Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review.

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation.

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Treatment regimens and disease activity could alter salivary myeloperoxidase levels in patients with inflammatory bowel diseases.

INTRODUCTION: Inflammatory bowel diseases (IBDs) present with alternating periods of exacerbation and remission; therefore, it is necessary to develop noninvasive diagnostic tools to control the disease activity and improve therapeutic effectiveness. Recently, we have found that patients with ulcerative colitis (UC) who qualified for biologic therapy had significantly lower salivary myeloperoxidase (MPO) levels. OBJECTIVES: This cross­sectional study aimed to assess the impact of IBD activity and applied treatment on salivary antioxidant system as reflected by the levels of catalase, total antioxidant status, and MPO. PATIENTS AND METHODS: The study group comprised 99 patients diagnosed with Crohn disease (CD) and 61 patients with UC. The Crohn Disease Activity Index and modified Mayo scale were used to estimate the clinical activity of CD and UC, respectively. Unstimulated whole mixed saliva was collected. Salivary levels of selected markers were measured with enzyme­linked immunosorbent assays and colorimetric assays. RESULTS: The patients with clinically active UC showed significantly decreased median (interquartile range) salivary MPO levels (79.4 [30.1-157.5] vs 94.8 [58.2-274.7] ng/ml) with significant correlations with the endoscopic stage on the Mayo scale (R = 0.423; P = 0.02). Receiver operating characteristic analysis confirmed a potential usefulness of MPO concentrations in predicting clinically active UC (area under the curve = 0.654; P = 0.03; cutoff <210.4 ng/ml). Moreover, in the patients treated with biologics and without steroid therapy, salivary MPO concentrations negatively correlated with neutrophil counts in the individuals with UC and positively with C­reactive protein level in the patients with CD. CONCLUSIONS: Salivary MPO levels changed depending on the disease activity in the patients with UC. Decreased MPO concentration in the saliva could be a predictor of clinically active UC.

Serum Phosphorus and Calcium as Biomarkers of Disease Status in Acromegaly.

Acromegaly is a chronic disease caused by the hypersecretion of growth hormone (GH), leading to changes in the growth of visceral tissues and glucose impairment. Serum biomarkers that correlate with disease status are still unclear. This study aims to assess the potential of phosphorus and calcium as biomarkers in the clinical evaluation of patients with acromegaly and clarify their relationship with SAGIT and other common biomarkers. We retrospectively analyzed data from 306 medical records of patients with acromegaly hospitalized between 2015 and 2020. Factors such as patient biometrics, duration of disease, SAGIT score, tumor size, GH, insulin-like growth factor 1 (IGF-1), calcium, phosphorus, parathormone, and vitamin D were analyzed concerning current disease status (naïve, non-remission, remission). The results showed that serum phosphorus significantly correlated with IGF-1 and SAGIT scores for patients with active acromegaly. Specifically, the best predictor for the remission of acromegaly was a phosphorus level < 3.98 mg/dL and serum calcium levels < 9.88 mg/dL. Based on logistic regression, the higher the serum phosphorus level, the lower the odds of achieving remission (an increase in one unit leads to a decrease in the chance of about 80%). In conclusion, phosphorus and calcium can be effective biochemical markers for predicting disease status in acromegaly.

Increased Myeloperoxidase Concentrations in Saliva could Reflect Increased Body Mass and Oral Microinflammation.

BACKGROUND: Increased myeloperoxidase (MPO) levels in saliva are thought to reflect ongoing periodontal inflammation. Less clear is whether and to what extent salivary MPO is increased as a result of systemic inflammation. METHODS: In the present study, we aimed to determine which demographic, anthropometric, biochemical, and dental parameters affect the level of MPO in whole mixed saliva in healthy adults with no apparent inflammatory lesions in the oral cavity. Thus, 113 individuals, aged 20-61 years (including 30.1% men and 23.9% smokers), were examined. RESULTS: In the univariate analysis, higher levels of MPO in saliva were found to be associated with age, an increased body mass index (BMI), higher levels of cytokines tumour necrosis factor-α and interleukin-6, as well as poorer oral hygiene, gingival status, and lower saliva flow. Multivariate logistic regression analysis determined that the main predictors of MPO concentration in saliva were BMI and stimulated saliva flow rate. CONCLUSIONS: Overall, an increase in MPO in saliva could be related to an increase in BMI, possibly as a result of subclinical chronic microinflammation, which also involves the gingiva.

Salivary Alterations of Myeloperoxidase in Patients with Systemic Diseases: A Systematic Review.

