An international consensus study to identify "what" outcomes should be included in a core outcome set for endodontic treatments (COSET) for utilization in clinical practice and research.

BACKGROUND: Development of a standardized set of topic-specific outcomes known as a Core Outcome Set (COS) is important to address issues of heterogeneity in reporting research findings in order to streamline evidence synthesis and clinical decision making. AIM: The aim of the current international consensus study is to identify "what" outcomes to include in the Core Outcome Set for Endodontic Treatments (COSET). Outcomes of various endodontic treatments (non-surgical root canal treatment, surgical endodontics, vital pulp treatment and revitalization procedures) performed on permanent teeth were considered. METHODS: A standard validated methodology for COS development and reporting was adopted. The process involved identification of existing outcomes through four published scoping reviews. This enabled creation of a list of outcomes to be prioritized via semi-structured patient interviews, e-Delphi process and a consensus meeting with a range of relevant global stakeholders. Outcomes were prioritized using a 1-9 Likert scale, with outcomes rated 7-9 considered critical, 4-6 are important and 1-3 are less important. Outcomes rated 7-9 by ≥70% and 1-3 by <15% of participants were considered to achieve consensus for inclusion in the COS. The outcomes that did not achieve consensus in the first round were considered for further prioritization in the second Delphi round and consensus meeting. Final decisions about the outcomes to include in COSET were made by voting during the consensus panel meeting using the Zoom Poll function. RESULTS: A total of 95 participants including patients contributed to the COS development process. The consensus panel recommended, with strong consensus, eight outcomes shared across all treatment modalities for inclusion in COSET: pain; signs of infection (swelling, sinus tract); further intervention/exacerbation; tenderness to percussion/palpation; radiographic evidence of disease progression/healing; function; tooth survival; and patient satisfaction. Additional treatment specific outcomes were also recommended. DISCUSSION: Many of the outcomes included in COSET are patient reported. All should be included in future outcomes studies. CONCLUSION: COSET identified outcomes that are important for patients and clinicians and validated these using a rigorous methodology. Further work is ongoing to determine "how" and "when" these outcomes should be measured.

Outcomes reporting in systematic reviews on revitalization: A scoping review for the development of a core outcome set.

BACKGROUND: Revitalization is a type of regenerative endodontic treatment (RET) that offers the exciting prospect of revitalizing damaged tissue, therefore improving outcomes for non-vital immature teeth. To evaluate its potential, there needs to be consistency in outcome reporting of clinical studies investigating revitalization to allow for evidence synthesis and inform clinical decision making. OBJECTIVES: The aim of this scoping review was to identify outcomes that are reported in systematic reviews on revitalization including how and when these outcomes are measured. Additionally, evidence of selective reporting bias in the reviews was assessed. METHODS: A comprehensive electronic search of healthcare databases and grey literature was conducted to identify systematic reviews published in the English language reporting outcomes of revitalization in permanent immature teeth. There was no restriction on the date of publication. Outcome data was extracted by four reviewers independently and mapped with a healthcare taxonomy into five core areas: survival, clinical/physiological changes, life impact, resource use and adverse events. Selective reporting bias and how it was measured was assessed independently by two reviewers. RESULTS: Twenty-six systematic reviews were included in this scoping review. There was lack of standardization in reporting and significant heterogeneity across reviews in outcome endpoints. The outcomes reported could be aligned within the five core areas of the taxonomy including tooth survival which was reported in nine reviews. Patient-reported outcomes were generally limited and no review reported on Oral Health Related Quality of Life. Many of the reviews reporting on randomized control trials were at low risk of selective reporting bias whilst other study designs were at higher risk. DISCUSSION: Consistency in outcome reporting is necessary to realize the benefits of old but particularly novel therapies. Data from this review confirmed heterogeneity in reporting outcomes of revitalization and the need for development of a core outcome set (COS). CONCLUSIONS: Several important outcomes including survival, root development, tooth discolouration and periapical healing have been identified in this review which could inform the development of a COS in this area. REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) database (registration no. 1879).

