Prospective Cohort Study Identifies Medical Predictors of Treatment-Related Oral Toxicities in Oral and Oropharyngeal Cancer Patients.

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

Salivary proteins offer insights into keratinocyte death during aphthous stomatitis. A case-crossover study.

BACKGROUND: The death of oral keratinocytes is a crucial step in the emergence of recurrent aphthous stomatitis (RAS, also known as aphthae or aphthous ulcers). Since there are no experimental models available to research aphthous ulcers, little is understood about this process. We hypothesize that saliva can be a data bank of information that offers insights on epithelial damage. METHODS: In this case-crossover study, we assessed the salivary proteome of patients with RAS (n = 36) in the presence and absence of ulcers using discovery proteomics and bioinformatics. Additionally, we contrasted these patterns with those of healthy individuals (n = 31) who had no prior aphthous ulceration. RESULTS: Salivary proteome showed that during the ulcerative phase, controlled cell death was downregulated. Due to its ability to distinguish between individuals with and without ulcers, the ATF6B protein raises the possibility that endoplasmic reticulum (ER) stress is responsible for the damage that leads to the death of oral keratinocytes. The high abundance of TRAP1 and ERN1 matches with this biological discovery. The type of death is immunogenic, according to the functional data found in a cell death database. CONCLUSION: We identified a cellular process that can lead to the death of oral keratinocytes in the etiopathogenesis process of RAS. Future studies should be conducted to identify what is responsible for the increase in ER stress signaling that would lead to an anti-cell death response.

Patient's perceptions of oral and oropharyngeal cancer diagnosis disclosure: communication aspects based on SPIKES protocol.

OBJECTIVE: Breaking bad medical news is a complex task of clinical practice. The manner in which this is done has a significant impact on patients. This study aimed to assess patient's perceptions regarding oral and oropharyngeal cancer diagnosis disclosure according to the "SPIKES" protocol. STUDY DESIGN: This cross-sectional study used a questionnaire with 21 SPIKES-based items. The questionnaire was administered to 100 patients with recently diagnosed oral and oropharyngeal squamous cell carcinoma who evaluated each item according to their preference and experience. RESULTS: Nineteen items showed a significant difference between patient's preference and recalled experience. Eighteen of these items showed lower experience scores primarily related to the amount of information desired by patients, presence of a companion, time to express feelings, and summary of information. Most patients preferred receiving as much information as possible about the diagnosis. However, only 35% reported that they had obtained sufficient information. Patients who were aware of cancer diagnostic suspicion had better communication experiences. CONCLUSIONS: Protocols may be useful to guide health professionals to support patient-centered strategies to disclose oral cancer diagnoses.

Burning mouth syndrome is an oral disease connected to emotions

Burning mouth syndrome presents several challenges, which involve the ignorance of the disease and the psychological and economic barriers for the patients who suffer from it. This letter has a reflection on how the syndrome is related to emotions.

Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer.

The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

Recurrent Aphthous Stomatitis Affects Quality of Life. A Case-Control Study.

Aim: To determine the impact of recurrent aphthous stomatitis on quality of life related to oral health, and then to determine the relationship between the observed impact and lesions characteristics. Methods: In this prospective case-control study (n=62), patients were divided into a healthy group (people with no history of ulcers) and recurrent aphthous stomatitis (people who had an active ulcer at study entry). The latter were also evaluated when the lesion disappeared (remission stage). We record the quality of life in all groups using the impact profile of oral health in its abbreviated Spanish version (OHIP-14SP). Finally, we correlate the clinical characteristics of the lesions with the levels of quality of life. Results: All the lesions were of the minor morphological type. Most of the lesions were located on the lining mucosa, primarily on the lips. Patients report a lower quality of life during ulcer episodes compared to ulcer-free periods, and this impact is positively related to the number and size of lesions. Conclusion: We concluded that recurrent aphthous stomatitis increased the negative effects of oral health on the quality of life of patients. The number and size of ulcers are responsible for this impact. Our results suggest that, if intervened locally, general relief of the condition could be achieved.

Improved Estimation of End-Milling Parameters from Acoustic Emission Signals Using a Microphone Array Assisted by AI Modelling.

This paper presents the implementation of a measurement system that uses a four microphone array and a data-driven algorithm to estimate depth of cut during end milling operations. The audible range acoustic emission signals captured with the microphones are combined using a spectral subtraction and a blind source separation algorithm to reduce the impact of noise and reverberation. Afterwards, a set of features are extracted from these signals which are finally fed into a nonlinear regression algorithm assisted by machine learning techniques for the contactless monitoring of the milling process. The main advantages of this algorithm lie in relatively simple implementation and good accuracy in its results, which reduce the variance of the current noncontact monitoring systems. To validate this method, the results have been compared with the values obtained with a precision dynamometer and a geometric model algorithm obtaining a mean error of 1% while maintaining an STD below 0.2 mm.

