OBJECTIVE: Jalili syndrome (JS) is an autosomal recessive disorder with cone-rod dystrophy and amelogenesis imperfecta caused by CNNM4 variants. This study describes salivary proteome patterns observed in a small female...OBJECTIVE: Jalili syndrome (JS) is an autosomal recessive disorder with cone-rod dystrophy and amelogenesis imperfecta caused by CNNM4 variants. This study describes salivary proteome patterns observed in a small female JS cohort to characterize the oral molecular environment. METHODS: Unstimulated saliva was collected from three related female JS patients carrying CNNM4 c.1475G>A (p.Gly492Asp) and six age-matched female unaffected controls. Tandem mass tag (TMT)-based quantitative proteomics was performed. RESULTS: Eighty-seven uniquely quantified salivary proteins were identified. Thirty-three proteins showed higher abundance in JS saliva (log2FC > 0.6; adjusted p < 0.05), including neutrophil/innate immune proteins (MPO, CTSG, SERPINB1) and carbohydrate-metabolism enzymes (ENO1/ENO2, GAPDH, TKT, TALDO1). LDHA showed a group-specific detection pattern, being detected in all JS samples but not detected in controls under the current workflow. Functional annotation and interaction analyses highlighted themes related to innate immunity and carbohydrate metabolism. CONCLUSIONS: In this small female-only cohort, the salivary proteome profile observed in JS was characterized by increased abundance of proteins annotated to innate immune defense and carbohydrate-associated metabolic processes. These findings are descriptive and should be interpreted in the context of oral clinical status.
OBJECTIVE: Legumain, also known as asparaginyl endopeptidase or δ-secretase, is a cysteine protease that plays a significant role in various biological and pathological processes. This study investigated the role of the...OBJECTIVE: Legumain, also known as asparaginyl endopeptidase or δ-secretase, is a cysteine protease that plays a significant role in various biological and pathological processes. This study investigated the role of the legumain-protease-activated receptor 2 (PAR2) signaling pathway in mechanical hypersensitivity in a rat model of tongue cancer. METHODS: Squamous cell carcinoma (SCC) cells were injected subcutaneously into the tongue. Mechanical head withdrawal reflex threshold (MHWT) was recorded after SCC inoculation or activated-legumain administration. The expression of legumain in the cancerous tongue and PAR2 in the trigeminal ganglion was measured. The effects of legumain inhibition on the MHWT in SCC-inoculated tongues were assessed. RESULTS: The SCC-inoculated tongue resulted in a significant decrease in MHWT. Legumain levels were elevated in the SCC-inoculated tongue, and administration of activated-legumain induced mechanical allodynia. Conversely, legumain inhibitor administration mitigated SCC-induced reduction in MHWT. PAR2 was identified in trigeminal ganglion neurons that innervate the tongue, and its blockade reduced mechanical hypersensitivity in the SCC-inoculated tongue. CONCLUSIONS: These findings suggest that legumain released from SCC cells activates PAR2 on primary afferent terminals, leading to the mechanical sensitization of cancerous tongues. This study provides novel insights into the peripheral mechanisms of oral SCC pain.
BACKGROUND: The oral cavity is a key reservoir for pathogens that cause oral diseases and may disseminate systemically. This study aimed to characterize clinically isolated oral pathogens and assess the antibiotic resist...BACKGROUND: The oral cavity is a key reservoir for pathogens that cause oral diseases and may disseminate systemically. This study aimed to characterize clinically isolated oral pathogens and assess the antibiotic resistance and virulence of predominant strains. METHODS: Clinical samples were collected from patients at a tertiary oral specialty hospital in Southwest China between 2018 and 2023, including secretions, sputum, pus, blood, and other oral-related specimens from patients with oral/maxillofacial tumors, jaw fractures, malocclusion, and fascial space infections. Klebsiella pneumoniae, the most frequent isolate, was analyzed for patient demographics, resistance genes, and virulence factors. Selected strains were inoculated into mice to assess their effects on gut homeostasis via histopathology. RESULTS: The most prevalent oral pathogens were Klebsiella pneumoniae, Staphylococcus aureus, Prevotella intermedia, Pseudomonas aeruginosa, and Acinetobacter baumannii. Most K. pneumoniae isolates were resistant to ampicillin. Nineteen carbapenem-resistant (CRKP) and 21 non-CRKP strains were further analyzed. Among CRKP isolates, bla was the dominant carbapenemase gene. In vivo experiments demonstrated that clinical K. pneumoniae strains could colonize the gut and impair intestinal integrity. CONCLUSION: K. pneumoniae is frequently detected in oral oncology and trauma settings, underscoring the need for continuous surveillance of CRKP strains with enhanced virulence potential.
