Search Results (424)

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disorder of the oral cavity, although its etiology is still unknown. The present study aimed to identify the proteomic profile associated with the RAS inflammatory process, thereby enhancing our understanding of its etiopathogenesis. We compared salivary protein profiles of RAS patients during an active episode of oral ulceration (30 patients, mean age 36.9) to those from healthy donors without a history of RAS (30 healthy subjects, mean age 37.9). Using 2D-electrophoresis and mass spectrometry (MALDI-TOF) analysis, we identified 17 proteins that were differentially expressed in the two groups. Notably, Cystatin SN (CST1) appeared to be significantly downregulated in RAS patients. These findings were validated by Western blot analysis: CST1 was detected in only 3 of the 30 RAS cases, while it was strongly expressed in all the healthy subjects. Although preliminary, our results suggest a potential role for CST1 in the etiopathogenesis of RAS. Interestingly, the relative absence of CST1 in RAS patients seems to align with some clinical and molecular features of this disease. Full article

Background and Clinical Significance: The 45,X0/46,XY mosaic karyotype is categorized as a disorder of sex development and can lead to atypical sexual development. Latent mosaicism involving Y chromosomal segments may be much more prevalent than previously assumed, according to a growing number of findings. This primarily depends on how sensitive cytogenetic methods are—such as traditional karyotype screening, FISH methods, or molecular analyses. Case Presentation: We present the case of a 10-week-old infant with hermaphroditic external genitalia. During pregnancy, ultrasonography revealed severe fetal development difficulties, including severe widespread edema. An abnormal 45,X0/46,XY mosaic karyotype was discovered during a genetic amniocentesis conducted during the 16th week of pregnancy. The infant was born in average general condition at 39 + 6 weeks of gestation. Physical examination of the infant revealed features of facial dysmorphia, webbed neck, and hermaphroditic external genitalia. The testicle was palpable on the left side, but the gonad was absent on the right. Laboratory tests revealed a typical hormonal profile of the mini-puberty period in boys. Moreover, a hormone panel and thyroid ultrasound were performed; congenital hypothyroidism was diagnosed. Three separate independent sources of biological material were used in cytogenetic analysis to determine the karyotype: skin fibroblasts (to confirm tissue mosaicism), oral epithelial cells (FISH), and peripheral blood lymphocytes. It showed that a mosaic occurred very early in embryogenesis by confirming the existence of karyotypes 45,X and 46,XY in various tissues (mosaic tissue distribution). Conclusions: Tissue mosaicism should be compared to the analysis of tissues from other embryonic origins, including blood and oral tissue. Support for gender identity and treatment decisions, including the prediction of the future risk of gonadoblastoma, as well as multidisciplinary care, is necessary. Full article

Background/Objectives: Brown tumors are bone manifestations of hyperparathyroidism, and they are characterized by histologic similarities with Central Giant Cell Granuloma (CGCG). Their diagnosis requires clinical, microscopic, macroscopic, and serologic correlation, as there is usually an elevation in parathormone levels due to the underlying metabolic disorder. Methods: This case describes a patient with a left mandibular lesion and a history of CGCG. Results: Through the joint analysis of clinical, histologic, and serologic findings, the diagnosis of a brown tumor associated with hyperparathyroidism was confirmed. Conclusions: This case highlights the importance of a comprehensive evaluation of oral and systemic features for accurate diagnoses and appropriate patient management. Full article

Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Tongue cancer, the most aggressive subtype of oral cancer, presents critical challenges due to the limited number of specialists available and the time-consuming nature of conventional histopathological diagnosis. To address these issues, we developed an intelligent diagnostic system integrating Mueller matrix microscopy with deep learning to enhance diagnostic accuracy and efficiency. Through Mueller matrix polar decomposition and transformation, micro-polarization feature parameter images were extracted from tongue cancer tissues, and purity parameter images were generated by calculating the purity of the Mueller matrices. A multi-stage feature dataset of Mueller matrix parameter images was constructed using histopathological samples of tongue cancer tissues with varying stages. Based on this dataset, the clinical potential of Mueller matrix microscopy was preliminarily validated for histopathological diagnosis of tongue cancer. Four mainstream medical image classification networks—AlexNet, ResNet50, DenseNet121 and VGGNet16—were employed to quantitatively evaluate the classification performance for tongue cancer stages. DenseNet121 achieved the highest classification accuracy of 98.48%, demonstrating its potential as a robust framework for rapid and accurate intelligent diagnosis of tongue cancer. Full article