Structural complexity of the craniofacial trabecular bone in multiple myeloma assessed by fractal analysis.

Purpose: This study aimed to evaluate the structural complexity of craniofacial trabecular bone in multiple myeloma by fractal analysis of panoramic and lateral skull radiography, and to compare the fractal dimension values of healthy patients (HPs), pre-treatment patients (PTPs), and patients during bisphosphonate treatment (DTPs). Materials and Methods: Pairs of digital panoramic and lateral skull radiographs of 84 PTPs and 72 DTPs were selected. After application of exclusion criteria, 43 panoramic and 84 lateral skull radiographs of PTPs, 56 panoramic and 72 lateral skull radiographs of DTPs, and 99 panoramic radiographs of age- and sex-matched HPs were selected. The fractal dimension values from panoramic radiographs were compared among HPs, PTPs, and DTPs and between anatomical locations within patient groups using analysis of variance with the Tukey test. Fractal dimension values from lateral skull radiographs were compared between PTPs and DTPs using the Student t-test. Pearson correlation coefficients were used to assess the relationship between the mandible from panoramic radiographs and the skull from lateral skull radiographs. Intra-examiner agreement was assessed using intraclass correlation coefficients (α=0.05). Results: The fractal dimension values were not significantly different among HPs, PTPs, and DTPs on panoramic radiographs or between PTPs and DTPs on lateral skull radiographs (P>0.05). The mandibular body presented the highest fractal dimension values (P≤0.05). The fractal dimension values of the mandible and skull in PTPs and DTPs were not correlated. Conclusion: Fractal analysis was not sensitive for distinguishing craniofacial trabecular bone complexity in multiple myeloma patients using panoramic and lateral skull radiography.

Follistatin-related protein 1 interacting partner of Syndecan-1 promotes an aggressive phenotype on Oral Squamous cell carcinoma (OSCC) models.

Syndecans belong to the family of transmembrane heparan sulfate proteoglycans and are associated with many physiopathological processes, including oral cancer. As previously shown soluble syndecan-1 (SDC1) fragments and synthetic SDC1 peptide were able to induce cell migration in oral cancer cell lines. In order to explore the role of SDC1 in oral cancer, we have investigated SDC1 interacting partners and its functional role in oral cancer models. Here we have shown that SDC1 interacts with follistatin-related protein 1 (FSTL1) by its ectodomain (ectoSDC1) and extracellular juxtamembrane peptide (pepSDC1) and that their transcript levels can affect tumor events. Using orthotopic mouse model we identified that the knock-down for FSTL1 (shFSTL1) or for both FSTL1 and SDC1 (sh2KD) produced less aggressive and infiltrative tumors, with lower keratinization deposition, but with increased levels of epithelial-mesenchymal transition and proliferation compared to control and SDC1 knock-down. Based on cell culture assays, we suggest that the shFSTL1 effect on tumor tissues might be from significant increase of mRNA levels of Activin A (ActA) and its resceptors. This study shows for the first time two different complexes, SDC1 and FSTL1; pepSDC1 and FSTL1, exhibiting a close relationship in cell signaling events, as FSTL1 promotes a more aggressive phenotype. SIGNIFICANCE: This work contributes to the understanding of new SDC1 functions, based on the investigation of protein-protein complex formation in Oral Squamous cell carcinoma (OSCC) models. The FSTL1 identification, as an interacting partner of SDC1 ectodomain and of its derived peptide promotes molecular events that favors cancer development and progression, as highlighted by Activin A (ActA) and Epithelial-mesenchymal transition (EMT) gene expression and by changes in the phenotype of orthotopic OSCC mouse tumor tissues when SDC1-FSTL1 expression is modulated.

A multi-modal algorithm based on an NSGA-II scheme for phylogenetic tree inference.

The analysis of evolutionary data allows uncovering information about the organisms and how they have adapted and evolved. This information could provide us with new insights about the specialisation of organisms (or part of them), how they adapt, how similar they are with other species, among others. Unfortunately, this evolutionary history can only be estimated, and for that, several computational methods exist. Among the methods, optimisation methods are one of the main approaches to deal with this problem, with multiobjective optimisation producing promising results. In this paper, we deal with multiobjective phylogenetic inference, using a multi-modal metaheuristic approach that exploits the decision space in the multiobjective formulation of the problem. In particular, we incorporate a new metric based on a topological tree distance. We compare the method with state of the art algorithms in terms of performance. Additionally, we perform a thorough analysis of a study case on a yeast Saccharomyces cerevisiae dataset. Results show that our proposal is able to improve the diversity of solutions while improving or keeping the quality of solutions in terms of hypervolume.

