CS only in female patients. Lastly, age was a significant predictor for MA in females., Conclusions: The magnitude of MA and CS varied with different endodontic diagnoses, with CS being correlated with increases in MA. Only in female patients were age, preoperative pain duration, and intensity significant predictors for the development of MA and CS., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Cell therapy in regenerative endodontics introduces an alternative option to classic treatment strategies for complex endodontic cases. The aim of this case report was to describe cell-based therapy using allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) encapsulated in a bioscaffold for a complex case of a mature permanent tooth with apical periodontitis and accidental root perforation., Methods: A healthy 19-year-old man undergoing orthodontic treatment was referred for endodontic treatment in tooth #7; he was diagnosed with apical periodontitis during a previously initiated treatment associated with accidental perforation of the radicular cervical third. The root perforation was sealed with glass ionomer and composite resin, and the root canal was instrumented, disinfected, and dressed with calcium hydroxide. After 3 weeks, allogeneic UC-MSCs were encapsulated in platelet-poor plasma and then implanted into the root canal, and Biodentine (Septodont, Saint-Maur-des-Fosses, France) was placed below the cementoenamel junction. Finally, the tooth was restored with composite resin., Results: Follow-up examinations were performed 6 months and 1 year later. The examinations included periapical radiography, cone-beam computed tomographic imaging, and sensitivity and vitality tests. Radiographic and cone-beam computed tomographic images indicated remission of the apical lesion. Clinical evaluations revealed normal responses to percussion and palpation tests; the tooth was responsive to the electric pulp test, and the vitality test indicated low blood perfusion units., Conclusions: This case report reveals the potential use of allogeneic cellular therapy using encapsulated UC-MSCS in a platelet-poor plasma scaffold for a complex case of a permanent tooth with apical periodontitis and root perforation., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

External root resorption (ERR) is often a complication of traumatic injury to the teeth. Traditionally, external inflammatory root resorption is treated with calcium hydroxide. The outcome of ERR, especially replacement resorption, is unpredictable. The purpose of the present case report was to describe regenerative endodontic procedures (REPs) for 1 replanted avulsed tooth with severe external root resorption and root perforation (tooth #9) and 1 extruded tooth (tooth #8). A 9-year-old girl was referred for the treatment of teeth #8 and #9 4 months after the initial trauma. Clinical examination showed that tooth #9 had a sinus tract present near the periapical area, was tender to percussion and palpation, and did not respond to pulp sensibility tests. Tooth #8 responded to pulp sensibility tests. Periapical radiographic and cone-beam computed tomographic examination showed that tooth #9 had a periapical radiolucent lesion and severe ERRs with a root perforation. Tooth #9 was diagnosed with a necrotic pulp and symptomatic apical periodontitis. Regenerative endodontic procedures (REPs) were initiated. Tooth #8 became nonresponsive to pulp sensibility tests and developed a periapical lesion 12 months after REPs of tooth #9 and was also treated with REPs. The clinical symptoms and apical lesions resolved for both teeth after REPs. The severe ERRs were arrested, and root perforation was repaired for tooth #9. Teeth #8 and #9 underwent canal obliteration by hard tissue formation after REPs and were in function at 18 months and 30 months, respectively. REPs may be used to manage traumatized immature permanent teeth with a necrotic pulp and apical periodontitis associated with severe ERR and root perforation., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of the present study was to compare the immunomodulatory effect of azithromycin (AZM), ampicillin (AMP), amoxicillin (AMX), and clindamycin (CLI) in vitro and AZM on preexisting periapical lesions compared with AMP., Methods: The susceptibility of 4 common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disk diffusion assay. Preexisting periapical lesions in C57BL/6J mice were treated with AZM, AMP, or phosphate-buffered saline (PBS). Periapical bone healing and the pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro-computed tomographic and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated nuclear factor kappa B activation and the production of interleukin 1 alpha and tumor necrosis factor alpha was assessed