Does Periodontitis Increase the Risk for Future Cardiovascular Events? Long-Term Follow-Up of the PAROKRANK Study.

BACKGROUND AND AIM: The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD-compared to periodontally healthy individuals-are at increased risk for cardiovascular (CV) events and death. METHODS: A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%-66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2-12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan-Meier method and Cox regression. RESULTS: The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01-1.57; p = 0.038), following adjustment for age, smoking and diabetes. CONCLUSION: The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Endodontic Inflammatory Disease and Future Cardiovascular Events and Mortality: A Report from the PAROKRANK Study.

INTRODUCTION: Prospective studies assessing the relation between endodontic inflammatory disease and subsequent cardiovascular events are few. The present aim was to explore associations between endodontic variables and future cardiovascular events in patients with myocardial infarction and matched controls participating in the PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study. METHODS: Eight-hundred five patients hospitalized for a first myocardial infarction and 805 controls were recruited between 2010 and 2014. Signs of endodontic inflammatory disease were assessed in panoramic radiographs taken at baseline. Mortality and morbidity data during the approximately 8 years of follow up were obtained from national registries. The risk for future cardiovascular events (first of mortality and nonfatal myocardial infarction, stroke, or hospitalization for heart failure) was analyzed with the log-rank test and Cox proportional hazards regression adjusted for the following confounders: sex, age, smoking, myocardial infarction, diabetes, education, marital status, family history of cardiovascular disease, and marginal periodontitis. RESULTS: In total, 285 future events were observed during the follow-up period. Unadjusted analyses revealed that ≥1 root-filled tooth increased the risk of a future event. After adjustment, the number of remaining teeth and non-root-filled teeth decreased the risk of future events, whereas a higher Decayed, Missing and Filled Teeth score increased the risk and ≥1 primary apical periodontitis decreased the risk of suffering cardiovascular events. A higher Decayed, Missing and Filled Teeth score and decayed teeth increased the risk of all-cause mortality. CONCLUSIONS: Tooth loss is a strong indicator of an increased risk for future cardiovascular events. Root-filled teeth seem of limited value as a risk indicator when accounting for other risk factors. The potential effect of dental interventions on future events should be assessed in future research.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Periradicular surgery: a longitudinal registry study of ten-year outcomes and factors predictive of post-surgical extraction.

AIM: This historical prospective cohort study of the adult population of Sweden is based on data from a national registry: the primary aim was to evaluate the long-term survival of teeth after periradicular surgery. A secondary aim was to identify factors predictive of extraction within 10 years of registration of periradicular surgery. METHODOLOGY: The cohort consisted of all individuals who had undergone periradicular surgery to treat apical periodontitis, as reported to the Swedish Social Insurance Agency (SSIA) during 2009. The cohort was followed until December 31, 2020. Subsequent registrations of extractions were collected for Kaplan-Meier survival analyses and survival tables. The patients' sex, age, dental service provider and tooth group were also retrieved from SSIA. Only one tooth per individual was included in the analyses. Multivariable regression analysis was used and P < 0.05 was considered statistically significant. The reporting guidelines STROBE and PROBE were followed. RESULTS: After data cleaning, and exclusion of 157 teeth, 5 622 teeth/individuals remained for analysis. The mean age of the individuals at the time of the periradicular surgery was 60.5 years (range 20-97, standard deviation 13.31); 55% were women. At the end of the follow-up, that is, up to 12 years, a total of 34.1% of the teeth had been reported as extracted. The multivariate logistic regression analysis, based on follow-up data at 10 years after registration of the periradicular surgery, included 5 548 teeth, of which 1 461 (26.3%) had been extracted. Significant associations between the independent variables tooth group and dental care setting (both P < 0.001) and the dependent variable extraction were found. The highest odds ratio (OR) for extraction applied to tooth group: compared to maxillary incisors and canines, mandibular molars were at greatest risk of extraction (OR 2.429, confidence interval 1.975-2.987, P < 0.001). CONCLUSIONS: After periradicular surgery in predominantly elderly people in Sweden, approximately three quarters of the teeth are retained over a 10-year period. The type of tooth is associated with extraction: mandibular molars are at greater risk of extraction than maxillary incisors and canines.

Endodontic inflammatory disease: A risk indicator for a first myocardial infarction.

AIM: To study the association between endodontic inflammatory disease and a first myocardial infarction (MI). METHODOLOGY: The study comprised 805 patients with recent experience of a first MI, each gender, age and geographically matched with a control. Panoramic radiographs were available for 797 patients and 796 controls. Endodontic inflammatory disease was assessed radiographically. The sum of decayed, missing and filled teeth (DMFT) was calculated, and the number of root filled teeth and teeth with periapical lesions were recorded. The associated risk of a first MI was expressed as odds ratios (OR) with 95% confidence intervals (CI), unadjusted and adjusted for confounders (family history of cardiovascular disease, smoking habits, marital status, education and diabetes). RESULTS: Patients who had suffered a first MI had higher DMFT (mean 22.5 vs. 21.9, p = .013) and more missing teeth (mean 7.5 vs. 6.3; p < .0001) than the healthy controls. The number of missing teeth was associated with an increased risk of a first MI (adjusted OR 1.04; CI 1.02-1.06). Conversely, decay-free, filled teeth were associated with decreased risk (adjusted OR 0.98; CI 0.96-1.00). Analysis based on age disclosed the following variables to be associated with an increased risk of a first MI: number of decayed teeth (adjusted OR 1.18; CI 1.02-1.37, in patients <60 years), any primary periapical lesion (adjusted OR 1.57; CI 1.08-2.29, in patients <65 years) and the proportion of root filled teeth (adjusted OR 1.18; CI 1.03-1.36, in patients ≥65 years). CONCLUSIONS: More missing teeth was independently associated with an increased risk of a first MI. In addition, endodontic inflammatory disease may contribute as an independent risk factor to cardiovascular disease since untreated caries, periapical lesions and root fillings, depending on age, were significantly associated with a first MI.