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article

(1) Aim: To compare transverse dimensions measured on AI-generated intra-oral models and conventional digital intra-oral models. (2) Methods: A group of 38 patients treated with clear aligners was selected retrospectively from those whose records featured both AI-generated and conventional digital intra-oral models taken at the same timepoint. Transverse dimensions (inter-canine, inter-premolar, and inter-molar distances) on both upper and lower arches were evaluated and compared. Intra-class correlation index and paired t-test were applied to test the repeatability of measurements and statistically significant differences, respectively. Statistical significance was set at 0.05. (3) Results: Intra-class correlation index showed good repeatability. Paired t-test showed differences in measurements of the distances between the thicket area of gingiva on the palatal side of the upper first molar (p = 0.002), the gingival margin of the lower first molar (p = 0.014), and the mesio-vestibular cusps of the lower first molars (p = 0.019). (4) Conclusions: Transverse measurements were similar on AI-generated and conventional intra-oral .stl renderings. Statistical differences were found on posterior areas of both upper and lower dental arches, but are unlikely to be clinically significant. Full article

Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article

The immune landscape of tumor-draining lymph nodes (TDLNs) plays a critical role in shaping antitumor responses and influencing prognosis in oral squamous cell carcinoma (OSCC). Among patients with lymph node (LN) metastasis, clinical outcomes vary widely, yet reliable biomarkers for prognostic stratification remain limited. This study aimed to identify immune features in tumors and LNs that differentiate between favorable and poor outcomes in OSCC patients with nodal metastasis. We analyzed T cell receptor (TCR) CDR3 repertoires and the expression of immune-related genes in primary tumors and paired sentinel LNs from OSCC patients who underwent tumor resection and lymphadenectomy. Patients were divided into three groups: Group A (no nodal metastasis), Group B1 (metastasis without recurrence), and Group B2 (metastasis with recurrence). TCR diversity was assessed using the Shannon index. The expression of immune-related genes (e.g., CD3E, CD4, CD8B, FOXP3, CTLA4, IL2, IL4) was measured by quantitative PCR and normalized to GAPDH. TCR diversity was lower in tumors than in non-metastatic LNs, reflecting clonal expansion. Metastatic LNs exhibited tumor-like diversity, suggesting infiltration by tumor-reactive clones. Tumor gene expression did not differ across groups, but LNs from metastatic cases showed the reduced expression of several immune genes. Notably, CD3E, CD8B, CTLA4, IL2, and IL4 distinguished B1 from B2. The immune profiling of LNs offers superior prognostic value over tumor analysis in OSCC patients with LN metastasis. LN-based evaluation may aid in postoperative risk stratification and personalized postoperative management and could inform decisions regarding adjuvant therapy and follow-up strategies. Full article

Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. Background/Objectives: To integrate risk factors associated with tumor progression: the TSR, TB and TSR/tumor budding model, whose prognostic significance in oral cancer has not yet been evaluated. Methods: An observational cohort retrospective study assembled according to STROBE guidelines on histological materials from 196 patients with invasive squamous cell carcinoma of the oral cavity. The goal of the analysis was to evaluate the association between the tumor stroma ratio, tumor budding, and the combined model of TSR/TB with the clinical and pathologic features of patients with squamous cell carcinoma of the oral cavity and to determine the prognostic value of this model in relation to disease-free survival (DFS) Results: The analysis did not show that the tumor stroma ratio (TSR), tumor budding, and the combined model of TSR/tumor budding were statistically significantly associated with the occurrence of metastatic disease at the start of treatment or during postoperative follow-up, but confirmed the value of depth-of-invasion (DOI) as a negative prognostic factor (HR 15.3, p < 0.001). Conclusions: The TSR, TB, and the combined TSR/TB model were not found to be statistically significant predictors for the disease progression in the Cox regression survival analysis but were found to have a significant correlation with known negative prognostic factors: DOI, neural invasion, and T category. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and related anatomical structures. Although magnetic resonance imaging (MRI) is considered a noninvasive and highly informative imaging modality for assessing TMJ soft tissues, few studies have examined how TMJ structural features observed on MRI findings relate to oral function and craniofacial morphology in female patients with malocclusion. To investigate the associations among TMJ structural features, oral function, and craniofacial morphology in female patients with malocclusion, using MRI findings interpreted in conjunction with a preliminary assessment based on selected components of the DC/TMDs Axis I protocol. Methods: A total of 120 female patients (mean age: 27.3 ± 10.9 years) underwent clinical examination based on DC/TMDs Axis I and MRI-based structural characterization of the TMJ. Based on the structural features identified by MRI, patients were classified into four groups for comparison: osteoarthritis (OA), bilateral disk displacement (BDD), unilateral disk displacement (UDD), and a group with Osseous Change/Disk Displacement negative (OC/DD (−)). Occlusal contact area, occlusal force, masticatory efficiency, tongue pressure, and lip pressure were measured. Lateral cephalometric analysis assessed skeletal and dental patterns. Results: OA group exhibited significantly reduced occlusal contact area (p < 0.0083, η² = 0.12) and occlusal force (p < 0.0083, η² = 0.14) compared to the OC/DD (−) group. Cephalometric analysis revealed that both OA and BDD groups had significantly larger ANB angles (OA: 5.7°, BDD: 5.2°, OC/DD (−): 3.7°; p < 0.0083, η² = 0.21) and FMA angles (OA: 32.4°, BDD: 31.8°, OC/DD (−): 29.0°; p < 0.0083, η² = 0.17) compared to the OC/DD (−) group. No significant differences were observed in masticatory efficiency, tongue pressure, or lip pressure. Conclusions: TMJ structural abnormalities detected via MRI, especially osteoarthritis, are associated with diminished oral function and skeletal Class II and high-angle features in female patients with malocclusion. Although orthodontic treatment is not intended to manage TMDs, MRI-based structural characterization—when clinically appropriate—may aid in treatment planning by identifying underlying joint conditions. Full article

Objectives: Odontogenic sinusitis (ODS) is common but frequently overlooked condition that differs from rhinogenic sinusitis (CRS) and should be suspected in each case of unilateral sinusitis. Clinical symptoms such as foul smell, congestion, rhinorrhea, and unilateral maxillary sinus opacification with overt dental pathology on radiological scans are more suggestive of ODS than CRS, but the distinctive microbiological flora are another clinical factor in diagnosis. The aim of this study was to compare the microbiological load of ODS and CRS and their clinical presentation for better disease recognition and its predisposing factors. Methods: Adult patients scheduled for endoscopic sinus surgery were included in the study. Clinical data and radiological images were analyzed. The otolaryngologist assessed nasal endoscopy for mucopurulence or edema in middle meatus or sinuses, whereas dental specialist confirmed or ruled out the dental cause. Microbiological samples were collected after endoscopic maxillary antrostomy. After irrigation with 0,9% saline, the aspirated rinse was collected into sterile sets and sent for culturing. Results: The study group consisted of 84 patients, 55 with CRS and 29 with ODS. Streptococcus spp prevailed in the CRS group, whereas Staphylococcus spp prevailed in the ODS group. Statistically significant differences between the groups were found in type of discharge, degree of edema, and presence of polyps. However, no statistical correlations were noted for presence of bacteria in the culture and endoscopic or radiological findings. Conclusions: ODS and CRS share some common features: ODS more often presents with purulent discharge, localized maxillary involvement, and the presence of oral pathogens, and Staphylococcus spp in microbial profile. Full article

