Impact of systemic health on treatment outcomes in endodontics.

BACKGROUND: The healing of periapical lesions after root canal treatment (RCT) is not the result of the curative action of the treatment. The process of healing begins with inflammation, and is resolved by the clearance of the immunogen that induces the immune response. Then, the periapical tissue itself carries out the healing of the periapical lesion, by repair or by a combination of repair and regeneration, depending on the host's reparative response working properly. The ultimate objective of RCT is to achieve wound healing by removing the source of bacterial antigens and toxins, allowing chronic inflammatory tissue to become reparative tissue. Some systemic conditions increase the susceptibility of the host to infection or impair the tissue reparative response, maintaining the inflammatory process and periapical bone resorption after RCT. This can cause the failure of RCT and even the need for extraction of the affected tooth. OBJECTIVE: To analyse the scientific literature on the possible influence of systemic conditions on the treatment outcomes in endodontics, as well as to discuss the biological mechanisms that may be involved. METHODS: The search was carried out in PubMed, SCOPUS and EMBASE. The inclusion criteria established were original scientific articles reporting data about some systemic condition in relation to treatment outcomes in endodontics, including clinical studies and studies carried out in animal models. RESULTS: Systemic factors (age, nutrition, stress, hormones, smoking habits), and systemic diseases, such as diabetes, cardiovascular diseases, osteoporosis, HIV infection, inflammatory bowel disease, and others, can influence or interfere in the repair of periapical tissues after RCT. DISCUSSION: Some of these systemic diseases can alter bone turnover and fibroblast function, preventing or delaying periapical wound healing. Others can alter the microvasculature, reducing nutrients and oxygen supply to periapical tissues. As a result, these systemic conditions can decrease the success rate of RCT and provoke incomplete wound healing (typically granulomatous tissue formation) in the periapical region. CONCLUSIONS: The results of this narrative review show worse success rate of RCT, with higher percentage of postoperative radiolucent periapical lesions and higher proportion of non-retained teeth (RFT), associated with several systemic conditions, such as smoking habits and diabetes.

Periapical and endodontic status of patients with inflammatory bowel disease: Age- and sex-matched case-control study.

AIM: Crohn's disease (CD) and ulcerative colitis (UC) are two chronic recurrent inflammatory processes of the gastrointestinal tract, grouped under the name inflammatory bowel disease (IBD), causing clinical episodes of intestinal inflammation. The aim of this study was to investigate the possible association between IBD and the prevalence of apical periodontitis (AP) and root canal treatment. METHODOLOGY: A case-control study design matched to age and sex was used. The study group (SG) included 28 patients with IBD (13 with CD, 15 with UC). Another 28 healthy subjects, without IBD and age- and sex-matched, were included in the control group (CG). Radiographic records were analysed and AP was diagnosed as radiolucent periapical lesions (RPLs), using the periapical index score. Student's t-test, χ2 test and multivariate logistic regression were used in the statistical analysis. RESULTS: In the CG, only 17 subjects (61%) had at least one tooth with AP, whilst in the SG group they were 23 patients (82%; OR = 2.98; 95% CI = 0.87-10.87; p = .08). The number of subjects with one or more root filled teeth (RFT) in the CG was 14 (50%), whilst in the SG they were 22 (79%; OR = 3.67; 95% CI = 1.14-11.79; p = .026). At least one RFT with AP was evident in three subjects (10.7%) in the CG, whilst in the SG 15 patients (53.6%) showed RFT with AP (OR = 9.60; 95% CI = 2.35-39.35; p = .001). In the multivariate logistic regression analysis, only endodontic status was found to be associated with IBD (OR = 1.86; 95% CI = 1.24-2.80; p = .003). CONCLUSION: IBD, UC and Crohn's disease are associated with higher prevalence of RFT and higher percentage of RFT with periapical lesions. Dentists should consider these findings when caring for IBD patients by monitoring the evolution of periapical lesions of endodontically treated teeth.

Biomaterials in periapical regeneration after microsurgical endodontics: A narrative review.