Chemotherapy as a risk factor for caries and gingivitis in children with acute lymphoblastic leukemia: A retrospective cohort study.

BACKGROUND: Dental and oral anomalies are among the most common long-term side effects of childhood cancer therapy. AIM: To evaluate chemotherapy as a risk factor for caries lesions and gingivitis in children with acute lymphoblastic leukemia (ALL) treated with the ALL IC-BFM 2009 chemotherapy protocol. DESIGN: A retrospective cohort study was designed. Clinical records of 23 paediatric patients with ALL exposed to chemotherapy in the Regional Hospital in Valdivia, Chile, and 46 unexposed patients assessed every 3 months for 24 months were analyzed. The data on gender, age, index of the number of decayed, missing, or filled teeth, and the presence of gingivitis were recorded (Mann-Whitney U test and logistic regression analysis, p ≤ .05). RESULTS: A significantly greater frequency of gingivitis (69.57%; p < .002) and a mean of new caries lesions were observed in children treated with chemotherapy than in the unexposed children (p < .01). The chemotherapy protocol presented a relative risk of 2.15 (95% CI = 1.22 - 2.66; p = .01) for new caries lesions and 2.29 (95% CI = 1.76 - 3.82; p = .002) for gingivitis. CONCLUSION: The ALL IC-BFM 2009 chemotherapy protocol in patients with ALL is a risk factor for new caries lesions and gingivitis.

Awareness of the risk of radiation-related caries in patients with head and neck cancer: A survey of physicians, dentists, and patients.

OBJECTIVES: Radiation-related caries (RRC) is one of the most aggressive complications of radiotherapy (RT) in survivors of head and neck cancer (HNC). Lack of RRC awareness may contribute to the occurrence of this oral cavity complication. RRC may be considered a "forgotten oral complication" by patients with HNC, oncologists, and dentists. The present study aimed to assess the level of awareness of RRC among physicians, dentists, and patients. STUDY DESIGN: Physicians (group 1, G1), dentists (group 2, G2), and patients with HNC undergoing RT (group 3, G3) answered questionnaires concerning their awareness of RRC. Physicians (G1) were divided into group 1A (oncological experience) and group 1B (general physicians/other specialties). Dentists (G2) were divided into group 2A (oncological experience) and group 2B (general dentists/other specialties). Personalized questionnaires were designed for each group. RESULTS: Recruitment was as follows: physicians (n = 124): 1A (n = 64), 1B (n = 60); dentists: (n = 280), 2A (n = 160), 2B (n = 120). In addition, 58 patients answered the questionnaire. In terms of RRC awareness, 46.77% of physicians, 81.78% of dentists, and 24.13% of patients had some knowledge of the problem. CONCLUSION: Patient awareness of RRC was poor. The heterogeneity of answers among physicians and dentists suggests an opportunity to improve patient education and prevention of this serious oral complication of RT.

Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria.

There are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case-control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacterium Neisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1) and hemoglobin subunit beta (HBB) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.

Impact of radiation on tooth loss in patients with head and neck cancer: a retrospective dosimetric-based study.

OBJECTIVE: To characterize the dental adverse events after head and neck radiation therapy (HNRT) and to investigate the impact of regional radiation dose upon tooth loss outcomes. STUDY DESIGN: A retrospective dosimetric-based analysis was conducted to assess dental events affecting post-HNRT extracted teeth and the impact of 3 different radiation doses (<30 Gy, 30-60 Gy, and >60 Gy) upon tooth loss. In addition, post-HNRT extractions outcomes and mean parotid glands dosimetry and salivary changes were analyzed. RESULTS: Sixty-six patients who underwent HNRT were included in the analysis. Radiation caries was the most frequent (67.8%) post-HNRT dental adverse event, and maxillary molars ipsilateral to the tumor were lost earlier compared with the others (P < .001). The odds ratio for post-HNRT tooth extraction risk was approximately 3-fold higher for teeth exposed to >60 Gy (confidence interval, 1.56-5.35; P < .001), followed by an increased risk of delayed healing and osteoradionecrosis (ORN) in sites receiving doses above 50 Gy. CONCLUSIONS: Radiation caries was the major cause of dental extractions after HNRT, and the dosimetric analysis suggested that a high dose of radiation may negatively impact the dentition of survivors of head and neck cancer, increasing the risk of tooth loss and ORN.

Altered cardiometabolic profile in girls with central precocious puberty and adipokines: A propensity score matching analysis.

