Efficacy of Antibiotics Used as an Adjunct in the Treatment of Peri-implant Mucositis and Peri-implantitis: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review aimed to assess the clinical efficacy of antibiotics when used as an adjunct in treating peri-implant diseases. MATERIALS AND METHODS: A systematic search of papers published between January 1980 and March 2020 was conducted. Randomized clinical trials with at least 10 patients who had peri-implant diseases, treated with or without adjunctive antibiotics in combination with surgical or nonsurgical therapies, and with a minimum of at least 3 months of follow-up were included. Meta-analyses were conducted to analyze weighted mean differences in probing depth reduction, radiographic bone level gain, and odds ratio of treatment success. RESULTS: From the 856 articles identified, 10 articles met the inclusion criteria and were selected. Of these, 7 articles were used for the meta-analysis. The adjunctive use of antibiotics in the treatment of peri-implant diseases yielded significantly greater probing depth reduction (weighted mean differences = 0.56 mm at 3 months, P = .001; 0.77 mm at 6 months, P < .00001; 0.92 mm at 12 months, P < .00001), radiographic bone level gain (weighted mean differences = 0.64 mm, P = .03), and treatment success (odds ratio = 1.74, P = .04) compared to the same treatment without antibiotics. CONCLUSION: Based on the existing evidence, the use of adjunctive antibiotics to treat peri-implant diseases, especially peri-implantitis, provided potential benefits in clinical outcomes for up to 12 months posttherapy.

Revisit incidence of complications after impacted mandibular third molar extraction: A nationwide population-based cohort study.

Most of complications after impacted mandibular third molar (iLM3) extraction surgeries are transient and resolved spontaneously within one or two weeks, but some of them are more complicated and required further treatments to alleviate the symptoms. The aim of study is to revisit incidence and predictors of complications after iLM3 surgery by reviewing previous literature and investigating a population-based data. From Taiwan National Health Insurance Research Database, records of 16,609 patients who had received iLM3 extraction under ambulatory settings were retrieved for analysis. Outcomes of interest included dry socket (DS), prolonged temporomandibular joint symptoms (TMD), and surgical site infection (SSI), which necessitated additional appointments to manage. Odds ratios of having those complications between different variables were analyzed. The incidence rates of DS, TMD, and SSI were 3.6%, 0.41%, 0.17%, respectively; while they ranged from 0.33-19.14% (DS), 0-4.17% (TMD), and 0.2-5.17% (SSI) in previous studies. Logistic regression revealed DS significantly correlated with complexity of odontectomy (2.5-fold of risk) and history of gingivitis or pericoronitis (1.3-fold of risk). More TMD was found in female than male patients (0.5% versus 0.3%). However, no factors associated with SSI was found; neither did we find aging as a risk in association with any of above complications. Compared to previous studies, our data supports that surgical intervention should be considered in iLM3 with risk of gingivitis or pericoronitis to reduce the occurrence of DS. The original information in this article, which provides a "real-world" evidence, along with the organizing data we summarized from previous article, can serve as a reference for clinicians in assessing the complication risks before treatment of iLM3.

ATP dynamic regeneration strategy for enhancing co-production of glutathione and S-adenosylmethionine in Escherichia coli.

OBJECTIVES: In general, a sufficient supply of ATP can promote the synthesis of ATP-driven metabolites, but excessive ATP will lead to the inhibition of cell growth. For enhancing the co-production of glutathione(GSH) and S-adenosylmethionine(SAM), a dynamic ATP regeneration strategy was developed. RESULTS: The novel ATP regeneration strategy consisting of ATP-sensing riboswitch ydaO motif, polyphosphate kinase (PPK), and Vitreoscilla hemoglobin (VHb) was successfully applied in Escherichia coli. The intracellular ATP level was always around 0.60 mg/g dry cell weight during the fermentation process, resulting in significantly enhanced co-production of GSH and SAM. The GSH titer and SAM titer in the strain CGS-2 increased by 137.40% and 82.18% after fermentation for 24 h, compared with the control strain. CONCLUSIONS: The ATP regulation strategy is expected to be a favorable tool to improve the efficiency of microbial cell factories. The proposed ATP dynamic regeneration approach may be applicable for cost-effective, high-yield production of ATP-driven metabolites.

Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia.

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.

Pretreatment pain predicts perineural invasion in oral squamous cell carcinoma: A prospective study.