BACKGROUND: The objective of this narrative review was to analyze the available scientific evidence regarding the application of biomaterials in endodontic microsurgery and its influence in post-surgical tissue repair. MATERIAL AND METHODS: The review question was Do biomaterials used in endodontic microsurgery influence post-surgical tissue repair and regeneration? Systematic MEDLINE/PubMed review was used to evaluate and present the results. RESULTS: The search yielded 131 references, 82 of which were selected for full text review after reading the abstracts. After a manual search in the references of the articles selected, 52 references were eliminated. Finally, 30 articles were selected. CONCLUSIONS: Bone grafts, membranes and bioceramics, especially MTA, are biomaterials with the ability to stimulate periapical tissue regeneration. This is one of many reason why bioceramics are the best choice as retrograde sealing materials. However, microsurgically treated periapical lesions can heal completely without the need to use bone grafts or membranes. Those techniques are indicated in endodontic microsurgery when additional stimulation of tissue regeneration is required, or when bone collapse needs to be prevented. Key words:Bioactive endodontic cements, endodontic surgery, periapical repair.

Smoking and Radiolucent Periapical Lesions in Root Filled Teeth: Systematic Review and Meta-Analysis.

AIM: This systematic review and meta-analysis aimed to investigate the association between smoking habits and the prevalence of radiolucent periapical lesions (RPLs) in root-filled teeth (RFT). METHODS: The Population, Intervention, Comparison, and Outcome (PICO) question was: in adult patients who have RFT, does the absence or presence of a smoking habit affect the prevalence of RPLs associated with RFT? Systematic MEDLINE/PubMed, Wiley Online Database, Web of Science, Scopus, and PRISMA protocol were used to evaluate and present the results. Studies comparing smokers with control non-smoker subjects, including RFT, and providing data on the prevalence of RFT with RPLs, were included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for certainty in the evidence. The risk of bias was assessed according to Cochrane Collaboration common scheme for bias and ROBINS-I tool. Cumulative meta-analysis was performed with a random effects model. PROSPERO registration code: CRD42020165279. RESULTS: Four studies reported data on inclusion criteria, representing data from 9257 root-filled teeth-4465 from non-smokers and 4792 from smoker patients. The meta-analysis provided an odds ratio indicating a significant association between smoking and higher prevalence of root filled teeth with radiolucent periapical lesions (OR = 1.16; 95% CI = 1.07-1.26; p = 0.0004). The certainty of the literature assessment was moderate per GRADE. The ROBINS-I tool classified three studies as low risk of bias, and the fourth as moderate risk of bias. CONCLUSIONS: Moderate, quality scientific evidence indicates a weak but significant relationship between smoking and the prevalence of RPLs in RFT. Smoking can be considered a negative prognostic factor for the outcome of root canal treatment. Endodontic providers should be aware of the relationship between smoking and persistent apical periodontitis, assessed as RPLs, in RFT.

Cigarette Smoking and Root Filled Teeth Extraction: Systematic Review and Meta-Analysis.

AIM: The aim of this systematic review and meta-analysis was to investigate the possible association between smoking habits and the occurrence of root-filled teeth (RFT) extraction. MATERIAL AND METHODS: The Population, Intervention, Comparison, and Outcome (PICO) question was in adult patients who had RFT, does the absence or presence of smoking habits affect the prevalence of extracted RFT? Systematic MEDLINE/PubMed, Wiley Online Database, Web of Science, and PRISMA protocol was used to evaluate and present the results. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for certainty in the evidence. The risk of bias was assessed according to Cochrane Collaboration common scheme for bias and ROBINS-I tool. Cumulative meta-analysis was performed with a random effects model. PROSPERO registration code: CRD42020165279. RESULTS: After search strategy, 571 articles were recovered, seven were selected for full-text analysis, and two reported data on inclusion criteria, including 516 RFT, 351 in non-smokers, and 165 in smoker subjects. The meta-analysis provided an odds ratio indicating significant association between smoking and the prevalence of extracted RFT (OR = 3.43, 95% CI = 1.17-10.05, p = 0.02, I² = 64%). The certainty of the literature assessment was low per GRADE. Both studies were considered as moderate risk of bias. CONCLUSIONS: Tobacco smoking should be considered a negative prognostic factor for the outcome of root canal treatment, although the quality of the evidence is low. RFT of smoking patients are three times more likely to be extracted. Continuing to smoke after endodontic treatment may increase the risk of treatment failure. However, the overall strength of evidence is low. This must be considered a limitation of the present study and the conclusion should be valued with caution.

Expression and immunohistochemical localization of leptin in human periapical granulomas.