OBJECTIVES: Non-plaque-induced gingivitis encompasses a heterogeneous group of conditions as defined in the 2017 Classification of Periodontal and Peri-Implant Diseases and Conditions. Recognition is challenging and ofte...OBJECTIVES: Non-plaque-induced gingivitis encompasses a heterogeneous group of conditions as defined in the 2017 Classification of Periodontal and Peri-Implant Diseases and Conditions. Recognition is challenging and often leads to diagnostic delay. This study aimed to evaluate diagnostic delay in a cohort of patients with non-plaque-induced gingivitis presenting as desquamative gingivitis, and to identify associated factors. MATERIALS AND METHODS: In this observational study, patients were recruited from public and private oral medicine centres. Participants completed a questionnaire collecting demographic, social, and clinical information related to their condition. Association between variables and diagnostic delay were analyzed using the Student's t-test (significance p < 0.05). RESULTS: Eighty-six patients (43 from private and 43 from public centres) were enrolled. The mean diagnostic delay was 10 months. No statistically significant associations were observed between diagnostic delay and age, gender, symptom presence, smoking habits, or definitive diagnosis. In contrast, diagnostic delay was significantly higher in private oral health centre patients (11.19 months vs. 8.75 months p < 0.05) and in patients living more than 34 km from the diagnostic centre (p < 0.05). CONCLUSIONS: Proximity to specialized diagnostic centres and the type of centre (public vs. private) were identified as determinants to reduce diagnostic delay in patients with desquamative gingivitis.
INTRODUCTION: Oral care is an essential nursing practice in intensive care units, as it influences oral mucosal integrity and complications in mechanically ventilated patients. While chlorhexidine is widely used, ozonate...INTRODUCTION: Oral care is an essential nursing practice in intensive care units, as it influences oral mucosal integrity and complications in mechanically ventilated patients. While chlorhexidine is widely used, ozonated water and hypochlorous acid have attracted attention due to their potential mucosal protection and lower cytotoxicity. However, comparative data on their effectiveness are limited. OBJECTIVE: To compare the effects of ozonated water, hypochlorous acid, and 0.12% chlorhexidine gluconate on oral mucosal integrity in mechanically ventilated patients. METHOD: A randomized controlled trial was conducted according to CONSORT guidelines, including 63 adult intensive care patients intubated within 24 h of mechanical ventilation. Participants were randomly assigned to receive oral care with ozonated water, hypochlorous acid, or 0.12% chlorhexidine gluconate. Trained nurses provided care four times daily, and mucosal integrity was evaluated using the Oral Assessment Scale for seven consecutive days. RESULTS: No significant difference was found among the groups during the first 3 days. From the fourth day onward, the ozonated water group showed significantly better oral mucosal integrity than the hypochlorous acid and chlorhexidine groups (p < 0.001). CONCLUSION: Ozonated water was the most effective solution for maintaining oral mucosal integrity. Hypochlorous acid demonstrated moderate protective effects compared with chlorhexidine. TRIAL REGISTRATION: This study was registered in the Clinical Trials Registry with registration number NCT06942026.