OBJECTIVES: Perineural invasion (PNI) is an established poor prognostic pathological feature for oral squamous cell carcinoma (OSCC). The purpose of this study was to analyze the role of pretreatment parameters in predicting PNI for OSCC. MATERIALS AND METHODS: We prospectively enrolled into our study 102 newly diagnosed OSCC patients, who were surgically treated from 2011 to 2012. Before treatment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 and the visual analogue scale (VAS) for cancer pain. Pathological examination was performed to ascertain PNI status in all patients. Patients were divided into two groups, those with PNI and without PNI. Pretreatment parameters were compared between the two groups. RESULTS: In univariate analysis, clinical T classification (P<0.001), painkiller use (P=0.001), problem with social eating (P<0.001) and social contact (P=0.002), VAS scores of primary pain (P<0.001) and referred pain (P=0.004) were found to be associated with PNI. Multivariate logistic regression analysis further revealed VAS score of primary pain (P=0.001, OR 2.014) and T3-4 classification (P=0.014, OR 6.422) were independent predictors of PNI. A regression equation incorporating pretreatment pain was developed to predict the probability of having PNI. CONCLUSION: PNI can be predicted by higher pretreatment VAS score of primary pain, as well as more advanced clinical T classification. Careful evaluation of pretreatment pain of primary tumor can thus be helpful in improving treatment decision making for OSCC.

Forkhead factor FOXQ1 promotes TGF-ß1 expression and induces epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) promotes tumor invasion and metastasis, but the coordination and integration mechanisms of these processes are still not fully understood. In this study, we used a cross-species expression profiling strategy of Hela cells to determine an important genetic program transfers. In particular, we have discovered a new transfer function, which is not previously known about transcription factor forkhead box Q1 (FOXQ1). The shRNA anti-FOXQ1 gene was synthesized and transfected into the Hela and EpRas cells. RT-PCR assay was performed to detect the mRNA levels in cells. Cell adhesion and separation assay were used to examine the cell-cell adhesion and separation among cells. Wound healing assay was utilized to examine cell migration and invasion ability. Chromatin immunoprecipitation assay was used to investigate the interaction between E-cadherin and N-cadherin and FOXQ1 promoter region. The results indicated that ectopic expression of FOXQ1 increased cell migration and invasion in vitro, enhanced mammary epithelial cells in vivo lung metastasis, and triggered significant EMT. In contrast, the opposite effects in vitro and in vivo of FOXQ1 knockdown phenotypes were caused by these mechanisms. Notably, FOXQ1 repressed core EMT regulation of the expression of TGF-ß1. FOXQ1 protein directly interacts with E-cadherin and N-cadherin promoter region. And surveys show that FOXQ1 expression regulation by TGF-ß1 and blockade induced EMT both morphological and molecular levels. Our findings emphasize the feasibility of cross-species expression profiles, as a strategy to identify metastasis-related genes. The induction of EMT by FOXQ1 defines a new transfer function in promoting cancer behind possible mechanisms.

TGF-ß1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition in some tumor lines.

More and more studies have reported that epithelial-mesenchymal transition (EMT) involved in the process of cancer development and progression occurs. The EMT also plays an important role in the movement and transfer of the tumors. Transforming growth factor-ß (TGF-ß) could induce the EMT in some cancer cell types. However, the mechanism underlying this transition process has also not been entirely clarified. In this study, the results indicated that TGF-ß1-mediated EMT in the tumor was associated with the estrogen receptor (ER). The decreased expression of vimentin and snail resulted in the decrease of the ER expression by small interfering RNA-mediated silencing and preventing the TGF-ß-induced EMT. In conclusion, our results indicated that TGF-ß1 is an estrogen receptor signaling and essential novel downstream targets and could act as an important factor in the TGF-ß-induced EMT.

Prognostic value of hypercalcaemia and leucocytosis in resected oral squamous cell carcinoma.

