The multispecies microbial cluster of Fusobacterium, Parvimonas, Bacteroides and Faecalibacterium as a precision biomarker for colorectal cancer diagnosis.

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.

Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma.

Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.

Global DNA Methylation in Dental Implant Failure Due to Peri-Implantitis: An Exploratory Clinical Pilot Study.

BACKGROUND: Peri-implantitis (PIT) is highly prevalent in patients with dental implants and is a challenging condition to treat due to the limited outcomes reported for non-surgical and surgical therapies. Therefore, epigenetic therapeutics might be of key importance to treat PIT. However, developing epigenetic therapeutics is based on understanding the relationship between epigenetics and disease. To date, there is still scarce knowledge about the relationship between epigenetic modifications and PIT, which warrants further investigations. AIM: The purpose of this study was to evaluate the level of global DNA methylation associated with implant failure (IF) due to PIT compared to periodontally healthy (PH) patients. MATERIAL AND METHODS: A total of 20 participants were initially enrolled in this pilot, exploratory, single-blinded, cross-sectional clinical human study in two groups: 10 in the PH group and 10 in the IF group. In the participants who have completed the study, gingival tissue and bone samples were harvested from each participant and were used to perform global DNA methylation analysis. The percentage of global DNA methylation (5-mC%) was compared (1) between groups (PH and IF); (2) between the subgroups of gingival tissue and bone separately; (3) in the whole sample, comparing gingival tissue and bone; (4) within groups, comparing gingival tissue and bone. Demographic, periodontal, and peri-implant measurements as well as periodontal staging, were also recorded. All statistical comparisons were made at the 0.05 significance level. RESULTS: Out of the initially enrolled 20 patients, only 19 completed the study and, thus, were included in the final analysis; 10 patients in the PH group and 9 patients in the IF group, contributing to a total of 38 samples. One patient from the IF group was excluded from the study due to systemic disease. The mean implant survival time was 10.8 years (2.17-15.25 years). Intergroup comparison, stratified by group, indicated a similar 5-mC% between the PH and IF groups in both gingival tissue and bone (p = 0.599), only in bone (p = 0.414), and only in gingival tissue (p = 0.744). Intragroup comparison, stratified by the type of sample, indicated a significantly higher 5-mC% in gingival tissue samples compared to bone in both the PH and IF groups (p = 0.001), in the PH group (p = 0.019), and in the IF group (p = 0.009). CONCLUSIONS: Within the limitations of this study, higher global DNA methylation levels were found in gingival tissue samples compared to bone, regardless of the study groups. However, similar global DNA methylation levels were observed overall between the IF and PH groups. Yet, differences in the global DNA methylation levels between gingival tissues and bone, regardless of the study group, could reflect a different epigenetic response between various tissues within the same microenvironment. Further studies are necessary to elucidate the present findings and to evaluate the role of epigenetic modifications in IF due to PIT.

Efficacy of growth factors for the treatment of peri-implant diseases: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis on the efficacy of growth factors (GF) on clinical outcomes after treatment (surgical/non-surgical) of peri-implant diseases (peri-implant mucositis and peri-implantitis). MATERIALS AND METHODS: A protocol was developed to answer the following focused question: Is there any difference for the use of GF for treatment of peri-implant diseases versus comparative GF treatment or without GF? Electronic database and manual searches were independently conducted to identify randomized controlled trials (RCTs). Publications were selected based on eligibility criteria and then assessed for risk-of-bias using the Cochrane Handbook. The primary outcome was probing depth (PD) and bleeding on probing (BOP) reduction along with changes in vertical defect depth (VDD). Changes in clinical attachment level, gingival recession, and plaque index, among others, were studied as secondary outcomes. Based on primary outcomes, random-effects meta-analysis was conducted. RESULTS: A total of five RCTs were included. GF enhance the reduction of PD (standardized mean difference (SMD) = - 1.28; 95% confidence interval (CI) - 1.75, - 0.79; p = < 0.0001) and BOP (SMD = - 1.23; 95% CI - 1.70, - 0.76; p = < 0.0001) in the management of peri-implant mucositis. For the treatment of peri-implantitis, the use of GF yielded to significantly greater improvement in VDD (SMD = 0.68; 95% CI 0.22, 1.14; p = 0.004); however, there were no significant differences in terms of PD (SMD = 0.08; 95% CI - 1.08, 1.26; p = 0.887) and BOP (SMD = 0.211; 95% CI - 0.20, 0.63; p = 0.317). The overall risk of bias of the included studies was low to unclear. CONCLUSION: The results of the present systematic review suggest that the addition of GF might enhance the outcomes in the treatment of peri-implant mucositis. However, there is a lack of evidence for supporting additional benefit of GF managing peri-implantitis. CLINICAL RELEVANCE: Within the limitations of the current systematic review and based on the meta-analyses, (1) the addition of GF for the treatment peri-implant mucositis might be associated with better outcomes in terms of PD and BOP, and (2) an additional benefit of GF for the treatment peri-implantitis could not be determined on the basis of the selected evidence.

