Pakistan journal of pharmaceutical sciencesWeifeng Meng, Lingfei Fu, Hui Huang
BACKGROUND: Budesonide suspension is a first-line inhaled corticosteroid for elderly patients with inflammatory airway diseases, but existing research lacks targeted safety data for the very elderly (≥80 years), systematic analysis of adverse reaction (ADR) temporal distribution and quantitative evidence for modifiable clinical risk factors. OBJECTIVE: To investigate the safety profile, ADR temporal patterns and independent modifiable risk factors of nebulized budesonide suspension in elderly patients, with a focus on ≥80 years. METHODS: A retrospective analysis of 128 elderly patients (39 ≥80 years) treated with budesonide suspension (2 ml:1 mg) from January 2023 to June 2025 was conducted. ADRs were identified via medical record cross-check and verified by an expert team, with causality assessed using the WHO-UMC system. ADR incidence, type and temporal distribution were observed; univariate and multivariate logistic regression analyses were used to screen independent risk factors. RESULTS: The overall incidence of mild ADRs was 17.97%, with local ADRs (78.26%, predominantly oropharyngeal candidiasis) and systemic ADRs (21.74%). ADRs peaked at 8-14 days (39.13%). Age ≥80 years (OR=3.245, p=0.030), treatment duration >14 days (OR=2.897, p=0.048) and inadequate mouth rinsing (OR=4.126, p=0.008) were independent risk factors. ADR incidence was higher in patients with ≥3 underlying diseases (25.00% vs. 11.76%). CONCLUSION: Nebulized budesonide suspension is well tolerated in elderly patients, with no severe ADRs. This study clarifies temporal patterns of ADRs and identifies inadequate mouth rinsing as a key modifiable risk factor, providing targeted safety data for the very elderly. Standardized mouth rinsing and short-course medication are recommended for high-risk groups to reduce ADR risk. Notably, this study is limited by its single-center, retrospective design, which may introduce selection and information bias and the findings require validation in prospective multi-center studies with larger sample sizes.
Oral and maxillofacial surgery clinics of North AmericaProkopios P Argyris, Mark W Lingen
Oral cavity squamous cell carcinoma (OCSCC) represents the 16th most prevalent cancer worldwide accounting for greater than 389,000 cases annually. Most examples of OCSCC are preceded by a diverse group of lesions exhibiting variable risk of transformation to cancer, collectively termed oral potentially malignant disorders (OPMDs). The identification of salivary, serologic, and/or tumor tissue biomarkers holds substantial promise for improving detection, prognosis, and treatment of OPMDs and OCSCC. Although certain biomarkers have become standard of care in the management of patients, continued robust validation and stringent protocol standardization efforts are critical to ensure both diagnostic accuracy and widespread utilization.
Oral and maxillofacial surgery clinics of North AmericaMadison E Richards, Michael T Brennan
Head and neck cancer (HNC) patients are uniquely susceptible to adverse oral health outcomes following head and neck radiation therapy (RT). Various risk factors for these oral health outcomes post-RT were identified in the OraRad study, which followed HNC patients from pre-RT to 2 y post-RT. Chronic oral complications include hyposalivation, trismus, dental caries, periodontal disease, tooth loss, exposed bone, and osteoradionecrosis of the jaw. Results from OraRad provide a framework for oral health care providers both in preparing patients for RT and in managing sequelae of RT for best outcomes for the HNC patient population.
Oral and maxillofacial surgery clinics of North AmericaRachelle Wolk, Alexander Ross Kerr
Diagnostic adjuncts for oral potentially malignant disorders such as leukoplakia or erythroplakia can aid the clinician in triaging abnormal lesions and facilitate both biopsy site selection and surgical management. No adjuncts replace gold standard biopsy and histopathological examination, and their optimal use requires training and experience. This article covers the potential applications, both in primary and expert settings, of adjuncts, such as tissue autofluorescence, toluidine blues staining, and cytopathology. It covers new and emerging adjuncts such as confocal microscopy, liquid biopsy, oral microbiome testing, and the role of artificial intelligence. Incisional biopsy site selection and techniques will also be discussed.
Oral and maxillofacial surgery clinics of North AmericaOmar Kujan
Oral potentially malignant disorders (OPMDs) include a range of oral mucosal lesions and conditions that carry an increased risk of progressing to oral squamous cell carcinoma. This review compiles current knowledge on the changing definition and terminology of OPMDs. It also examines the factors associated with malignant transformation, the usefulness of diagnostic adjuncts for general dental practitioners, and current and emerging management strategies. This study draws from consensus reports, clinical reviews, recent findings, and future directions to provide a comprehensive understanding of OPMDs, aiming to assist both specialists and general practitioners in effectively identifying, diagnosing, and managing these conditions.
Oral and maxillofacial surgery clinics of North AmericaNika Mehrnia, Stephen Sonis
An association between periodontitis and oral cancer risk and progression has been suggested. It seems most likely that periodontitis plays an indirect role in oral cancer risk and progression in which its contribution to a chronic inflammatory state characterized by the persistent release of pro-inflammatory cytokines contributes to oxidative stress and DNA damage, potentially favoring carcinogenic processes. Periodontal health status of an individual may serve as a surrogate for general health as those factors which contribute to good general health, environment, lifestyle, and access to care are also determinants of oral health and impact cancer risk.