Fiedler M, Off A, Eichberger J
… +10 more, Gottsauner M, Schuderer JG, Maurer M, Eckmüller S, Himmelstoß K, Bauer RJ, Gerken M, Reichert TE, Weber F, Ettl T
BACKGROUND: Immune checkpoints such as, LAG-3, TIM-3, and IDO1 have emerged as potential therapeutic targets beyond PD-1/PD-L1 blockade. Their expression patterns in oral squamous cell carcinoma, especially among patient...BACKGROUND: Immune checkpoints such as, LAG-3, TIM-3, and IDO1 have emerged as potential therapeutic targets beyond PD-1/PD-L1 blockade. Their expression patterns in oral squamous cell carcinoma, especially among patients without smoking or alcohol exposure, remain poorly understood. METHODS: Immunohistochemical expression of LAG-3, TIM-3, and IDO1 was examined in 130 oral squamous cell carcinoma specimens. Expression levels were correlated with clinicopathological features, immune infiltration (CD4, CD8, FoxP3, CD1a), PD-1/PD-L1 status, and smoking and drinking history. Tumors co-expressing all checkpoints (LAG-3/TIM-3/IDO1/PD-L1) were classified as "comprehensive checkpoint-positive." RESULTS: High LAG-3, TIM-3, and IDO1 expression was significantly associated with never-smoking/never-drinking status (p ≤ 0.039) and increased CD4, CD8, and FoxP3 T-cell densities (p ≤ 0.015). All markers showed strong correlations with PD-1/PD-L1 and with each other (p ≤ 0.002). The comprehensive checkpoint-positive phenotype occurred in 16.8% of cases, more often in never-smoking/never-drinking patients (p = 0.011), females (p = 0.026), and well-differentiated tumors (p = 0.007). CONCLUSION: Co-expression of LAG-3, TIM-3, and IDO1 characterizes an immune-active but potentially exhausted microenvironment, particularly in never-smoking, never-drinking oral squamous cell carcinoma. This pattern may define an immunologically distinct subtype with possible relevance for combinatorial immunotherapy approaches.
BACKGROUND: Pleomorphic adenoma (PA) is the most common salivary gland tumor, and a subset may recur as recurrent PA (RPA) or progress to carcinoma ex pleomorphic adenoma (CXPA). However, comparative evaluations of their...BACKGROUND: Pleomorphic adenoma (PA) is the most common salivary gland tumor, and a subset may recur as recurrent PA (RPA) or progress to carcinoma ex pleomorphic adenoma (CXPA). However, comparative evaluations of their biological behavior and prognostic factors remain limited. OBJECTIVE: To characterize and compare the clinical features, pathological patterns, treatment outcomes, and prognostic factors of PA, RPA, and CXPA over a 20-year period at a Brazilian tertiary referral center. MATERIALS AND METHODS: A retrospective review of 234 cases (148 PA, 23 RPA, 63 CXPA) diagnosed between 2004 and 2024. Analyses included Fisher's exact test and chi-square test for group comparisons and Cox proportional hazards models for overall (OS) and disease-specific survival (DSS). RESULTS: PA and RPA mainly affected younger females and presented smaller tumors and shorter clinical evolution than CXPA (p < 0.01). In CXPA, perineural invasion, angiolymphatic invasion, necrosis, recurrence, symptomatology, distant metastasis, and capsular invasion pattern were associated with reduced OS and DSS (p < 0.05). CONCLUSION: This retrospective study demonstrates distinct clinical and pathological profiles across PA, RPA, and CXPA. In CXPA, clinical and histological factors strongly predict survival and should guide risk stratification, therapeutic decisions, and follow-up strategies.
OBJECTIVE: To characterize the oral bacterial and fungal microbiota of symptomatic oral lichen planus patients undergoing topical corticosteroid therapy and to explore microbial patterns potentially associated with subse...OBJECTIVE: To characterize the oral bacterial and fungal microbiota of symptomatic oral lichen planus patients undergoing topical corticosteroid therapy and to explore microbial patterns potentially associated with subsequent oral candidiasis. METHODS: Twelve patients with clinically and histologically confirmed OLP were enrolled. Unstimulated saliva and tongue dorsum swabs were collected at baseline and weekly for three weeks during betamethasone therapy. Bacterial communities were profiled using shallow shotgun metagenomics analyzed with METAnnotatorX2, and fungal communities through ITS sequencing and QIIME 2 workflows. Beta-diversity analyses assessed the effects of time, clinical variables, and later candidiasis development. Associations between bacterial taxa and Candida abundance were evaluated using Spearman correlations. RESULTS: Oral candidiasis developed in three patients (25%). Microbiota composition showed marked inter-individual variability but high intra-subject stability, with no consistent shifts linked to corticosteroid therapy. Commensal taxa such as Streptococcus, Rothia, and Actinomyces were negatively associated with candidiasis and Candida abundance, whereas anaerobic species including Porphyromonas gingivalis, Prevotella multiformis, and Lachnoanaerobaculum gingivalis displayed positive correlations with fungal proliferation. CONCLUSIONS: Despite overall stability of the oral microbiota during therapy, specific bacterial signatures were associated with subsequent Candida overgrowth. These findings suggest that cross-kingdom interactions may influence susceptibility to corticosteroid-associated candidiasis and warrant validation in larger cohorts.
