The ‘Focal Infection Era in Dentistry’ in the late 19th and early 20th century resulted in widespread implementation of tooth extraction and limited the progress of endodontics. The theory proposed that bacteria and toxins entrapped in dentinal tubules could disseminate systemically to remote body parts, resulting in many types of degenerative systemic diseases. This theory was eventually refuted due to anecdotal evidence. However, lately there has been increased interest in investigating whether endodontic disease could have an impact on general health. There are reviews that have previously been carried out on this subject, but as new data have emerged since then, this review aims to appraise the available literature investigating the dynamic associations between apical periodontitis, endodontic treatment, and systemic health. The available evidence regarding focal infection theory, bacteraemia and inflammatory markers was appraised. The review also collated the available research arguing the associations of apical periodontitis with cardiovascular diseases, diabetes mellitus, adverse pregnancy outcome and autoimmune disorders, along with the effect of statins and immunomodulators on apical periodontitis prevalence and endodontic treatment prognosis. There is emerging evidence that bacteraemia and low-grade systemic inflammation associated with apical periodontitis may negatively impact systemic health, e.g., development of cardiovascular diseases, adverse pregnancy outcomes, and diabetic metabolic dyscontrol. However, there is limited information supporting the effect of diabetes mellitus or autoimmune disorders on the prevalence and prognosis post endodontic treatment. Furthermore, convincing evidence supports that successful root canal treatment has a beneficial impact on systemic health by reducing the inflammatory burden, thereby dismissing the misconceptions of focal infection theory. Although compelling evidence regarding the association between apical periodontitis and systemic health is present, further high-quality research is required to support and establish the benefits of endodontic treatment on systemic health.

Aim: The aim of the study was to measure serum levels of molecular markers of inflammation in patients undergoing non‐surgical root canal retreatment (Re‐RCT) and periapical surgery (PS) for the treatment of apical periodontitis and to establish if such levels are influenced by the size of apical radiolucencies at baseline and by the treatment outcome.Methodology: A total of 115 participants were recruited (n = 50 Controls, n = 35 Re‐RCT, n = 30 PS). Preoperative periapical radiographs and cone beam CT (CBCT) scans of teeth were taken. Blood was collected from treatment groups at baseline, 3‐, 6‐, and 12‐month post‐treatment and from controls at baseline and 12 months. Serum levels of IL‐1β, IL‐6, IL‐8, TNF‐α, Pentraxin 3, ICAM‐1, VCAM‐1, hs‐CRP, FGF‐23, MMP‐2, MMP‐8, MMP‐9, C3 and ADMA were analysed using multiplex immunoassay and enzyme‐linked immunosorbent assay. Different time points within the same group were compared using Wilcoxon signed‐rank test, and differences between groups were analysed using the Mann–Whitney test. Non‐linear association between different factors was assessed using Spearman's correlation.Results: Preoperative serum levels of FGF‐23, IL‐1β, hs‐CRP and ADMA were significantly higher in the diseased groups compared with controls (p < .001; p = .008; p < .001; p = .013, respectively). The preoperative size of the radiolucency was associated with increased levels of FGF‐23, IL‐1β and IL‐6. At 3‐months following treatment, IL‐1β, IL‐8, hs‐CRP, C3, MMP‐2 and MMP‐9 levels increased compared with baseline in treatment groups. IL‐1β and IL‐8 further increased at 6 months, whereas FGF‐23, hs‐CRP, C3, MMP2 and MMP‐9 decreased. One‐year post‐treatment, FGF‐23, pentraxin‐3 and ADMA were significantly reduced below baseline levels. At the 1‐year review, CBCT revealed that 25.9% of treated cases completely healed, while 63% were healing, and 11.1% failed. Treatment outcome was found to be influenced by preoperative levels of ADMA and IL‐8 levels at 6 months.Conclusions: Both symptomatic and asymptomatic apical periodontitis (AP) can contribute to increased levels of molecular markers of inflammation. A further transient inflammatory markers rise after root canal retreatment and apical surgery were demonstrated. Successful endodontic treatment and periapical surgery result in a long‐term reduction in inflammatory marker levels.