Hypercalcaemia and leucocytosis are common in our patients with progressive oral squamous cell carcinoma (SCC). However, the precise incidence, prognostic value, and correlation with the condition of the tumour remain obscure. A total of 618 patients with oral SCC who were treated primarily between 2007 and 2012 and had serum calcium concentrations and white blood cell count (WCC) measured postoperatively were included in the study. Primary TNM stage, pathological features, and the presence of locoregional recurrence or distant metastasis after comprehensive surgical treatment were recorded. The incidence of hypercalcaemia was 9.1% and that of leucocytosis 7.2%. Hypercalcaemia correlated significantly with size of primary tumour (T status), nodal involvement (N status), TNM stage, perineural invasion, lymphovascular permeation, and recurrence or metastasis of disease. Leucocytosis, however, correlated only with T status, lymphovascular permeation, and recurrence or metastasis. In multivariate analysis of survival, recurrence, metastasis, hypercalcaemia, and leucocytosis were strong independent prognostic factors. Median survival was low if the patient had hypercalcaemia or leucocytosis (179 (range 3-73) days if the patient had distant metastasis, and 43 (range 3-102) days if the patient had locoregional recurrence). The incidence of hypercalcaemia and leucocytosis was high during the course of the disease, and both conditions have an adverse impact on survival from oral SCC. Periodic evaluation of serum calcium concentrations and WCC should be routine during the postoperative period.

Histone modification patterns correlate with patient outcome in oral squamous cell carcinoma.

BACKGROUND: Patterns of global histone modifications have been suggested to be predictors of clinical outcome in many cancers. However, the role of global histone modification patterns in oral squamous cell carcinoma (OSCC) is unclear. METHODS: A retrospective clinicopathologic analysis was undertaken of 186 patients with oral squamous cell carcinoma who received complete ablative surgical treatment. Tissue arrays were made from those paraffin-embedded OSCC samples and examined by immunohistochemistry for histone 3 lysine 4 acetylation (H3K4ac), histone 3 lysine 18 acetylation (H3K18ac), histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and histone 3 lysine 27 trimethylation (H3K27me3). RESULTS: A low level of H3K4ac and a high level of H3K27me3 were associated with advanced T status, N status, tumor stage, and perineural invasion. They were also correlated with cancer-specific survival (CSS) and disease-free survival (DFS). The 5-year CSS and DFS in H3K4ac(low) vs. H3K4ac(high) were 74.8% versus 92.5% (P = .010), and 51.4% versus 76.2% (P = .001), respectively. The 5-year CSS and DFS in H3K27me3(low) versus H3K27me3(high) were 94.7% versus 62.3% (P < .001) and 76.4% versus 32.3% (P < .001), respectively. We also found improved prediction for DFS after combining the H3K4ac(low) and H3K27me3(high) profiles and comparing the scores with the other modification patterns (P < .0001). CONCLUSIONS: This research demonstrates the potential prognostic utility of global histone modification analysis for OSCC.

Chromosome instability modulated by BMI1-AURKA signaling drives progression in head and neck cancer.

Chromosomal instability (CIN) is widely considered a hallmark of cancer, but its precise roles in cancer stem cells (CSC) and malignant progression remain uncertain. BMI1 is a member of the Polycomb group of chromatin-modifier proteins that is essential for stem cell self-renewal. In human cancers, BMI1 overexpression drives stem-like properties associated with induction of epithelial-mesenchymal transition (EMT) that promotes invasion, metastasis, and poor prognosis. Here, we report that BMI1 mediates its diverse effects through upregulation of the mitotic kinase Aurora A, which is encoded by the AURKA gene. Two mechanisms were found to be responsible for BMI1-induced AURKA expression. First, BMI1 activated the Akt pathway, thereby upregulating AURKA expression through activation of the ß-catenin/TCF4 transcription factor complex. Second, BMI1 repressed miRNA let-7i through a Polycomb complex-dependent mechanism, thereby relieving AURKA expression from let-7i suppression. AURKA upregulation by BMI1 exerts several effects, including centrosomal amplification and aneuploidy, antiapoptosis, and cell-cycle progression through p53 degradation and EMT through stabilization of Snail. Inhibiting Aurora A kinase activity attenuated BMI1-induced tumor growth in vivo. In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis. Together, our results link CSCs, EMT, and CIN through the BMI1-AURKA axis and suggest therapeutic use from inhibiting Aurora A in head and neck cancers, which overexpress BMI1.

Predictors and impact of microsurgical complications in patients with locally advanced oral squamous cell carcinoma.

