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Aims: Dental pulp stem cells (DPSCs) contain a population of stem cells with a broad range of differentiation potentials, as well as more lineage‐committed progenitors. Such heterogeneity is a significant obstacle to experimental and clinical applications. The aim of this study is to isolate and characterize a homogenous neuronal progenitor cell population from human DPSCs. Methodology: Polysialylated‐neural cell adhesion molecule (PSA‐NCAM+) neural progenitors were isolated from the dental pulp of three independent donors using magnetic‐activated cell sorting (MACS) technology. Immunofluorescent staining with a panel of neural and non‐neural markers was used to characterize the magnetically isolated PSA‐NCAM+ fraction. PSA‐NCAM+ cells were then cultured in Neurobasal A supplemented with neurotrophic factors: dibutyryl cyclic‐AMP, neurotrophin‐3, B27 and N2 supplements to induce neuronal differentiation. Both PSA‐NCAM+ and differentiated PSA‐NCAM+ cells were used in Ca2+ imaging studies to assess the functionality of P2X3 receptors as well as membrane depolarization. Results: PSA‐NCAM+ neural progenitors were isolated from a heterogeneous population of hDPSCs using magnetic‐activated cell sorting and anti‐PSA‐NCAM MicroBeads. Flow cytometry analysis demonstrated that immunomagnetic sorting significantly increased the purity of PSA‐NCAM+ cells. Immunofluorescent staining revealed expression of pan‐neuronal and mature neuronal markers, PGP9.5 and MAP2, respectively, as well as weak expression of the mature sensory markers, peripherin and islet1. ATP‐induced response was mediated predominately by P2X3 receptors in both undifferentiated and differentiated cells, with a greater magnitude observed in the latter. In addition, membrane depolarizations were also detected in cells before and after differentiation when loaded with fast‐voltage‐responding fluorescent molecule, FluoVolt™ in response to potassium chloride. Interestingly, only differentiated PSA‐NCAM+ cells were capable of spontaneous membrane oscillations. Conclusions: In summary, DPSCs contain a population of neuronal progenitors with enhanced neural differentiation and functional neural‐like properties that can be effectively isolated with magnetic‐activated cell sorting (MACS). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence and evaluation of postoperative pain following root canal treatment. It highlights the increase in clinical trials focusing on postoperative pain as a primary outcome, but questions the relevance of short-term pain studies in determining the efficacy of different irrigation protocols. The article emphasizes the subjective nature of pain and the presence of confounding factors that make it challenging to attribute pain solely to irrigation. It suggests that longer-term follow-up or the control of various variables is necessary for more meaningful results. The article concludes by suggesting the consideration of objective surrogate outcomes, such as inflammatory markers, in future studies. [Extracted from the article]

Background: The ESE previously published quality guidelines for endodontic treatment in 2006; however, there have been significant changes since not only in clinical endodontics but also in consensus and guideline development processes. In the development of the inaugural S3‐level clinical practice guidelines (CPG), a comprehensive systematic and methodologically robust guideline consultation process was followed in order to produce evidence‐based recommendations for the management of patients presenting with pulpal and apical disease. Aim: To develop an S3‐level CPG for the treatment of pulpal and apical disease, focusing on diagnosis and the implementation of the treatment approaches required to manage patients presenting with pulpitis and apical periodontitis (AP) with the ultimate goal of preventing tooth loss. Methods: This S3‐level CPG was developed by the ESE, with the assistance of independent methodological guidance provided by the Association of Scientific Medical Societies in Germany and utilizing the GRADE process. A robust, rigorous and transparent process included the analysis of relevant comparative research in 14 specifically commissioned systematic reviews, prior to evaluation of the quality and strength of evidence, the formulation of specific evidence and expert‐based recommendations in a structured consensus process with leading endodontic experts and a broad base of external stakeholders. Results: The S3‐level CPG for the treatment of pulpal and apical disease describes in a series of clinical recommendations the effectiveness of diagnosing pulpitis and AP, prior to investigating the effectiveness of endodontic treatments in managing those diseases. Therapeutic strategies include the effectiveness of deep caries management in cases with, and without, spontaneous pain and pulp exposure, vital versus nonvital teeth, the effectiveness of root canal instrumentation, irrigation, dressing, root canal filling materials and adjunct intracanal procedures in the management of AP. Prior to treatment planning, the critical importance of history and case evaluation, aseptic techniques, appropriate training and re‐evaluations during and after treatment is stressed. Conclusion: The first S3‐level CPG in endodontics informs clinical practice, health systems, policymakers, other stakeholders and patients on the available and most effective treatments to manage patients with pulpitis and AP in order to preserve teeth over a patient's lifetime, according to the best comparative evidence currently available. [ABSTRACT FROM AUTHOR]

