Effectiveness of full Pulpotomy compared with Root canal treatment in managing teeth with signs and symptOms indicative of irreversible pulpitis: a protocol for prospectiVE meta-analysis of individual participant data of linked randomised clinical trials (PROVE).

BACKGROUND: Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment. METHODS: Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists. RESULTS: The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023. DISCUSSION: PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development. TRIAL REGISTRATION: PROSPERO CRD42023446809. Registered on 08 February 2023.

Alterations of mitochondrial dynamics, inflammation and mineralization potential of lipopolysaccharide-induced human dental pulp cells after exposure to N-acetyl cysteine, Biodentine or ProRoot MTA.

AIM: To investigate the effects of N-acetyl cysteine (NAC), Biodentine, ProRoot MTA and their combinations, on cell viability, mitochondrial reactive oxygen species (mtROS) production, mineralization and on the expression of genes related to inflammatory cytokine production, mitochondrial dynamics and cell apoptosis of lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs). METHODOLOGY: Isolated hDPCs were exposed to 20 µg mL-1 of Escherichia coli (E. coli) LPS for 24 h, before the experiment, except for the control group. Eight experimental groups were assigned: (i) control (hDPCs cultured in regular medium), (ii) +LPS (hDPCs cultured in LPS medium throughout the experiment), (iii) -LPS/Media, (iv) -LPS/BD, (v) -LPS/MTA, (vi) -LPS/NAC, (vii) -LPS/BD + NAC and (viii) -LPS/MTA + NAC. Cell viability was measured using Alamar blue assay at 24 and 48 h. Production of mtROS was evaluated at 6 and 24 h by MitoSOX Red and MitoTracker Green. The expressions of IL-6, TNF-α, Bcl-2, Bax, Mfn-2 and Drp-1 genes were investigated at 6 h using reverse transcriptase-polymerase chain reaction (RT-PCR). For differentiation potential, cells were cultured in the osteogenic differentiation media and stained using Alizarin red assay at 14 and 21 days. The Kruskal-Wallis test, Mann-Whitney U test and one-way anova were performed for statistical analysis. RESULTS: NAC was associated with significantly greater LPS-induced hDPC viability (P < 0.05). Both Biodentine and MTA extracts promoted cell survival, whereas the combination of NAC to these material extracts significantly increased the number of viable cells at 24 h (P < 0.05). Biodentine, MTA or NAC did not alter the mtROS level (P > 0.05). NAC supplementation to the MTA extract significantly reduced the level of IL-6 and TNF-α expression (P < 0.05). Regarding mitochondrial dynamics, the use of NAC alone promoted significant Mfn-2/Drp-1 expression (P < 0.05). Most of the groups exhibited a level of Bcl-2/Bax gene expression similar to that of the control group. The increases in mineralization productions were observed in most of the groups, except the LPS group (P < 0.05). CONCLUSIONS: The antioxidant effect of NAC was not evident under the LPS-induced condition in DPC in vitro. NAC combined either with Biodentine or MTA improved LPS-induced hDPCs survival at 24 h. The combination of NAC with MTA promoted mineralization.

Biodentine™ Partial Pulpotomy of a Young Permanent Molar with Signs and Symptoms Indicative of Irreversible Pulpitis and Periapical Lesion: A Case Report of a Five-Year Follow-Up.

The purpose of this paper was to report the five-year success of Biodentine™ partial pulpotomy in a young permanent molar, with signs and symptoms indicative of irreversible pulpitis and periapical lesion, in a nine-year-old girl. Preoperative clinical examination revealed a large carious lesion of the left mandibular permanent first molar. The patient reported pain on percussion. The tooth responded positively to the electric pulp test and had lingering pain after cold testing. A periapical radiograph showed a deep carious lesion and periapical lesion. Based on the clinical and radiographical examination, the tooth had signs and symptoms indicative of irreversible pulpitis and periapical lesion. During caries removal, pulp exposure occurred, and 2-3 mm in depth of pulp tissue at the exposure site was removed. Haemorrhage was controlled within four minutes with 2.5% sodium hypochlorite-moistened cotton pellets. Biodentine™ was then applied as both a pulp dressing and a temporary restoration. At the following visit, composite resin was placed over the Biodentine™ as a final restoration. During a five-year follow-up, the tooth was asymptomatic, had positive responses to sensibility tests, and had no discolouration. Follow-up radiographs showed a dentine bridge and periapical healing.

Partial pulpotomy with two bioactive cements in permanent teeth of 6- to 18-year-old patients with signs and symptoms indicative of irreversible pulpitis: a noninferiority randomized controlled trial.

AIM: To compare the outcome of partial pulpotomy using two cements, ProRoot MTA (Dentsply, Tulsa Dental Specialties, Tulsa, OK, USA) and Biodentine (Septodont, Saint-Maur-des-Fossés, France), in permanent teeth of 6- to 18-year-old patients with signs and symptoms indicative of irreversible pulpitis. Furthermore, the frequencies of perceptible grey discoloration caused by the cements were compared. METHODOLOGY: Sixty-nine permanent first molars with signs and symptoms indicative of irreversible pulpitis, from 69 patients, were included. All operators performed partial pulpotomy under a standardized protocol. Teeth were allocated, using a website-generated number of simple randomization, to partial pulpotomy with either ProRoot MTA (37 teeth) or Biodentine (32 teeth) and were restored with composite resin or stainless steel crowns. Patients were recalled every 6 months. To be categorized as having success, the evaluated tooth must have had both clinical and radiographic success. In addition, photographs of treated teeth were evaluated for frequency of perceptible grey discoloration. Success rates between the two cements were compared using the Fisher exact test. The frequencies of perceptible grey discoloration were compared using the chi-square test. The percentage difference was estimated by 95% confidence interval, and the level of significant difference was P < 0.05. RESULTS: At a mean follow-up of 32.2 ± 17.9 months, a total of 67 teeth, 37 with ProRoot MTA and 30 with Biodentine, were available for evaluation. The mean age of participants was 10 ± 2.1 years and, there were no differences in the baseline variables (gender, age, tooth type, periapical status, stage of root development, final restoration and follow-up period) between the groups. The overall success in both groups was 90%, with 92% for ProRoot MTA and 87% for Biodentine (difference, 5%; 95% confidence interval, -9% to 19%, P = 0.487), suggesting that Biodentine was noninferior to ProRoot MTA. Perceptible grey discoloration was observed in both groups, 80% for teeth treated with ProRoot MTA and 27% for teeth treated with Biodentine, with a significant difference between the materials (P < 0.001). CONCLUSIONS: Permanent teeth with signs and symptoms indicative of irreversible pulpitis in 6- to 18-year-old patients were successfully treated with partial pulpotomy using both cements. Biodentine exhibited significantly less frequency of discoloration than did ProRoot MTA.