Outcome of Pulpotomy
Outcome of Pulpotomy
com/scientificreports
                                 Treatment planning is key to clinical success. Permanent teeth diagnosed with “irreversible
                                 pulpitis” have long been implied to have an irreversibly damaged dental pulp that is beyond repair
                                 and warranting root canal treatment. However, newer clinical approaches such as pulpotomy, a
                                 minimally invasive and biologically based procedure have re-emerged to manage teeth with pulpitis.
                                 The primary aim of the study was to conduct a meta-analysis to comprehensively estimate the
                                 overall success rate of pulpotomy in permanent teeth with irreversible pulpitis as a result of carious
                                 pulp exposure. The secondary aim of the study was to investigate the effect of predictors such as
                                 symptoms, root apex development (closed versus open), and type of pulp capping material on the
                                 success rate of pulpotomy. Articles were searched using PubMed, Scopus, CENTRAL, and Web of
                                 Science databases, until January 2021. Outcomes were calculated by pooling the success rates with
                                 a random effect model. Comparison between the different subgroups was conducted using the z
                                 statistic test for proportion with significance set at alpha = 0.05. A total of 1,116 records were retrieved
                                 and 11 studies were included in the quantitative analysis. The pooled success rate for pulpotomy
                                 in teeth with irreversible pulpitis was 86% [95% CI: 0.76–0.92; I2 = 81.9%]. Additionally, prognostic
                                 indicators of success were evaluated. Stratification of teeth based on (1) symptoms demonstrated
                                 that teeth with symptomatic and asymptomatic irreversible pulpitis demonstrated success rate of
                                 84% and 91% respectively, with no significant difference (p = 0.18) using z-score analysis; (2) open apex
                                 teeth demonstrated a significantly greater success rate (96%) compared to teeth with closed apex
                                 (83%) (p = 0.02), and (3) pulp capping materials demonstrated that Biodentine yielded significantly
                                 better success rates compared to Mineral Trioxide Aggregate (MTA), calcium hydroxide, and Calcium
                                 Enriched Mixture (CEM.) Collectively, this is the first meta-analytical study to determine the clinical
                                 outcome of pulpotomy for carious teeth with irreversible pulpitis and it’s predictors for success.
                                 Moreover, we identify the stage of root development and type of biomaterial as predictors for success
                                 of pulpotomy.
                                  According to the Global Burden of Disease census, untreated dental caries in permanent teeth is the most
                                  prevalent health condition1. Failure to treat dental caries can lead to the spread of bacteria and their toxins
                                  into the dental pulp causing varying degrees of i nflammation2. From a clinical point of view, pulpal inflamma-
                                  tion is dichotomously classified as “reversible” or “irreversible” based on the presumed ability of the pulp to
                                 heal3. According to AAE Consensus Conference Recommended Diagnostic T            erminology3, irreversible pulpitis
                                  is defined as “A clinical diagnosis based on subjective and objective findings indicating that the vital inflamed
                                  pulp is incapable of healing and that root canal treatment is indicated.”. As a result, pulp extirpation remains to
                                  be the mainstay treatment option for teeth diagnosed with irreversible pulpitis3. However, the validity of the
                                  diagnostic term “irreversible pulpitis” has come into question as an emerging body of evidence has shown that
                                 1
                                  Department of Endodontics, Virginia Commonwealth University School of Dentistry, Richmond, VA 23298,
                                 USA. 2Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl
                                 Drive, San Antonio, TX 78229, USA. 3Department of Population Health Sciences, UT Health San Antonio, 7703
                                 Floyd Curl Drive, San Antonio, TX 78229, USA. *email: ruparel@uthscsa.edu
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                                            Focused question. This study adhered to the PIO framework to address the following clinical question:
                                            “What is the success rate of pulpotomy in human permanent teeth with a diagnosis of irreversible pulpitis?”,
                                            wherein the population (P) is “human permanent teeth with irreversible pulpitis as a result of carious pulp expo-
                                            sure”; intervention (I) is “pulpotomy”; outcome of interest (O) is “success rate based on clinical and radiographic
                                            criteria”.
Inclusion criteria.
                                            1. Original clinical data namely, clinical trials, prospective and retrospective observational studies reporting
                                               on pulpotomy in human permanent teeth
                                            2. Teeth with carious pulp exposure and signs and symptoms suggestive of irreversible pulpitis
                                            3. Studies that had appropriate use of both clinical and radiographic criteria to judge and report success rate.
                                               Clinical success was defined as absence of clinical manifestations such as pain on percussion/palpation and
                                               spontaneous pain, and devoid of need for further root canal treatment. Radiographic success was defined
                                               as maintenance of normal periapical tissues (in case of absence of pre-operative lesions) or complete or
                                               continued healing of periapical tissues (in case of presence of pre-operative lesions).