Background: Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however, their accuracy is unknown. Objectives: (1) Calculate sensitivity, specificity and diagnostic odds ratio (DOR) of previously investigated pulpitic biomarkers; (2) Determine if biomarker levels discriminate between clinical diagnoses of pulpitis based on the presence or absence of spontaneous pain (3) Evaluate if biomarker level can predict VPT outcome. Methods: Searches: PubMed/MEDLINE, Ovid SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase, Web of Science and Scopus in May 2023. Inclusion: prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well‐defined pulpal diagnosis. Exclusion: deciduous teeth, in vitro and animal studies. Risk of bias was assessed with modified‐Downs and Black quality assessment checklist. Meta‐analysis was performed using bivariate random effect model in Meta‐DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Results: Fifty‐six studies were selected, reporting >70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL‐8 and IL‐6 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low‐certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy. Discussion: The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non‐spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair. Conclusions: Low‐quality evidence suggests IL‐8 and IL‐6 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation. Registration: PROSPERO CRD42021259305. [ABSTRACT FROM AUTHOR]

Background: Oral health is a key contributor to a person's overall health. Previous studies indicate that oral health deteriorates throughout ventilation and may contribute to the development of ventilator‐associated pneumonia (VAP). Oral health at the time of initial ventilation may impact on this deterioration. Aims: To determine the quantitative clinical assessment methods used to measure oral health and what is currently known regarding the oral health of patients at the time of initial ventilation. Study Design: A systematic literature search using electronic bibliographic databases MEDLINE/PubMed, Embase, CINAHL, and the Cochrane Library was undertaken for this scoping review. Studies were included if patients were >18 years old and mechanically ventilated for <48 h at the time of the first oral assessment. Results: In total, 12 studies were included. The review demonstrates a limited understanding of clinical oral health at the time of initial ventilation. Significant variation in both assessment methods and reporting of oral health makes comparison of results difficult resulting in a poor overall understanding of oral health at the time of intubation. Conclusion: Standardized assessment and reporting methods may improve clinical application of findings and help direct future research. We suggest developing a core outcome set to ensure consistent use of assessment tools as well as standardized reporting of results. Relevance to Clinical Practice: It is essential that a good understanding of oral health at the time of initial ventilation is gained so that patients receive more targeted oral hygiene intervention in ICU, potentially leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The importance of good oral hygiene for patients in Intensive Care Units (ICUs) is well recognized, however, the most effective way to achieve good oral care in the ICU is unclear. Aim: This study aimed to provide a national picture of oral care practices in adult ICUs in the United Kingdom (UK) to identify areas for improvement. Study Design: A national one‐day point prevalence study was undertaken in adult ICUs in the UK in the period from 30th September to 14th October 2021. Data were collected on all patients in the ICU on the date of data collection. Using a validated electronic data collection form, anonymised data were collected on methods and frequency of oral care provided, and the use of oral care protocols within the ICU. Data were analysed using descriptive analysis. Results: Data from 195 patients in 15 ICUs in England, Wales and Northern Ireland were collected. Written oral care protocols were available for use in the care of 65% (n = 127) of patients. 73% (n = 142) of patients received oral care within the 24‐h period. Oral care methods included toothbrushing 41% (n = 79), foam sticks 3% (n = 5), moisturizing the oral cavity 10% (n = 19) and mouth rinse with chlorhexidine 3% (n = 5) and other oral care methods not specified 12% (n = 23). 44% (n = 85) of patients had an oral assessment within the 24‐h period and variable assessment methods were used. Conclusion: There is large variability in oral care provision and methods for intubated ICU patients and a lack of consensus was revealed in the study. Oral assessment is conducted less frequently using multiple tools. Optimal oral care standards and further research into oral care provision is pivotal to address this important patient‐relevant practice. Relevance to Clinical Practice: Oral care is a fundamental part of care for ICU patients, however, there is a large degree of variability, and oral care is often not based upon oral assessment. The use of an oral care protocol and oral assessments would help to improve patient care, ease of use for staff and provide a tailored oral care plan for patients, improving efficiency and preventing wasted resources. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether there is an association between subgingival microbial diversity and reduced respiratory function. Materials and Methods: A group of dentate 58–72‐year‐old men in Northern Ireland had a comprehensive periodontal examination including subgingival plaque sampling. DNA was extracted from plaque samples and the V1–V3 regions of the 16S rRNA gene were analysed by high‐throughput sequencing and a microbial diversity index (MDI) was derived. Spirometry measurements were made using a wedge bellows spirometer. The primary outcome variable of interest was the percentage of predicted forced expiratory volume in 1 s (% predicted FEV1). Analysis included multiple linear regression with adjustment for various confounders. Results: Five‐hundred and seven men were included in the analysis. The mean age was 63.6 years (SD = 3.1). Of these, 304 (60.0%) men had no or mild periodontitis, 105 (20.7%) had moderate periodontitis and 98 (19.3%) had severe periodontitis. Multiple linear regression analysis showed that a one unit increase in MDI was associated with a 0.71% loss (95% confidence interval: 0.06%–1.35%; p =.03) in % predicted FEV1 after adjustment for all confounders. Conclusions: In this group of dentate men from Northern Ireland, subgingival microbial diversity was associated with reduced respiratory function. [ABSTRACT FROM AUTHOR]