Potentially malignant disorders of the oral cavity and oral dysplasia: A systematic review and meta-analysis of malignant transformation rate by subtype.

IMPORTANCE: Potentially malignant disorders of the oral cavity (OPMD) are a heterogeneous group of lesions associated with a variable risk of malignant transformation (MT) to invasive cancer. Leukoplakia (LE), lichen planus (LP), oral lichenoid lesions (OLL), oral erythroplakia (OE), oral submucous fibrosis (OSF), and proliferative verrucous leukoplakia (PVL) are among the most common of these lesions. Oral dysplasia is a mucosal area characterized by cellular and architectural derangement, which may be associated with OPMDs or not. OBJECTIVE: To define the MT rate of OPMDs and the risk of development into cancer of mild vs moderate/severe oral dysplasia. This in order to implement adequate follow-up strategies and treatment decisions. STUDY DESIGN: We performed a systematic review and meta-analysis on studies reporting the MT rates of OPMDs and oral dysplasia. Ninety-two studies were included for the analysis. Cumulative rates were reported for OPMDs overall and as a subgroup, a comparison was made of mild vs moderate/severe dysplasia. Meta-regression on OPMD and year of publication was also performed. MAIN OUTCOME AND MEASURES: Overall MT rates of OPMDs and odds ratio of MT of mild vs moderate/severe dysplasia. RESULTS: Overall MT rate across all OPMD groups was 7.9% (99% confidence interval [CI] 4.9%-11.5%). MT rates of the specific OPMD subgroups were as follows: LP 1.4% (99% CI 0.9%-1.9%), LE 9.5 (5.9%-14.00%), OLL 3.8% (99% CI 1.6%-7.00%), OSF 5.2% (99% CI 2.9%-8.00%), OE 33.1% (99% CI 13.6%-56.1%), and PVL 49.5% (99% CI 26.7%-72.4%). Regarding the dysplasia grades comparison, the meta-analysis showed that moderate/severe dysplasia is meaningfully associated to a much greater risk of MT compared to mild dysplasia with an odds ratio of 2.4 (95% CI 1.5-3.8) [Correction added on 27 December 2019, after first online publication: CI updated from 99% to 95%.]. Heterogeneity was not significant. Annual MT rates were approximated based on the average follow-up as reported in the various subgroups. Lichen planus had an annual MT of 0.28%, OLL of 0.57%, leukoplakia of 1.56%, PVL of 9.3%, and OSF of 0.98%. Mild dysplasia had an annual MT of 1.7%, while severe dysplasia of 3.57%. Meta-regression showed a significant negative correlation of PVL MT rate and year of the study (P value <.001). CONCLUSIONS AND RELEVANCE: OPMDs and oral dysplasia are relatively common conditions that general practitioners, head and neck, and oral medicine specialists, face in their everyday practice. Our analysis confirms the significant risk of MT of these lesions, although variable among the subgroups. Moderate/severe dysplasia bears a much higher risk of cancer evolution than mild dysplasia. It is important to raise public health awareness on the MT rates of these conditions, at the same time efficacious communication with the patient is of utmost importance. This, coupled with strict follow-up measures and optimal treatment strategies, would help in reducing the transformation of these oral conditions into invasive cancer.

Three-dimensional bone evaluation after surgical treatment with plasma rich in growth factors of Medication Related Osteonecrosis of the Jaw (MRONJ): A report of 3 cases.