Xdrop: Targeted sequencing of long DNA molecules from low input samples using droplet sorting.

Long-read sequencing can resolve regions of the genome that are inaccessible to short reads, and therefore are ideal for genome-gap closure, solving structural rearrangements and sequencing through repetitive elements. Here we introduce the Xdrop technology: a novel microfluidic-based system that allows for targeted enrichment of long DNA molecules starting from only a few nanograms of DNA. Xdrop is based on the isolation of long DNA fragments in millions of droplets, where the droplets containing a target sequence of interest are fluorescently labeled and sorted using flow cytometry. The final product from the Xdrop procedure is an enriched population of long DNA molecules that can be investigated by sequencing. To demonstrate the capability of Xdrop, we performed enrichment of the human papilloma virus 18 integrated into the genome of human HeLa cells. Analysis of the sequencing reads resolved three HPV18-chr8 integrations at base-pair resolution, and the captured fragments extended up to 30 kb into the human genome at the integration sites. Further, we enriched the complete TP53 locus in a leukemia cell line and could successfully phase coexisting mutations using PacBio sequencing. In summary, our results show that Xdrop is an efficient enrichment technology for studying complex genomic regions.

Tooth Survival after Surgical or Nonsurgical Endodontic Retreatment: Long-term Follow-up of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine long-term tooth survival after endodontic retreatment and whether the presence of intraradicular posts influences the outcome. METHODS: Ninety-five teeth were randomly assigned to surgical or nonsurgical endodontic retreatment. Forty-seven teeth in 45 patients were treated by conventional endodontic surgery and 48 teeth (47 patients) by nonsurgical retreatment, including the removal of intraradicular posts in 37 (77%). The outcome was tooth survival; follow-up continued until the tooth had been extracted, at least 10 years had elapsed since retreatment, the patient declined further follow-up, or the patient died. The Fisher exact test was used to analyze differences between the groups. RESULTS: The median follow-up time was 10.1 years (range, 0.0-15.6 years). The overall survival rate was 76%, with no significant differences in long-term tooth survival between retreatment methods or the presence of an intraradicular post. The reasons for tooth extraction were related to the retreatment method. Vertical root fractures were significantly more frequent in the nonsurgical group when retreatment included post removal (P = .036). CONCLUSIONS: There was no significant difference in long-term tooth survival after surgical or nonsurgical retreatment. The presence of intraradicular posts did not affect long-term tooth survival, but for teeth with posts, those retreated nonsurgically were more frequently extracted because of vertical root fractures than those retreated surgically (P = .036). The major limitations of the study were a smaller sample size and the use of outmoded retreatment techniques.

Further Treatments of Root-filled Teeth in the Swedish Adult Population: A Comparison of Teeth Restored with Direct and Indirect Coronal Restorations.

INTRODUCTION: The aim of this study was to evaluate the frequencies of nonsurgical retreatment, root-end surgery, extraction, and further restoration of root-filled teeth in Sweden in 2009 during a follow-up period of 5 years and to compare the outcomes in teeth restored with direct or indirect restorations. METHODS: Data from the Swedish Social Insurance Agency were analyzed, and the frequencies of nonsurgical retreatment, root-end surgery, extractions, and further restoration were calculated for all teeth registered as root filled during 2009. Chi-square tests were applied to detect any significant differences in the frequency of further treatment in teeth registered as restored with either a direct or an indirect restoration within 6 months of root filling. RESULTS: Of the 248,299 teeth reported root filled in Sweden in 2009, nonsurgical retreatment was registered in 2.2%, root-end surgery in 1.0%, and extractions in 9.2% during the follow-up period. Of the teeth restored with a direct restoration within 6 months after the root filling, 30.3% were registered as having undergone at least 1 further direct restoration; the corresponding percentage of teeth with indirect restorations was 6.4%. A statistically significant difference in the frequency of nonsurgical retreatment, extraction, and further restoration was found; teeth restored with an indirect restoration within 6 months of root filling had fewer of these treatments than those restored by direct restoration. CONCLUSIONS: Low frequencies of nonsurgical retreatment and root-end surgery were reported 5 years after root filling, whereas extraction was more common. Fewer additional treatment procedures were registered for teeth with indirect restorations than for those with direct restorations.

Endodontic retreatment strategies used by general dental practitioners.

PURPOSE: Root-filled teeth with persistant periapical radiolucencies are often classified as endodontic failures. Studies have shown that general dental practitioners (GDP) do not consistantly suggest retreatment of "failures." The "Praxis Concept" (PC) theory hypothesizes that dentists conceive periapical health and disease as different states on a continuum. This study examined endodontic retreatment concepts among 157 GDPs from Värmland, Sweden. STUDY DESIGN: In 6 simulated cases the periapical condition, quality of root filling and presence of a root canal-retained post were systematically varied. Five options were offered: no therapy, wait and see, nonsurgical retreatment, surgical retreatment, and extraction. RESULTS: The investigation showed large interindividual variation in retreatment behavior among the GDPs. Only 9 dentists (6%) where found to repeatedly suggest retreatment of endodontic failures. A majority of GDPs (79%) performed in accordance with PC. CONCLUSIONS: The data indicate that several retreatment decision rules are used by Swedish GDPs, but PC-derived strategies attract the majority.