Metronidazole may display anti-inflammatory features in periodontitis treatment: A scoping review.

AIM: Metronidazole (MTZ) is an antimicrobial agent used to treat anaerobic infections. It has been hypothesized that MTZ may also have anti-inflammatory properties, but the evidence is limited and has not been previously reviewed. Thus, this scoping review aimed to answer the following question: "What is the evidence supporting anti-inflammatory properties of metronidazole that are not mediated by its antimicrobial effects?" METHODS: A scoping review was conducted according to the PRISMA-ScR statement. Five databases were searched up to January 2023 for studies evaluating the anti-inflammatory properties of MTZ used as monotherapy for treating infectious and inflammatory diseases. RESULTS: A total of 719 records were identified, and 27 studies (21 in vivo and 6 in vitro) were included. The studies reported experimental evidence of MTZ anti-inflammatory effects on (1) innate immunity (barrier permeability, leukocyte adhesion, immune cell populations), (2) acquired immunity (lymphocyte proliferation, T-cell function, cytokine profile), and (3) wound healing/resolution of inflammation. CONCLUSION: Taken together, this scoping review supported a potential anti-inflammatory effect of MTZ in periodontitis treatment. We recommend that future clinical studies should be conducted to evaluate specific MTZ anti-inflammatory pathways in the treatment of periodontitis.

How efficacious is the combination of substitute bone graft with autogenous bone graft in comparison with substitute bone graft alone in the horizontal bone gain? A systematic review and meta-analysis.

Background: A systematic review (SR) was conducted to answer the following focused question based on PICO strategy: In patients who were submitted to horizontal guided bone regeneration, "how efficacious is the combination of substitute bone graft with autogenous bone graft in comparison with substitute bone graft alone, in terms of bone gain?" Material and Methods: MEDLINE (PubMed), Scopus, Embase, Web of Science databases were searched, and hand searches were made up to June 2021, to find randomized clinical trials comparing the clinical effects of autogenous bone graft + substitute bone graft versus substitute bone graft alone in the treatment of horizontal guided bone regeneration. Results: Four trials representing 109 individuals were included. All studies included in this SR used allogeneic bone graft. The meta-analysis did not show any statistically significant difference between the groups, for horizontal bone gain at a distance of 0 mm (MD: -0.46; 95%CI: -1.03 - 0.11) or at a distance of 4 to 5 mm from the top of the crestal alveolar ridge (MD: 0.17; 95%CI: -1.08 - 1.42). Conclusions: Within limitations of this systematic review, it was concluded that the addition of autogenous bone graft to the allogeneic bone graft did not significantly increase the quantity of regenerated bone. Key words:Bone graft, bone regeneration, allograft.

Whole Tooth Regeneration: Can Animal Studies be Translated into Clinical Application?

Tooth loss leads to several oral problems and although a large number of treatments have been proposed to rehabilitate partially or totally edentulous patients, none of them is based on replacement of a missing tooth by a new natural whole tooth. In the field of tissue engineering, some animal models have been developed to regenerate a natural tooth in the oral cavity. This review shows the state of the art in whole tooth regeneration based on data from in vivo studies. A systematic scoping review was conducted to evaluate studies that described whole-tooth regeneration and eruption in the oral cavity. The data demonstrated that over 100 animals were used in experimental studies and all of them received implants of tooth germs constructed by bioengineering processes. Mini pigs and pigs were used in four studies followed by mice (n = 1) and dog (n = 1). Over 58 (44%) animals showed whole tooth eruption around 3.5 months after tooth germ implantation (1 to 13.5 months). Most of specimens revealed the presence of odontoblasts, dentin, dentinal tubules, dental pulp, root analogue, cementum, blood vessels, and alveolar bone. It could be concluded that in vivo whole tooth regeneration was proved to be possible, but the challenge to overcome translational barriers and test these approaches in humans still remains. Impact Statement Advances in tissue engineering have led to the development of new methods to regenerate and replace tissues and organs, including teeth. Tooth regeneration is the main goal for the replacement of tooth loss and therefore current evidence showed that tissue engineering might provide this treatment in future.

Innovative reflection on oral cancer research priorities: the contribution of social network analysis.

The objective of this study is to present a tool to help understand how variables associated with oral cancer prevention relate to each other in a social network. A search of the Scopus database was performed using terms related to oral cancer and prevention from 2000 to 2020. The keywords were used as nodes and were analyzed using NodeXL, which produced the network graphic analysis. From the 1004 publications available, 4038 different keywords were obtained and then grouped into 75 constructs based on conceptual similarity. The most influential nodes were risk factors, comorbidities, epidemiology, and treatment. However, topics such as technology, telemedicine, self-examination, and diagnostic delay remain far removed from central relations. Network analysis enabled us to observe the bias of biological and basic science in the field and identify a need for studies concerning primary prevention, behavioral interventions, and inequalities in oral cancer.

