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Featured researches published by Mia Rakic.


Clinical Oral Implants Research | 2013

Bone loss biomarkers associated with peri‐implantitis. A cross‐sectional study

Mia Rakic; Vojislav Lekovic; Natasa Nikolic-Jakoba; Danilo Vojvodic; Aleksandra Petkovic-Curcin; Mariano Sanz

AIM To investigate the levels of biomarkers associated with osteoclastogenesis in patients suffering peri-implantitis and to compare them with levels in healthy peri-implant sites and severe chronic periodontitis. MATERIAL AND METHODS Peri-implant/gingival crevicular fluid samples and clinical parameters including: bleeding on probing, modified Plaque Index (PlI), pocket depth and clinical attachment level were collected from 70 patients (23 with peri-implantitis, 25 with healthy peri-implant tissues and 22 with severe chronic periodontitis). The concentrations of sRANKL, RANK and OPG were evaluated using enzyme-linked immunosorbent assays; they were compared between the groups and correlated with the clinical findings. RESULTS sRANKL (P = 0.01), RANK (P = 0.01) and OPG (P = 0.03) concentrations were significantly higher in peri-implantitis sites when compared to those in healthy implant sites, although differences in the sRANKL/OPG ratio were not statistically significant. In these sites all three markers were significantly correlated with the clinical parameters, with exception of OPG/PI correlation that remained insignificant (P = 0.121). When comparing peri-implantitis and periodontitis findings, RANK was significantly higher in peri-implantitis sites whereas, sRANKL (P = 0.03) and sRANKL/OPG ratio (P = 0.004) were significantly higher in periodontitis sites. Among periodontitis and healthy implant sites the same differences have been observed for both sRANKL (P = 0.000) and sRANKL/OPG ratio (P = 0.000), furthermore RANK was higher in periodontitis sites as well (P = 0.010). CONCLUSION The findings of this preliminary study on a relatively small sample size suggest that the PICF levels of biomarkers sRANKL, RANK, and OPG are associated with peri-implant tissue destruction and the pattern of these biomarkers differed when compared to periodontitis.


International Journal of Oral & Maxillofacial Implants | 2016

The Microbiologic Profile Associated with Peri-Implantitis in Humans: A Systematic Review.

Mia Rakic; Maria Gabriella Grusovin; Luigi Canullo

PURPOSE To qualitatively investigate the microbiologic profile in peri-implantitis by systematically reviewing the published literature on peri-implant infection. MATERIALS AND METHODS Searches of the US National Institutes of Health free digital archives of the biomedical and life sciences journal literature (PubMed) and The Cochrane Library of the Cochrane Collaboration (CENTRAL), as well as a hand search of other literature, were conducted to identify articles potentially relevant for the review. Randomized clinical trials, prospective cohort studies, longitudinal studies, case-control studies, and cross-sectional studies in humans reporting microbiologic findings in patients with diagnosed peri-implantitis were considered eligible for this review. Screening, data extraction, and quality assessment were conducted independently and in duplicate. RESULTS Twenty-one articles were eligible for inclusion in this review. Early studies focused on the identification of target periopathogens, whereas more recent studies used advanced molecular techniques for comprehensive overview of the peri-implantitis-associated microbiome. In summary, the microbiologic profile in peri-implantitis (1) is complex and variable, (2) consists of gram-negative anaerobic periopathogens and opportunistic microorganisms in almost the same ratio, (3) is frequently associated with the Epstein-Barr virus and nonsaccharolytic anaerobic gram-positive rods, (4) is not so strictly associated with Staphylococcus aureus, and (5) is different from that of periodontitis. A meta-analysis could not be performed because of the heterogeneity of the reviewed studies. CONCLUSION Although a comparison of the published results was limited because of the inhomogeneity of the studies, it is clear that the microbiologic profile of peri-implantitis consists of aggressive and resistant microorganisms and is distinct from that of periodontitis. It seems that the quantitative characteristics of the microflora cohabitants represent the key determinant of disease, rather than the qualitative composition, which is very similar in healthy and peri-implantitis states.