INTRODUCTION: Medication Related Osteonecrosis of the Jaw (MRONJ) is an adverse effect of antiresorptive and antiangiogenic agents that consists of progressive bone destruction in the maxillofacial area. The purpose of this study is to analyze the effect on bone volume of a surgical protocol using plasma rich in growth factors (PRGF) for successfully treating MRONJ. METHODS: Three patients were treated combining surgical debridement with PRGF. Cone bean computed tomography scans were taken prior to surgery and 12 months after to measure bone volume changes. Biopsies were taken for histology analysis during surgery. RESULTS: All patients showed a complete soft tissue and bone healing with pain, discomfort, and neural symptoms resolution for a follow up period of 30 months. A total of 12 to 30% of bone volume gain was found at 12 months after surgery. CONCLUSIONS: PRGF in combination with surgery may be effective in treating MRONJ. Future trials must be performed to confirm these results, including bone volume analysis.

Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options.

BACKGROUND: There are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. METHODS: We performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017. Trials had to compare systemic interventions and radiotherapy (RT) approaches for locally advanced, non-metastatic HNC. Trials recruiting patients whose surgery was the first treatment option, sample size less than 20 per arm or that did not use randomization for treatment allocation were excluded from the analysis. Summary estimates on Overall survival (OS), Progression-free survival (PFS) and toxicity outcomes (grade 3-4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Chocrane risk of bias assessment tool. We performed a set of pair-wise meta-analyses using a random effect model. We also performed a random effect network meta-analysis under a Bayesian framework. FINDINGS: From the 57 included trials, including 15,723 patients, was possible to conduct analysis on 26 treatments for OS, 22 treatments for PFS and 10 treatments for toxicity. In terms of OS Concurrent chemoradiotherapy (CCRT) with cisplatin (HR 0.70, 95% CrI [credible interval] 0.62-0.78) and cetuximab on top of CCRT (HR 0.7, 95% CrI 0.5-0.97) are clearly superior to conventional RT alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74, 95% CrI 0.52-0.95), IC with docetaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.54-0.89) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.34-0.89) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74, 95% CrI 0.64-0.84). Altered fractionation RT is not superior to conventional RT (HR 0.95, 95% CrI 0.85-1.06). Regarding PFS, CCRT with cisplatin (HR 0.72, 95% CrI 0.63-0.83), cisplatin and fluorouracil (HR 0.67, 95% CrI 0.5-0.88), carboplatin (HR 0.63, 95% CrI 0.46-0.87), carboplatin and fluorouracil (HR 0.75, 95% CrI 0.56-1), IC with cisplatin and fluorouracil (HR 0.59, 95% CrI 0.45-0.78), IC with docetaxel, cisplatin and fluorouracil (HR 0.53, 95% CrI 0.41-0.68) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59, 95% CrI 0.35-0.99) are superior to conventional RT and altered fractionation RT. IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73 95% CrI 0.58-0.92). Altered fractionation RT is not superior to conventional RT (HR 0.91, 95% CrI 0.81-1.02). Altered fractionation increases the risk of developing grade 3-4 mucositis compared to conventional RT (OR 3.74 95% 1.64-8.67) INTERPRETATION: CCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have a impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be reevaluated.

Long-Term Implant Survival After 100 Maxillary Sinus Augmentations Using Plasma Rich in Growth Factors.

PURPOSE: To identify determinants of long-term implant survival after sinus augmentation procedure (SAP) using a combination of plasma rich in growth factors (PRGF) and graft material. MATERIALS AND METHODS: Patients were included in this retrospective study if they underwent SAP through a lateral wall approach using PRGF in combination with mainly xenograft, and received implants restored for at least 1 year. Sociodemographic, behavioral and implant characteristics (clinical factors, implant details, surgical details, prosthesis details, and complications) were analyzed. RESULTS: Sixty-seven patients received 217 implants in 100 augmented sinuses. The mean follow-up was 7.2 years. Overall, 22 implants failed in 15 patients (90% cumulative implant survival). Multivariable models showed greater implant survival with implants placed with ≥5 mm of residual crestal bone height (RBH) compared with those placed with <3 mm of RBH. There was also an improvement in survival comparing implant lengths. In addition, immediate loading of implants significantly increased the risk of implant failure. CONCLUSION: The use of PRGFs for maxillary sinus grafting may be an effective and safe treatment option for the rehabilitation of atrophic edentulous posterior maxillae. However, randomized clinical trials are needed to confirm these findings.