Salivary myeloperoxidase (MPO) is a key mediator of the oral immune system, acting as an enzyme that utilises H2O2 to generate molecules with high bactericidal activity. While MPO determination in plasma is quite common, the use of saliva is still rare. Our systematic review was designed to answer the question "Are salivary levels of myeloperoxidase altered in patients with systemic diseases?". Following the inclusion and exclusion criteria, we included twenty-six studies. Altered MPO levels in saliva were most commonly found in patients with cardiovascular and gastrointestinal diseases. Most studies concerned unstimulated whole saliva, and only a few of them stimulated, mainly by chewing paraffin. Enzyme-linked immunosorbent assay (ELISA) was the most common method for determination of MPO concentrations in saliva. Increased salivary MPO levels were more often observed for inflammatory diseases, except patients with inflammatory bowel diseases who were eligible for biologic therapy. In conclusion, MPO could be altered in the saliva of patients with systematic diseases, especially cardiovascular or gastrointestinal diseases. However, further investigations are recommended to validate these outcomes.

Characteristics of E-Scooter-Related Maxillofacial Injuries over 2019-2022-Retrospective Study from Poznan, Poland.

Recently, there has been a considerable rise in the popularity and use of electric scooters. Because of this, the number of accidents involving them has also risen. Head and neck injuries are the most common. The aim of the study was to determine the most frequent craniofacial injuries resulting from accidents involving electric scooters, and to identify the risk factors directly related to their placement and severity. The study carried out a retrospective analysis of the medical records of patients of the Clinic of Maxillofacial Surgery over 2019-2022, in terms of craniofacial injuries suffered as a result of e-scooter-related accidents. In the study population (31 cases), of which 61.3% were men, the median age was 27 years. At the time of the accident, 32.3% patients were under the influence of alcohol. Accidents were most common in the 21-30 age group; more often than not, they occurred during warm months and on weekends. The study identified a total of 40 fractures in the patients. The most common craniofacial injuries were mandibular fractures (37.5%), zygomatic-orbital fractures (20%) and frontal bone fractures (10%). A multidimensional correspondence analysis was also performed, which showed that at an age of under 30, alcohol consumption and female gender were associated with a higher likelihood of mandibular fracture. Proper education on the risks associated with the use of e-scooters is essential, with particular emphasis on the impact of alcohol on the driver. It is important to develop diagnostic and therapeutic algorithms for doctors, both in ED and in specialised departments.

Salivary Alterations in Autoimmune Thyroid Diseases: A Systematic Review.

Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.

Smoking as a Risk Factor for Dry Socket: A Systematic Review.

Dry socket is one of the postoperative complications of tooth extraction. It is the partial or total loss of the post-extraction blood clot, resulting in severe pain that usually starts one to five days postoperatively, with clinical evidence of exposed alveolar bone, necrotic debris, halitosis, and tenderness on examination. The purpose of our systematic review was to answer the question "Is there a relationship between smoking and dry socket?". After meeting the inclusion and exclusion criteria, eleven studies were included in this systematic review (according to the PRISMA statement guidelines). Based on a meta-analysis, tobacco smokers had a more than three-fold increase in the odds of dry socket after tooth extraction. Overall, the combined incidence of dry socket in smokers was found to be about 13.2% and in non-smokers about 3.8%. Despite the heterogeneity of the included studies (different types of teeth extracted, different age groups), cigarette smoking was related to an increased risk of dry socket after tooth extraction.

Salivary Melatonin Changes in Oncological Patients: A Systematic Review.

Melatonin is known as a regulator of circadian sleep and waking rhythm. This hormone secreted by the pineal gland also has protective, oncostatic, and antioxidant properties. This systematic review was designed to answer the question "Is there a relationship between salivary melatonin changes and oncological diseases?". Following the inclusion and exclusion criteria, ten studies were included, according to PRISMA statement guidelines. In all included studies, the diagnostic material was unstimulated whole saliva, in which the melatonin changes were determined by different laboratory methods. Most studies concerned changes in melatonin levels in patients with brain tumours due to a direct effect on the circadian rhythm centres. Other studies focused on disorders of melatonin secretion and its inclusion as a diagnostic marker in patients with prostate cancer and oral squamous cell carcinoma. The association between melatonin changes and sleep quality and chronotype in patients with newly diagnosed lung cancer and lymphoma survivors was also investigated. In conclusion, our systematic review may suggest trends for melatonin secretion alterations in oncological patients. However, due to the significant heterogeneity of the included reports, it is not possible to clearly determine a link between changes in salivary melatonin levels and the oncological diagnosis.