Background/Objectives: This systematic review analyzed the epidemiologic and macro/microscopic features of manifestations of hypersensitivity reactions with oral and extra-oral involvement in orthodontic patients with fixed (FAs) or removable (RAs) appliances or clear aligners (CAs), and evaluated them based on patient and treatment characteristics to provide clinical recommendations. Methods: The study protocol followed the PRISMA guidelines and was registered on PROSPERO (CRD42024517942). Results: Thirty-one studies were qualitatively assessed and synthetized, involving 858 subjects (114 males and 714 females, 9–49 years old), of whom there were 86 with a history of allergy, and 743 wearing recorded appliances (FAs = 656, FAs and RAs = 81, intra- and extra-oral RAs = 3, CAs = 3), with a mean treatment duration of 21.5 months (6 weeks–40 months). Among 75 reports, 29 (38.67%), describing burning, gingival hyperplasia, erythema, and vesicles, had oral involvement, while 46 (61.33%) had skin, eye, and systemic involvement, with erythema, papules, conjunctival hyperemia, and vertigo. Positive allergy tests concomitant with the manifestations identified nickel 451 times, cobalt 6 times, titanium 5 times, and chromium 4 times. Management included antihistamines or corticosteroids and removing the offending materials, with treatment discontinuation/appliance substitution. Conclusions: Pre-treatment evaluations, including patient histories and allergy testing, are essential to identify potential allergens and select hypoallergenic materials like titanium or ceramic brackets; regular monitoring and early intervention during treatment are crucial to prevent severe outcomes. Full article

Odontogenesis, the development of teeth, is a complex, multistage process that unfolds from early embryogenesis through tooth eruption and maturation. It serves as a classical model of organogenesis due to the intricate reciprocal interactions between cranial neural crest-derived mesenchyme and oral epithelium. This narrative review synthesizes current scientific knowledge on human tooth development, tracing the journey from the embryological origins in the first branchial arch to the formation of a fully functional tooth and its supporting structures. Key morphogenetic stages—bud, cap, bell, apposition, and root formation—are described in detail, highlighting the cellular events and histological features characterizing each stage. We discuss the molecular and cellular regulatory networks that orchestrate odontogenesis, including the conserved signaling pathways (Wnt, BMP, FGF, SHH, EDA) and transcription factors (e.g., PAX9, MSX1/2, PITX2) that drive tissue patterning and cell differentiation. The coordinated development of supporting periodontal tissues (cementum, periodontal ligament, alveolar bone, gingiva) is also examined as an integral part of tooth organogenesis. Finally, developmental anomalies (such as variations in tooth number, size, and form) and the fate of residual embryonic epithelial cells are reviewed to underscore the clinical significance of developmental processes. Understanding the normal course of odontogenesis provides crucial insight into congenital dental disorders and lays a foundation for advances in regenerative dental medicine. Full article

Cutaneous manifestations can serve as early and sometimes the first clinical indicators in various hereditary cancer predisposition syndromes. This review provides a comprehensive overview of the dermatological signs associated with these syndromes, aiming to facilitate their recognition in clinical practice. Hereditary Breast and Ovarian Cancer syndrome is notably linked to an increased risk of melanoma. BAP1 tumor predisposition syndrome is characterized by BAP1-inactivated melanocytic tumors. Muir–Torre syndrome, a variant of Lynch syndrome, presents with distinctive cutaneous neoplasms such as sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas. PTEN hamartoma tumor syndrome commonly features hamartomatous growths, trichilemmomas, acral keratoses, oral papillomas, and genital lentiginosis. Gorlin syndrome is marked by basal cell carcinomas and palmoplantar pits, while Peutz–Jeghers syndrome is identified by mucocutaneous pigmentation. In familial adenomatous polyposis, the cutaneous findings include epidermoid cysts, fibromas, desmoid tumors, and lipomas. Additionally, we examined monogenic disorders associated with cancer risk and skin involvement, such as xeroderma pigmentosum, neurofibromatosis type 1, familial atypical multiple-mole melanoma syndrome, and Fanconi anemia. The early recognition of these dermatologic features is essential for a timely diagnosis and the implementation of appropriate surveillance strategies in individuals with hereditary cancer syndromes. Full article