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Aleksandar Jakovljević

Društvene mreže:

A. Jakovljević, H. Fransson, A. Bakhsh, J. Jaćimović, Ema Krdžović Lazić, Katarina Beljic Ivanovic, A. Lemic, Elisabetta Cotti, H. Duncan

BACKGROUND There is limited and conflicting data on the reduction of circulatory inflammatory mediators in patients with apical periodontitis (AP) following endodontic treatment. OBJECTIVE To answer the following research question: in adult healthy patients with AP [Population (P)], is there a difference before [Comparator (C)] and after various endodontic treatments (nonsurgical, surgical or retreatment) [Intervention (I)] on systemic levels of inflammatory biomarkers [Outcome (O)] in the follow-up period [Time (T)]? METHODS An electronic literature search was conducted in the databases Scopus, PubMed, Clarivate Analytics' Web of Science, Cochrane Database of Systematic Reviews and Grey literature from inception to July 2024 with no language restrictions. Observational studies examining changes in serum levels of inflammatory mediators were included. Two independent reviewers selected studies, extracted data and critically appraised the included studies. Qualitative and quantitative (meta-analysis) data synthesis methods were employed. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. RESULTS Sixteen studies met the inclusion criteria, of which six were included in the meta-analysis. These studies were published between 1992 and 2024, involving a total of 596 patients (54% females) aged between 16 and 75 years. The meta-analysis of pooled data showed a significant decrease in high-sensitive C-reactive protein (hs-CRP) levels in the serum of patients with AP 6 months after treatment [2.26 ± 1.76 versus 1.28 ± 1.06 mg/L, (Z = 2.03, p = .04)] and a decrease in interleukin-1β (IL-1β) levels 12 months after treatment [13.01 ± 5.95 versus 10.86 ± 3.52 pg/mL, (Z = 3.72, p < .01)]. One study was assessed as poor quality, while all others were considered high quality. DISCUSSION Despite the differences in methodologies across the included studies, it has been established that effective endodontic treatment leads to a reduction in systemic inflammatory biomarkers in the body. CONCLUSION Following effective endodontic treatment in patients with AP, the systemic levels of hs-CRP and IL-1β exhibit a significant reduction at 6 and 12 months, respectively. Further clinical studies should investigate whether effective endodontic treatment and reduced levels of investigated biomarkers may change the clinical presentation of systemic diseases. REGISTRATION PROSPERO database (CRD42024559271).

G. Tzanetakis, X. Petridis, A. Jakovljević, D. Koletsi, V. Nagendrababu, H. Duncan, P. Dummer

OBJECTIVES To evaluate the reporting quality of Scoping Reviews (ScRs) in endodontics according to the PRISMA Extension Checklist for Scoping Reviews (PRISMA-ScR) and to analyse their association with a range of publication and methodological/reporting characteristics. METHODS Pubmed, Scopus, and Web of Science databases were searched up to 31 January 2024 to identify scoping reviews in the field of endodontics. An additional search was performed in three leading endodontic journals. Study selection and appraising the quality of the studies was carried out independently by two reviewers. Each of the 20 PRISMA-ScR items were allocated a score of either 0, 0.5 or 1 to reflect the completeness of the reporting. An item-specific and overall percentage reporting quality score was calculated and reported through descriptive statistics across a range of publication, as well as methodological/reporting characteristics. A univariable and multivariable quantile regression was performed to identify the effect of publication and methodological/reporting characteristics (year of publication, journal, inclusion of an appropriate reporting guideline, and study registration) on the overall percentage reporting quality score. Association of reporting quality score with publication characteristics was then investigated. RESULTS A total of 40 ScRs were identified and included for appraisal. Most of the studies were published from 2021 onwards. The overall median reporting quality score was 86%. The most frequent items not included in the studies were: a priori protocol registration (22/40 compliant; 55%), and reporting of funding (16/40 compliant; 40%). Other key elements that were inadequately reported were the abstract (7/40 compliant; 18%), the rationale and justification of the ScR (21/40 compliant; 52%) and the objectives of the study (18/40 compliant; 45%). Studies that adhered to appropriate reporting guidelines were associated with greater reporting quality scores (β-coefficient: 10; 95%CI: 1.1, 18.9; p = .03). ScRs with protocols registered a priori had significantly greater reporting quality scores (β-coefficient: 12.5; 95%CI: 6.1, 18.9; p < .001), compared with non-registered reviews. CONCLUSIONS The reporting quality of the ScRs in endodontics varied and was greater when the ScR protocols were registered a priori and when the authors adhered to reporting guidelines.