Innovative reflection on oral cancer research priorities: the contribution of social network analysis

Abstract: The objective of this study is to present a tool to help understand how variables associated with oral cancer prevention relate to each other in a social network. A search of the Scopus database was performed using terms related to oral cancer and prevention from 2000 to 2020. The keywords were used as nodes and were analyzed using NodeXL, which produced the network graphic analysis. From the 1004 publications available, 4038 different keywords were obtained and then grouped into 75 constructs based on conceptual similarity. The most influential nodes were risk factors, comorbidities, epidemiology, and treatment. However, topics such as technology, telemedicine, self-examination, and diagnostic delay remain far removed from central relations. Network analysis enabled us to observe the bias of biological and basic science in the field and identify a need for studies concerning primary prevention, behavioral interventions, and inequalities in oral cancer.

Self-perception of periodontal health status among individuals with Fanconi anemia

ABSTRACT Introduction: Fanconi anemia (FA) is a rare genetic disease characterized by congenital malformations and bone marrow failure. One of the most common oral diseases in individuals with FA is periodontitis and adequate self-perception of periodontal status could contribute to its prevention and early detection. Aim: To compare oral health self-perception, measured by a questionnaire, with the clinical oral condition of patients with FA. Methods and Results: Fifty-six patients with FA, over 11 years of age, answered a questionnaire about dental history and self-reported oral health. Decayed, missing, and filled teeth (DMFT), Visible Plaque Index (VPI) and Gingival Bleeding Index (GBI) were measured. The median age of participants was 21 years (min 11, max 44), 31 (55%) were females and 25 (45%) males. Thirty-five (62.5%) participants rated their oral condition as satisfactory and 7 (12.5%) participants reported tooth mobility, 10 (17.9%) exposed roots and 21 (37.5%) gingival bleeding. Clinical examination detected average DMFT = 5.23, VPI = 31.36% and GBI = 33.77%. The gingival bleeding report was more frequent among individuals with higher GBI (p = 0.014). The DMFT was higher in those who had already undergone dental treatments (p = 0.031). There was an association between participants who presented dental caries and who rated their oral health as poor (p = 0.03). The question "Do your gums bleed easily?" had good accuracy in the evaluation of periodontal disease (p = 0.68). Conclusion: Oral health self-perception of individuals with FA about gingival inflammation was associated with their gingival bleeding index.

Clinical, microbiological, and immunological effects of systemic probiotics in periodontal treatment: study protocol for a randomized controlled trial.

BACKGROUND: The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for periodontitis stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological, and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. METHODS: Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6, and 12 months post-therapy and analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. STATISTICAL ANALYSES: The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests and among groups (at each time point) using either ANOVA/ANCOVA or Kruskal-Wallis tests, depending on normality of the data. The chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤ 4 sites with PD ≥ 5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. TRIAL REGISTRATION: ClinicalTrials.gov NCT03733379. Registered on November 7, 2018.

Is the use of platelet-rich fibrin effective in the healing, control of pain, and postoperative bleeding in the palatal area after free gingival graft harvesting? A systematic review of randomized clinical studies.

OBJECTIVE: A systematic review (SR) was conducted to answer the following focused question based on PICO strategy: In patients who were submitted to harvesting palatal free gingival graft, could platelet-rich fibrin (PRF) application in comparison with another method improve the healing, pain, and control of postoperative bleeding in the palatal area in randomized clinical trials? METHODS: A SR was conducted according to the PRISMA guidelines. The MEDLINE (PubMed), Scopus, Embase, and Web of Science databases were searched, and hand searches were made, covering the period up to August 2020, for randomized clinical trials (RCTs) reporting the effect of PRF membrane in postoperative palatal healing management compared with any other methods. The risk of bias (RoB) of the studies included was assessed by using the RoB 2 tool. RESULTS: The electronic search strategy identified 150 articles. After title screening and abstract reading, 141 studies were excluded, and 9 full-text publications were comprehensively evaluated. Finally, 8 articles were included in the systematic review. Six studies showed that the PRF membrane was effective in improving wound healing during the first 2 weeks. As regards patient-centered outcomes, five studies showed that PRF promoted less postoperative pain. Finally, five studies that evaluated bleeding showed that the PRF membrane improved control of postoperative bleeding. RoB was classified as low in 4 studies, 3 with some concerns, and only one study did not describe the outcome data, and as this was missing, it was not possible to verify the protocol of data analysis for this study; therefore, it was classified as having high RoB. CONCLUSION: Within the limitations of this study, the collective evidence emerging from this SR may support the use of PRF membrane in the palatal area after free gingival graft harvesting. The results of this review must be interpreted with caution, due to the low number of RCTs included and high degree of heterogeneity among the PRF protocols. Further well-designed RCTs with accurate protocol and standard PRF parameters are required in order to gain clear understanding of the influence of PRF on wound healing and patient-centered outcomes. CLINICAL RELEVANCE: The use of PRF membrane for the protection of the palatal donor site following free gingival graft harvesting procedures improves wound healing and patients' quality of life.