Oral and maxillofacial surgery clinics of North AmericaMalak Al-Hadlaq, Lama Alabdulaaly, Sook-Bin Woo
Proliferative leukoplakia (PL) is an uncommon yet aggressive variant of oral leukoplakia characterized by its high rates of malignant transformation and recurrence. Primarily affecting older, non-smoking females, PL can present as homogenous, verrucous, or erythroleukoplakia lesions. PL is associated with high DNA aneuploidy, alterations in tumor suppressor genes (TP53, CDKN2A), and exhibits immune evasion markers, such as PD-L1. Histopathologically, lesions may demonstrate architectural or cytologic dysplasia. Treatment of PL remains challenging with limited options. Recent findings support further research into molecular and immune-based therapies. There are current inconsistencies in terminology and diagnostic criteria for PL which emphasize the need for an international consensus to support standardized reporting, timely management, and conduct of clinical trials.
Oral and maxillofacial surgery clinics of North AmericaOreste Iocca, Ghayoour Mir, Imraan Jan, Guglielmo Ramieri, Rabie M Shanti
Oral cavity carcinoma management always requires the involvement of a multidisciplinary team. Surgery is the mainstay of treatment, although other therapeutic modalities such as chemotherapy and radiotherapy are often needed in a multimodal treatment approach. Accurate staging is of great importance to better define the best therapeutic strategy, in addition to specific pathologic characteristics, tumor location, and patient-specific considerations. Guidelines help the clinicians in defining the best treatment plan. These guidelines define 2 major groups of patients, early stage and late stage disease, for which they provide specific algorithms/flow charts for an updated evidence-based decision-making process.
Oral and maxillofacial surgery clinics of North AmericaOreste Iocca, Ghayoour Mir, Imraan Jan, Guglielmo Ramieri, Rabie M Shanti
Specific considerations must be made in the treatment course of oral cavity carcinoma (OCC). Given the role of oral cavity in important functions such as speaking, eating, and esthetics, the choice of the optimal reconstructive option is of utmost importance. For small residual defects local flaps provide an acceptable solution, while for larger defects the adoption of the more complex revascularized free flaps is considered the gold standard. Another challenge is the management of recurrent OCC, which is characterized by a dismal prognosis. In this case, surgery is the first treatment option, when feasible, sometimes integrated with radiotherapy or chemotherapy.
Oral and maxillofacial surgery clinics of North AmericaAdrian Cristian, Nandita Keole, Romer Orada, Claire Callan, Jay Hyun Seo, Dessi D Dakova, Mary Owens, Lori Halton
Oral cancer survivors are at an increased risk for developing physical impairments that can adversely affect physical function and quality of life due to the cancer location and treatment that includes surgery and chemoradiation therapy. Many of these impairments can present long after completion of treatment. Surveillance, screening, and treatment of these impairments require a multidisciplinary rehabilitative team that is an integral part of the care of this fragile population. This review article addresses the assessment and treatment of physical impairments commonly encountered during and after completion of oral cancer treatment.
BMJ case reportsShama Jawed, Brandon Daffue, Michael Riordan, Frances Enright
We report a rare case of a monogenic form of hypertension where a boy in early childhood presented with a 2-day history of right-sided facial palsy. Severe hypertension was evident with signs of end-organ damage. This report aims to highlight the diagnostic process when a common presentation, such as facial palsy, uncovers a serious and rare underlying condition that demands urgent multidisciplinary care. Further workup revealed that the patient had hypokalaemic metabolic alkalosis with low serum renin and aldosterone levels. His urinary steroid profile was suggestive of Apparent Mineralocorticoid Excess. A homozygous autosomal recessive variant in the hydroxysteroid 11-beta dehydrogenase 2 gene confirmed a diagnosis of 11β-hydroxysteroid dehydrogenase type 2 deficiency. The syndrome has fewer than one hundred cases documented to date, with reversal of the mineralocorticoid effect as the primary treatment. This case highlights the importance of a step-by-step approach to paediatric hypertension and the need for an early urinary steroid profile.
The journal of headache and painDonghai Chen, Jian Jiang
The study by Wang and colleagues proposes that three connected brain areas link facial nerve injury to pain and depression-like behavior in mice. The experiments are ambitious and potentially important. However, the nerve-injury model differs from the defining pattern of human trigeminal neuralgia, several behavioral and drug controls leave alternative explanations open, and measurements from many cells were not clearly separated from the animals that supplied them. Clarifying these issues, and distinguishing results from whole tissue from results specific to neurons, would make the causal and clinical implications more secure.