                                            4. Minimum follow up period of 6 months
                                            5. English language only
Exclusion criteria.
                                            Search strategy.      Electronic search was conducted by two independent reviewers (A.A. and B.P.) using
                                            databases such as PubMed, Scopus, CENTRAL, and Web of Science. Keywords pertinent to the topic in question
                                            were used in various combinations using Boolean operators to extract the relevant studies. Search strategy used
                                            on PubMed was adapted for other databases (Supplementary Table S1). Articles published between January 1960
                                            and January 2021 were included in the screening process. In addition, the bibliography of included articles and
                                            review papers were screened to find any missing studies. The identified studies were then exported into Mende-
                                            ley reference manager (Mendeley Desktop, version 1.17.11; Mendeley Ltd., George Mason University, Fairfax,
                                            VA) and any duplicate articles were removed.
                                            Study selection process. A two-phase search strategy was followed, wherein two independent reviewers
                                            (A.A. and B.P.) screened the titles and abstract of all extracted articles in the first phase and subjected them to the
                                            inclusion/exclusion criteria to perform preliminary elimination of ineligible studies. In the second stage, full text
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                                  of the articles was retrieved and evaluated for inclusion in the meta-analysis. Any duplication of data presented
                                  in studies was noted and eliminated for statistical analysis. Any disagreements in the search and screening pro-
                                  cess between the reviewers was resolved by discussion.
                                  Data extraction.         Two independent reviewers (A.A., B.P.) performed data extraction from eligible stud-
                                  ies using customized data retrieval forms on Microsoft Excel (Microsoft Office; Microsoft, Redmond, WA).
                                  Extracted data included author/year, study design, sample size, diagnosis, root apex development (open or
                                  closed), capping material, pulpotomy type (partial or full), proportion of successful cases, follow up period, and
                                  recall rate. In cases of duplication of data amongst different studies, study with the maximum follow up period
                                  was included for cumulative analysis. In studies reporting on mixed clinical scenarios, efforts were made to
                                  extract raw data pertinent to the inclusion criteria and for evaluating secondary objectives of the meta-analysis.
                                  In case of missing information, authors of the reports were contacted via email to gather further details.
                                  Quality evaluation of included studies. The risk of bias of included studies was assessed based on the
                                   study design. The non-randomized studies were assessed by modified Down and Black’s c hecklist14. This check-
                                  list is based on 27 questions divided amongst 5 different sections: reporting, external validity, internal validity,
                                  confounding and selection bias, and power of the study. The total score ranging from 0 to 28 was assigned to each
                                  study14. Randomized clinical trials were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool15,16. This tool has
                                   fixed domains with signaling questions which can derive information about key aspects of clinical trials relevant
                                   to risk of bias. Studies can be rated as having “low”, “some concerns” or “high” risk of bias. The assessments were
                                   performed by two examiners (A.A., B.P.). Any discrepancy in quality evaluation was resolved via discussion.
                                   Data synthesis and statistical analysis. The primary outcome formulated after data collection was the
                                   overall success rate of pulpotomy in cariously involved permanent teeth with irreversible pulpitis. The goal of the
                                   subgroup analysis was to assess secondary outcomes which included comparison of success rate under different
                                   clinical contexts. This included estimation of outcome based on symptoms (symptomatic versus asymptomatic),
                                   stage of root apex development (closed versus open), and pulp capping material used.
                                        All the outcomes were calculated by pooling the success rates with a random effect m    odel17. Heterogeneity
                                   across the studies was assessed using Cochrane I2 statistic (I2 value of > 60% was considered as significant hetero-
                                   geneity)18. Comparison between the different subgroups was conducted using the z statistic test for proportion
                                   with significance set at alpha = 0.05. Publication bias was assessed using funnel plot and performing the Egger’s
                                   test19. In case of publication bias, trim and fill method was used to impute missing studies and adjust the effect of
                                  bias20. Comprehensive Meta-Analysis (Version 3; Biostat, Englewood, NJ) software package was used to perform
                                  the meta-analyses and publication-bias analyses.