in vitro by luciferase assay and enzyme-linked immunosorbent assay., Results: All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI. AZM significantly attenuated periapical bone loss versus PBS. PBS resulted in widely diffused infiltration of mixed inflammatory cells. By contrast, AZM brought about localized infiltration of neutrophils and M2 macrophages and advanced fibrosis. Although the effect of AMP on bone was uncertain, inflammatory cell infiltration was considerably milder than PBS. However, most macrophages observed seemed to be M1 macrophages. AZM suppressed pathogen-stimulated nuclear factor kappa B activation and cytokine production, whereas AMP, AMX, and CLI reduced only cytokine production moderately., Conclusions: This study showed that AZM led to the resolution of preexisting experimental periapical inflammation. Our data provide a perspective on host response in antibiotic selection for endodontic treatment. However, well-designed clinical trials are necessary to better elucidate the benefits of AZM as an adjunctive therapy for endodontic treatment when antibiotic therapy is recommended. Although both AZM and AMP were effective on preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to summarize data on apical periodontitis (AP) and nonsurgical root canal treatment (NSRCT) prevalence and risk factors related to age, gender, and quality of restorative and endodontic treatment in the general population from cross-sectional studies published between 2012 and 2020., Methods: An electronic search was performed in the following databases: Web of Science, Scopus, and PubMed. The conducted literature search covered studies published between 2012 and 2020, without restrictions on language. The STROBE and NOS tools were used for quality assessment of the included studies., Results: Sixteen articles were included in the review. In total, 200,041 teeth were examined. On average, 6.3% of teeth had AP, and 7.4% had NSRCT. Forty-one percent of RCT teeth had AP, and 3.5% of untreated teeth had AP. Female patients were less prone to AP in endodontically treated teeth only, compared with male patients (P < .001). Variable stratification of age subgroups among included studies prevented us from conducting a meta-analysis. An increase in AP frequency was found in teeth with inadequate restorative and endodontic treatment (P < .001 and P < .001, respectively). Because of high heterogeneity, these results should be taken with caution., Conclusions: There is an increased AP prevalence in the adult general population compared with data from 2012 (6.3% versus 5.4%) in both endodontically treated (41.3% versus 35.9%) and untreated teeth (3.5% versus 2.1%). In addition, AP developed less frequently in female patients with endodontically treated teeth and in teeth with inadequate compared with adequate restorative and endodontic treatment., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study compared the main clinical, radiographic, and histologic features of true and bay apical cysts., Methods: The study material comprised 95 biopsy specimens of apical periodontitis lesions obtained attached to the root tip of both untreated and root canal-treated teeth. Clinical and radiographic data were recorded. Specimens were obtained by extraction or periradicular surgery and were meticulously processed for histopathologic and histobacteriologic methods. All cases diagnosed as apical cysts (n = 23) were divided into the true and bay types, which were then compared for tooth location, patient's sex, lesion size, severity of clinical symptoms, presence of a sinus tract, previous abscess episodes, and prevalence of bacteria in the main root canal lumen and ramifications, on the outer root surface, and within the cyst cavity., Results: Eleven specimens were classified as true (48%) and 12 (52%) as bay cysts. Bacteria were found in all specimens, regardless of the histopathologic diagnosis. Planktonic bacteria were observed in the main root canal in all true cysts and in 11 of 12 (92%) bay cyst cases. Biofilms were detected in the main canal in 10 cases from each diagnostic group and were frequently observed in ramifications. Extraradicular biofilms occurred in a few specimens only. Bacteria were visualized within the cavity of both true (4/11, 36%) and bay (6/12, 50%) cyst specimens. The severity of histologic inflammation was always high. There were no significant differences between true and bay cysts for all the clinical, radiographic, histopathologic, and histobacteriologic parameters assessed., Conclusions: Except for the morphologic relationship of the cyst cavity with the root canal space, true and bay cysts exhibited no other significant differences in the various parameters evaluated. The 2 cyst types were always associated