Environmental geochemistry and healthFernando Igne Rocha, Ana Carolina Borsanelli, Aline Pacobahyba de Oliveira, Cecílio Viega Soares Filho, Marcia Reed Rodrigues Coelho, Stefan Schwab, Carlos Mag…
Forest-to-pasture conversion can alter soil properties, forage composition, and microbial communities, but whether these changes are associated with bovine periodontitis remains unclear. We compared eight pasture systems in the Western Brazilian Amazon classified by high or low herd-level prevalence of periodontal lesions. Soil physicochemical properties, forage composition, microbial communities in soil, forage, and bovine subgingival biofilms, and the relative abundance of the streptomycin biosynthesis gene strB1 were evaluated. Although the systems had similar deforestation histories, low-prevalence pastures had finer-textured soils, greater soil Cu and forage Zn, and greater representation of Bacilli and Gammaproteobacteria. High-prevalence pastures had sandier soils, greater soil C:N ratios, lower micronutrient availability, and greater representation of Actinobacteria and Bacteroidetes. Microbial communities differed between prevalence classes in all three compartments, with higher alpha and gamma diversity and more compartmentalized co-occurrence networks in high-prevalence systems. Tax4Fun predicted greater representation of pathways related to carbohydrate metabolism and glycan biosynthesis in these systems, while qPCR showed higher strB1 abundance normalized to bacterial 16S rRNA gene abundance in soil and forage. These concurrent differences in soil properties, forage composition, and microbial communities were associated with bovine periodontitis prevalence. They do not demonstrate microbial transfer or causality but support the hypothesis that soil and forage conditions may influence environmental exposures related to oral microbiome dysbiosis.
Neurosurgical reviewAnish Kalyana, Daniel Coles, Sameer Khalil, Mohammad Mahmud, Roshni Beeharry, Sanjay Cheema, Anouk Borg, Tim M Young
Trigeminal neuralgia affects approximately 3% of patients with multiple sclerosis - a far higher prevalence than in the general population. The associated pain often proves refractory to medication, prompting consideration of neurosurgical intervention. The variable efficacy, tolerability, and durability of available procedures, compounded by factors such as multiple sclerosis subtype and neuroimaging findings, require evidence to guide personalised surgical decision-making. This systematic review evaluates surgical interventions for trigeminal neuralgia in multiple sclerosis, analysing how patient and disease-specific variables influence outcomes. A systematic review with narrative synthesis was performed. Following PRISMA guidelines, Embase, PubMed, and Scopus were searched (January 2000 - April 2026). Studies assessing pain relief from surgical procedures for trigeminal neuralgia in multiple sclerosis using the Barrow Neurological Institute Pain Scale were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Thirty-two studies, encompassing 1617 patients, met the inclusion criteria. Microvascular decompression in cases with demonstrable neurovascular conflict provided durable outcomes offset by higher risks of serious complications (including one fatality), despite inherent diagnostic uncertainty regarding whether pain was specifically driven by multiple sclerosis. Partial sensory rhizotomy displayed favourable pain relief (initial success range: 95.3-100%) and durability (recurrence ranging from 20.1 to 79 months). Whilst some studies noted a lack of major complications, some cases of severe trigeminal dysfunction including anaesthesia dolorosa were reported (n = 3; 7.5%). Percutaneous ablative procedures (initial success ranging from 58 to 100%) and gamma knife radiosurgery (initial success ranging from 52.7 to 97.3%) achieved comparable pain control rates to classical trigeminal neuralgia cohorts. They also featured a mild complication profile, though durability was suboptimal (recurrence ranging from 7.4 to 74.5 months for gamma knife radiosurgery and 8-60 months for percutaneous procedures) and repeat procedures were typically tolerable. Differing gamma knife radiosurgery dosages (</>80 Gy) were not associated with significant differences in pain control. Preliminary outcomes of arachnoid-trigeminal nerve release from a 2025 study highlighted promising results with 75% of patients achieving Barrow Neurological Institute Pain Scale I at final follow-up. Gamma knife radiosurgery and percutaneous ablative procedures represent well-tolerated surgical options with comparable outcomes to primary trigeminal neuralgia cohorts regardless of plaque burden. Partial sensory rhizotomy demonstrated notable efficacy and durability in refractory multiple sclerosis-associated trigeminal neuralgia, particularly in the absence of neurovascular conflict, and warrants earlier consideration in the surgical pathway. Microvascular decompression may offer long-term durability where neurovascular conflict is demonstrated. However, its higher procedural risk and the diagnostic uncertainty inherent in multiple sclerosis-associated trigeminal neuralgia cases with concurrent neurovascular conflict necessitate cautious patient selection. High-resolution preoperative imaging is therefore recommended to guide personalised modality selection. Prospective studies are needed to further validate surgical decision-making and establish standardised outcome reporting in this population.