OBJECTIVE: To compare cardiometabolic factors and adipokines between patients with recently diagnosed CPP and controls without CPP, paired by BMI Z scores (BMIz) and classified into girls with adequate nutritional status and girls who are overweight or obese. METHODS: This cross-sectional study was performed from January 2012 to May 2015 at two tertiary care pediatric centers in Mexico City. We included female patients with idiopathic CPP without other chronic pathology and healthy controls. Patients were divided into groups, BMI < 85th and BMI ≥ 85th percentile, according to 2000 CDC Growth Charts. Anthropometric data and fasting plasma concentrations of lipids, glucose, insulin, and leptin were assessed. RESULTS: There were 73 patients with CPP and 82 without CPP. Sixty-six patients were matched between the groups; no significant difference was noted between the groups according to zBMI. However, differences in the bone/chronological age relationship, birth weight and proportions in different Tanner stages were observed. Among girls with normal BMI, the percentage of body fat (24.6% vs 18.9%, p < 0.001), serum triglycerides (102.9 vs 54.3 mg/dl, p < 0.001), leptin (7.46 vs 5.4 ng/ml, p = 0.010) and free leptin (0.44 vs 0.29 ng/ml, p = 0.044) were higher in those with CPP; additionally, girls with CPP presented a higher proportion of hypertriglyceridemia. In the overweight/obese group, adiponectin levels were lower in girls with CPP (6.23 vs 7.28 pg/ml, p = 0.011). CONCLUSIONS: Girls with CPP and normal BMI at diagnosis had a worse cardiometabolic profile, as reflected by higher levels of free leptin, and higher proportion of hypertriglyceridemia than girls without CPP.

Risk factors for recurrent aphthous stomatitis: a systematic review / Factores de riesgo para la estomatitis aftosa recurrente: revisión sistemática

SUMMARY: The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

RESUMEN: Aún se desconoce la causa y cómo prevenir la estomatitis aftosa recurrente (más conocida como aftas). En esta revisión sistemática (registro PROSPERO #CRD42019122214) mostramos que la mayoría de los factores de riesgo para la enfermedad son polimorfismos genéticos de un solo nucleótido en genes relacionados con el funcionamiento del sistema inmune (TLR4, MMP9, E- selectin, IL-1 beta y TNF-alfa). Los polimorfismos genéticos de un solo nucleótido no constituyen un riesgo modificable.Ello indica que, al menos en parte, la susceptibilidad para las aftas es hereditaria y que esos factores no pueden ser modificados.

Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.

Meta-omics analysis indicates the saliva microbiome and its proteins associated with the prognosis of oral cancer patients.

Saliva is a biofluid that maintains the health of oral tissues and the homeostasis of oral microbiota. Studies have demonstrated that Oral squamous cell carcinoma (OSCC) patients have different salivary microbiota than healthy individuals. However, the relationship between these microbial differences and clinicopathological outcomes is still far from conclusive. Herein, we investigate the capability of using metagenomic and metaproteomic saliva profiles to distinguish between Control (C), OSCC without active lesion (L0), and OSCC with active lesion (L1) patients. The results show that there are significantly distinct taxonomies and functional changes in L1 patients compared to C and L0 patients, suggesting compositional modulation of the oral microbiome, as the relative abundances of Centipeda, Veillonella, and Gemella suggested by metagenomics are correlated with tumor size, clinical stage, and active lesion. Metagenomics results also demonstrated that poor overall patient survival is associated with a higher relative abundance of Stenophotromonas, Staphylococcus, Centipeda, Selenomonas, Alloscordovia, and Acitenobacter. Finally, compositional and functional differences in the saliva content by metaproteomics analysis can distinguish healthy individuals from OSCC patients. In summary, our study suggests that oral microbiota and their protein abundance have potential diagnosis and prognosis value for oral cancer patients. Further studies are necessary to understand the role of uniquely detected metaproteins in the microbiota of healthy and OSCC patients as well as the crosstalk between saliva host proteins and the oral microbiome present in OSCC.

The impact on quality of life in patients with burning mouth syndrome: A systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to evaluate the evidence on health-related quality of life (HRQL) and oral health-related quality of life (OHRQL) in patients with burning mouth syndrome (BMS). STUDY DESIGN: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42020175288). An electronic search was carried out in March 2020 and included clinical trials, cross-sectional studies, and case-control studies. The following databases were screened: Embase, LILACS, PubMed, Web of Science, and Scopus. A gray literature search was performed on Google Scholar and ProQuest Dissertations & Theses Global. The eligibility criteria comprised publications that assessed HRQL or OHRQL in patients with BMS. The risk of bias was evaluated through The Joanna Briggs Institute Critical Appraisal tools. The Grading of Recommendation, Assessment, Development, and Evaluation system was used for the assessment of evidence quality. RESULTS: Thirty-three studies were included, and most presented a low risk of bias. Three meta-analyses were performed based on results of 6 observational studies and showed worse OHRQL (P < .00001) and HRQL (P < .0001) in patients with BMS compared to controls. CONCLUSION: Patients with BMS reported poor HRQL and poor OHRQL compared to control groups, evidencing that this condition affects patients' well-being.