Does enamel matrix derivative application provide additional clinical benefits in the treatment of maxillary Miller class I and II gingival recession? A systematic review and meta-analysis.

OBJECTIVE: This review aimed to evaluate the effects of enamel matrix derivative (EMD) in association with coronally advanced flap (CAF) or CAF + connective tissue graft (CTG) when compared with CAF alone or CAF + CTG for the treatment of gingival recessions (GR) in maxillary teeth. METHODS: Five databases and gray literature were searched up to April 2020, to find randomized clinical trials comparing the clinical effects of CAF + EMD versus CAF alone (first group) or CAF + CTG + EMD versus CAF + CTG (second group) in the treatment of Miller class I and II or Cairo type I gingival recessions (GR). Random effects model of mean differences was used to determine the GR reduction, gain in keratinized tissue width (KTW), and gain in clinical attachment level (CAL). The trial sequential analysis (TSA) was implemented to determine the optimal information size (OIS) and imprecision using the GRADE approach. Bayes factors were calculated as complementary statistical evidence of p value. RESULTS: From 1349 titles identified, 9 trials representing 336 GR were included. The meta-analysis showed a statistically significant difference for GR reduction and CAL gain in favor CAF + EMD (p ≤ 0.05). The additional effect of EMD showed a statistically significant difference in GR reduction in favor CAF + CTG + EMD (p ≤ 0.05). The differences in KTW gain proved to be not statistically significant in both comparison groups. The OIS were not met among meta-analyses. Evidence certainty according the GRADE approach proved to be moderate for GR reduction and gain in CAL, but very low for gain in KTW. CONCLUSION: The adjunctive application of EMD in the treatment of GR in maxillary teeth either with CAF or CTG provided moderate certainty evidence in favor of their use for reduction in GR and gain in CAL at 6 and 12 months. However, their effect on the increase in keratinized tissue band height showed very low evidence certainty for its use. CLINICAL RELEVANCE: To know if EMD could improve the results for root coverage.

Self-perception of periodontal health status among individuals with Fanconi anemia.

INTRODUCTION: Fanconi anemia (FA) is a rare genetic disease characterized by congenital malformations and bone marrow failure. One of the most common oral diseases in individuals with FA is periodontitis and adequate self-perception of periodontal status could contribute to its prevention and early detection. AIM: To compare oral health self-perception, measured by a questionnaire, with the clinical oral condition of patients with FA. METHODS AND RESULTS: Fifty-six patients with FA, over 11 years of age, answered a questionnaire about dental history and self-reported oral health. Decayed, missing, and filled teeth (DMFT), Visible Plaque Index (VPI) and Gingival Bleeding Index (GBI) were measured. The median age of participants was 21 years (min 11, max 44), 31 (55%) were females and 25 (45%) males. Thirty-five (62.5%) participants rated their oral condition as satisfactory and 7 (12.5%) participants reported tooth mobility, 10 (17.9%) exposed roots and 21 (37.5%) gingival bleeding. Clinical examination detected average DMFT = 5.23, VPI = 31.36% and GBI = 33.77%. The gingival bleeding report was more frequent among individuals with higher GBI (p =  0.014). The DMFT was higher in those who had already undergone dental treatments (p =  0.031). There was an association between participants who presented dental caries and who rated their oral health as poor (p =  0.03). The question "Do your gums bleed easily?" had good accuracy in the evaluation of periodontal disease (p =  0.68). CONCLUSION: Oral health self-perception of individuals with FA about gingival inflammation was associated with their gingival bleeding index.

Evaluación longitudinal de la mucositis oral en el trasplante de células madre hematopoyéticas: un estudio piloto / Longitudinal evaluation of oral mucositis in hematopoietic stem cell transplantation: a pilot study

Resumen Objetivo: Describir la incidencia y el puntaje de la mucositis oral (MO) y las morbilidades relacionadas en individuos sometidos a trasplante de células madre hematopoyéticas (TCMH) a lo largo del período de inmunosupresión. Métodos: Los sujetos con enfermedades onco / hematológicas, mayores de 14 años, sometidos a TCMH alogénico fueron evaluados diariamente por la presencia y clasificación de OM, nivel de dolor, disfagia, disgeusia y xerostomía. El examen comenzó dos días antes de la infusión de células madre hematopoyéticas y finalizó veinte días después. La OM se clasificó de acuerdo con la escala de la OMS y se utilizó la escala analógica visual (EVA) para medir el nivel de dolor. Resultados: Se reclutaron 23 individuos, el 83% con enfermedades malignas y el 91% con OM. La mediana del grado máximo de OM fue 3 y el nivel máximo de dolor fue 9. Hubo una mediana de 11 días de uso de medicación opioide. Los sujetos que tuvieron el mayor número de días con dolor en la boca alcanzaron el grado máximo de OM y el mayor número de días y el uso de opioides. Conclusión: Hubo una alta incidencia y puntuaciones más altas de OM, pérdida de masa corporal y dolor en esta muestra.