Inflammation research : official journal of the European Histamine Research Society ... [et al.]Raza Ali Naqvi, Jack Maddalozzo, Kreena Amin, Kristelle Capistrano, Araceli Valverde, Rani Rahat, Hasan Siddiqui, Wei Li, Christine D Wu, Shaoping Zhang, Mary …
BACKGROUND: Periodontitis (PD) is characterized by localized inflammatory tissue destruction, yet the lesion-associated microRNA (miRNA)networks that regulate host immune responses remain incompletely defined. In this study, we aimed to identify and characterize dysregulated gingivalmiRNAs in PD that modulate inflammatory responses. METHODS: Using a split-mouth design, miRNA expression was profiled in gingival biopsies fromperiodontal lesions and clinically healthy sites. Differentially expressed miRNAs were identified by microarray analysis, and selected candidates werevalidated by RT-qPCR. The responses of candidate miRNAs to periodontal bacterial challenge were evaluated, followed by functional studies ofmacrophage polarization, phagocytosis, inflammatory cytokine production, and target-gene regulation. RESULTS: Microarray analysis identified 48differentially expressed miRNAs, including several upregulated non-canonical miRNAs. Among these, the Dicer-independent miRNAs miR-451a andmiR-1228 showed dose- and time-dependent induction following periodontal bacterial challenge. miR-451a, but not miR-1228, promoted a pro-inflammatory M1-like macrophage phenotype, characterized by increased HLA-DR and CD32 and reduced CD206 and CD163 expression. miR-451adirectly targeted multiple genes associated with M2 macrophage polarization, and its expression in inflamed gingival tissues inversely correlated with M2markers. miR-451a overexpression also reduced macrophage phagocytosis of E. coli and P. gingivalis while increasing pro-inflammatory cytokineproduction. Mechanistically, miR-451a directly suppressed SOCS3 and SOCS5, key negative regulators of JAK/STAT signaling, in TLR4-stimulated cells.The antagonistic expression patterns of miR-451a, SOCS3, and SOCS5 in PD further supported the functional relevance of this regulatory axis. CONCLUSION: miR-451a is a pathogen-responsive, PD-associated miRNA that promotes pro-inflammatory macrophage polarization, impairs bacterialphagocytosis, and amplifies inflammation through suppression of SOCS-mediated immune regulation. These findings identify the miR-451a-SOCS3/SOCS5 axis as a potential mechanism linking bacterial challenge to dysregulated macrophage responses in PD.
Immune checkpoint inhibitors (ICIs) are increasingly incorporated into perioperative cancer treatment, raising challenges in distinguishing immune-related adverse events (irAEs) from postoperative complications. We report a case of postoperative immune-related colitis following head and neck reconstructive surgery in a patient receiving long-term nivolumab. A man receiving nivolumab for gastric cancer, who was maintained on prednisolone for prior immune-related myositis, underwent subtotal glossectomy for advanced tongue cancer. Despite perioperative steroid coverage, he developed grade 3 diarrhoea on postoperative day 4. After infectious causes were excluded and CT revealed diffuse colitis, empirical corticosteroid therapy was initiated, with rapid symptom resolution; colonoscopy and biopsy supported a diagnosis of immune-related colitis. This case illustrates that irAE colitis should remain in the differential diagnosis of postoperative diarrhoea in patients with prior ICI exposure. As perioperative use of ICIs expands, clinicians should maintain a high index of suspicion for irAEs in patients presenting with postoperative diarrhoea.
PURPOSE: The purpose of this review paper is to provide an integrative algorithmic approach to the diagnosis of salivary gland tumors, including pertinent histologic features, immunohistochemical patterns and molecular driver mutations and/or fusions. METHODS: Review of the literature was performed to provide an up-to-date synopsis of salivary gland tumors, in a concise and summarized format. RESULTS: Diagnostic workflow algorithms are created and included to complement the histomorphologic subgroups, to provide a user-friendly tool when approaching salivary gland tumors in routine surgical pathology. CONCLUSION: Histomorphologic features and immunophenotype of majority of salivary gland tumors, including select molecular surrogate immunohistochemical stains, are the most important starting point in diagnostic interpretation. Molecular data can provide an additional data point for further supporting evidence and/or to aid in challenging cases.
PloS oneDayron M Leyva Rodriguez, Michelle B Visser
Periodontitis (PD) is a common chronic inflammatory condition and a risk factor for cardiovascular diseases (CVD), yet underlying linking mechanisms remain unclear. The cytokine Oncostatin M(OSM) is elevated in both PD and CVD and has emerged as a potential mediator linking oral inflammation to vascular dysfunction. Neutrophils represent a prominent source of OSM during PD and OSM production is elevated by the periodontal pathobiont Treponema denticola (Td). This study investigated the role of exogenous and neutrophil-derived OSM in endothelial cell (EC) dysfunction and the contribution of heterogenous oral Treponema species in OSM production. Human aortic endothelial cells (HAoEC) were used to evaluate the effects of exogenous purified OSM and neutrophil-derived OSM on endothelial cell function. Endothelial permeability, neutrophil transmigration, cytokine production, cell activation and junctional integrity were assessed using transwell assays, ELISA, real-time PCR, immunoblotting and immunofluorescence microscopy. Exogenous OSM significantly increased HAoEC permeability, neutrophil transmigration and promoted endothelial activation; characterized by increased E-selectin, ICAM-1 and IL-6 expression. Mechanistically, OSM activated OSMR-STAT3 signaling and altered organization of VE-cadherin in adherens junctions and decreased expression of occludin in tight-junctions. Heterogeneous oral Treponema species promote OSM transcription and production from mouse and human neutrophils in vitro and in vivo using a mouse air pouch model of infection. T. denticola most robustly induced OSM release, likely independent of prominent virulence factors dentilisin and Msp. Co-culture model experiments revealed conditioned media from T. denticola-stimulated neutrophils promoted endothelial cell permeability and IL-6 while reducing endothelial nitric oxide synthase (eNOS) production. These effects were abolished by antibody neutralization of OSM, supporting a casual role of neutrophil-derived OSM. Overall, these findings provide mechanistic insight into putative links between PD and adverse cardiovascular events and identify OSM signaling as critical mediator in inflammation-driven endothelial dysfunction.