                                  Results
                                  Selected studies. The study selection process is outlined in Fig. 1. The initial search yielded 1,116 records,
                                  out of which 866 were screened based on title and abstract. After exclusion of 835 articles, 31 full text arti-
                                  cles were retrieved and screened for eligibility. 11 studies met the inclusion c riteria7,22–31, and relevant data was
                                  extracted for performing the meta-analysis. Reasons for exclusion of each full text article is listed in Supplemen-
                                  tary Table S2. Overall, there were 5 randomized control t rials22,25,27–29, 5 prospective clinical s tudies23,24,26,30,31 and
                                  one retrospective study7. The details and characteristics of included studies7,22–31 are outlined in Table 1.
                                  Quality assessment. After analysis using modified Downs and black’s checklist, the quality assessment of
                                  non-randomized studies7,23,24,26,30,31 revealed all studies to be of fair quality (Supplementary Table S3). For rand-
                                  omized control trials assessed with the RoB 2 tool, 2 studies had “some concerns” with risk of b      ias27,28, whereas
                                                                   22,25,29
                                  3 studies had “low” risk of bias         (Supplementary Table S4).
                                   Primary analysis. Pooled success rate of pulpotomy in IP. After combining the results from 11 selected
                                  studies7,22–31 with random effects model, the overall pooled success rate of pulpotomy in carious permanent teeth
                                   with irreversible pulpitis (asymptomatic and symptomatic) was 86% [CI: 0.76–0.92] with significant heterogene-
                                   ity across the studies (I2 = 81.9%) (Fig. 2).
                                  Subgroup analysis. Pooled success rate of pulpotomy in teeth diagnosed with symptomatic and asymptomatic
                                  irreversible pulpitis. The data were further analyzed to assess the outcome of pulpotomy in carious teeth with
                                  symptomatic versus asymptomatic irreversible pulpitis. This resulted in 9 studies7,22–29 meeting the inclusion cri-
                                  teria of symptomatic irreversible pulpitis, which were combined to yield a success rate of 84% [CI: 0.72–0.92],
                                  with a significant heterogeneity across the studies (I2 = 83.3%) (Fig. 3). Data from 3 studies26,30,31 reporting on
                                  asymptomatic irreversible pulpitis were combined to yield a success rate of 91.3% [CI: 0.80–0.96.5], with no
                                  observed statistical heterogeneity across the studies (I2 = 0.00%) (Fig. 4). On comparing symptomatic versus
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                                            asymptomatic teeth, there was no significant difference observed in terms of pulpotomy success rate (z value for
                                            proportion: −1.34; p = 0.18).
                                             Pooled success rate of pulpotomy for irreversible pulpitis in teeth with closed versus open apex. The data were
                                             stratified to identify the effect of closed versus open root apex on success rate of pulpotomy in carious teeth
                                             with irreversible pulpitis. 8 studies23–28,30,31 were identified with pulpotomy performed in teeth with complete
                                             root development (closed apex); after pooling these studies with random effects model, the overall success rate
                                             of pulpotomy in teeth with irreversible pulpitis and closed apex was 83% [CI: 0.69–0.91], with significant het-
                                             erogeneity amongst the studies (I2 = 82%) (Fig. 5). In comparison to teeth with closed apices, there were only 3
                                            studies24,26,29 reporting on pulpotomy in teeth with incomplete root development (open apex), which demon-
                                             strated a cumulative success rate of 95.8% [CI: 0.81–0.99], with no evidence of heterogeneity across the studies
                                             (I2 = 0.00%) (Fig. 6). Open apex teeth demonstrated a significantly higher success rate when compared to teeth
                                             with closed apex (z value for proportion: 2.33; p = 0.02).
                                            Pooled success rate of pulpotomy for irreversible pulpitis in teeth restored with various pulp capping materials. The
                                            effect of pulp capping materials on success rate were compared with indirect comparisons between studies7,22–31.
                                            Biodentine demonstrated a statistically significant higher success rate when compared to MTA, Calcium
                                            Enriched Mixture (CEM), and calcium hydroxide. MTA yielded a significantly higher success rate when com-
                                            pared to calcium hydroxide; however, it was not significantly superior to CEM. Similarly, there was no significant
                                            difference observed between CEM and calcium hydroxide (Supplementary Table S5).
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                                           Table 1.  Characteristics of the included studies in the systematic review. IP—irreversible pulpitis, SIP—
                                           symptomatic irreversible pulpitis, AIP—asymptomatic irreversible pulpitis, MTA—mineral trioxide aggregate,
                                           BD—biodentine, CEM—calcium enriched mixture, Ca(OH)2—calcium hydroxide, n—successful outcomes,
                                           N—sample size, NR—not reported.