The promotion of minimally invasive treatments focussed on the maintenance of pulp vitality has become a priority area in Endodontics. These vital pulp treatments (VPT) include partial and full pulpotomy, during which diseased coronal pulp tissue is removed prior to placement of a capping biomaterial and restoration. Traditionally, pulpotomies were confined to the treatment of carious primary and traumatized permanent teeth. However, these treatments have now been proposed as definitive solutions for cariously exposed permanent teeth with mild symptoms or even symptoms indicative of irreversible disease. Until recently, it was recommended that carious exposure of mature permanent teeth be managed by root canal treatment. The promotion of pulpotomy as an alternative treatment has opened up a wave of laboratory and clinical research aimed at improving therapies or evaluating clinical outcomes. In modern evidence‐based endodontics, it is imperative that the outcomes of both partial and full pulpotomy are considered and important prognostic factors identified, so that improvements can be made to aid clinical decision‐making and to direct new research. In this narrative review, the outcomes of partial and full pulpotomy are discussed, before analysis of patient, intraoperative and postoperative factors that influence the outcome of the pulpotomy procedure. The review highlights that although partial and full pulpotomy for the treatment of even pulpal disease are highly successful procedures, this is based on low‐quality evidence with a lack of prospective, comparative trials investigating potential prognostic factors. Based on current evidence, it appears that age, gender, tooth type, root development and intraoperative pulpal haemorrhage do not impact significantly on pulpotomy outcome, whilst others such as caries depth, inflammatory status of the pulp, capping material, level of inflammatory pulpal‐biomarkers and the final restoration integrity do. Other factors, including the influence of exposure type, periodontal condition, pulpal lavage, magnification, operator experience, isolation of the operating field and type of pulpotomy, require further experimental investigation before definitive conclusions can be made relating to the success of the pulpotomy procedure. Finally, there is not only a need for future well‐designed prospective research addressing these issues but also a widening of our understanding of outcome to include patient‐reported as well as clinician‐reported outcomes. [ABSTRACT FROM AUTHOR]