OBJECTIVES: To assess the clinical applicability of Raman spectroscopy using serum and saliva for the identification and stratification of oral potentially malignant disorders (OPMDs) and to differentiate Oral Leukoplakia and Oral Submucous Fibrosis from tobacco habit controls. MATERIALS AND METHODS: This case control study was conducted on 60 patients divided into three groups: leukoplakia (L), Oral submucous Fibrosis (OSMF), and tobacco controls (TC). Serum and saliva samples were collected and analyzed using a confocal Raman spectroscope. Multivariate analysis using principal component analysis (PCA) and linear discriminant analysis (LDA) was performed to generate classification models. RESULTS: Spectral variations were observed among the groups in both serum and saliva, particularly in protein, lipid, nucleic acid related bands. Serum-based models demonstrated higher classification accuracy (~ 87.5%) compared to saliva (~ 80%) in 2-Class analyses. Combined 3-Class models showed accuracies of 70% and 60% in serum and saliva respectively. Class-specific sensitivity, specificity and predictive values for the three-class serum and saliva models are reported. CONCLUSION: In this exploratory case-control study, Raman spectroscopy of serum and saliva distinguished tobacco controls from patients with Oral Leukoplakia or OSMF with moderate-to-good classification accuracy, and serum-based models outperformed saliva-based models. These preliminary findings suggest that RS warrants further investigation as a minimally invasive adjunct for classification of OPMDs; validation in larger, prospective, multicentre cohorts with longitudinal follow-up is required before any early-detection or screening role can be established. CLINICAL RELEVANCE: Raman spectroscopy-based classification might eventually support risk-based triage for biopsy in high-burden settings. The present cross-sectional case-control design demonstrates group discrimination only, and does not by itself establish a screening, early-detection, or longitudinal-monitoring role.
Rheumatology internationalMuhammed Zahid Sahin, Saltanat K Yerkebayeva, Neslihan Gokcen
Behçet's disease (BD) is a chronic multisystem inflammatory disease in which cognitive impairment is increasingly recognized but remains incompletely understood. Although cognitive dysfunction is more common in patients with Neuro-Behçet's disease (NBD), it has also been reported in patients without clinically apparent neurological involvement, suggesting that mechanisms beyond focal inflammatory lesions may contribute to cognitive impairment. The glymphatic system is a brain-wide perivascular clearance pathway that maintains cerebral homeostasis by facilitating the exchange of cerebrospinal and interstitial fluid and the removal of inflammatory mediators and metabolic waste products. Previous neuroimaging studies have demonstrated white matter microstructural abnormalities in both NBD and neurologically asymptomatic BD, with more extensive alterations in NBD. Furthermore, studies in systemic lupus erythematosus have identified an increased burden of enlarged perivascular spaces, choroid plexus enlargement, and lower diffusion tensor imaging along the perivascular space (DTI-ALPS) indices, providing preliminary imaging evidence of alterations putatively related to glymphatic function in systemic inflammation and neuropsychiatric involvement. However, the relationship between glymphatic dysfunction and cognitive impairment has not yet been directly investigated in BD. We hypothesize that chronic neuroinflammation, endothelial dysfunction, blood-brain barrier disruption, vascular inflammation, and sleep disturbance may impair glymphatic clearance in BD, leading to persistent neuroinflammation, white matter injury, and cognitive dysfunction. This proposed relationship has not yet been directly tested in BD. We further propose that glymphatic dysfunction may occur not only in patients with NBD but also in a subset of BD patients without overt neurological involvement, although it is likely to be more pronounced in NBD. If validated, this hypothesis could provide a novel mechanistic framework for cognitive impairment in BD and support the development of imaging biomarkers and adjunctive therapeutic strategies targeting glymphatic function.
Journal of neurologyAngela Rosenbohm, Francisco Herrera-Angeles, Hans-Jürgen Huppertz, Karl Georg Haeusler, Jochen H Weishaupt, Hans-Peter Müller, Jan Kassubek
Facial onset sensory and motor neuronopathy (FOSMN) is an exceptionally rare condition characterized by progressive facial paresthesia and the subsequent appearance of bulbar symptoms with rostro-caudal motor and sensory deficits sometimes extending to the hand muscles. The pathophysiological understanding of this disorder is very limited. In order to identify patterns of neuroanatomical involvement within the brain, we applied advanced magnetic resonance imaging-based techniques to a group of six patients with the diagnosis of FOSMN, using unbiased analysis techniques with atlas-based volumetry of volume-rendering T1-weighted data and whole brain-based spatial statistics of diffusion tensor imaging (DTI). The volumetric data showed significant global atrophy with prominent involvement of the medulla oblongata, while DTI demonstrated significant decreases in the right-hemispheric frontal lobe and bilaterally along the superior and inferior longitudinal fasciculi. In summary, this application of volumetry and DTI to a group of FOSMN patients demonstrated, beyond global brain atrophy as a correlate of a systemic disease process, regional atrophy in the brainstem/medulla oblongata, together with tract alterations of polymodal frontotemporoparietal interconnections. Future neuroimaging studies in larger patient groups of FOSMN are needed for detailed phenotype-neuroimaging correlations.