                                           Figure 2.  Success rate of pulpotomy in carious teeth with irreversible pulpitis. ∫ corresponds to reference
                                           number 23, whereas * corresponds to reference number 24.
                                               Visual analysis of the funnel plot and Egger’s regression test (p < 0.04) indicated potential publication bias
                                           (Supplementary Table S6). Using the “trim and fill” method, 4 studies were imputed to the left of the funnel
                                           plot, which yielded a point estimate of 0.786 (95% CI: 0.66–0.87). This point estimate, subsequent to adjusting
                                           for potential publication bias, indicates a 78.6% success rate of pulpotomy in teeth with irreversible pulpitis.
                                           Grading of evidence. The certainty of evidence was graded as “very low” (Table 2), which means that the
                                           true effect is probably markedly different from the estimated effect of 86% pooled success of pulpotomy in cari-
                                           ous teeth with irreversible pulpitis.
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                                            Figure 3.  Success rate of pulpotomy in carious teeth with symptomatic irreversible pulpitis. ∫ corresponds to
                                            reference number 23, whereas * corresponds to reference number 24.
Figure 4. Success rate of pulpotomy in carious teeth with asymptomatic irreversible pulpitis.
                                            Discussion
                                            Pulpotomy, an often-overlooked vital pulp therapy procedure, has now re-emerged as a minimally invasive,
                                            biologically based treatment option for teeth diagnosed with pulpitis and involves partial/ complete removal
                                            of coronal pulp tissue, following which a biocompatible material is placed onto the pulp tissue to promote
                                            healing6. Specifically, it was seldom used as a definitive treatment modality in teeth with symptomatic irreversible
                                             pulpitis based on diagnostic modalities that predominantly serve to assess neuronal function as a measure of
                                             pulpal health32. However, with recent advances in newer biocompatible, anti-inflammatory and osteo-inductive
                                            biomaterials, the face of VPT has e volved32. Therefore, we conducted a systematic review and meta-analysis to
                                            assess the outcome of pulpotomy in teeth with irreversible pulpitis using available clinical data. With very low
                                            certainty, our study demonstrates pulpotomy to be a successful intervention for carious teeth with irreversible
                                            pulpitis with a favorable outcome of 86%. Our results substantiate the findings by Cushley et al., wherein success-
                                            ful outcomes were demonstrated in 88% of cases at 3-years12. Additionally, the present study computed success
                                            rates using meta-analytical methods to include relative weight of each study and allows for random variation in
                                            the success rate among studies. The present study also performed a comprehensive assessment of risk factors on
                                            the outcome of clinical success. Our results of this subset analyses evaluated the following variables/risk factors:
                                            teeth diagnosed with symptomatic versus asymptomatic irreversible pulpitis, teeth with mature (closed) versus
                                            immature (open) root apex, and choice of pulp capping material used.
                                                 Based on the clinical presentation and diagnostic testing, irreversible pulpitis is classified as symptomatic
                                            or asymptomatic3. In symptomatic cases, pulpotomy has traditionally been used as an emergency procedure to
                                             relieve pain33. In addition, presence of acute preoperative symptoms is typically regarded as a negative outcome
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                                        Figure 5.  Success rate of pulpotomy in carious closed apex teeth with irreversible pulpitis. ∫ corresponds to
                                        reference number 23, whereas * corresponds to reference number 24.
                                        Figure 6.  Success rate of pulpotomy in carious open apex teeth with irreversible pulpitis. ∫ corresponds to
                                        reference number 23.
                                        Table 2.  Grading of recommendations assessment, development and evaluation approach to grade quality of
                                        evidence. There are some concerns with the randomization process and in the measurement of outcome. There
                                        are serious concerns with the inconsistency as evidenced by the significant heterogeneity amongst studies.
                                        Total number of subjects with successful outcome is less than 400. There are some concerns with controlling
                                        the confounding factors. Overall effect size is too large compared to the sample size.