Alveolar ridge preservation after tooth extraction: a Bayesian Network meta-analysis of grafting materials efficacy on prevention of bone height and width reduction.

AIMS: To conduct a traditional meta-analysis and a Bayesian Network meta-analysis to synthesize the information coming from randomized controlled trials on different socket grafting materials and combine the resulting indirect evidence in order to make inferences on treatments that have not been compared directly. MATERIALS AND METHODS: RCTs were identified for inclusion in the systematic review and subsequent statistical analysis. Bone height and width remodelling were selected as the chosen summary measures for comparison. First, a series of pairwise meta-analyses were performed and overall mean difference (MD) in mm with 95% CI was calculated between grafted versus non-grafted sockets. Then, a Bayesian Network meta-analysis was performed to draw indirect conclusions on which grafting materials can be considered most likely the best compared to the others. RESULTS: From the six included studies, seven comparisons were obtained. Traditional meta-analysis showed statistically significant results in favour of grafting the socket compared to no-graft both for height (MD 1.02, 95% CI 0.44-1.59, p value < 0.001) than for width (MD 1.52 95% CI 1.18-1.86, p value <0.000001) remodelling. Bayesian Network meta-analysis allowed to obtain a rank of intervention efficacy. CONCLUSIONS: On the basis of the results of the present analysis, socket grafting seems to be more favourable than unassisted socket healing. Moreover, Bayesian Network meta-analysis indicates that freeze-dried bone graft plus membrane is the most likely effective in the reduction of bone height remodelling. Autologous bone marrow resulted the most likely effective when width remodelling was considered. Studies with larger samples and less risk of bias should be conducted in the future in order to further strengthen the results of this analysis.

Treatment of an Unusual Non-Tooth Related Enamel Pearl (EP) and 3 Teeth-Related EPs with Localized Periodontal Disease Without Teeth Extractions: A Case Report.

Enamel may be found ectopically as enamel pearls (EPs), which are frequently associated with advanced localized periodontal (LP) destruction. This study presents a case in which an unusual non-tooth-related enamel pearl and three teeth-related enamel pearls with LP disease were found and treated without teeth extractions. A 47-year-old female patient presented at the New York University College of Dentistry with four EPs, three of which were associated with periodontal pockets and/or bleeding on probing (BOP), and one of them not related to any tooth. Periodontal therapy included scaling and root planing and open flap debridement with removal of the EPs. Two pearls were histologically analyzed by polarizing microscopy and scanning electron microscope (SEM). Clinical periodontal parameters, including probing depth and BOP, were measured. All enamel found in the pearls had the same general morphologic appearance when examined by a SEM. The non-tooth-related pearl could be classified as Rodriguez Ponte "adamantinóidea" pearl. Probing depths at 3 months and 9 months after EP removal diminished considerably. Only after the treatment was there no BOP. Before treatment it was in some areas, as shown in Table 1. The LP related to the EP was resolved. The authors conclude that early recognition of enamel pearls is important in the prevention of periodontal destruction, and removal of EPs by a surgical approach as an adjunct to mechanical periodontal treatment resulted in resolution of the LP. The authors state that this is the first time an "adamantinóideas" pearl is being reported on clinically in the literature.

Histomorphometric Analysis of a Biopsy Harvested 10 Years After Maxillary Sinus Augmentation With Anorganic Bovine Bone Matrix and Plasma Rich in Growth Factors: A Case Report.

PURPOSE: To evaluate the histologic and histomorphometric data 10 years after grafting of maxillary sinus in a case using anorganic bovine bone matrix (ABBM) and plasma rich in growth factors (PRGF). MATERIALS AND METHODS: Histomorphometric measures were performed for newly formed bone, ABBM particles remnants, marrow spaces, and the presence of osteoblastic and osteoclastic activity. RESULTS: Histologic analysis showed ABBM particles surrounded by new compact and mature vital bone. Osteocytes were noted within lacunae. Some osteoblastic and osteoclastic activity could be identified. The histomorphometric results were 21.7% of newly formed bone, 33.9% of ABBM, and 44% was composed of marrow spaces. CONCLUSIONS: After 10 years postoperatively, the histologic evaluation of this case report demonstrated slow replacement of the ABBM particles by newly formed bone, even with the addition of PRGF. The residual ABBM particles were found in close contact to the newly formed bone.