BMC oral healthDalia Ghalwash, Ahmed Hamdy, Shehad Wael, Al-Hassan Diab, Ahmed Ammar
BACKGROUND: Dentin hypersensitivity (DH) is a prevalent clinical condition characterized by pain arising from exposed dentin in response to external stimuli. Despite its clinical relevance, epidemiological data from Egypt and the Middle East remain limited. This study aimed to assess the prevalence, symptom characteristics, and oral hygiene-related correlates of self-reported dentin hypersensitivity among Egyptians adults. METHODS: A cross-sectional questionnaire-based study was conducted among 370 Egyptian adults recruited from multiple governorates between January and August 2025. Data was collected using a structured questionnaire that underwent expert review, pilot testing, and reliability assessment. Information regarding self-reported dentin hypersensitivity, triggering stimuli, oral hygiene habits, behavioral factors, and sociodemographic characteristics was obtained. Multivariable logistic regression analyses were performed to explore factors associated with self-reported gingival recession and frequent or persistent dentin hypersensitivity symptoms. RESULTS: Self-reported dentin hypersensitivity was reported by 86 participants, yielding an overall prevalence of 23.2% (95% CI: 19.2-27.8%). The most common trigger was cold stimuli, and the most common symptom pattern was intermittent discomfort. Most participants reporting hypersensitivity were younger adults, although no significant association with sex was observed. Self-reported gingival recession was reported by 27.9% of participants with dentin hypersensitivity. Multivariable regression analyses did not identify significant independent predictors of self-reported gingival recession or frequent/persistent hypersensitivity symptoms. CONCLUSION: Self-reported dentin hypersensitivity affected nearly one-quarter of surveyed Egyptian adults, with cold-triggered symptoms predominating. The absence of strong independent predictors supports the multifactorial nature of dentin hypersensitivity. These findings provide region-specific epidemiological data and highlight the need for future studies incorporating standardized clinical assessment to validate self-reported symptoms and further investigate associated factors.
Oral and maxillofacial surgeryRamanathan Snega, Thoshi Tarun K, Muthupandian Saravanan
BACKGROUND: Oral mucositis is a debilitating inflammatory condition requiring effective topical formulations with antimicrobial and wound healing properties. This study aimed to formulate and evaluate Gracilaria foliifera-mediated zinc oxide nanoparticles (ZnO-NPs) incorporated into a sodium alginate gel for potential oral mucosal applications. METHODS: The formulated ZnO-NPs-infused gel was characterized using UV-visible spectroscopy, FT-IR, SEM, EDX, and X-ray diffraction. Physical stability was assessed based on appearance, pH, texture, and phase separation. Antioxidant, anti-inflammatory, antimicrobial, and antibiofilm activities were evaluated in vitro. Drug-release behavior and cytotoxicity were also investigated. RESULTS: UV-visible spectroscopy showed absorption peaks at 321 and 320 nm at 0 and 24 h, respectively, indicating good nanoparticle stability within the gel matrix. SEM revealed irregularly shaped ZnO-NPs with an average size of 166 nm. EDX confirmed Zn (41.48%), O (19.7%), and C (38.7%), while X-ray diffraction showed 64.9% crystallinity. The formulation exhibited 74.3% radical-scavenging activity at 100 µg/mL and 64.07% inhibition of albumin denaturation at 400 µg/mL. It demonstrated antimicrobial activity against Streptococcus mutans, Escherichia coli, and Candida albicans and reduced S. mutans biofilm formation. Approximately 50% of the loaded ZnO-NPs were released within 12 h, while cytotoxicity assessment indicated good in vitro biocompatibility at 5-75 µg/mL. CONCLUSION: The ZnO-NPs-infused sodium alginate gel exhibited antioxidant, anti-inflammatory, antimicrobial, and antibiofilm properties in vitro, supporting further investigation for oral mucosal applications. However, mucosal safety and therapeutic efficacy remain to be established through in vivo studies.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerMotahareh Tahmasebi, Romina Kaveh-Ahangaran, Maryam Barkhordar, Mazda Rad-Malekshahi, Mohammad Vaezi, Leyla Sharifi Aliabadi, Mobina Sadat Zarabadi, Bita Shahr…
PURPOSE: Oral mucositis (OM) is a frequent and clinically important toxicity of conditioning therapy for hematopoietic cell transplantation (HCT). This trial evaluated whether prophylactic N-acetylcysteine (NAC) mouthwash reduces the incidence and severity of OM in HCT recipients. METHODS: In this single-center, double-blind, randomized, placebo-controlled trial, adults undergoing autologous or allogeneic HCT were assigned 1:1 to NAC mouthwash (600 mg every 6 h; 2400 mg/day) or matching placebo from the first day of conditioning until day +14 after transplantation or neutrophil engraftment, whichever occurred first. OM was assessed daily using the World Health Organization (WHO) Oral Toxicity Scale. The primary outcomes were the incidence of any OM and severe OM (WHO grades 3-4). Safety and exploratory predictors of OM were also evaluated. RESULTS: A total of 106 patients were randomized (NAC, n = 54; placebo, n = 52) and included in the intention-to-treat efficacy analysis. Any-grade OM occurred in 33/54 patients (61.1%) receiving NAC and 38/52 patients (73.1%) receiving placebo (P = 0.190). Severe OM was significantly less frequent with NAC than with placebo (3/54 [5.6%] vs. 13/52 [25.0%]; P = 0.006), and the overall distribution of WHO grades favored NAC (P = 0.046). NAC was well tolerated; gastrointestinal adverse events were mild and infrequent. In multivariable analysis, allogeneic HCT, myeloablative conditioning, suboptimal adherence, and placebo assignment were associated with higher odds of OM. CONCLUSION: NAC mouthwash did not significantly reduce the overall incidence of OM but significantly reduced severe OM in adults undergoing HCT. Given its low cost, availability, and favorable tolerability, NAC mouthwash may be a practical supportive-care strategy for reducing clinically consequential mucosal toxicity. Multicenter trials with standardized formulations and patient-reported outcomes are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT07325383 (registered on November 16, 2025); Iranian Registry of Clinical Trials (IRCT20140818018842N42).