Aim: To investigate serum biomarkers of inflammation 2 years following non‐surgical root canal re‐treatment (Re‐RCT) and peri‐apical surgery (PS). The results were correlated with signs and symptoms, treatment outcome, metabolic syndrome factors, infection with severe acute respiratory syndrome coronavirus 2 SARS‐CoV‐2 (COVID‐19) infection and COVID‐19 vaccination.Methodology: Subjects from our previous study were recalled for 2 years post‐treatment follow‐up. Changes to the patient's history (medical, dental, social) were noted. Periapical health of the treated teeth was examined both clinically and radiographically. Blood pressure, fasting HbA1C and low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides and total cholesterol (TC) levels were measured. Serum inflammatory marker levels were assayed using a Bio‐Rad Bio‐Plex 200 analyser and values at different time points within the same group were compared using a Wilcoxon signed‐rank test and differences between groups with a Mann–Whitney test. Linear associations were tested using Pearson's correlations.Results: The recall percentage at 2 years was 56.9% (n = 37), with a 100% radiographic success rate using periapical radiographs. In total, 21 cases (56.8%) were completely healed, and 16 cases (43.2%) were healing. Higher matrix metalloprotease 2 (MMP2) levels were present in the healing group compared to the healed group. Serum levels of high‐sensitivity C‐reactive protein (hs‐CRP), asymmetric dimethylarginine (ADMA) and MMP‐2 were significantly reduced (p ≤ .001) whereas other biomarkers showed significant increases at 2 year compared to pre‐operative levels, while FGF‐23 and ICAM‐1 were not significantly increased. HbA1C (p = .015), TC (p = .003), LDL (p = .003) and HDL (p = .003) reduced significantly at 2 years post‐treatment compared to their preoperative levels. COVID infection showed a significant association with MMP‐9 (p = .048).Conclusions: hs‐CRP, ADMA and MMP‐2 can be regarded as prognostic biomarkers of successful Re‐RCT and PS as they reduced at 2 year recall in cases which showed evidence of clinical and radiographic success. The successful treatment of chronic apical periodontitis is correlated with improvements in metabolic syndrome indicators, better glycemic control, and reduction at 2 year of some systemic inflammatory markers which are related to risks of cardiovascular disease events.

Purpose: This study compared the antimicrobial efficacy of calcium silicate sealers (BioRoot RCS and Total Fill BC) and conventional sealers (AH Plus and Tubli-seal) against planktonic bacteria and a nutrient-stressed multispecies biofilm. Methods: Antimicrobial properties of freshly mixed sealers were investigated using the direct contact test (DCT) and a nutrient-stressed multispecies biofilm comprised of five endodontic strains. Antimicrobial activity was determined using quantitative viable counts and confocal laser scanning microscopy (CLSM) analysis with live/dead staining. The pH of the sealers was analysed over a period of 28 days in Hanks Balanced Salt Solution (HBSS). Analysis of variance (ANOVA) with Tukey tests and the Kruskal–Wallis test were used for data analysis with a significance of 5%. Results: All endodontic sealers exhibited significant antimicrobial activity against planktonic bacteria (p < 0.05). BioRoot RCS caused a significant reduction in viable counts of the biofilms compared to AH Plus and the control (p < 0.05), while no significant difference could be observed compared to TotalFill BC and Tubli-seal (p > 0.05). CLSM analysis showed that BioRoot RCS and TotalFill BC exhibited significant biofilm inhibition compared to Tubli-seal, AH Plus and the control (p < 0.05). BioRoot RCS presented with the highest microbial killing, followed by TotalFill BC and Tubli-seal. Alkalizing activity was seen from the onset by BioRoot RCS, TotalFill BC and AH Plus. After 28 days, BioRoot RCS demonstrated the highest pH in HBSS (pH > 12). Conclusions: Calcium silicate sealers exhibited effective antimicrobial properties. This was demonstrated by superior biofilm inhibition capacity and microbial killing, with strong alkalizing activity compared to epoxy-based and zinc oxide-eugenol-based sealers.

Bacteraemia associated with invasive dental treatments can propagate infective endocarditis in high-risk cardiac patients. Over the past decade, antibiotic prophylaxis before dental treatment has been questioned. This review aims to compare the variations between the UK, European and American antibiotic prophylaxis guidelines before dental treatments. Antibiotic prophylaxis guidelines by the National Institute for Health and Care Excellence (NICE)—Clinical Guideline 64, Scottish Dental Clinical Effectiveness Programme (SDCEP), American Heart Association (AHA), European Society of Cardiology (ESC), European Society of Endodontology (ESE) and Belgian Health Care Knowledge Centre (KCE) position statements were compared regarding the indications, high-risk patients and prophylaxis regimens before dental treatments. In the United Kingdom, the NICE—Clinical Guideline 64 and SDCEP—Implementation Advice do not advise the prescription of prophylactic antibiotics for the majority of high-risk cardiac patients undergoing routine dental treatments. On the contrary, the AHA, ESC and KEC recommend the prescription of antibiotics prior to invasive dental procedures in high-risk cardiac individuals. The ESE also indicates prophylaxis before endodontic procedures for patients with other conditions, including impaired immunologic function, prosthetic joint replacement, high-dose jaw irradiation and intravenous bisphosphonates. Among these guidelines, there are variations in antibiotic prophylaxis regimens. There are variations regarding the indications and antibiotic prophylaxis regimens before invasive dental treatments among these available guidelines.