Microvascular free flap transfer for post-oncologic reconstructive surgery in oral cancer is considered to be a challenge due to the complexity of the anatomy and function of the region. We sought to identify possible factors associated with microsurgical complications and to assess the impact of these complications in relation to patient survival. Following the inclusion and exclusion protocol, 142 patients with stage III and IV oral squamous cell carcinoma (OSCC) who underwent immediate free flap reconstruction after tumor ablation were included in the study. Clinical and surgical procedural-related factors were retrieved from a database and analyzed retrospectively; survival data were evaluated using the Kaplan-Meier method. Major complications that required re-anastomosis of the flap vessels occurred in 23 patients (16.2%); total necrosis of the flaps, regardless of salvage treatment, occurred in seven cases, with 95.1% of full flap survival. The American Society of Anesthesiologists classification, types of neck dissection, and number of flaps were regarded as strong predictors for surgical complications. Patients with these complications appeared to have a shortened survival (5-year cancer-specific survival of approximately 60%, both in stage III and IV OSCC). However, the impact of surgical complications on survival was significant only in stage III OSCC (P = 0.037). Strategies to minimize surgical complications should be used to ensure better prognoses for these patients.

Analysis of p16(INK4A) expression of oral squamous cell carcinomas in Taiwan: prognostic correlation without relevance to betel quid consumption.

OBJECTIVES: In this study, we examined the role of p16(INK4A) , a surrogate biomarker of HPV-related head and neck cancers with better prognosis, in an endemic area of betel quid (BQ)-related oral squamous cell carcinoma (OSCC). METHODS: p16(INK4A) immunohistochemistry was examined in 165 OSCCs, statistical analyses were performed to elucidate the correlation between p16(INK4A) expression and BQ habits/pathologic features, and the prognostic impact of p16(INK4A) and different parameters were analyzed. RESULTS: The incidence of p16(INK4A) expression was similar between BQ chewers and non-chewers. p16(INK4A) expression was significantly associated with nodal metastasis (P = 0.005). There was a trend suggesting that the loss of p16(INK4A) expression was more frequent in higher T stages, however, this was found only in patients without lymph node metastasis (P = 0.059). A poorer prognosis and a higher risk of tumor recurrence were found in OSCCs without p16(INK4A) expression. (The HR for cancer-specific mortality and cancer recurrence was 3.55 and 1.89, respectively.) CONCLUSION: Although it has been suggested that BQ chewers had a greater tendency toward tumor recurrence and poor outcome, our data demonstrated that p16(INK4A) expression is unrelated to BQ habit and that p16(INK4A) downregulation is a strong predictor for OSCC progression, recurrence and survival in Taiwan.

Comprehensive rehabilitation after severe maxillofacial injury in a cleft patient.

We present here a complex oral rehabilitation procedure for a 19-year-old male patient with an operated cleft lip and palate who suffered motorcycle accident injuries including facial lacerations, and a severe mandible fracture with loss of teeth, gingiva and alveolar bone. His initial skeletal and occlusal relationship made the emergent surgical management extremely difficult. Emergent soft tissue repair and open reduction surgery for the comminuted fracture at the mandible were performed during the intensive care period. A 2-year period of comprehensive procedures including surgical/orthodontic treatment, implant surgery and bone graft and prosthetic restoration for oral and maxillofacial rehabilitation to treat the severely compromised soft and hard tissue status, intermaxillary jaw discrepancy, and severe malocclusion, were sequentially performed. Satisfactory results were observed after a 5-year follow-up.

Detection and screening of oral cancer and pre-cancerous lesions.

Oral cancer is a fatal disease, accounting for the fourth highest incidence of malignancy in males and the seventh in females in Taiwan. The relatively high prevalence of oral cancer in Taiwan is mainly because there is a high-risk group of 2.5 million people with the habit of smoking and betel nut chewing. Unfortunately, 50% of new cases in our medical center who present with TNM stage III or IV lesions have a shorter than 5-year survival after treatment. This highlights the need for: (1) early treatment of fresh oral cancer cases; (2) screening of the high-risk population to detect new lesions; (3) careful follow-up of cases after treatment; and (4) detection of occult early neck nodal adenopathy in surgical cases. It is generally accepted that prevention and screening of oral cancer are equally important to treatment due to its location. In this review article, we describe the nature of oral cancer and highlight the various conventional and novel methods of screening for this disease and ongoing important related research. Related literature is reviewed and future work that needs to be done is detailed.

The Val allele of HER-2 codon 655 predicts the progression of oral squamous cell carcinoma.