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                                            predictor for long-term success of V    PT34, thereby precluding application of pulpotomy as a definitive treatment
                                            modality. However, in this meta-analysis, we demonstrate a success rate of 84% of pulpotomy in teeth with SIP,
                                            which was not significantly different from the outcome observed in teeth with asymptomatic irreversible pul-
                                            pitis. Studies that included teeth with symptomatic irreversible pulpitis defined these cases as teeth with either
                                            spontaneous pain and/or pain exacerbated by cold stimuli with prolonged episodes of pain even after the thermal
                                            stimulus had been removed7,22–27.This favorable outcome in symptomatic irreversible pulpitis can be attributed
                                            to the fact that pulpotomy procedures regulate immune responses and can reduce levels of pro-inflammatory
                                            cytokines within the dental pulp35. In addition, histologic studies have demonstrated that in teeth with irreversible
                                            pulpitis, the damage and inflammation was mostly confined to only a portion of the coronal pulp, with the rest
                                            of the coronal and radicular pulp being intact and healthy4. Furthermore, anti-inflammatory properties of new
                                            generation tricalcium silicate materials promote reversal of residual inflammation and maintenance of a healthy
                                            pulp tissue thereafter36. Collectively, these above mentioned reasons suggest that the removal of the coronally
                                            inflamed pulp might be sufficient to maintain viability and health of the radicular pulp, making pulpotomy an
                                            effective emergency procedure as well as a definitive treatment modality in this subset of patient population.
                                                Traditional VPT procedures were aimed at promoting continued root development (apexogenesis)37. There-
                                            fore, clinically, teeth with fully formed apices (closed apex) were excluded from VPT case selection. However,
                                            with the growing knowledge about the repair potential of the dental p       ulp38, VPT such as pulpotomy protocols
                                            have been introduced to treat teeth with closed apex with a diagnosis of irreversible p       ulpitis12. The results from
                                            this meta-analysis demonstrate that pulpotomy in teeth with closed apex yields a cumulative success rate of 83%.
                                            In contrast, teeth with open apex demonstrated a significantly favorable outcome. This can be attributed to the
                                            increased vascularity and cellularity of pulp in immature t eeth39. In addition, aging of dental pulp is associated
                                            with reduced regenerative potential of dental stem c ells40. However, with a success rate of 83% in mature teeth
                                            with irreversible pulpitis, pulpotomy should be considered a viable and definitive treatment approach in these
                                            cases. These results are in accordance with the findings demonstrated by Tan et al.34 and Kunert et al.41, wherein
                                            favorable success rates were reported for both young immature as well as mature teeth.
                                                Pulp capping agents can affect the outcome of pulpotomy p        rocedures37. Traditionally, calcium hydroxide
                                            has been the most popular pulp capping agent, owing to its antimicrobial nature and the capability to form a
                                            hard tissue barrier; however, issues such as high solubility, lower mechanical resistance and presence of tun-
                                            nel defects in the mineralized barrier were reported as concerns especially for vital pulp therapy p         rocedures42.
                                            Tricalcium silicate-based materials such as MTA and alike have now become the material of choice for pul-
                                            potomy because of several added advantages such as biocompatibility, reduced microleakage, ability to induce
                                            a thicker dentinal bridge with fewer defects and ability to release growth factors from dentin36,41. MTA as a
                                            pulp capping material has few disadvantages such as its potential to discolor tooth and high solubility owing
                                            to the slow setting reaction43. Other bioceramic materials such as Biodentine and CEM have been introduced
                                            to overcome these shortcomings of MTA. In contrast to MTA, Biodentine has been demonstrated to cause
                                            lesser tooth discoloration44. CEM is another bioceramic material introduced in 2006 with properties similar to
                                            MTA, however with better physical characteristics and shorter setting time45. We therefore wanted to evaluate
                                            the success rate of pulpotomy in teeth with irreversible pulpitis based on the types of biomaterial used. In our
                                            meta-analysis, Biodentine demonstrated to be superior to other pulp capping materials, in terms of success rate
                                            for pulpotomy. This finding might be attributed to the ability of biodentine to cause a greater release of calcium
                                            ions and bioactive growth factors46. MTA was found to be superior to calcium hydroxide, which corroborates the
                                            results from study done by Li et al.32. Interestingly, CEM and calcium hydroxide demonstrated similar success
                                            rates. Collectively, these data suggest that use of bioceramic pulp capping materials such as MTA and Biodentine
                                            can lead to more favorable clinical outcomes in teeth with irreversible pulpitis. Our findings substantiate the
                                            results of a recent systematic review by Sabeti et al., wherein a 93% success rate with VPT procedures utilizing
                                            bioceramic pulp capping materials was o      btained47.
