Clinical effectiveness of pit and fissure sealants in primary and permanent teeth of children and adolescents: an umbrella review.

PURPOSE: This umbrella review aimed to critically appraise the evidence published in systematic reviews (SRs) on the clinical effectiveness of sealants compared with each other/the non-use in primary/permanent teeth of children and adolescents with at least 12-month follow-up. METHODS: A systematic literature search on 4 electronic databases was conducted up to January 18th, 2023. Following handsearching, two review authors independently screened retrieved articles, extracted data, and assessed the risk of bias (RoB) using the risk of bias in systematic reviews (ROBIS) tool. Based on a citation matrix, the overlap was interpreted by the corrected covered area (CCA). RESULTS: Of 239 retrieved records, 7 SRs met the eligibility criteria with a moderate overlap among them (CCA = 7.4%). For primary molars, in 1120 1.5- to 8-year-old children, data on the clinical effectiveness of sealants were inconclusive. For permanent molars, 3 SRs found a significant caries risk reduction for sealants versus non-use (≤ 36-month follow-up). There was insufficient evidence to proof superiority of sealants over fluoride varnish for caries prevention (3 SRs), and to rank sealant materials according to the best clinical effectiveness in permanent molars. One study was rated at low and 6 at high RoB, which did not allow for a valid quantitative synthesis. CONCLUSION: Considering the limitations of this umbrella review, sealants are more effective for caries prevention in children's permanent molars compared to no treatment. Future well-implemented RCTs are needed to draw reliable conclusions on the clinical effectiveness of sealants in primary and permanent teeth of children and adolescents.

Best clinical practice guidance for treating deep carious lesions in primary teeth: an EAPD policy document.

PURPOSE: The European Academy of Paediatric Dentistry (EAPD) has developed this best clinical practice guidance to help clinicians manage deep carious lesions in primary teeth. METHODS: Three expert groups conducted systematic reviews of the relevant literature. The topics were: (1) conventional techniques (2) Minimal Intervention Dentistry (MID) and (3) materials. Workshops were held during the corresponding EAPD interim seminar in Oslo in April 2021. Several clinical based recommendations and statements were agreed upon, and gaps in our knowledge were identified. RESULTS: There is strong evidence that indirect pulp capping and pulpotomy techniques, and 38% Silver Diamine Fluoride are shown to be effective for the management of caries in the primary dentition. Due to the strict criteria, it is not possible to give clear recommendations on which materials are most appropriate for restoring primary teeth with deep carious lesions. Atraumatic Restorative Technique (ART) is not suitable for multi-surface caries, and Pre-formed Metal Crowns (PMCs) using the Hall technique reduce patient discomfort. GIC and RMGIC seem to be more favourable given the lower annual failure rate compared to HVGIC and MRGIC. Glass carbomer cannot be recommended due to inferior marginal adaptation and fractures. Compomers, hybrid composite resins and bulk-fill composite resins demonstrated similar values for annual failure rates. CONCLUSION: The management of deep carious lesions in primary teeth can be challenging and must consider the patient's compliance, operator skills, materials and costs. There is a clear need to increase the use of MID techniques in managing carious primary teeth as a mainstream rather than a compromise option.

Clinical effectiveness of restorative materials for the restoration of carious lesions in pulp treated primary teeth: a systematic review.

PURPOSE: To systematically review the clinical performance of restorative materials after pulp therapy of carious primary teeth. It is part 2 of a systematic review on the clinical effectiveness of restorative materials for the management of carious primary teeth supporting the European Academy of Paediatric Dentistry (EAPD) guideline development. METHODS: Four electronic databases were systematically searched up to December 28th, 2020. Randomised controlled clinical trials (RCTs) on restorative materials for the restoration of carious primary teeth after pulp therapy were included. Failure rate, annual failure rate (AFR) and reasons for failure were recorded. Studies were sorted by restorative materials. The Cochrane Risk of bias tool for randomised trials (RoB 2.0) was used for quality assessment. RESULTS: After identification of 1685 articles and screening of 41 papers from EAPD review group 1, 5 RCTs were included. Restored primary molars with pulpotomy presented the following AFRs: composite resin (CR) 0%, preformed metal crowns (PMCs) 2.4-2.5%, resin-modified glass-ionomer cement combined with CR 3.8%, compomer 8.9%, and amalgam 14.3%. Maxillary primary incisors receiving pulpectomy exhibited AFRs of 0-2.3% for composite strip crowns (CSCs) depending on the post chosen. Reasons for failure were secondary caries, poor marginal adaptation, loss of retention and fracture of restoration. All studies were classified as high risk of bias. Meta-analyses were not feasible given the clinical/methodological heterogeneity amongst studies. CONCLUSION: Considering any limitations of this review, CR and PMCs can be recommended for primary molars after pulpotomy, and CSCs for primary incisors receiving pulpectomy. However, a need for further well-designed RCTs was observed.

Caries-inhibiting Effect of Microencapsulated Active Components in Pit and Fissure Sealants.