OBJECTIVE: To assess the correspondence between periodontitis categories defined by 1999 AAP and 2018 AAP/EFP classification systems, and to characterize clinical features within Grade C periodontitis. METHODS: A cross-s...OBJECTIVE: To assess the correspondence between periodontitis categories defined by 1999 AAP and 2018 AAP/EFP classification systems, and to characterize clinical features within Grade C periodontitis. METHODS: A cross-sectional study was conducted on patients with periodontitis. Participants were examined and classified according to both classifications. Comparative analyses between aggressive (AgP) and chronic (CP) periodontitis within Grade C included age, bone loss patterns, clinical attachment loss, furcation involvement, and tooth mobility. The association between classifications was illustrated using alluvial diagrams and analyzed using V Cramer's coefficient. RESULTS: Among 427 patients, Grade A and B periodontitis corresponded to CP. Grade C included cases previously classified as AgP as well as severe CP. Correspondence between periodontitis types and grades showed a significant association p < 0.001. The strength of this association was large V = 0.63 95% CI [0.55, 0.76]. Although grouped under the same grade, significant differences were observed between AgP and CP. AgP cases were younger and had more frequent, preferential involvement of incisors and first molars, vertical or combined bone loss, advanced furcation defect, and hypermobility. CONCLUSION: While the 2018 classification has advanced diagnostic criteria for periodontal diseases, future revision of the Grade C category could enhance diagnostic specificity by integrating phenotypic variations.
OBJECTIVE: To systematically review and compare recurrence rates associated with different management strategies for simple and plunging ranulas. METHODS: A PRISMA-guided search of PubMed, Embase, Web of Science, Scopus,...OBJECTIVE: To systematically review and compare recurrence rates associated with different management strategies for simple and plunging ranulas. METHODS: A PRISMA-guided search of PubMed, Embase, Web of Science, Scopus, and CINAHL was performed. Studies reporting post-treatment outcomes of ranulas with clearly defined initial management strategies were included. Two reviewers independently screened studies and extracted data on ranula subtype, treatment details, duration of follow-up, and recurrence. Risk of bias was assessed using study design-appropriate tools. Given the predominance of retrospective case series with heterogenous designs and incomplete outcome reporting, quantitative pooling was not feasible; results were synthesized descriptively. RESULTS: Seventy-one studies comprising 809 patients (563 simple, 246 plunging) met inclusion criteria. Excision with ipsilateral sublingual gland removal (30%) was associated with recurrence rates below 10%. Excision without gland removal and marsupialization demonstrated higher and more variable recurrence rates, ranging from 15%-30% across cohorts. Sclerotherapy outcomes varied by agent, with recurrence rates of 3%-10% for bleomycin and over 50% for OK-432, particularly in plunging ranulas. Most recurrences occurred within 3-6 months. CONCLUSION: Sublingual gland excision was consistently associated with the lowest recurrence rates, while outcomes following marsupialization and sclerotherapy varied by technique and agent.