                                                From a clinical and research point of view, there are several factors in vital pulp therapy, which still need
                                            to be standardized. There is a lack of agreement regarding the indications for pulpotomy procedures48. This is
                                            partly attributable to the diagnostic ambiguity of our current pulp testing methods to establish the true inflam-
                                            matory status of p   ulp38. As for the choice of type of pulpotomy, there is some evidence that full pulpotomy is
                                            more successful than partial pulpotomy especially in cases with irreversible p       ulpitis9. Interestingly, most of the
                                            included studies in our meta-analysis employed full coronal pulpotomy7,23,24,26–31, therefore a subset analysis based
                                            on type of pulpotomy was not performed. Traditionally, a minimum of 3–6 months follow up time has been
                                            established to determine the prognosis of a vital pulp therapy procedure49–51. This follow up time point interval
                                            is critical, as majority of the early failures present during this period and it has been demonstrated that pain or
                                            symptoms during the first 3 months after VPT are associated with poor outcomes49. Accordingly, studies with at
                                            least a 6-month follow up period were included in this meta-analysis7,22–31. The included studies had intra- and
                                            inter- study variation in patient recruitment which led to a wide range of follow up periods. In addition, only
                                            select studies reported on long term outcomes (> 2 years) of VPT procedures7,22,26,27,30. As a result, data was not
                                            analyzed based on specific follow up time intervals. Regarding the coronal seal after pulpotomy, all the included
                                            studies had either a permanent restoration placed immediately after the procedure or a glass ionomer liner
                                            placement followed by a temporary restoration. None of the studies delayed the placement of final restoration
                                            beyond a month’s duration7,22–31.
                                                Our study has some limitations and should be interpreted with caution. One of the limitations was the
                                            considerable heterogeneity across the included s tudies7,22–31. This heterogeneity could be attributed to multiple
                                            factors such as variation in study design, patient selection, type of pulpotomy, choice of biomaterial, and follow
                                            up period, to mention a few. However, we explored the reasons for heterogeneity in our meta-analysis by per-
                                            forming subgroup analysis. No heterogeneity was reported when analysis was restricted to immature teeth and
                                            asymptomatic teeth subgroups. None of the other studied variables could resolve the observed heterogeneity
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                                  in the meta-analysis. Another key limitation to note is the inconsistency of the included studies with the use of
                                  sensibility testing at follow-up periods7,22–31. Only 4 studies utilized sensibility testing as a criterion at follow-up
                                  appointments to evaluate success22,25,30,31. Therefore, while radiographic assessment satisfies one of the criteria
                                  for disease-centered outcome, inclusion of vitality of treated teeth would define a true disease-centered outcome
                                  and greatly increase the pragmatic significance to both, clinicians and patients.
                                      There are several confounding moderators, which need to be taken into account and should be consistently
                                  reported in future vital pulp therapy research. These include patient and tooth specific factors (such as age, gen-
                                  der, tooth type), operator factors (investigator specialty and experience), technical factors (type of pulpotomy,
                                  details of hemostatic agent used and time for hemostasis, choice of biomaterial and permanent restoration) and
                                  data from recall appointments. Having these factors reported in future studies will help other researchers and
                                  clinicians to understand the outcomes better and will also improve the applicability and generalizability of the
                                  results.
                                  Conclusion
                                  The success rate obtained in this meta-analysis adds to the emerging body of evidence supporting the role of
                                  pulpotomy as a definitive treatment modality in carious teeth with irreversible pulpitis. Given the potential of
                                  pulpotomy in managing teeth with pulpitis and global rise in minimally invasive dentistry, there is a tremendous
                                  need for conducting well-designed randomized clinical trials on this understudied topic.
                                  Data availability
                                  The datasets generated during and/or analyzed during the current study are available from the corresponding
                                  author on reasonable request.
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                                            Author contributions
                                            A.A., N.B.R., and B.P. designed research; A.A., N.B.R. and J.G. conducted research and analyzed data; A.A.,
                                            N.B.R., J.G. and B.P. wrote the manuscript; A.A. and B.P. evidence certainty assessment; A.A. and J.G. statistical
                                            data; A.A., B.P. and N.B.R. analyzed and interpreted data; A.A. and N.B.R. had primary responsibility for final
                                            content. All authors read and approved the final manuscript and all authors agree to be accountable for all aspects
                                            of work ensuring integrity and accuracy.
                                            Funding
                                            This research work did not receive any specific grant from funding agencies in the public, commercial, or not-
                                            for-profit sectors.
                                            Competing interests
                                            The authors declare no competing interests.
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