OBJECTIVE: The aim of the present in vitro study was to examine the caries-inhibiting effect of a pit and fissure sealant (PFS) containing ion-releasing microcapsules under cariogenic conditions in a biofilm artificial mouth. METHODS AND MATERIALS: Forty-eight human third molars were divided into four groups (n=12 per group). Fissures were extended with burs and sealed with experimental PFS. The four groups of specimens were treated as follows: 1) EPFS 1: EPFS (Premier Dental) of increasing viscosity, containing microcapsules loaded with remineralizing agents (calcium, phosphate, and fluoride ions); 2) US: fluoride-releasing PFS (UltraSeal XT plus, UltraDent Products, South Jordan, UT, USA); 3) EPFS 2: experimental PFS of constant viscosity containing microcapsules loaded with calcium, phosphate, and fluoride ions; and 4) FT: glass ionomer cement (GIC) (GC Fuji Triage CAPSULE WHITE glass ionomer cement, GC Europe NV, Leuven, Belgium). FT and US were used as control groups. EPFS 1 and EPFS 2 were the experimental groups. Specimens were stored in distilled water for 14 days at 37°C, subjected to 10,000 thermocycles (5°C and 55°C) and finally exposed to microbiological cycling in a Streptococcus mutans-based artificial mouth for 10 days. Replicas were made for scanning electron microscopic (SEM) evaluation and specimens were cut for fluorescence microscopy. RESULTS: Overall demineralization depths at the margin of Fuji Triage were significantly shallower than in the other groups (p<0.05). Overall demineralization depths adjacent to the experimental pit and fissure sealant EPFS 2 (59±15 µm) were comparable to the values of the resin-based pit and fissure sealant UltraSeal XT plus (58±10 µm, p≥0.05). SEM revealed surface roughness of the GIC-based PFS. CONCLUSIONS: The experimental PFS with microcapsules containing active components for remineralization did not show a caries-inhibiting effect compared to a fluoride-releasing resin-based PFS. Lower demineralization depths adjacent to GIC sealants indicate an anticariogenic effect through fluoride ion release.

Clinical effectiveness of restorative materials for the restoration of carious primary teeth without pulp therapy: a systematic review.

PURPOSE: To systematically search the available evidence and evaluate the clinical effectiveness of restorative materials for restoration of carious primary teeth. The findings aimed to support the European Academy of Paediatric Dentistry (EAPD) guidelines development. METHODS: Literature search was performed by searching 4 electronic databases for eligible randomised controlled clinical trials (RCTs) comparing restorative materials for the restoration of carious primary teeth up to December 28th, 2020. Quality assessment was performed with the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). RESULTS: Of 1685 identified articles 29 RCTs were finally deemed as eligible for inclusion. Annual failure rates were: Amalgam 1-28%; atraumatic restorative treatment 1.2-37.1%; glass-ionomer cement (GIC) 7.6-16.6%, metal-reinforced GIC 29.9%, resin-modified GIC 1.9-16.9%, high-viscosity GIC 2.9-25.6%; glass carbomer ≤ 46.2%; compomer 0-14.7%; composite resin (CR) 0-19.5%, bulk-fill CR 0-16.9%; zirconia crowns 3.3%, composite strip crowns 15%, and preformed metal crowns (Hall-Technique) 3.1%. Secondary caries, poor marginal adaptation, loss of retention, and fracture of restoration were reported as reasons for failure. Four studies were evaluated at unclear and 25 at high risk of bias. Clinical and methodological heterogeneity, and the diversity of tested materials across included studies did not allow for meta-analyses. CONCLUSIONS: Within the limitations of this systematic review, namely, the heterogeneity and the overall high risk of bias among included studies, clear recommendations based on solid evidence for the best restorative approach in primary teeth cannot be drawn. There is a need for future thoroughly implemented RCTs evaluating restorations in primary teeth to close this knowledge gap.

Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy.

Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.

Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells.

We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest. The theory is independent of which of the classically associated oncogenic mutations have already occurred. PACCs have been generally disregarded as senescent or dying cells. Our theory states that therapeutic resistance is driven by PACC formation that is enabled by accessing a polyploid program that allows an aneuploid cancer cell to double its genomic content, followed by entry into a nondividing cell state to protect DNA integrity and ensure cell survival. Upon removal of stress, e.g., chemotherapy, PACCs undergo depolyploidization and generate resistant progeny that make up the bulk of cancer cells within a tumor.

Prevalence of molar-incisor-hypomineralisation (MIH) among 6-12-year-old children in Central Hesse (Germany).

AIM: The aim of the present cross-sectional study was to assess and compare the prevalence of MIH among 6-12-year-old school children living either in a rural area of Central Hesse (Germany) or in the city of Frankfurt on the Main (Germany). A possible association between hypomineralised second primary molars (HSPM) and MIH was investigated. Furthermore, the MIH prevalence data of the rural area were compared with those of a previous study conducted in this area in the school year 2002/2003. METHODS: In the school year 2014/2015, 2103 children (6-12 years of age) were examined during the annual school-based dental examinations prescribed by law at nine schools in the rural area of Central Hesse (LDK) and five schools in the city of Frankfurt on the Main (Ffm). Eight previously calibrated dentists working for the public healthcare authorities assessed the prevalence of HSPM/MIH (EAPD criteria/severity scale by Wetzel and Reckel) and the caries experience (dmft/DMFT). RESULTS: The prevalence of HSPM/MIH amounted 3.2%/9.4% in LDK and 2.9%/17.4% in Ffm. In the majority of cases, children with MIH had demarcated opacities. In LDK, hypomineralised first permanent molars were most commonly affected by severity degree 2, whereas in Ffm, severity degree 1 was predominant. Children suffering from HSPM had an odds ratio of 11.32 (95% CI: 6.73-19.03) for having MIH as well. Compared with the results of 2002/2003 in LDK (prevalence of MIH 5.9%), the MIH prevalence increased by 3.5% in the rural area. All in all, the caries experience among children under investigation was low (DMFT 0.14-0.15). SIGNIFICANCE: MIH may be diagnosed in school children living in different areas of Germany with regional variations (rural-urban comparison). The presence of HSPM is of predictive value for MIH. The increasing number of hypomineralised first permanent molars over 12 years of time in the rural area indicates a need for further investigation on the aetiology of MIH.