Journal of Periodontology | 2014

Estimation of Bone Loss Biomarkers as a Diagnostic Tool for Peri-Implantitis

Mia Rakic; Xavier Struillou; Aleksandra Petkovic-Curcin; Smiljana Matic; Luigi Canullo; Mariano Sanz; Danilo Vojvodic

BACKGROUND The aims of this study are to estimate the profile of bone loss biomarkers in peri-implant tissues and to identify potential prognostic biomarkers of peri-implantitis. METHODS Peri-implant crevicular fluid samples collected from 164 participants (52 patients with peri-implantitis, 54 with mucositis, and 58 with healthy peri-implant tissues) were analyzed using enzyme-linked immunosorbent assays to evaluate concentrations of the receptor activator of nuclear factor-κB (RANK), soluble RANK ligand (sRANKL), osteoprotegerin (OPG), cathepsin-K, and sclerostin. RESULTS Concentrations of RANK, sRANKL, OPG, and sclerostin were significantly increased in patients with peri-implantitis compared with patients with healthy peri-implant tissues. Comparisons between peri-implantitis and mucositis demonstrated significantly higher values of sclerostin in peri-implantitis samples. Comparisons between mucositis and healthy peri-implant tissues showed significantly increased levels of RANK and cathepsin-K in mucositis. CONCLUSION These results are suggestive of a role of sRANKL, OPG, and sclerostin as prognostic biomarkers in peri-implantitis.


Journal of Periodontology | 2016

The Association Between Periodontal Inflammation and Labor Triggers (Elevated Cytokine Levels) in Preterm Birth: A Cross-Sectional Study

Neda Perunovic; Mia Rakic; Ljubinka I. Nikolic; Sasa Jankovic; Zoran Aleksic; Darko V. Plecas; Phoebus N. Madianos; Sasa Cakic

BACKGROUND Periodontitis is considered to be a risk factor for preterm birth. Mechanisms have been proposed for this pathologic relation, but the exact pathologic pattern remains unclear. Therefore, the objective of the present study is to evaluate levels of four major labor triggers, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in gingival crevicular fluid (GCF) and serum samples between women with preterm birth (PTB) and full-term birth (FTB) and correlate them with periodontal parameters. METHODS PGE2, IL-1β, IL-6, and TNF-α levels were estimated using enzyme-linked immunosorbent assays in GCF and serum samples collected 24 to 48 hours after labor from 120 women (60 FTB, 60 PTB). RESULTS Women with PTB exhibited significantly more periodontitis, worse periodontal parameters, and increased GCF levels of IL-6 and PGE2 compared with the FTB group; there were no significant differences in serum levels of measured markers. GCF levels of IL-1β, IL-6, and PGE2 and serum levels of TNF-α and PGE2 were significantly higher in women with periodontitis compared with periodontally healthy women. Serum levels of PGE2 were positively correlated with probing depth (PD) and clinical attachment level (CAL) as well as with GCF levels of TNF-α in women with PTB. CONCLUSIONS Women with PTB demonstrated worse periodontal parameters and significantly increased GCF levels of IL-6 and PGE2 compared with those with FTB. Based on significant correlations among serum PGE2 and PD, CAL, and GCF TNF-α in PTB, periodontitis may cause an overall increase of labor triggers and hence contribute to preterm labor onset.


Journal of Clinical Periodontology | 2016

EFP Delphi study on the trends in Periodontology and Periodontics in Europe for the year 2025

Phoebus N. Madianos; William Papaioannou; David Herrera; Mariano Sanz; Amelie Baeumer; Anna Bogren; Philippe Bouchard; Maria Chomyszyn-Gajewska; Korkud Demirel; Rok Gašperšič; Marina Giurgiu; Filippo Graziani; Karin Jepsen; Søren Jepsen; Tiernan O′Brien; Ioannis Polyzois; Philip M. Preshaw; Mia Rakic; Michele Reners; Nives Rincic; Andreas Stavropoulos; Serdar Sütcü; Christian Verner; Juan Carlos Llodra

AIM The aim was to assess the potential trends in Periodontology and Periodontics in Europe that might be anticipated by the year 2025, using the Delphi method. MATERIAL AND METHODS The expert opinion of 120 experts was sought through the use of an open-ended questionnaire, developed by an advisory group, containing 40 questions concerning the various trends in periodontology. RESULTS The experts (113 responders) expect a stabilization of the prevalence of periodontitis, both for the chronic as well as the aggressive cases, but an increase in implant-related diseases up to the year 2025. Concurrently, the importance of implants is seen to be increasing. They foresee an increased demand for postgraduate periodontology and implantology training. This is mirrored in an increase in publications for implant dentistry and increase in demand and need for training. Concerning the patients, better-informed individuals seeking more routine check-ups are expected. CONCLUSION A continued need for specialized periodontists, but also well trained dental practitioners is foreseen for next decade in Europe. Apart from periodontology they will be increasingly exposed to and trained in implant dentistry.