Abstract Aim: To describe the oral mucositis (OM)` incidence and score, and related morbidities in individuals submitted to Hematopoietic Stem Cell Transplantation (HSCT) throughout the immunosuppression period of time. Methods: Subjects with onco / hematological diseases, older than 14 years, submitted to allogeneic HSCT were daily evaluated by the presence and classification of OM, pain level, dysphagia, dysgeusia and xerostomia. The examination started two days before the infusion of hematopoietic stem cells and ended twenty days later. The OM was classified according to the WHO scale and visual analog scale (VAS) was used to measure pain level. Results: Twenty-three individuals were recruted, 83% with malignant diseases and 91% had OM. The median of maximum OM degree was 3 and the maximum pain level was 9. There was a median of 11 days of opioid medication use. The subjects who had the highest mean number of days with mouth pain reached the maximum degree of OM and higher number of days and opiod use. Conclusion: There was a high incidence and high scores of OM, loss of body mass and pain in this sample.

Oral cancer in Fanconi anemia: Review of 121 cases.

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by aplastic anemia, progressive pancytopenia, congenital anomalies, and increased risk of cancer development. After hematopoietic stem cell transplant (HSCT), patients have an estimated 500-fold increase in the risk of developing head and neck cancer compared to a non-affected, and the oral cavity is affected in one-third of cases. Thus, this study aimed to better understand the natural history of oral cavity cancer in patients affected by FA. After conducting a keyword search on MEDLINE, we found 121 cases of oral cavity cancer in patients who had been affected by FA. In conclusion, HSCT may increase the risks of oral cancer development, especially after 5 years after the transplant. In the normal population, the tongue is the most affected area. FA patients should be informed of the risks of oral malignant transformation and encouraged to be undergo medical surveillance.

Mouth examination performance by children's parents and by adolescents in Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a rare genetic syndrome characterized by increased risk of developing malignant neoplasms, particularly oral squamous cell carcinoma. This study aims to ascertain the extent to which adolescents and guardians/parents of children with FA are aware of their oral cancer risks and assess their ability to perform mouth examination (ME). PROCEDURE: A cross-sectional study was conducted among patients with FA (between 6 and 16 years) and their parents. A total of 45 patients, 19 children and 26 adolescents, participated in the study. Among children less than 12 years of age, caregivers performed ME and adolescents between 12 and 16 years of age performed mouth self-examination (MSE). All parents were given a self-reporting questionnaire to collect sociodemographic data, information about health-related behaviors, and oral cancer awareness. Performance was evaluated using criteria for mucosal visualization and retracting ability. Subsequently, a dentist clinically examined all patient participants. RESULTS: Performance evaluation indicated that the examination quality was unsatisfactory in both groups. Statistical significance was found between ability to perform ME by marital status (P < 0.036), where divorced parents had more difficulty performing ME than nondivorced parents. CONCLUSION: Oral mucosa surveillance performed by parents and adolescents seems to be inaccurate. However, as an oral examination is a relatively inexpensive form of secondary prevention, it merits attention to teaching the technique to patients with FA and their caregivers.

Mouth self-examination as a screening tool for oral cancer in a high-risk group of patients with Fanconi anemia.

OBJECTIVE: Oral cancer usually occurs at accessible sites, enabling early detection by visual inspection. Fanconi anemia (FA) is a recessive disorder associated with a high risk of developing head and neck solid tumors. The aim of this study was to assess the ability to perform mouth self-examination (MSE) in these patients. STUDY DESIGN: A total of 44 patients with FA, aged ≥ 18 years, were given a self-reported questionnaire to collect sociodemographic data and information about health-related behaviors and oral cancer awareness. They were asked to perform MSE, which was evaluated using criteria for mucosal visualization and retracting ability. Subsequently, an oral medicine specialist clinically examined all participants, and these findings were considered to be the gold standard. RESULTS: The sensitivity and specificity values of MSE were 43% and 44%, respectively. The MSE accuracy was 43%. Most patients (73%) reported that MSE was easy or very easy, although 75% showed insufficient performance. CONCLUSIONS: The accuracy of MSE alone is not sufficient to indicate whether MSE should be recommended as a strategy to prevent oral cancer in patients with FA. Nevertheless, the present results indicate that this inexpensive technique could be used as a tool for early detection of cancer in these patients.