with an intraradicular infection and sometimes with an extraradicular infection. Findings question the need to differentiate true and bay cysts and do not support the assumption that true cysts are self-sustainable entities not maintained by infection., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study evaluated the microbiological conditions of the apical root canal system of teeth with posttreatment apical periodontitis and correlated them with observations from cone-beam computed tomographic (CBCT) imaging, micro-computed tomographic (micro-CT) imaging, and histopathology., Methods: Root apices were obtained from 36 root canal-treated teeth subjected to periradicular surgery. CBCT examination was available before surgery. The apical root specimens were scanned in a micro-CT device and then cryopulverized. The powder was subjected to DNA extraction for real-time polymerase chain reaction quantification of total bacteria, Streptococcus species, members of the phylum Actinobacteria, and Enterococcus faecalis. Microbiological findings were evaluated for associations with CBCT, micro-CT, and histopathologic data. An association between lesion size and the proportion of unfilled apical canal system volume was also assessed., Results: All cryopulverized specimens were positive for total bacteria. Actinobacteria and streptococci occurred in 35 and 33 specimens, respectively, and were usually dominant in the community. Actinobacteria counts were 2.23 times higher in granulomas than in cysts. Streptococci were significantly more present in small lesion cases. E. faecalis was detected in only 7 samples, always as a dominant community member. The association of total bacteria, streptococci, and Actinobacteria counts with the unfilled canal volume was significant in the univariate analyses but not confirmed in the adjusted analyses. Large lesions were significantly associated with a higher volume of unfilled apical canals., Conclusions: Bacterial infection occurred in all root apices, with high prevalence and dominance of Actinobacteria and streptococci. The volume of the unfilled apical canal system was significantly associated with the lesion size and possibly with bacterial counts. Findings illustrate the need to thoroughly disinfect and fill the apical root canal of infected teeth during endodontic therapy., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This randomized clinical study compared the in vivo antibacterial efficacy of Reciproc Blue (RB), XP-endo Shaper (XP-S), and XP-endo Shaper associated with XP-endo Finisher (XP-F) systems in infected oval-shaped root canals with primary apical periodontitis., Methods: In this study, 28 human teeth with a single root and a single canal were randomly assigned to 2 groups according to the instrumentation technique: group 1, RB (n = 14) and group 2, XP-endo (XP-S and XP-F, n = 14). The single-rooted teeth were prepared by reciprocating and rotary nickel-titanium instruments with 5.25% sodium hypochlorite irrigation. Samples were collected from the canal at the baseline (S1), after chemomechanical preparation (S2), and after XP-F instrumentation (S3). The DNA extracts were subjected to quantitative analysis for total bacterial counts by quantitative real-time polymerase chain reaction. The data were analyzed using the analysis of variance test, and the level of significance was set at 5%., Results: All samples tested positive for the presence of bacteria at baseline, and the bacterial counts substantially reduced after treatment procedures (P < .01). The results showed no statistical difference between RB and XP-S instrumentation with respect to the bacterial reduction (P > .05). A marked bacterial reduction was observed after the use of the XP-F instrument (P < .01)., Conclusions: The XP-S and RB systems sharply reduced the bacterial load in oval-shaped root canals with primary apical periodontitis. XP-F used as a supplementary instrument to chemomechanical preparation promoted a significantly higher bacterial reduction., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study assessed the cleaning, shaping, and disinfection abilities of 2 instrumentation systems in molar root canals using a novel correlative analytical approach., Methods: The root canals from extracted mandibular and maxillary molars with apical periodontitis were pair matched according to anatomic similarities as determined by micro-computed tomographic analysis and prepared with either XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (n = 16) or Reciproc Blue (VDW, Munich, Germany) (n = 16) instruments and 2.5% sodium hypochlorite irrigation. Pre- and postpreparation micro-computed tomographic scans were used to identify and calculate the unprepared surface areas (shaping), which were