Clinical Oral Implants Research | 2017

The predictive value of microbiological findings on teeth, internal and external implant portions in clinical decision making.

Luigi Canullo; Sandro Radovanovic; Boris Delibasic; Juan Antonio Blaya; David Peñarrocha; Mia Rakic

AIM The primary aim of this study was to evaluate 23 pathogens associated with peri-implantitis at inner part of implant connections, in peri-implant and periodontal pockets between patients suffering peri-implantitis and participants with healthy peri-implant tissues; the secondary aim was to estimate the predictive value of microbiological profile in patients wearing dental implants using data mining methods. MATERIAL AND METHODS Fifty participants included in the present case─control study were scheduled for collection of plaque samples from the peri-implant pockets, internal connection, and periodontal pocket. Real-time polymerase chain reaction was performed to quantify 23 pathogens. Three predictive models were developed using C4.5 decision trees to estimate the predictive value of microbiological profile between three experimental sites. RESULTS The final sample included 47 patients (22 healthy controls and 25 diseased cases), 90 implants (43 with healthy peri-implant tissues and 47 affected by peri-implantitis). Total and mean pathogen counts at inner portions of the implant connection, in peri-implant and periodontal pockets were generally increased in peri-implantitis patients when compared to healthy controls. The inner portion of the implant connection, the periodontal pocket and peri-implant pocket, respectively, presented a predictive value of microbiologic profile of 82.78%, 94.31%, and 97.5% of accuracy. CONCLUSION This study showed that microbiological profile at all three experimental sites is differently characterized between patients suffering peri-implantitis and healthy controls. Data mining analysis identified Parvimonas micra as a highly accurate predictor of peri-implantitis when present in peri-implant pocket while this method generally seems to be promising for diagnosis of such complex infections.


Clinical Oral Investigations | 2015

CD14 and TNFα single nucleotide polymorphisms are candidates for genetic biomarkers of peri-implantitis

Mia Rakic; Aleksandra Petkovic-Curcin; Xavier Struillou; Smiljana Matic; Novak Stamatovic; Danilo Vojvodic

ObjectivesThis study aims to investigate whether CD14-159 C/T and TNFα -308 A/G single nucleotide polymorphisms are associated with peri-implantitis and to evaluate their effects on bone resorption by correlating with local levels of receptor activator nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG).Material and methodsStudy population included 369 Southeastern Europe Caucasians (180 with peri-implantitis and 189 with healthy peri-implant tissues). Genotyping was performed using polymerase chain reaction from the periphery blood samples, while RANKL and OPG were evaluated in peri-implant crevicular fluid specimens using enzyme-linked immunosorbent assay.ResultsAnalysis of CD14-159 C/T polymorphism showed that genotype of CC nucleic acid combination was associated with peri-implantitis demonstrating a fivefold increased risk in these carriers. Furthermore, for TNFα -308 A/G polymorphisms, it was evidenced that AG genotype was associated with peri-implantitis and a fivefold increased risk in these carriers. Peri-implantitis patients with CC genotype at CD14-159 exhibited significantly higher concentrations of RANKL and relative ratio RANKL/OPG when compared to patients with CT genotype, while concentration of biomarkers between different genotypes at TNFα -308 remained insignificant.ConclusionWithin the limitations of the study, we can conclude that CD14-159 C/T and TNFα -308 A/G polymorphisms are associated with peri-implantitis and may present biomarkers for peri-implantitis.Clinical relevanceInvestigated genetic markers might serve as precious parameters in clinical practice in course of treatment planning and prognosis, since preventive and treatment approach could be positively shifted and adjusted depending on present genotype.


Clinical Oral Investigations | 2018

How frequent does peri-implantitis occur? A systematic review and meta-analysis.