Salivary Metabolomics for Oral Squamous Cell Carcinoma Diagnosis: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in which the consumption of tobacco and alcohol is considered to be the main aetiological factor. Salivary metabolome profiling could identify novel biochemical pathways involved in the pathogenesis of various diseases. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of oral squamous cell carcinoma?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). In all included studies, the diagnostic material was unstimulated whole saliva, whose metabolome changes were determined by different spectroscopic methods. At the metabolic level, OSCC patients differed significantly not only from healthy subjects but also from patients with oral leukoplakia, lichen planus or other oral potentially malignant disorders. Among the detected salivary metabolites, there were the indicators of the impaired metabolic pathways, such as choline metabolism, amino acid pathways, polyamine metabolism, urea cycle, creatine metabolism, glycolysis or glycerolipid metabolism. In conclusion, saliva contains many potential metabolites, which can be used reliably to early diagnose and monitor staging in patients with OSCC. However, further investigations are necessary to confirm these findings and to identify new salivary metabolic biomarkers.

Regional Odontodysplasia: A Systematic Review of Case Reports.

Regional odontodysplasia is a rare developmental disorder characterised by hypoplasia and hypomineralisation of enamel and dentin. Our systematic review aimed to organise the knowledge on localisation, symptomatology and treatment methods in patients with regional odontodysplasia based on case reports published in the databases PubMed, Scopus and Web of Science. Case reports were described in 28 different countries, considering 180 patients (including 91 females). Regional odontodysplasia occurs mainly in both deciduous and permanent dentition (66.1%). The affected teeth were observed more frequently in the maxilla (70.0%), especially on the left side (45.6%). The most common reported symptoms were ghost teeth, poorly developed buds, yellowish-brown colour of crowns and delayed eruption of permanent teeth in affected quadrants. The most popular treatment method was surgical treatment (78.6%) with subsequent prosthetic therapy (34.6%). Based on the review of cases, pathognomonic clinical and radiological signs can be found, however, it is difficult to reach a consensus on the choice of treatment method.

Salivary Metabolomics for Systemic Cancer Diagnosis: A Systematic Review.

Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive method in oncological diagnosis. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of systemic cancers?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). Changes in salivary metabolome were most commonly determined in patients with breast cancer, gastrointestinal cancers, and lung cancer. Most studies involved unstimulated whole saliva as the diagnostic material, evaluated by different spectroscopic methods. Among the found saliva metabolites, the alterations in the metabolic pathways of amino acids and polyamines were most frequently observed, which showed significant predictive values in oncological diagnostics. The most frequently encountered risks of bias were the absence of data regarding blinding, sample size justification, and randomisation. In conclusion, salivary metabolites seem to be potentially reliable for detecting the most common systemic cancers. However, further research is desirable to confirm these outcomes and to detect new potential metabolic biomarkers in saliva.

Oral Health Status in Patients with Inflammatory Bowel Diseases: A Systematic Review.

Inflammatory bowel diseases (IBD) are chronic disorders that affect the gastrointestinal tract, including the oral cavity. This systematic review was designed to answer the question "Is there a relationship between oral health status and inflammatory bowel diseases?". Following the inclusion and exclusion criteria, fifteen studies were included (according to PRISMA statement guidelines). Due to their heterogeneity, only six articles about the prevalence of periodontal disease in IBD patients were included in the meta-analysis. Both Crohn's disease (CD) and ulcerative colitis (UC) patients had an increased odds of periodontitis coincidence compared to the controls, more than 2- and 3-fold, respectively. Moreover, in most studies, patients with IBD were characterized by higher values of caries indices. In conclusion, despite the conducted systematic review, the risk of oral diseases in IBD patients cannot be clearly established due to the possible association of other factors, e.g., sociodemographic or environmental factors.

Potential Salivary Markers for Differential Diagnosis of Crohn's Disease and Ulcerative Colitis.

The properties of the saliva of patients with inflammatory bowel disease (IBD) are poorly recognized. Likewise, the diagnostic potential of saliva for differentiating various forms of IBD is largely unexplored. Therefore, we compared the concentrations of several parameters in unstimulated whole mixed saliva collected in a standardized manner from patients with active IBD unresponsive to conventional therapy. The samples were received from 27 patients with Crohn's disease (CD), 24 patients with ulcerative colitis (UC), and 51 healthy individuals. Compared to the controls, the salivary concentrations of S100A8/calprotectin, myeloperoxidase, and IgA were significantly decreased in both CD and UC patients. In addition, patients with UC had decreased levels of TNF-R1 and decreased catalase activity. Interestingly, the concentrations of myeloperoxidase and TNF-R1 showed a high differentiation potential for CD and UC (AUC = 0.690 and 0.672, respectively). All these findings are discussed in the context of host defense in the oral cavity, patients' prior treatment regimens, and smoking habits.

The Impact of the COVID-19 Pandemic on the Spectrum of Performed Dental Procedures.