Endodontic therapy aims to preserve teeth by preventing and treating apical disease, therefore, evaluation of treatment outcome in clinical trials and outcomes studies should effectively assess if it achieves these aims. Traditionally, treatment outcomes have been reported by clinicians after history and clinical examination in what is known as clinician‐reported outcomes (CROs). Much less commonly employed however, are patient‐reported outcomes (PROs) in which patients directly report on their condition. Endodontic treatment outcome reporting is evolving from a focus on CROs to increasing consideration for patient and disease‐focused outcomes, with different criteria being proposed for assessment of treatment outcomes. Unfortunately, this has led to considerable variability and a lack of consensus on the definition, appropriate measurement and reporting of these outcomes. Heterogeneity in outcome reporting in clinical research provides a significant major barrier to conduct meta‐analysis, guidelines development, clinical decision making, and ultimately affecting patient care. These effects could, however, be reduced by the establishment of a core outcome set (COS) in endodontics, which is defined as an agreed, standardized set of outcomes that should be included, measured and reported as a minimum in all trials and outcome studies. COS development is a regulated and validated process requiring involvement of appropriate stakeholders as well as a rigorous methodology. To date, COS has been developed for the management of traumatic dental injuries, orthodontic and periodontal treatment and is currently being developed for endodontic treatment. The aim of this review is to discuss the importance of COS in endodontics with focus on the evidence for and impact of heterogeneity in reporting endodontic treatment outcomes. An overview of an ongoing process for development of COS for different endodontic treatment modalities will also be provided. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the expression and function of the nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in caries induced pulpitis. Methodology: NLRP3 expression was determined with immunohistochemistry in the dental pulp and qPCR in dental pulp cells (DPCs). THP‐1 macrophages expressing the apoptosis‐related speck‐like protein (ASC) and green fluorescent protein (GFP) fusion protein were used to assess NLRP3 inflammasome activation by live cell imaging, following treatment with lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Caspase I inhibitor was used to confirm inflammasome activation. An ex‐vivo pulpitis model in which the DPCs were co‐cultured with THP‐1 macrophages was used to study the effect of the NLRP3 inflammasome inhibitor (MCC950), and cytokines were measured using ELISA and multiplex array. Data were analysed using the t‐test or anova followed by a Bonferroni post hoc test with the level of significance set at p ≤.05. Results: NLRP3 inflammasome was differentially expressed in dental pulp of sound and carious teeth. Treatment of DPCs with LTA significantly upregulates NLRP3 and IL‐1 β‐expression (p <.05) and in induces more ASC specks formation compared to LPS. IL‐β release in response to LTA treatment is significantly reduced with Caspase I inhibitor suggesting inflammasome dependent mechanism (p <.01). NLRP3‐specific inhibitor, MCC950, significantly reduced IL‐1β and IL‐6 in an ex‐vivo pulpitis model (p <.01) but had no effect on IL‐8 or matrix metalloproteinase‐9 (MMP‐9). Conclusions: Expression and upregulation of NLRP3 inflammasome with caries and LTA treatment suggest a role in caries‐induced pulpitis. NLRP3 inhibitor attenuated the release of selective inflammatory cytokines and could be a potential treatment target that merit further investigation. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background: Studies related to non‐surgical root canal treatment are amongst the most frequently performed clinical studies in endodontics. However, heterogeneity in reporting outcomes and lack of standardization is a significant challenge to evidence synthesis and guideline development. Objectives: The aims of the present scoping review were to (a) identify outcomes reported in systematic reviews evaluating non‐surgical root canal treatment; (b) identify how and when the reported outcomes were measured; (c) assess possible selective reporting bias in the included studies. The information obtained in this study should inform the development of a core outcome set (COS) for non‐surgical root canal treatment. Methodology: Structured literature searches were performed to identify systematic reviews on non‐surgical root canal treatments published in English between January 1990 and December 2020. Two reviewers undertook study selection and data extraction. Outcomes were categorized according to a healthcare taxonomy into five core areas (survival, clinical/physiological changes, life impact, resource use, and adverse events). The outcome measurement tools and length of follow‐up were recorded. Results: Seventy‐five systematic reviews were included, of which 40 included meta‐analyses. Most reviews reported on physiological and clinical outcomes, primarily pain and/or radiographic assessment of periapical status, and a variety of measurement tools and scales were used. Few reviews focused on tooth survival, life impact, resources, and adverse events. The heterogeneity amongst the reviews was large on all parameters. Less than 40% of the reviews assessed the risk of selective reporting. Discussion: Overall aims of the included reviews were highly heterogenic; thus, outcomes and how they were measured also varied considerably. Patient‐centred outcomes and the use of resources were rarely reported on. Conclusions: Most studies reported on physiological and clinical outcomes, in particular pain and/or radiographic healing. Measurement tools, scales, thresholds, and follow‐up periods varied greatly within each outcome, making comparison across studies complicated. Less than 40% of the reviews assessed risk of selective reporting; thus, selective bias could not be ruled out. The presented information on reported outcomes, measurement tools and scales, and length of follow‐up may guide the planning of future research and inform the development of a COS for non‐surgical root canal treatment. [ABSTRACT FROM AUTHOR]