Mia Rakic; Pablo Galindo-Moreno; Alberto Monje; Sandro Radovanović; Hom Lay Wang; David L. Cochran; Anton Sculean; Luigi Canullo

ObjectivesThe objective of this study is to estimate the overall prevalence of peri-implantitis (PI) and the effect of different study designs, function times, and implant surfaces on prevalence rate reported by the studies adhering to the case definition of Sanz & Chapple 2012.Material and methodsFollowing electronic and manual searches of the literature published up to February 2016, data were extracted from the studies fitting the study criteria. Meta-analysis was performed for estimation of overall prevalence of PI while the effects of the study design, function time, and implant surface type on prevalence rate were investigated using meta-regression method.ResultsTwenty-nine articles were included in this study. The prevalence rate in all subset meta-analyses was always higher at patient level when compared to the prevalence rate at the implant level. Prevalence of PI was 18.5% at the patient level and 12.8% at the implant level. Meta-regression analysis did not identify any association for different study designs and function times while it was demonstrated the significant association between moderately rough surfaces with lower prevalence rate of PI (p = 0.011).ConclusionsThe prevalence rate of PI remains highly variable even following restriction to the clinical case definition and it seems to be affected by local factors such as implant surface characteristics. The identification of adjuvant diagnostic markers seems necessary for more accurate disease classification.Clinical relevanceThe occurrence of PI is affected by local factors such as implant surface characteristics hence the careful assessment of the local factors should be performed within treatment planning.


International Journal of Oral & Maxillofacial Implants | 2018

What is the Impact of Epstein-Barr Virus in Peri-implant Infection?

Luigi Canullo; Paolo Pesce; Daniele Botticelli; Ugo Covani; Sasha Jankovic; Tanja Jovanovic; Mia Rakic

PURPOSE To compare the qualitative and quantitative profile of Epstein-Barr virus (EBV) at external and internal implant surfaces between participants with peri-implantitis and healthy peri-implant tissues and to quantitatively assess the relation between EBV and periopathogens inside the microbiologic profile associated with peri-implantitis. MATERIALS AND METHODS Microbiologic specimens were retrieved from 84 patients wearing 190 implants to estimate the levels of EBV and 10 periopathogens in the peri-implant pocket and internal-implant connection using quantitative polymerase chain reaction. RESULTS The study sample consisted of 113 healthy and 77 peri-implantitis-affected implants. Statistical significance was not reached in EBV prevalence between peri-implantitis and healthy controls. EBV-positive participants demonstrated higher levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with EBV-negative participants. A positive correlation was demonstrated among EBV and Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn), and Cr levels in peri-implantitis-affected implants, while healthy controls demonstrated a positive correlation between EBV and Aggregatibacter actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION EBV cannot be considered as a microbiologic marker of peri-implantitis. However, EBV could be considered as a risk factor and a peri-implantitis enhancer based on its positive correlations with pathogens associated with peri-implantitis.


Dental Materials Journal | 2018

Evaluation of a hydrogel membrane on bone regeneration in furcation periodontal defects in dogs

Xavier Struillou; Aurélien Fruchet; Mia Rakic; Zahi Badran; Gildas Rethore; Sophie Sourice; Borhane Hakim Fellah; Laurent Le Guehennec; Olivier Gauthier; Pierre Weiss; Assem Soueidan

The aim of the study was to evaluate bone regeneration using a canine model with surgically created periodontal defects filled for 12 weeks using a stratified biomaterial consisting in a biphasic calcium phosphate (BCP) covered with a crosslinking hydrogel acting as polymer membrane of silated hydroxypropyl methylcellulose (Si-HPMC) as the tested new concept. Bilateral, critical-sized, defects were surgically created at the mandibular premolar teeth of six adult beagle dogs. The defects were randomly allocated and: (i) left empty for spontaneous healing or filled with: (ii) BCP and a collagen membrane; (iii) BCP and hydrogel Si-HPMC membrane. At 12 weeks, the experimental conditions resulted in significantly enhanced bone regeneration in the test BCP/Si-HPMC group. Within the limits of this study, we suggest that the hydrogel Si-HPMC may act as an occlusive barrier to protect bone area from soft connective tissue invasion and then effectively contribute to enhance bone regeneration.

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Smiljana Matic

Military Medical Academy

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Mariano Sanz

Complutense University of Madrid

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