PROPHYLACTIC ANTIBIOTICS DURING THE IMPLANT PROSTHETIC PHASE MAY NOT SUBSTANTIALLY DECREASE THE INCIDENCE OF INFECTIOUS COMPLICATIONS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Does the Prosthetic Phase of Dental Implants Justify the Prescription of Preventive Antibiotics in Healthy Patients? A Systematic Review. Salgado-Peralvo AO, Uribarri A, Peña-Cardelles JF, Kewalramani N, Rodríguez JLG, Velasco-Ortega E. J Oral Implantol. 2023 Feb 1;49(1):93-101. SOURCE OF FUNDING: The authors declared that no funding was received to support the study. TYPE OF STUDY/DESIGN: Systematic review.

Impact of diabetes mellitus on the frequency of post-operative complications after carotid endarterectomy.

BACKGROUND: There is significant controversy surrounding the link between diabetes mellitus and post-operative complications after carotid endarterectomy (CEA). The aim of this study was to identify the possible effects of diabetes on the frequency of post-operative complications after CEA. METHODS: This prospective study was conducted at the Dedinje Clinic for Vascular Surgery, Belgrade. The patients who underwent CEA were divided into two groups: group A (37.7%) included 98 (35.1%) insulin-dependent and 181 (64.9%) insulin-independent diabetic patients, and group B (62.3%) comprised non-diabetic subjects. RESULTS: The pre-operative characteristics were similar, except for a greater prevalence of dyslipidaemia in patients with diabetes. Post-operative cardiac events occurred more often in patients with diabetes (3.6%) than in non-diabetic patients (1.1%) (p = 0.039); post-operative neurological events among patients with diabetes were 3.6% and among non-diabetics, 0.9% (p = 0.009). Peri-operative mortality rate was 2.5% in the diabetic group and 0.9% in the non-diabetic group. The total percentage of post-operative complications was two or more times higher in the diabetic group than the non-diabetic group (8.5 vs 18.3%, p < 0.001). CONCLUSIONS: Diabetes mellitus increased the surgical risk of CEA. Higher rates of mortality and post-operative complications were observed in patients being treated with oral antidiabetics than in those on insulin.

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis-An umbrella review.

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 the 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-1ß) + 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 the included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G > A and IL-1ß + 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.

Methylation of tumour suppressor genes in benign and malignant salivary gland tumours: a systematic review and meta-analysis.

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.

Gene polymorphisms in odontogenic keratocysts and ameloblastomas: A systematic review.

OBJECTIVES: The aim of this systematic review was to critically analyze available data on gene polymorphisms in odontogenic keratocysts (OKC) and ameloblastomas, including their possible relationship with clinical and histological features of these lesions. MATERIALS AND METHODS: A comprehensive search of Web of Science Scopus, PubMed, Cochrane Central Register of Controlled Trials and EMBASE was conducted using relevant key terms and supplemented by a gray literature search. Quality assessment of included studies was performed using criteria from the Strengthening the Reporting of Genetic Association (STREGA) statement. RESULTS: Ten studies were included in the final review. Survivin -31G/C, interleukin IL-1α -889 C/T, p53 codon 72 G/C, tumor necrosis factor TNF-α (-308G>A) and its receptor TNF-R1 (36A>G), glioma-associated oncogene homolog 1 rs2228224 and matrix metalloproteinase 2 rs243865 gene polymorphisms were reported to be associated with OKC. For ameloblastomas, p53 codon 72 G/C, X-ray repair cross-complementing protein 1-codons 194 and 399 and matrix metalloproteinase 9 rs3918242 gene polymorphisms were identified as risk factors. It was not possible to establish a relationship between specific polymorphisms and clinical and histological features of investigated lesions. CONCLUSIONS: Several gene polymorphisms might be considered as a risk factor for the development of these lesions. Future studies should investigate whether these polymorphisms might be used to identify patients with increased risk of recurrence or aggressive disease.

Tumor Necrosis Factor Alpha -308 G/A Single-Nucleotide Polymorphism and Apical Periodontitis: An Updated Systematic Review and Meta-analysis.