Background: A large number of research reports on vital pulp treatment (VPT) has been published over the last two decades. However, heterogeneity in reporting outcomes of VPT is a significant challenge for evidence synthesis and clinical decision‐making. Objectives: To identify outcomes assessed in VPT studies and to evaluate how and when outcomes are measured. A subsidiary aim was to assess evidence for selective reporting bias in the included studies. The results of this review will be used to inform the development of a core outcome set (COS) for endodontic treatments. Methods: Multiple healthcare bibliographic databases, including PubMed/MEDLINE, Ovid EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science were searched for systematic reviews published between 1990 and 2020, reporting on VPT. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Outcomes' information was extracted and aligned with a healthcare taxonomy into five core areas: survival, clinical/physiological changes, life impact, resource use and adverse events. Results: Thirty‐six systematic reviews were included, 10 reporting on indirect pulp capping or selective caries removal, nine on direct pulp capping, eight on pulpotomy and nine on combined VPTs. There was considerable variation in the outcomes reported in these reviews and their included studies. Clinician‐reported outcomes were used considerably more often than patient‐reported outcomes. A range of instruments and time points were used for measuring outcomes. Several of the reviews were assessed as having low risk of selective reporting bias, but many did not specifically report this domain, whilst others did not provide risk of bias assessment at all. Discussion: Considerable variation in selection of outcomes and how and when they are measured and reported was evident, and this heterogeneity has implications for evidence synthesis and clinical decision‐making. Conclusions: Whilst there is a lack of consistency, several potentially important outcomes for VPT, including pulp survival, incidence of post‐operative pain and need for further intervention, have been identified which could inform the development of a COS for endodontic treatment. Registration: Core Outcome Measures in Effectiveness Trials (COMET) (No. 1879). [ABSTRACT FROM AUTHOR]

Background: Evidence‐informed decision‐making in health care relies on the translation of research results to everyday clinical practice. A fundamental requirement is that the validity of any healthcare intervention must be supported by the resultant favourable treatment outcome. Unfortunately, differences in study design and the outcome measures evaluated often make it challenging to synthesize the available research evidence required for secondary research analysis and guideline development. Core outcome sets (COS) are defined as an agreed standardized set of outcomes, which should be measured and reported as a minimum in all clinical trials on a specific topic. The benefits of COS include less heterogeneity, a reduction in the risk of reporting bias and ensuring all trials contribute data to facilitate meta‐analyses; given the engagement of key stakeholders, it also increases the chances that clinically relevant outcomes are identified. The recognition of the need for COS for assessing endodontic treatment outcomes leads to the development of Core Outcome Sets for Endodontic Treatment modalities (COSET) protocol, which is registered (No. 1879) on the Core Outcome Measures in Effectiveness Trials (COMET) website. Objectives: The objectives of this scoping review are to: (1) identify the outcomes assessed in studies evaluating surgical endodontic procedures; (2) report on the method of assessment used to measure the outcomes; (3) and assess selective reporting bias in the included studies. The data obtained will be used to inform the development of COS for surgical endodontics. Methods: A structured literature search of electronic databases and the grey literature was conducted to identify systematic reviews on periradicular surgery (PS), intentional replantation (IR) and tooth/root resection (RR), published between January 1990 and December 2020. Two independent reviewers were involved in the literature selection, data extraction and the appraisal of the studies identified. The type of intervention, outcomes measured, type of outcomes reported (clinician‐ or patient‐reported), outcome measurement method and follow‐up period were recorded using a standardized form. Results: Twenty‐six systematic reviews consisting of 19 studies for PS, three studies for IR and four studies for RR were selected for inclusion. Outcome measures identified for PS and IR included pain, swelling, mobility and tenderness, outcomes related to periodontal/soft tissue healing (including sinus tract), periradicular healing, tooth survival, life impact (including oral health‐related quality of life), resource use and/or adverse effects. For RR, in addition to tooth survival, endodontic complications and adverse effects, the outcome measures were primarily periodontal‐related, including pocket depth reduction, attachment gain, periodontal disease and periodontic–endodontic lesions. The majority of outcome measures for PS, IR and RR were assessed clinically, radiologically and/or via patient history. Specific tools such as rating scales (Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale and other scales) were used for the assessment of pain, swelling and tenderness, and validated questionnaires were used for the assessment of oral health‐related quality of life. The range of follow‐up periods was variable, dependent on the outcome measure and the type of intervention. Conclusions: Outcome measures, method of assessment and follow‐up periods for PS, IR and RR were identified and categorized to help standardize the reporting of outcomes for future research studies. Additional outcome measures that were not reported, but may be considered in the COSET consensus process, include loss of root‐end filling material, number of clinic visits, surgery‐related dental anxiety and mucogingival aesthetic‐related measures, such as scarring, black triangles, root surface exposure and tissue discoloration. Registration: COMET (No. 1879). [ABSTRACT FROM AUTHOR]