BACKGROUND: Ehlers-Danlos syndromes are rare hereditary connective tissue disorders; however, their oral manifestations remain poorly characterized in molecularly confirmed individuals. The aim of this study was to descr...BACKGROUND: Ehlers-Danlos syndromes are rare hereditary connective tissue disorders; however, their oral manifestations remain poorly characterized in molecularly confirmed individuals. The aim of this study was to describe the oral phenotype of patients with non-vascular Ehlers-Danlos syndromes compared to healthy controls. METHODS: In this single-center, cross-sectional study, 14 patients molecularly diagnosed with non-vascular Ehlers-Danlos syndromes and 30 matched healthy controls underwent a complete clinical and radiological oral examination. Data were compared using chi-squared, Fisher's exact, Student's t-tests, or Wilcoxon tests as appropriate. RESULTS: Compared to controls, patients with non-vascular Ehlers-Danlos syndromes had a significantly higher prevalence of temporomandibular disorders (64.3% vs. 16.7%; p = 0.004), gingivitis (85.7% vs. 56.7%; p = 0.017), and lingual parafunction (57.1% vs. 16.7%; p = 0.012). Anatomical variations were also more frequent, including atrophy of the lingual (85.7% vs. 10.0%; p < 0.001) and inferior labial frenula (78.6% vs. 20.0%; p < 0.001), pulpal retractions (61.5% vs. 27.6%; p = 0.047), and dental root hypoplasia (57.1% vs. 20.0%; p = 0.034). CONCLUSION: Our findings suggest that patients with non-vascular Ehlers-Danlos syndromes present a distinct pattern with oral manifestations. These findings, including notably frenula atrophy and specific dental anomalies. These oral findings commonly observed in non-vascular Ehlers-Danlos syndromes patients can aid in diagnosis and underscore the need for specialized dental care.
BACKGROUND: Research on micro/nanoplastics (MNPs) focuses largely on systemic toxicity from gastrointestinal or respiratory exposure, overlooking the oral cavity as a critical first contact point. This gap obscures under...BACKGROUND: Research on micro/nanoplastics (MNPs) focuses largely on systemic toxicity from gastrointestinal or respiratory exposure, overlooking the oral cavity as a critical first contact point. This gap obscures understanding of early exposure pathways and initial local effects. METHODS: This review systematically establishes the oral cavity as an "initial target organ." It synthesizes evidence on oral MNP exposure routes, their unique accumulation in biofilms and dental calculus, and mechanisms like physical abrasion, microbial dysbiosis, and the "Trojan horse" effect to construct an oral-specific toxicity framework. RESULTS: Integrating advanced detection methods with models like PBTK reveals the oral cavity not as a passive conduit, but as an active "first amplifier" of MNP risk. The analysis details how MNPs initially interact with oral biological barriers. CONCLUSION: The study positions the oral cavity as the origin of systemic MNP health risks, demonstrates the long-term implications of oral MNP accumulation, and provides a scientific foundation for advancing the field of environmental oral health.
OBJECTIVES: To analyze the global burden, drivers, and disparities of oral diseases among adults aged 70 years and older from 1990 to 2021 and project trends to 2040. METHODS: Using Global Burden of Disease Study 2021 da...OBJECTIVES: To analyze the global burden, drivers, and disparities of oral diseases among adults aged 70 years and older from 1990 to 2021 and project trends to 2040. METHODS: Using Global Burden of Disease Study 2021 data, we analyzed incidence, prevalence, and disability-adjusted life-years (DALYs). Decomposition, inequality, and Bayesian age-period-cohort modeling assessed trends, drivers, and future burden. RESULTS: From 1990 to 2021, global incidence, prevalence, and DALYs of oral diseases in adults aged 70 years and older increased substantially (prevalence: 133.26 to 313.37 million), although age-standardized rates all declined slightly. Decomposition analysis showed population growth accounted for 107.01% to 111.36% of the increase, exceeding 100% due to an offsetting reduction from favorable epidemiological changes. Critically, the disease burden exhibited clear stratification: trends diverged by disease type, and significant disparities persisted across gender and geographic regions. By 2040, the age-standardized incidence rate is projected to reach 18,024 per 100,000 population, and the age-standardized DALY rate is expected to increase. CONCLUSION: The global burden of elderly oral diseases is growing in absolute terms, driven by population growth. Given the stratified patterns identified by disease type, gender, and region, targeted and context-specific public health strategies are urgently needed to improve elderly oral health worldwide.