INTRODUCTION: This study aimed to perform a more precise estimation of the association between tumor necrosis factor alpha (TNF-α) -308 G/A single-nucleotide polymorphism (SNP) and the risk of development of apical periodontitis (AP) and its phenotypes based on all available published studies. METHODS: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered in PROSPERO (CRD42020176190). The literature search was conducted via Clarivate Analytics Web of Science, Scopus, PubMed, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases from inception to December 2020 with no language restrictions. Two reviewers were involved independently in the study selection, data extraction, and appraising the studies that were included. The quality of the included studies was evaluated using the Strengthening the Reporting of Genetic Association and the Grading of Recommendations Assessment, Development and Evaluation system. The frequencies of the genotypes and alleles of the TNF-α (G>A 308, rs1800629) gene with 95% odds ratio were used. RESULTS: Four studies met the inclusion criteria with moderate risk of bias. This study revealed no significant association between TNF-α -308 G/A SNP and AP and the risk of AP development. Moreover, there was no significant association between genotype or allele frequency distribution and clinical manifestations (acute vs chronic) of AP. The certainty of evidence per the Grading of Recommendations Assessment, Development and Evaluation system was very low. CONCLUSIONS: Because of very low certainty of evidence, whether there is an association between TNF-α -308 G/A SNP and AP warrants further well-designed multicentric studies to adjudicate a better understanding of the role of genetic factors in the etiopathogenesis of AP.

Notch - a possible mediator between Epstein-Barr virus infection and bone resorption in apical periodontitis.

Objectives: This study aimed to investigate whether Epstein-Barr virus (EBV) positive periapical lesions exhibited higher mRNA levels of Notch signalling molecules (Notch2 and Jagged1), bone resorption regulators (receptor activator of nuclear factor kappa-ß ligand (RANKL) and osteoprotegerin (OPG)), and proinflammatory cytokines (tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6) compared to EBV negative lesions. Additionally, the potential correlation between investigated molecules in periapical lesions was analyzed.Materials and methods: Sixty-four apical periodontitis lesions were obtained subsequent to standard apicoectomy procedure. The presence of EBV was determined using nested PCR. Based on the presence of EBV all periapical lesions were divided into two groups, 29 EBV positive and 35 EBV negative lesions. A reverse transcriptase real-time PCR was used to determine mRNA levels of Notch2, Jagged1, RANKL, OPG, TNF-α, IL-1ß and IL-6.Results: Significantly higher mRNA levels of Notch2, Jagged1, RANKL and IL-1ß were observed in EBV positive compared to EBV negative lesions. Significant positive correlation was present between Notch2 and Jagged1, Jagged1 and RANKL, and IL-ß and TNF-α in EBV positive periapical lesions.Conclusions: Notch signalling pathway may be involved in alveolar bone resorption in apical periodontitis lesions infected by EBV.

Notch signaling pathway mediates alveolar bone resorption in apical periodontitis.

Apical periodontitis represents a chronic inflammatory process within periapical tissues, mostly caused by etiological agents of endodontic origin. Progressive bone resorption in the periapical region represents the hallmark of apical periodontitis and occurs as the consequence of interplay between polymicrobial infections and host response. The Notch signaling pathway is an evolutionary conserved cell-signaling system that plays an important role in a variety of cell functions including proliferation, differentiation and apoptosis. In recent years its involvement in bone homeostasis has attracted a significant consideration. We hypothesized that Notch signaling pathway, which has a complex interplay with proinflammatory cytokines and bone resorption regulators, contributes to alveolar bone resorption via increased Notch receptors on immune cell surface and stimulates Notch receptor intracellular domain (NICD) translocation into the nucleus. The potential benefit of medications aimed to down-regulate these pathways in apical periodontitis treatment remains to be assessed.

Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines.

INTRODUCTION: The exact mechanisms of periapical bone resorption have not been fully elucidated. This study aimed to analyze the expression of Notch signaling molecules (Notch2, Jagged1, and Hey1) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin [IL]-1ß, and IL-6) in human apical periodontitis lesions with different receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) ratios and determine their potential correlation. METHODS: The study group consisted of 50 periapical lesions collected in conjunction with apicoectomy. The relative gene expression of the investigated molecules (Notch2, Jagged1, Hey1, RANKL, OPG, TNF-α, IL-1ß, and IL-6) in all tissue samples was analyzed using reverse transcriptase real-time polymerase chain reaction. The Student t test, Mann-Whitney U test, and Spearman correlation were used for statistical analysis. RESULTS: Based on the RANKL/OPG ratio, periapical lesions were either RANKL predominant (RANKL > OPG, n = 33) or OPG predominant (RANKL < OPG, n = 17). Symptomatic lesions occurred more frequently in RANKL-predominant compared with OPG-predominant lesions (24 vs 7, P = .029). Notch2, Jagged1, Hey1, and TNF-α were significantly overexpressed in lesions with predominant RANKL compared with lesions with predominant OPG (P = .001, P = .001, P = .027, and P = .016, respectively). Significant correlations were observed between the investigated genes in periapical lesions. CONCLUSIONS: Notch signaling appeared to be activated in periapical inflammation. An increase in Notch2, Jagged1, Hey1, and TNF-α expression in RANKL-predominant periapical lesions corroborates their joined involvement in extensive periapical bone resorption.