An editorial is presented which addresses the development of an agreed-upon standardized set of outcomes (core outcome set) for endodontic treatment modalities, and it mentions the prevention and treatment of apical periodontitis, as well as outcome measurement instruments. Nonsurgical root canal treatment and apexification procedures are examined, along with a consensus process and

Objectives: The aims of this study were to investigate neuropeptide receptor expression regulation on STRO‐1 +ve periodontal ligament stem cells (PDLSCs) in response to inflammatory cytokines and to investigate a potential osteogenic effect of neuropeptides. Background: Nerve fibres innervating the periodontal tissues in humans contain several neuropeptides including neuropeptide Y and substance P. The role of neuropeptide receptors on PDLSCs, including their response to the local inflammatory environment of periodontitis, is currently unknown. Methods: A homogenous population of STRO‐1 +ve PDLSCs was prepared by immunomagnetic separation of cells obtained by the tissue out‐growth method from healthy premolar teeth from a single donor. Regulation of gene expression of the neuropeptide Y Y1 receptor and substance P receptor tachykinin receptor 1 was investigated. A potential osteogenic effect of neuropeptide Y and substance P was also investigated by measuring alkaline phosphatase (ALP) activity, Alizarin red staining and quantifying osteogenic gene expression. Results: Treatment of STRO‐1 +ve PDLSCs with tumour necrosis factor‐alpha or interleukin 1‐beta up‐regulated the expression of the neuropeptide Y's Y1 receptor, but down‐regulated substance P's receptor. Significantly increased ALP activity was observed in STRO‐1 +ve PDLSCs treated with neuropeptide Y but not substance P. Further studies showed that neuropeptide Y had a modest osteogenic effect on cells at both a functional level and a gene level. Conclusions: Expression of the neuropeptide Y Y1 receptor gene on STRO‐1 +ve PDLSCs was sensitive to local inflammatory cytokines. Treatment of cells with neuropeptide Y was found to produce a modest enhanced osteogenic effect. [ABSTRACT FROM AUTHOR]

AIMS: The European Society of Endodontology (ESE) is in the process of developing S3‐level clinical practice guidelines for the treatment of pulpal and apical disease. In order to support robust systematic literature reviews, appropriate outcome measures (OMs) with minimum follow‐up times must first be identified. Hence, the current project aimed to identify the appropriate OMs with minimum/maximum follow‐up time to assess the effectiveness of endodontic treatment for pulpitis and apical periodontitis for use in the development of ESE S3‐level guidelines through a standard consensus‐based methodology. METHODOLOGY: After a literature search, lists of relevant OMs were identified by the guideline development group (GDG) for the treatment of pulpitis (working group [WG] 1), the non‐surgical treatment of apical periodontitis (WG 2), the surgical treatment of apical periodontitis (WG 3) and the regenerative treatment of apical periodontitis (WG 4). OMs relevant to each WG were ranked by the 43 members of the GDG in their importance to the patient using a 9‐point Likert scale. Items with a score of 7–9 (critical importance) by more than 70% and items with a score of 1–3 (limited importance) by less than 30% of members were included, whereas the items with a score of 1–3 by more than 70% and items with a score of 7–9 by less than 30% were excluded. Several online Delphi meetings established an edited list of only important OMs. The ranked OMs were discussed by the GDG and harmonized to produce 'most critical', 'critical' and 'important' measures. After establishing the final ranked measures, the minimum and maximum length of follow‐up related to each OM was defined by the guideline steering group. RESULTS: The Delphi survey took place over two rounds. The patient‐reported outcome measure (PROM) 'tooth survival' was rated the 'most critical measure' in all four WGs, while other PROMs including 'pain' and 'need for medication' were considered 'critical', alongside the clinician‐reported outcome measures (CROM), 'radiographic assessment'. The PROMs 'The need for further intervention' and 'oral‐health‐related‐quality‐of‐life' (OHRQoL) were included, but as 'important' not 'critical' measures. Differences occurred between WGs with 'vitality testing' defined as critical in WG1 and 'increased length and width of the root' defined as 'critical' in WG4. A minimum of 1‐year and maximum of 'as long as possible' for all OMs were deemed necessary, except 'pain', 'swelling', 'medication' and 'OHRQoL', where shorter follow‐up was accepted. CONCLUSIONS: The GDG consensus process established the PROM "tooth survival" as the "most‐critical". The identified OMs and length of follow‐up will be applied to all the commissioned systematic reviews that will inform the subsequent process when developing the ESE S3‐level clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Aim: To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. Methodology: The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t‐test or ANOVA with the level of significance set at p ≤.05. Results: Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p =.0001 and.000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C‐C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p =.0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p <.001) and MMP9 (p <.05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 (p <.001) but had no significant effect on the other biomarkers. Conclusions: AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted. [ABSTRACT FROM AUTHOR]