A. Jakovljević, F. Ideo, J. Jaćimović, A. Aminoshariae, V. Nagendrababu, A. Azarpazhooh, E. Cotti

G. Tzanetakis, A. Jakovljević, D. Koletsi, J. Jaćimović, Venkateshbabu Nagendrabu, H. Duncan, P. Dummer

AIM To critically evaluate the reporting quality of a random sample of animal studies within the field of endodontics against the Preferred Reporting Items for Animal Studies in Endodontics (PRIASE) 2021 checklist and to investigate the association between the quality of reporting and several characteristics of the selected studies. METHODOLOGY Fifty animal studies related to endodontics were randomly selected from the PubMed database with publication dates from January 2017 to December 2021. For each study, a score of '1' was given when the item of the PRIASE 2021 checklist was fully reported, whereas a score of '0' was given when an item was not reported; when the item was inadequately or partially reported, a score of '0.5' was given. Based on the overall scores allocated to each manuscript, they were allocated into three categories of reporting quality: low, moderate, and high. Associations between study characteristics and reporting quality scores were also analysed. Descriptive statistics, and Fisher's exact tests were used to describe the data and determine associations. The probability value of 0.05 was selected as the level of statistical significance. RESULTS Based on the overall scores, four (8%) and 46 (92%) of the animal studies evaluated were categorised as 'High' and 'Moderate' reporting quality, respectively. A number of items were adequately reported in all studies related to background (Item 4a), relevance of methods/results (7a) and interpretation of images (11e), whereas only one item related to changes in protocol (6d) was not reported in any. No associations were confirmed between reporting quality scores and number of authors, origin of the corresponding author, journal of publication (endodontic specialty versus non- specialty), impact factor or year of publication. CONCLUSIONS Animal studies published in the specialty of endodontics were mostly of 'moderate' quality in terms of the quality of reporting. Adherence to the PRIASE 2021 guidelines will enhance the reporting of animal studies in the expectation that all future publications will be high-quality.

V. Nagendrababu, H. Duncan, A. Fouad, Lise-Lotte Kirkevang, P. Parashos, M. Pigg, M. Vaeth, J. Jayaraman, Nandini Suresh et al.

Observational studies play a critical role in evaluating the prevalence and incidence of conditions or diseases in populations as well as in defining the benefits and potential hazards of health-related interventions. There are currently no reporting guidelines for observational studies in the field of Endodontics. The Preferred Reporting Items for study Designs in Endodontology (PRIDE) team have developed and published new reporting guidelines for observational-based studies called the "Preferred Reporting items for OBservational studies in Endodontics (PROBE) 2023" guidelines. The PROBE 2023 guidelines were developed exclusively for the specialty of Endodontics by integrating and adapting the "STrengthening the Reporting of OBservational studies in Epidemiology (STROBE)" checklist and the "Clinical and Laboratory Images in Publications (CLIP)" principles. The recommendations of the Guidance for Developers of Health Research Reporting Guidelines were adhered to throughout the process of developing the guidelines. The purpose of this document is to serve as a guide for authors by providing an explanation for each of the items in the PROBE 2023 checklist along with relevant examples from the literature. The document also offers advice to authors on how they can address each item in their manuscript before submission to a journal. The PROBE 2023 checklist is freely accessible and downloadable from the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org/probe/).

P. Tomson, Juliana Vilela Bastos, J. Jaćimović, A. Jakovljević, Shaju Jacob Pulikkotil, V. Nagendrababu

BACKGROUND Pulpitis characterized by spontaneous pain can result in debilitating pain. Dogma has existed to offer only have two treatment options, namely, root canal treatment (RCT) or extraction although, pulpotomy has always remained a potential treatment modality. OBJECTIVE This review aimed to answer the following research question: "Does pulpotomy (partial or full)(I) result in better patient and clinical reported outcomes (O), compared to RCT (C) in permanent teeth with pulpitis characterized by spontaneous pain (P) evaluated at various time intervals? (T). METHODS Two authors independently performed study selection, data extraction and risk of bias assessment. The literature search was conducted in the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials. English language clinical trials comparing the patient and clinical reported outcomes between RCT and pulpotomy were included. The meta-analysis was performed on a fixed-effect model and the quality of evidence assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS Two randomised clinical trials, were included. Among two trials, one has published four reports at different time points involving same cohorts. The meta-analysis revealed no difference in postoperative pain (Day 7) between RCT and pulpotomy (OR= 0.99,95% CI 0.63 - 1.55,I2 =0%) and quality of evidence was graded as "High". Clinical success was high at year 1, 98% for both interventions, however decreased over time to 78.1% (pulpotomy) and 75.3% (RCT) at 5 years. DISCUSSION Pulpotomy is a definitive treatment modality that is as effective as RCT . This could have a significant impact on treatment of such patients affording the advantages of retaining a vital pulp and preventing the need for RCT. CONCLUSION This review could only include two trials, hence there is insufficient evidence to draw robust conclusions. The clinical data accumulated so far suggests no difference in pain between RCT and pulpotomy at day 7 postoperatively and a single randomised control trial suggests that the clinical success rate for both treatment modalities is similar long term. There is a need for more well-designed trials by different research groups to develop a stronger evidence base in this area.