The COVID-19 pandemic has significantly altered existing health care operations, including dentistry. The fear of SARS-CoV-2 infection and the need for increased protection measures have led to a reduction in the number of appointments and the range of performed procedures. Our study aimed to assess the impact of the COVID-19 pandemic (the pre-vaccine period) on the spectrum of performed dental services, with particular emphasis on the change in the proportion of conservative and surgical procedures. The patient base in the University Center of Dentistry and Specialized Medicine (Poznan, Poland) from two periods-pre-pandemic (1 February 2019-31 January 2020) and pandemic (1 February 2020-31 January 2021)-was analyzed. The number of dental services was standardized against the sum of all procedures in a given month. During the COVID-19 pandemic, the number of conservative procedures such as commercial restorations or filled canals has significantly decreased, while the number of surgical procedures has increased. The pandemic has undoubtedly affected the spectrum of dental procedures performed, especially in its acute phase. It is very important to return to performing conservative procedures and educating students in the former range while respecting all safety standards.

Salivary Biomarkers for Diagnosis of Inflammatory Bowel Diseases: A Systematic Review.

Saliva as a biological fluid has a remarkable potential in the non-invasive diagnostics of several systemic disorders. Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract. This systematic review was designed to answer the question "Are salivary biomarkers reliable for the diagnosis of inflammatory bowel diseases?". Following the inclusion and exclusion criteria, eleven studies were included (according to PRISMA statement guidelines). Due to their heterogeneity, the potential salivary markers for IBD were divided into four groups: oxidative status markers, inflammatory cytokines, microRNAs and other biomarkers. Active CD patients manifest decreased activity of antioxidants (e.g., glutathione, catalase) and increased lipid peroxidation. Therefore, malondialdehyde seems to be a good diagnostic marker of CD. Moreover, elevated concentrations of proinflammatory cytokines (such as interleukin 1ß, interleukin 6 or tumour necrosis factor α) are associated with the activity of IBD. Additionaly, selected miRNAs are altered in saliva (overexpressed miR-101 in CD; overexpressed miR-21, miR-31, miR-142-3p and underexpressed miR-142-5p in UC). Among other salivary biomarkers, exosomal PSMA7, α-amylase and calprotectin are detected. In conclusion, saliva contains several biomarkers which can be used credibly for the early diagnosis and regular monitoring of IBD. However, further investigations are necessary to validate these findings, as well as to identify new reliable salivary biomarkers.

Poor Oral Hygiene and High Levels of Inflammatory Cytokines in Saliva Predict the Risk of Overweight and Obesity.

The study aimed to determine if oral hygiene influences not only oral health but also potentially metabolic disorders such as overweight or obesity. Participants were 94 patients: 40 with increased body mass and 54 with normal body mass. The methods included dental examination, a questionnaire concerning hygienic habits and an assessment of selected salivary inflammatory markers. The new parameter named "cleaning index" (describing the interaction between average time of tooth brushing in minutes and its frequency per day) significantly correlated with Body Mass Index (RSpearman = 0.300). The multivariate regression model incorporating cleaning index, approximal plaque index, receptor 1 for tumor necrosis factor-alpha (TNFα-R1) and interleukin-15 (IL-15) had a high power to predict overweight or obesity (AUC = 0.894). Patients with poor oral hygiene (approximal plaque index >40%) were more than eight times more likely to suffer from obesity than patients with good oral hygiene. Cleaning index higher than 4 decreased the odds by about 85%. Oral hygiene habits, adjusted by salivary concentrations of selected inflammatory markers may allow predicting effectively overweight or obesity risk. Early proper dental prophylaxis and treatment could lead to the better prevention of metabolic disorders.

Characteristics of salivary inflammation in obesity.

INTRODUCTION: The discovery of the secretory function of adipose tissue has led to a new direction in research on obesity­ related health problems. Adipokines are present not only in blood but also in saliva. Numerous studies have indicated that obesity affects salivary concentrations of adipokines. OBJECTIVES: The aim of this study was to evaluate the levels of selected inflammatory markers in saliva and to determine their discriminatory value in obese individuals. PATIENTS AND METHODS: The study included 125 patients (82 women and 43 men), aged from 20 to 65 years. There were 59 patients with obesity (body mass index [BMI] >30 kg/m2) and 66 controls with normal body weight (BMI <25 kg/m2). Mixed saliva samples were collected from all participants to determine the concentrations of the following inflammatory markers: tumor necrosis factor­ α receptors 1 and 2, pentraxin 3, interleukin 15, monocyte chemoattractant protein 1, soluble intercellular adhesion molecule 1, and soluble CD40 ligand (sCD40L). RESULTS: Compared with controls, individuals with obesity had significantly higher levels of all inflammatory markers except sCD40L levels, which were lower. The salivary marker sCD40L seems to have the best discriminatory value in obesity regardless of sex, with the optimal cutoff point of 3.28 pg/ml and the area under the curve of 0.8. CONCLUSIONS: Obesity may be associated with altered levels of selected inflammatory markers in saliva. The discriminatory values determined in this study may facilitate the diagnosis of metabolic diseases.