Epstein-Barr virus infection induces bone resorption in apical periodontitis via increased production of reactive oxygen species.

Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed.

Human Cytomegalovirus and Epstein-Barr Virus Genotypes in Apical Periodontitis Lesions.

INTRODUCTION: Different genotypes of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) possess specific pathogenic abilities because of various interactions with the host's immune system and differences in cell tropism. The aim of this study was to determine the distribution of HCMV and EBV genotypes in apical periodontitis lesions in relation to their clinical and histopathologic features. METHODS: One hundred samples of apical periodontitis lesions and 25 control samples (healthy pulp tissue) were collected. The presence of HCMV glycoprotein B (gB) and EBV nuclear antigen-2 genotypes was analyzed by nested polymerase chain reaction and restriction fragment length polymorphisms analysis. RESULTS: EBV and HCMV were detected in apical periodontitis lesions at significantly higher frequencies than in healthy pulp controls (P = .020 and P = .020, respectively). HCMV gB type II was significantly more frequent compared with gB type I in the examined groups (P = .036). No HCMV gB type III or IV products were found. In both periapical lesions and controls, EBV-1 occurred more often compared with EBV-2 (P = .001). Dual EBV and HCMV coinfection was more frequently detected in large-size periapical lesions (P = .038). CONCLUSIONS: Both HCMV and EBV are associated with inflammatory processes of periapical bone destruction. HCMV gB type II and EBV-1 are the most prevalent genotypes in apical periodontitis lesions.

Pro-inflammatory cytokine levels in human apical periodontitis: Correlation with clinical and histological findings.

This study aimed to compare the levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) between apical periodontitis lesions with different clinical and histological features. Based on clinical data and history of disease, 100 human apical periodontitis lesions were categorised as either asymptomatic or symptomatic lesions. According to histological examination, lesions were divided into periapical granulomas and radicular cysts. Pulp tissues of 25 impacted wisdom teeth were used as controls. Homogenised tissue samples were centrifuged and supernatants were used for the determination of cytokine levels by enzyme-linked immunosorbent assay. Significantly higher levels of IL-1ß and IL-6 were found in symptomatic lesions compared with asymptomatic lesions and control tissues (P < 0.001, P < 0.001, respectively). The concentration of IL-1ß was significantly higher in radicular cysts compared with periapical granulomas (P = 0.003). Symptomatic lesions, as judged by high local production of IL-1ß and IL-6, represent an immunologically active stage of the disease.

Human cytomegalovirus and Epstein-Barr virus in etiopathogenesis of apical periodontitis: a systematic review.

INTRODUCTION: During the last decade, a hypothesis has been established that human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) may be implicated in the pathogenesis of apical periodontitis. The aim of this review was to analyze the available evidence that indicates that HCMV and EBV can actually contribute to the pathogenesis of periapical lesions and to answer the following focused question: is there a relationship between HCMV and EBV DNA and/or RNA detection and the clinical features of human periapical lesions? METHODS: The literature search covered MEDLINE, Science Citation Index Expanded (SCIexpanded), Scopus, and The Cochrane Library database. Quantitative statistical analysis was performed on the pooled data of HCMV and EBV messenger RNA transcripts in tissues of symptomatic and asymptomatic periapical lesions. RESULTS: The electronic database search yielded 48 hits from PubMed, 197 hits from Scopus, 40 hits from Web of Science, and 1 from the Cochrane Library. Seventeen cross-sectional studies have been included in the final review. The pooled results from quantitative systematic method analysis showed no statistically significant relationship between the presence of HCMV and EBV messenger RNA transcripts (P = .083 and P = .306, respectively) and the clinical features of apical periodontitis. CONCLUSIONS: The findings of HCMV and EBV transcripts in apical periodontitis were controversial among the included studies. Herpesviruses were common in symptomatic and large-size periapical lesions, but such results failed to reach statistical significance. Further studies, including those based on an experimental animal model, should provide more data on herpesviruses as a factor in the pathogenesis of periapical inflammation.