A. Jakovljević, J. Jaćimović, A. Aminoshariae, H. Fransson

BACKGROUND The exposed pulp has been the topic of numerous studies, but well-designed and well-executed comparative trials on the outcome and treatment of these teeth have been limited. OBJECTIVES This study was conducted to answer the following questions: in patients with non-traumatic pulpitis associated with no or non-spontaneous pain in permanent teeth, (i) is direct pulp capping or pulpotomy (partial/full) as effective as selective or stepwise caries removal [Population/participants, Intervention(s), Comparator(s)/control, Outcome(s) (PICO) 1], (ii) is pulpotomy (partial/full) as effective as direct pulp capping (PICO 2), and (iii) is pulpotomy (partial/full) as effective as a pulpectomy (PICO 3), in terms of a combination of patient and clinical reported outcomes, with "tooth survival" as the most critical outcome? METHODS A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception to November 3rd 2021. Grey literature and contents of the major subject journals were examined. Eligibility criteria followed the PICO questions. Two independent reviewers performed study selection, data extraction, and appraisal; disagreements were resolved by a third reviewer. The risk of bias was assessed by the revised Cochrane risk-of-bias tool for randomized trials. RESULTS Three randomized clinical trials (RCTs) were included in the review. No study fulfilled the criteria to answer PICO 1. There were no significant differences in the reported outcomes between investigated treatments in all included RCTs. None of the included studies reported the most critical outcome "tooth survival". A high loss of patients during the follow-up period was observed. DISCUSSION Although a few studies fulfilled strict eligible criteria, the results of this systematic review clearly highlight a paucity of available evidence. At the present time, clinical decisions cannot be substantiated by direct comparative trials. CONCLUSIONS Based on limited evidence, this systematic review discovered no significant differences in effectiveness between compared vital pulp treatments in managing non-traumatic pulpitis associated with no or nonspontaneous pain. Further high-quality RCTs are necessary to investigate the effectiveness of direct pulp capping or pulpotomy (partial/full) compared to selective or stepwise caries removal.

A. Jakovljević, J. Jaćimović, A. Georgiou, N. Nikolic, A. Aminoshariae, S. V. van der Waal, V. Nagendrababu

BACKGROUND The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. OBJECTIVES This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area, and (iii) present recommendations to conduct future clinical studies and systematic reviews. METHODS A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) - 2 tool. Two independent reviewers were involved in study selection, data extraction, and appraising the included reviews; disagreements were resolved by a third reviewer. RESULTS The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor - alpha (TNF-α) -308 G>A and interleukin 1-beta (IL-1β) +3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed. DISCUSSION The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G>A and IL-1β +3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution. CONCLUSIONS No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

N. Nikolic, J. Čarkić, J. Jaćimović, A. Jakovljević, B. Aničić, Z. Jezdić, J. Milašin

ABSTRACT The aim of the present systematic review was to critically analyse the relationship between tumour suppressor genes (TSGs) promoter methylation, a potent mechanism of gene silencing, and the development of salivary gland tumours, as well as the possible effect on clinical/histological characteristics. Review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (registration ID CRD42020218511). A comprehensive search of Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials was performed utilizing relevant key terms, supplemented by a search of grey literature. Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for the quality assessment of included studies. Sixteen cross-sectional and 12 case-control studies were included in the review, predominantly dealing with methylation in TSGs related to DNA repair, cell cycle, and cell growth regulation and differentiation. Quantitative synthesis could be performed on P16 (inhibitor of cyclin-dependent kinase 4a), RASSF1A (Ras association domain family 1 isoform A) and MGMT (O6-methylguanine DNA methyltransferase) genes only. It showed that P16 and RASSF1A genes were more frequently methylated in salivary gland tumours compared to controls (P = .0002 and P < .0001, respectively), while no significant difference was observed for MGMT. Additionally, P16 did not appear to be related to malignant transformation of pleomorphic adenomas (P = .330). In conclusion, TSG methylation is involved in salivary gland tumour pathogenesis and several genes might play a considerable role. Further studies are needed for a better understanding of complex epigenetic deregulation during salivary gland tumour development and progression.

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