Bioactive materials offer particular clinical benefits in the field of dental implantology, where differentiation of stem cells towards an osteoblastic lineage is required for osseointegration and appropriate function of implants in vivo. The aim of this study was to evaluate the osteoblastic response of Stro-1 +ve periodontal ligament stem cells (PDLSCs) to three well-characterized biomaterial surfaces: an abraded titanium surface (cpTi) control; a polycrystalline titanium surface, with both micro and nanotopography produced by radio frequency magnetron sputtering (TiTi); and the same surface incorporating a sputter deposited calcium phosphate coating (CaP-TiTi). The CaP-TiTi surfaces were nonstoichiometric, carbonated, and calcium rich with a Ca/P ratio of 1.74. PDLSCs were grown on each surface in the absence of supplementary osteogneic-inducing agents. Osteoblastic responses were assessed for up to 21 days in culture by measuring gene expression using real time q-PCR and via assessment of intracellular alkaline phosphatase (ALP) activity. Gene expression analysis for the CaP-TiTi surfaces showed a significant late stage up-regulation of Secreted Phosphoprotein 1. Additionally, there was a significant up-regulation of the Wnt signaling genes β-catenin and Wnt Family Member 5 A on days 14 and 21, respectively for the CaP-TiTi surface. A significant increase in intracellular ALP at day 21 for the CaP-TiTi surface was also observed. These data suggest that the CaP-TiTi surfaces provide the bioactive conditions required for direct osteoblastic differentiation of PDLSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1692-1702, 2017. [ABSTRACT FROM AUTHOR]

Background Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa. Aim To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan. Methods The investigation was a case-control design. Cases with AgP ( n = 132) and controls ( n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom Mass ARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency ( MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP. Results One candidate gene rs1537415 ( GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan ( n = 147) and remained significant ( p = 0.013) after correction for multiple testing. Conclusion The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that the sympathetic nervous system may have a role in modulating neurogenic inflammation and bone remodelling. Neuropeptide Y (NPY) is a well-characterized neuropeptide transmitter in the peripheral sympathetic nervous system. NPY is known to be present in human dental pulp; however, quantitative data on NPY levels in pulpal health and disease in an adult population remain to be determined. The aims of the current study were to assess, quantitatively, NPY levels by radioimmunoassay and confirm the distribution of NPY fibres by immunocytochemistry in carious and non-carious adult human pulp tissue. Our results suggest changes in the levels and distribution of NPY in human dental pulp during the caries process, with significantly higher levels of NPY in carious compared with non-carious adult human teeth. Within the carious samples studied, our finding, that NPY levels were significantly elevated in mild/moderate caries, concurs with the hypothesis that NPY could have a modulatory role in pulpal inflammation and in reparative dentine formation. [ABSTRACT FROM AUTHOR]

Background: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa., Aim: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan., Methods: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP., Results: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing., Conclusion: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)