histobacteriologically evaluated for the presence of residual bacteria (disinfection) and pulp tissue remnants (cleaning) in each canal third., Results: Unprepared canal surface areas for XP-endo Shaper and Reciproc Blue in the full canal length were approximately 26% and 19% (P < .05), respectively (30% and 23% in the apical part of the canal, P > .05). Preparation with Reciproc Blue resulted in 37.5% canals free of bacteria in all sections examined and 56% in the apical sections only. XP-endo Shaper resulted in 44% canals free of bacteria in all sections, and 56% in the apical part of the canal only. Pulp tissue remnants were not observed in 31% (all canal sections) and 50% (apical canal sections) of specimens from both instrument systems. No significant differences were observed between instruments when comparing the amount of pulp tissue remnants and the number of cases negative for bacteria and tissue remnants (P > .05)., Conclusions: Although the Reciproc Blue instrument had superior shaping ability in comparison with XP-endo Shaper, both systems performed similarly in cleaning and disinfecting root canals. Irregular canals and difficult-to-reach areas were not thoroughly cleaned and disinfected by any of the tested systems., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study radiographically analyzed the prevalence of root canal treatment (RCT) and apical periodontitis (AP) in type 1 diabetes mellitus (T1DM) and nondiabetic individuals and its association with the history/current status of T1DM., Methods: In a cross-sectional paired study, the radiographic records of 50 individuals with T1DM and 100 age- and sex-matched nondiabetic subjects were examined. The presence of RCT and AP was evaluated. Information regarding the history and current status of T1DM was collected from the medical records of each patient., Results: One or more RCTs were found in 76% and 44% of diabetic and nondiabetic subjects, respectively (P = .000). AP in 1 or more teeth was found in most T1DM patients (58%) and in 15% of the control subjects (P = .000). One or more RCTs associated with AP were found in 52% and 8% of T1DM and nondiabetic subjects, respectively (P = .000). Bivariate logistic regression analyses suggested that RCT (odds ratio [OR] = 10.435, P = .000), AP (OR = 3.508, P = .011), and RCT + AP (OR = 7.220, P = .000) were significantly associated with the presence of T1DM. Multivariate logistic regression showed that among T1DM individuals, there is an association between 11-15 years of diagnosis time and at least 1 RCT (OR = 46.316, P = .038) and an association between T1DM control and at least 1 tooth with AP (OR = 15.611, P = .016)., Conclusions: RCT, AP, and RCT with AP were more prevalent in individuals with T1DM than in nondiabetic individuals. RCT and AP were associated with the presence of T1DM, specifically RCT with diagnostic time and AP with glycemic control., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: Fused root variations of the root canal system increase the complexity of the inner root canal system anatomy. The aim of the present study was to determine, in in vivo conditions, the proportion of periapical lesions in association with endodontically treated maxillary and mandibular molars with fused roots presenting previous root canal treatment by assessing preexisting data via cone-beam computed tomographic volumes., Methods: A total of 1160 CBCT scans with an overall sample of 20,836 teeth were screened. A global count of 3701 maxillary molars and mandibular second molars were included in the study. The Cohen kappa test and interclass correlation coefficient tested the intra- and interrater reliability, respectively. The percentage of periapical lesions associated with molars with or without root fusion was determined. Proportions were expressed with 95% confidence intervals (CIs). The z test for proportions was used to analyze differences between subgroups, and an odds ratio was calculated in order to understand the association between periapical lesions and root configuration., Results: Fused molars presented a prevalence of periapical lesions in endodontically treated teeth of 74.0% (95% CI, 65.2%-82.8%), whereas nonfused molars had a proportion of periapical lesions in root canal-treated teeth of 69.5% (95% CI, 65.2%-73.8%; P > .05). Endodontically treated molars with fused roots presented with 1.3 higher odds of being associated with periapical lesions than endodontically treated molars with nonfused roots., Conclusions: A tendency of a higher proportion of periapical lesions was found in the fused rooted molars with a history of root canal treatment when compared with nonfused teeth; however, no statistically significant difference was noted., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)