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerPhitjira Sanguanboonyaphong, Anyamanee Lapmag, Warisada Silaon, Praneet Opanasopit, Woraanong Thiramontre, Suphatcha Khiewvarn, Kanokporn Chamalerk, Worranan R…
BACKGROUND: Chemotherapy-associated oral mucositis (OM) is a prevalent and debilitating complication in patients undergoing cancer treatment, lacking effective preventive and therapeutic options. Boesenbergia rotunda (BR), a traditional medicinal plant, exhibits potent anti-inflammatory and antimicrobial activities. The objective of this study was to evaluate a BR extract-based mouth gargle for the management of concurrent chemoradiotherapy (CCRT)-induced OM. METHODS: BR extract was evaluated for cytotoxicity and anti-inflammatory activity. The mucoadhesive mouth gargle was characterized by antimicrobial activity, salivary release, and mucosal deposition. Clinical evaluation was performed in patients with head and neck cancer receiving CCRT in a prospective randomized controlled trial conducted between September 2024 and November 2025. The primary outcome of the clinical phase was to compare the incidence of OM at 6 weeks. RESULTS: BR extract was non-cytotoxic at concentrations below 1 µg/mL and significantly suppressed nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. The formulation demonstrated antimicrobial activity, rapid release within 2 min, and effective mucosal deposition. Fifty-six patients were enrolled, with 73.98% adherence. The incidence of overall OM was significantly lower in the BR extract group than in the control group (30.4% vs. 41.1%, p = 0.04). Lip swelling at week 3 occurred less frequently in the BR group than in the non-intervention group (1.8% vs. 14.3%, p = 0.03), while other adverse events were comparable between groups. CONCLUSION: The BR extract-based mucoadhesive mouth gargle is biocompatible, exhibits anti-inflammatory and antimicrobial activities, and achieves effective mucosal delivery. These findings indicate its potential as a therapeutic strategy for managing CCRT-induced OM. CLINICAL TRIAL NUMBER: Not applicable.
OBJECTIVES: To compare the short-term salivary microbiome effects of a Coriandrum sativum essential oil (CSEO) mouthwash, chlorhexidine (CHX) as a benchmark comparator, and water in patients with periodontitis. MATERIALS AND METHODS: In this randomized three-arm trial, participants with periodontitis rinsed twice daily for 14 days with water, CSEO, or 0.12% CHX. Preclinical anti-Porphyromonas gingivalis and fibroblast cytotoxicity assays informed CSEO concentration selection. Shotgun metagenomic sequencing was performed on 54 saliva libraries, two per participant, from 27 participants sampled at baseline and week 2 (H2O n = 9, CSEO n = 8, CHX n = 10). Alpha diversity, within-subject Bray-Curtis change, and differential abundance were analysed longitudinally. RESULTS: Both active agents inhibited P. gingivalis in vitro, with CHX showing greater potency. In the clinical trial, no statistically detectable difference between CSEO and water was observed for the primary species-level Bray-Curtis outcome (q = 0.413), alpha diversity (all q ≥ 0.259), or differential abundance. CHX showed greater species-level Bray-Curtis change than water (q = 0.020), lower species-level Simpson diversity (q = 0.014), and broad taxonomic restructuring. CONCLUSIONS: Under the tested formulation and exposure conditions, CSEO did not produce a statistically detectable group-level salivary microbiome shift relative to water. CHX provided a benchmark for broad ecological perturbation. The CSEO null finding does not exclude modest or heterogeneous effects in a larger cohort. CLINICAL RELEVANCE: No clinical benefit can be inferred from the absence of a detectable CSEO-associated microbiome shift. Larger studies integrating clinical, inflammatory, and direct functional outcomes are needed. TRIAL REGISTRATION: ISRCTN79156900, retrospectively registered on 11 May 2026.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerA M G A Laheij, J E Raber-Durlacher, B Hasséus, M C Huysmans, S J M van Leeuwen, K Garming Legert, J E Johansson, S Isom, D M Kline, M D Hazenberg, F R Rozema,…
PURPOSE: The percentage of cases with fever of unknown origin after hematopoietic cell transplantation (HCT) is high. An often overlooked clinical infection in HCT recipients may be chronic inflammation from the oral cavity. Therefore, the aim of the present study was to assess fever in the pre-engraftment phase after HCT and to examine the relationship between oral foci of infection before and in the first weeks after HCT and fever. METHODS: Adult patients, scheduled for autologous or allogeneic HCT, were included in this prospective, observational multicenter cohort study. Oral health was determined pre-HCT. Following HCT conditioning, fever was registered daily; and oral mucositis and other oral side effects were registered three times weekly. RESULTS: Data from 186 patients were available. The mean age was 53.0 years (± 12.9), and 55.4% were male. The most common malignancies were multiple myeloma, acute myeloid leukemia, and lymphoma. In total, 69.4% of the patients developed fever and 43.1% had an oral ulcerative lesion. After correction for age, site, conditioning regimen, diarrhea, vomiting, and duration of leukopenia, oral ulceration size remained significantly associated with fever, especially when fever was defined as ≥ 38.5°C. Pre-HCT chronic dental and oral conditions showed no association with post-HCT fever. CONCLUSION: Fever was common during the pre-engraftment phase after HCT and significantly associated with the extent of oral ulcerations. In contrast, pre-HCT dental and oral conditions showed no association with post-HCT fever, highlighting the specific role of mucosal injury in febrile episodes.