HER-2 proto-oncogene is important for oral carcinogenesis. HER-2 codon 655 polymorphism, either isoleucine (Ile: ATC) or valine (Val: GTC), was associated with the risk of breast carcinoma. This study investigated the clinicopathological implications of this polymorphism in oral carcinoma. We found that 79% of oral carcinoma patients had A/A (Ile/Ile) genotype and 21% had A/G (Ile/Val) genotype, with a G (Val) allelic frequency of 0.10. Univariate analysis indicated a significantly higher Val allelic frequency in cases having nodal metastasis or tumor recurrence; and Val allele was associated with poorer recurrence-free survival of patients. Multivariate analysis after adjusting confounding factors by logistic regression analysis indicated that patients carrying Val allele had a 8.79- and 4.25-fold higher risk for nodal metastasis and recurrence, respectively. Using Cox proportional hazard model, the risk of tumor recurrence was 3.35-fold higher in patients carrying Val allele. This is the first report demonstrating that the Val allele of HER-2 codon 655 could be an independent predictor for oral carcinoma progression.

Multimodality treatment for rehabilitation of adult orthodontic patient with complicated dental condition and jaw relation.

A 50-year-old man with severe malocclusion requested comprehensive oral rehabilitation. He presented with retrognathic mandible, anterior deep bite and a gummy smile in the premaxilla, and tenting occlusal plane with severe buccal crossbite of the left maxillary posterior teeth. Inappropriate fixed prostheses spanned the maxilla and the mandible with a class II jaw relationship. A detailed analysis indicated the need for orthodontic treatment, orthognathic surgery, bone graft at the deficient alveolar ridge for implant surgery and a revision of all prostheses. Over a 2-year-period of management, the patient received anterior osteotomy for intrusion of lower anterior teeth, bilateral sagittal splitting osteotomy for mandible advancement and posterior osteotomy for inward upward repositioning of posterior teeth of the left maxilla to correct major jaw deformities. The deficient alveolar ridge in the premaxilla was augmented by autogenous bone graft harvested during the orthognathic surgery. He sequentially had mini-plate and dental implant as anchorage assisting teeth alignment in the mandible. Two 3-fixture-supported implant prostheses were delivered in the premaxilla and the mandible. The improvement in cosmesis, stability and function through treatment and a 2-year clinical follow-up were considered satisfactory.

Sarcomas and sarcomatoid tumor after radiotherapy of oral squamous cell carcinoma: analysis of 4 cases.

Radiation-induced sarcoma (RIS) or postirradiation sarcoma has been reported rarely as a long-term complication of radiation therapy (RT). We report 4 cases of oral sarcomas or sarcomatoid tumors with a rather short latency period after radiotherapy of the prior OSCC. Histopathological evaluation and immunohistochemical study were performed using a panel of markers including vimentin, cytokeratin, S-100, desmin, myoglobin, HHF-35, p53, and p16. All reported cases were positive for vimentin and negative for cytokeratin. Two cases were positive for myoglobin, desmin, or HHF-35, and were probably myogenic origin. One case was possibly a fibrosarcoma and the subclassification of the other one was not specified. Diverse expression of p53 and p16 was further observed in these 4 cases. Report of the complicated clinical processes and the analysis of genetic markers of these cases provide useful clinical and pathogenetic insights of mesenchymal malignancies associated with a status post OSCC radiation.

Application of in vivo stain of methylene blue as a diagnostic aid in the early detection and screening of oral squamous cell carcinoma and precancer lesions.

BACKGROUND: Early detection of oral malignant or precancerous lesion by screening individuals with high-risk factors may identify candidates who should receive treatment to prevent cancer progression and reduce patient mortality. Among the diagnostic tools, in vivo staining is advocated as a simple, inexpensive, and fairly sensitive method. METHODS: The present study involved the examination of 58 patients suspected of having oral malignant or precancerous lesions by methylene blue staining. The results of methylene blue uptake were compared with a simultaneous biopsy of these lesions. The pathologically confirmed precancers and cancers were the positive targets of this screening, while benign epithelial lesions were sorted as negative subjects of screening. RESULTS: The results revealed sensitivity of 90%, specificity of 69%, positive predictive value of 74%, and negative predictive value of 87%. CONCLUSION: We consider that methylene blue staining is a useful diagnostic adjunct in a large, community-based oral cancer screening program for high-risk individuals.

Use of methylene blue as a diagnostic aid in early detection of oral cancer and precancerous lesions.

We assessed the sensitivity, specificity, and positive and negative predictive value of methylene blue staining in the diagnosis of oral cancer in 58 patients. The sensitivity was 90%, the specificity 69%, positive predictive value 74%, and negative predictive value 87%. Because of the number of false negatives and false positives we recommend that the diagnosis should always be confirmed by histopathological examination of a biopsy specimen. Methylene blue staining may, however, be useful as a screening tool for oral cancer in large, high-risk groups in a similar way to the more expensive toluidine blue.