OBJECTIVE: We aim to investigate the association between oral hygiene habits, including frequency of toothbrushing and regularity of dental check-ups, and oral cancer risk. MATERIALS AND METHODS: A systematic review and...OBJECTIVE: We aim to investigate the association between oral hygiene habits, including frequency of toothbrushing and regularity of dental check-ups, and oral cancer risk. MATERIALS AND METHODS: A systematic review and meta-analysis was developed following the PRISMA and the MOOSE guidelines. We searched electronic databases until 4th December 2024 (CRD42021242709). RESULTS: A total of 15 studies were included. Overall, the results indicated that poor oral hygiene habits are potential risk factors for oral cancer. Compared to brushing once/day or more, toothbrushing < 1/day or never significantly increased the risk for oral cancer, with an OR of 1.85 (95% CI, 1.06-3.22). Toothbrushing < 2/day compared with ≥ 2/day also showed a positive association with oral cancer risk, with an OR of 1.32 (95% CI, 1.17-1.48). Irregular dental check-ups, defined as less than once a year or never, also significantly increased oral cancer risk (OR, 1.58; 95% CI, 1.29-1.92). CONCLUSION: Infrequent toothbrushing and irregular dental check-ups are risk factors for oral cancer. Toothbrushing twice or more daily and visiting a dentist once a year could be recommended to reduce oral cancer risk. The study reinforces the importance of good oral health as a preventive measure in the control of oral cancer.
OBJECTIVE: Many countries have implemented health technology assessment of their public medical insurance programs owing to rising social security costs from ageing populations and expensive emerging medical technologies...OBJECTIVE: Many countries have implemented health technology assessment of their public medical insurance programs owing to rising social security costs from ageing populations and expensive emerging medical technologies. Clarifying factors that affect health utility scores is essential for implementing treatments that reflect social values. Therefore, this prospective, observational study aimed to investigate the longitudinal changes in the health utility scores of patients with oral cancer eligible for radical treatment perioperatively. METHODS: Overall, 219 patients with oral cancer who received standard therapy and completed utility assessments using the EQ-5D-5L at treatment completion and at 1, 3, 6 months, and 1 year post-treatment were evaluated. Longitudinal changes in utility scores and factors influencing these scores were analysed. RESULTS: The 1-year post-treatment utility scores were significantly higher than those before treatment (p < 0.01). Utility scores did not differ significantly between older and non-older patients at all assessment time-points. Marital status significantly influenced utility scores. Furthermore, utility scores did not differ significantly according to employment or living conditions. CONCLUSIONS: Health utility disadvantages are not associated with standard treatment for older patients with oral cancer, provided that they have good physical and cognitive functions. Additionally, considering social support for unmarried patients with cancer is vital.
Kashyap M, Wright H, Byun J
… +15 more, Alintoff GB, Mandi A, Lathara M, Srinivasa G, Gross AC, Sammons MC, Ryan L, Chen SD, Roberts RD, Thway K, Jones RL, Tam YB, Huang PH, Darrow MA, Keller C
OBJECTIVE(S): Myoepithelial Carcinoma (MECA) is an ultra-rare soft tissue cancer with a rare EWSR1::KLF15 fusion reported in some cases. However, fusion positive MECA has been classified as a carcinoma, despite sharing q...OBJECTIVE(S): Myoepithelial Carcinoma (MECA) is an ultra-rare soft tissue cancer with a rare EWSR1::KLF15 fusion reported in some cases. However, fusion positive MECA has been classified as a carcinoma, despite sharing qualities with sarcomas in terms of fusion protein rearrangement. An exploration of MECA in the context of a sarcoma versus an adenocarcinoma could be crucial to the understanding of MECA with respect to other cancers. Beyond gene fusions, MECA can also be difficult to characterize, but functional genomics could reveal distinctions. SUBJECT(S) (OR MATERIALS) AND METHODS: We performed next generation DNA exome and RNA deep sequencing for a 27 patient cohort for this ultra-rare cancer. RESULTS: Our Principal Component Analysis that categorized MECA tumors among other sarcomas vs. salivary carcinomas, with closest relatedness to salivary Adenoid Cystic Carcinoma. Both fusion positive and fusion negative MECA over-express IGF1R. CONCLUSION(S): Despite sharing a chromosomal translocation partner (the EWSR1 gene) with sarcomas, MECA are most related to other salivary carcinomas. Further exploration of IGF1R as a therapeutic target in MECA is warranted. We also make available the 27 patients' next generation DNA exome and RNA sequencing through the EGA Repository.