BACKGROUND: Leptin, initially described as an adipocyte-derived hormone to regulate weight control, is expressed in normal and inflamed human dental pulp, being up-regulated during pulp experimental inflammation. Leptin receptor (LER) has been identified in human periapical granulomas. The aim of this study was to analyze and characterize the expression of leptin in human periapical granulomas. MATERIAL AND METHODS: Fifteen periapical inflammatory lesions were obtained from extracted human teeth and teeth which underwent periapical surgery. After their morphological categorization as periapical granulomas and gradation of the inflammatory infiltrate, they were examined by immunohistochemistry using human leptin policlonal antibodies. Leptin mRNA expression was also determined by quantitative real-time PCR (qRT-PCR) and the amount of leptin protein was analyzed by immunoblot. RESULTS: All periapical lesions exhibited the characteristic of chronic granulomatous inflammatory process with inflammatory infiltrate grade III. Leptin+ cells were detected in 13 periapical granulomas (86.6%). The median number of Leptin+ cells in periapical granulomas was 1.70 (0.00-7.4). Amongst the inflammatory cells in the periapical granulomas, only macrophages were reactive to leptin antibodies. Western blot analysis revealed the presence in all samples of a protein with apparent molecular weight of approximately 16 kDa, corresponding to the estimated molecular weights of leptin. The expression of leptin mRNA was confirmed by qRT-PCR analysis and the size of the amplified fragment (296 bp for leptin and 194 bp for cyclophilin) was assessed by agarose gel electrophoresis. CONCLUSIONS: For the first time, it has been demonstrated that human periapical granuloma expresses the adipokine leptin.

Leptin receptor is up-regulated in inflamed human dental pulp.

INTRODUCTION: After leptin receptor (LEPR) identification in hematopoietic, immune system, and other tissues, a role for leptin regulating inflammation and immune response has been accepted. This study aims to describe the possible expression of LEPR in healthy human dental pulp and to compare it with LEPR expression in inflamed human dental pulp. METHODS: Twenty-one pulp samples were obtained from freshly extracted caries-free and restoration-free human third molars. In 7 third molars (inflamed pulp group), inflammation was experimentally induced before extraction. Pulp samples were processed, and LEPR expression was determined by quantitative real-time polymerase chain reaction, and the amount of LEPR protein was analyzed by immunoblot. RESULTS: All healthy and inflamed dental pulp samples expressed LEPR. Western blot analysis of human dental pulp revealed the presence of a protein with an apparent molecular weight of approximately 120 kDa, which corresponds to the estimated molecular weight of LEPR. The expression of LEPR mRNA was confirmed by quantitative real-time polymerase chain reaction analysis, and the size of the amplified fragment (338 base pairs for LEPR and 194 base pairs for cyclophilin) was assessed by agarose gel electrophoresis. The relative amount of LEPR in inflamed pulps was approximately 50% higher than in healthy pulps (P < .05). CONCLUSIONS: The presence of LEPR in human dental pulp tissues has been demonstrated for the first time. The up-regulation of LEPR expression in inflamed pulp samples suggests that leptin can play a role in inflammatory and local immune responses in human dental pulp.

Tobacco smoking and radiographic periapical status: a retrospective case-control study.

INTRODUCTION: The aim of this study was to investigate radiographically the relationship of tobacco smoking and periapical status by using a retrospective case-control study design. METHODS: The records of 79 controls and 79 age- and sex-matched cases were examined. Case was defined as a patient who has at least 1 radiographically detectable periapical lesion in a tooth. Control was defined as a patient who has no radiographically detectable periapical lesion in any teeth. Periapical status was assessed by using panoramic radiographs and the periapical index score. The history of smoking and diabetes, the number of teeth and root-filled teeth, and the quality of root fillings were recorded. Statistical analyses were conducted by using the Cohen kappa test, χ(2) test, Student's t test, and logistic regression analysis. RESULTS: Among the case subjects, 75% had antecedents of smoking, whereas in the control group only 13% had been smokers (odds ratio, 20.4; 95% confidence interval, 8.8-46.9; P = .0000). After multivariate logistic regression analysis adjusting for covariates (age, gender, number of teeth, root-filled teeth, root-filled teeth with a root filling technically unsatisfactory, and diabetes), a strong association was observed between the presence of at least 1 radiographically detectable periapical lesion and antecedents of smoking (odds ratio, 32.4; 95% confidence interval, 11.7-89.8; P = .0000). CONCLUSIONS: After adjusting for age, gender, number of teeth, endodontic status, quality of root filling, and diabetic status, tobacco smoking is strongly associated with the presence of radiographically diagnosed periapical lesions.