Altered Toll-like receptor 2-mediated endotoxin tolerance is related to diminished interferon beta production.

Induction of endotoxin tolerance leads to a reduced inflammatory response after repeated challenge by LPS and is important for resolution of inflammation and prevention of tissue damage. Enterobacterial LPS is recognized by the TLR4 signaling complex, whereas LPS of some non-enterobacterial organisms is capable of signaling independently of TLR4 utilizing TLR2-mediated signal transduction instead. In this study we report that Porphyromonas gingivalis LPS, a TLR2 agonist, fails to induce a fully endotoxin tolerant state in a human monocytic cell line (THP-1) and mouse bone marrow-derived macrophages. In contrast to significantly decreased production of human IL-8 and TNF-α and, in mice, keratinocyte-derived cytokine (KC), macrophage inflammatory protein-2 (MIP-2), and TNF-α after repeated challenge with Escherichia coli LPS, cells repeatedly exposed to P. gingivalis LPS responded by producing less TNF-α but sustained elevated secretion of IL-8, KC, and MIP-2. Furthermore, in endotoxin-tolerant cells, production of IL-8 is controlled at the signaling level and correlates well with NF-κB activation, whereas TNF-α expression is blocked at the gene transcription level. Interferon ß plays an important role in attenuation of chemokine expression in endotoxin-tolerized cells as shown in interferon regulatory factor-3 knock-out mice. In addition, human gingival fibroblasts, commonly known not to display LPS tolerance, were found to be tolerant to repeated challenge by LPS if pretreated with interferon ß. The data suggest that the inability of the LPS-TLR2 complex to induce full endotoxin tolerance in monocytes/macrophages is related to diminished production of interferon ß and may partly explain the involvement of these LPS isoforms in the pathogenesis of chronic inflammatory diseases.

Pulpotomy for mature carious teeth with symptoms of irreversible pulpitis: A systematic review.

OBJECTIVES: Management of carious teeth with signs and symptoms indicative of irreversible pulpitis is traditionally invasive, but emerging evidence suggests successful treatment outcomes with less invasive vital pulp treatment such as coronal pulpotomy. The objective of this systematic review is to determine whether coronal pulpotomy is clinically effective in treating carious teeth with signs and symptoms indicative of irreversible pulpitis. SOURCES: MEDLINE; PubMed; Embase, Web of Science, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform and ClinicalTrials.gov were searched until December 2018. STUDY SELECTION: Prospective, retrospective and randomised clinical trials investigating coronal pulpotomy or comparing pulpotomy to root canal treatment in permanent mature carious teeth with signs and symptoms indicative of irreversible pulpitis were included. Studies were independently assessed for risk of bias using Cochrane Systematic Reviews of intervention criteria and modified Downs and Black quality assessment checklist. DATA: Eight articles were selected for analysis. The average success rate for coronal pulpotomy was 97.4% clinical and 95.4% radiographic at 12 month follow-up. This was reduced to 93.97% clinical and 88.39% radiographic success at 36 months follow-up. Results from the only comparative clinical trial showed pulpotomy to have comparable success to root canal treatment at 12, 24 and 60 month follow-up. CONCLUSIONS: The evidence suggests high success for pulpotomy for teeth with signs and symptoms of irreversible pulpitis, however, results are based on heterogeneous studies with high risk of bias. Well-designed, adequately powered randomised controlled trials are required for evidence to change clinical practice. CLINICAL SIGNIFICANCE: Management of carious teeth with irreversible pulpitis is traditionally invasive, but emerging evidence suggests potentially successful treatment outcomes with less invasive therapies such as coronal pulpotomy.

Sialylation of Porphyromonas gingivalis LPS and its effect on bacterial-host interactions.

Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a 'self-associated molecular pattern' and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells.