Tumor budding is a prognostic factor in head and neck squamous cell carcinoma: A comprehensive meta-analysis and trial sequential analysis.

BACKGROUND: Mortality is linked to tumor budding (TB) in certain neoplasms. TB as a relevant histopathological feature is conditioned by tumor site, a specific study on head and neck squamous cell carcinoma (HNSCC) is needed. METHODS: A comprehensive meta-analysis was undertaken to investigate the relationship between TB and HNSCC-related outcomes. RESULTS: Overall 42 studies were included. Patients harboring high TB reported an Overall Survival (OS) Hazard Ratio (HR) of 2.63 (95% confidential interval (CI) 2.04-3.39; p-value < 0.001), Disease-free Survival (DFS) HR of 1.88 (95%CI 1.57-2.24; p-value <0.001) and Disease-specific Survival (DSS) HR of 2.14 (95%CI 1.81-2.52; p-value <0.001). Lymph Node Metastasis (LNM) studies harbored null heterogeneity and marked association with TB (Odds Ratio (OR) = 4.48, 95%CI 2.97-6.76; p-value < 0.001). Trial Sequential Analysis (TSA) supported definitive results for DSS. CONCLUSION: The study has provided compelling evidence that there is a significant association between TB and a worse prognosis for HNSCC.

Correlation of Bcl-2 expression with prognosis and survival in patients with head and neck cancer: A systematic review and meta-analysis.

Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.

Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5-98.1) showing high/moderate expression compared to 45.7% (14.6-84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6-88.3) versus 22.9% (7.1-38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95-2.28); also, the rate of heterogeneity was low, as revealed by I2 = 31%. For DFS was 1.07 (95% CI 0.79-1.45) with I2 = 0% and DSS showed a HR of 0.88 (95% CI 0.69-1.12) with I2 = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC.

Efficacy of Ciprofloxacin, Metronidazole and Minocycline in Ordered Mesoporous Silica against Enterococcus faecalis for Dental Pulp Revascularization: An In-Vitro Study.

Pulp revascularization of teeth with necrotic pulp has become an alternative treatment in cases with immature apex. Microbial control is essential to achieve a successful outcome and continued root development. Enterococcus faecalis (E. faecalis) is the most frequently isolated bacterial species in root canals of endodontically failed teeth. Our main goal was to compare the in-vitro antimicrobial efficacy of different antibiotic formulations delivered by ordered mesoporous silica (OMS) against E. faecalis. To determine antibiotic susceptibility, we tested OMS and triple antibiotic paste (TAP; ciprofloxacin:metronidazole:minocycline) with different reagents in different concentrations, using the Kirby−Bauer disk diffusion method. OMS and metronidazole showed no antibacterial activity against E. faecalis. Mixtures of OMS and antibiotics in proportions of 2:2:14 and 4:1:7 (mg/L of ciprofloxacin:metronidazole:minocycline, respectively) showed the lowest antibacterial activity. The antibacterial activity of the combined solutions of ciprofloxacin and metronidazole was significantly higher (p < 0.005). Combinations in different concentrations of minocycline, ciprofloxacin, and metronidazole in OMS have shown activity against E. faecalis, although the combined use of ciprofloxacin and metronidazole has shown the most effective results. This study demonstrates the efficacy of intracanal antibiotic combination paste activity against E. faecalis, avoiding the use of minocycline, whose undesirable effect of teeth staining is a common problem for patients and professionals in dental clinic.

Allergic rhinitis improvement after septorhinoplasty in a sample of allergic rhinitis patients with septal deviation: a quasi-experimental study

ABSTRACT BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease that affects almost 30% of the adult population. OBJECTIVE: To describe and compare the evolution of symptoms in patients diagnosed with AR and septal deviation prior to and following septoplasty (STP). DESIGN AND SETTING: Quasi-experimental study developed in A Coruña University Hospital. METHODS: Patients aged 18-65 years who had been diagnosed with AR and septal deviation were recruited. Obstruction airflow was evaluated before and after surgery, by means of anterior rhinomanometry (RNM). Severity symptoms and quality of life were assessed using a visual analogue scale (VAS) and the ESPRINT questionnaire, respectively. RESULTS: A total of 50 subjects underwent STP and 42 were included in this study. Their mean age at the time of surgery was 34.16 ± 9.74 years (range 18-64). Significant reductions in mean VAS and ESPRINT were observed after surgery (P < 0.01). These outcomes were considered to represent an overall improvement in quality of life. The RNM results also improved significantly, from mean values of 478.07 ± 165.4 cm3/s before STP to 826.4 ± 175.5 cm3/s afterwards (P < 0.01). CONCLUSIONS: The negative correlations of VAS and ESPRINT with RNM, from before and to after STP, demonstrate the efficacy of scales and questionnaires as objective methods for determining obstruction in the absence of rhinomanometry. Patients with allergic rhinitis and septal deviation showed improvements in obstruction severity and medication use after STP.

Allergic rhinitis improvement after septorhinoplasty in a sample of allergic rhinitis patients with septal deviation: a quasi-experimental study.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease that affects almost 30% of the adult population. OBJECTIVE: To describe and compare the evolution of symptoms in patients diagnosed with AR and septal deviation prior to and following septoplasty (STP). DESIGN AND SETTING: Quasi-experimental study developed in A Coruña University Hospital. METHODS: Patients aged 18-65 years who had been diagnosed with AR and septal deviation were recruited. Obstruction airflow was evaluated before and after surgery, by means of anterior rhinomanometry (RNM). Severity symptoms and quality of life were assessed using a visual analogue scale (VAS) and the ESPRINT questionnaire, respectively. RESULTS: A total of 50 subjects underwent STP and 42 were included in this study. Their mean age at the time of surgery was 34.16 ± 9.74 years (range 18-64). Significant reductions in mean VAS and ESPRINT were observed after surgery (P < 0.01). These outcomes were considered to represent an overall improvement in quality of life. The RNM results also improved significantly, from mean values of 478.07 ± 165.4 cm3/s before STP to 826.4 ± 175.5 cm3/s afterwards (P < 0.01). CONCLUSIONS: The negative correlations of VAS and ESPRINT with RNM, from before and to after STP, demonstrate the efficacy of scales and questionnaires as objective methods for determining obstruction in the absence of rhinomanometry. Patients with allergic rhinitis and septal deviation showed improvements in obstruction severity and medication use after STP.

Efficacy of different formulations of nystatin in an experimental model of oral candidiasis in sialoadenectomized rats.

BACKGROUND/PURPOSE: Oral candidiasis is the most common fungal infection of the oral cavity and has become a focus of attention in recent years because of its association with highly topical immunosuppressive conditions. The aims of this study were to determine the value of microbiological, clinical and histological parameters of Candida albicans colonisation of the dorsal tongue surface as indicators of disease severity, and to evaluate therapeutic response to different formulations of nystatin. MATERIALS AND METHODS: We used 84 males, 2-month-old Sprague-Dawley sialoadenectomized rats. Different formulations of nystatin were used to evaluate the therapeutic response. The animals were randomized to 2 groups with each of 42 animals and received the experimental treatments from day 17-22. RESULTS: 100% of the rats showed evidence of infection. At 5 and 10 days of starting treatment with nystatin + chitosan, and at 10 days of starting nystatin + orabase, the number of animals with positive dorsal tongue culture decreased significantly (p < 0.05), acting the Nystatin + chitosan more rapidly against Candida. In the control group, the percentage of normal papillae on day 22 and 27 was 83.33% (SD = 1.50) and 79.08% (SD = 2.30), respectively. Significant differences were observed in the mean O'Grady score at 5 and 10 days (p < 0.0001). CONCLUSION: The model has been shown to be effective in inducing infection, and that the combination of nystatin and chitosan yielded the best therapeutic outcomes at both 5 and 10 days after infection.

Analysis of the unpredictable migration of impacted mandibular third molars: A pilot study.

BACKGROUND: Eruption of an impacted mandibular third molar (3MM) is often unpredictable. The objective of this study was to establish the radiographic parameters of migration in patients whose 3MMs evolved unpredictably. MATERIAL AND METHODS: This was a retrospective observational study. Patients with unusual 3MM migration (away from their physiological eruption position with changes in the longitudinal and horizontal axes) and with at least two panoramic radiographs were included. To evaluate the radiographic parameters, images were superimposed, using mandibular angle and ipsilateral condyle as references. RESULTS: Of a total of 2851 patients, four were included in our study. The average age of the patients at the time of the second X-ray was 41.75 (SD=8.42) years. The mean follow-up period was 111 (SD=59.09) months. The migration was caudal in three of the 3MMs (75%) and cranial in one (25%). CONCLUSIONS: Unpredictable 3MM migration is rare, and occurs mostly in the vertical direction with an average angle of 12 degrees. None of these migrations were related to any type of lesion. Our results reveal that, due to its unpredictable behaviour, impacted wisdom teeth have to be periodically radiographically evaluated even if surgical extraction is not indicated. Key words:Tooth migration, third molar, ectopic tooth.

Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC).

The aim of this present study was to comprehensively describe somatic DNA alterations and transcriptional alterations in the last extension of the HNSCC subsets in TCGA, encompassing a total of 528 tumours. In order to achieve this goal, transcriptional analysis, functional enrichment assays, survival analysis, somatic copy number alteration analysis and somatic alteration analysis were carried out. A total of 3491 deregulated genes were found in HNSCC patients, and the functional analysis carried out determined that tissue development and cell differentiation were the most relevant signalling pathways in upregulated and downregulated genes, respectively. Somatic copy number alteration analysis showed a "top five" altered HNSCC genes: CDKN2A (deleted in 32.03% of patients), CDKN2B (deleted in 28.34% of patients), PPFIA1 (amplified in 26.02% of patients), FADD (amplified in 25.63% of patients) and ANO1 (amplified in 25.44% of patients). Somatic mutations analysis revealed TP53 mutation in 72% of the tumour samples followed by TTN (39%), FAT1 (23%) and MUC16 (19%). Another interesting result is the mutual exclusivity pattern that was discovered between the TP53 and PIK3CA mutations, and the co-occurrence of CDKN2A with the TP53 and FAT1 alterations. On analysis to relate differential expression genes and somatic copy number alterations, some genes were overexpressed and amplified, for example, FOXL2, but other deleted genes also showed overexpression, such as CDKN2A. Survival analysis revealed that overexpression of some oncogenes, such as EGFR, CDK6 or CDK4 were associated with poorer prognosis tumours. These new findings help us to develop new therapies and programs for the prevention of HNSCC.

miRNAs expression of oral squamous cell carcinoma patients: Validation of two putative biomarkers.

microRNA expression patterns have provided new directions in the search of biomarkers with prognostic value and even in the search of novel therapeutic targets for several neoplasms. Specifically, miRNAs profiling in oral squamous cell carcinoma (OSCC) represents a web of intrigue in the study of oral carcinogenesis. The objective of the present study was twofold:The first study phase comprised case-control groups: A) 8 OSCC-affected patients and 8 healthy controls. Microarray technology (Affymetrix miRNA Array Plate 4.1) was used for miRNAs expression profile. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second phase, 2 miRNAs chosen for the subsequent RT-qPCR validation were studied in a second OSSC cohort (n = 8).Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Two miRNAs (miR-497-5p and miR-4417) were chosen for further validation via RT-qPCR. Prognostic analysis did not ascertain relevant relation between miR-497-5p or miR-4417 expression and clinical or pathological parameters, except high miR-4417 in the case of nodular affectation (P = .035) and diminished miR-497-5p radiotherapy-treated patients (P = .05). KEGG analysis revealed that deregulated miRNAs were implicated in several biological pathways such as Proteoglycans in cancer.Our data suggest an altered miRNAs profiling in OSCC-affected patients. We have verified the altered expression of miR-497-5p and miR-4417 in OSCC samples and related the deregulated miRNAs with the 'proteoglycans in cancer' pathway. Further longitudinal studies with large samples are warranted to confirm the present findings.