BMC oral healthMohamed Gamal Hassanin Atia, Mohamed Said Hamed, Asmaa Yousri Abdallah, Ahmed Abdelmohsen Younis
BACKGROUND: Immediate loading significantly improves oral health related quality of life (OHRQoL) as well as satisfaction of patients. Future trials will determine the role of immediate loading protocol in clinical scenarios with various amounts of available jaw bone using different numbers of implants to retain a fixed prosthetic restoration in partially edentulous maxilla. The aim of this study is to evaluate and compare the clinical stability and radiographic difference of osteointegration between immediate and delayed loaded dental implants in the anterior and premolar regions of the maxilla. METHODS: Sixteen patients aged from 20 to 55 were divided into two equal groups. Group 1 consisted of 8 implants that were placed and loaded 6 months after placement, while group 2 consisted of 8 implants that were placed and immediately loaded with a provisional PMMA restoration; after 6 months, the provisional restoration was replaced by a fixed restoration. Each implant was clinically evaluated for implant stability using the Osstell device and radiographically evaluated for bone density around the implant using postoperative indirect standardized digital radiographs taken immediately after implant placement and after 3 and 6 months. RESULTS: Both groups had a significant decrease in pain and swelling after surgery over time, but the immediate loading group had consistently lower values on day 1 (p = 0.001), day 3 (p = 0.023), and day 7 (p < 0.001). Moreover, the immediate loading group also had a significantly lower edema at all-time points (day 1: p = 0.005; day 3 and day 7: p < 0.001). Implant stability (ISQ) increased over time in both groups, while no statistically significant between-group difference was observed at baseline or at 6 months. Peri-implant bone density showed no significant differences between groups at any time point. CONCLUSIONS: Immediate implant loading was found to be a better alternative than delayed loading, as it provides comparable bone density and implant stability while significantly reducing postoperative pain and edema, consequently enhancing quality of life, aesthetic results, and early patient comfort without compromising radiographic performance. TRIAL REGISTRATION: NCT07381283 (registration date: February 2, 2026).
PURPOSE: The increasing use of cannabis for both medical and recreational purposes has been associated with negative effects on dental hygiene and oral health. This study examined the relationship between cannabis use and tooth loss. MATERIALS AND METHODS: Analyses included 577,848 adults who participated in the 2016, 2018, 2020, 2022, and 2024 cross-sectional Behavioral Risk Factor Surveillance System (BRFSS) surveys. The association between past 30-day cannabis use and tooth loss was evaluated using multinomial logistic regression, adjusting for age, sex, race/ethnicity, survey year, tobacco smoking status, and 10 chronic conditions. RESULTS: About 12.3% of participants reported using cannabis in the past 30 days, with 6.5% classified as infrequent users and 5.8% as daily or near-daily users. Smoking was the most common method, especially among daily or near-daily users. Cannabis use was more common among younger adults, men, non-Hispanic Black and multiracial adults, and current or former tobacco smokers. Use also increased over time, particularly among daily or near-daily users. Tooth loss increased with age and was more common among cannabis users, especially daily or near-daily users and those who smoked cannabis. Adults who smoked cannabis had a significantly higher prevalence of tooth loss than those using other consumption methods. After adjusting for factors such as age, sex, race/ethnicity, tobacco smoking, and 10 chronic conditions, daily or near-daily cannabis use remained significantly associated with greater odds of tooth loss, while infrequent use did not. Tooth loss was also strongly associated with chronic diseases, including arthritis, depression, asthma, and diabetes. Daily or near-daily users showed stronger associations with some chronic conditions, although no statistically significant association was found with heart attacks. CONCLUSION: Frequent and smoked cannabis use are associated with poorer oral health outcomes, particularly increased tooth loss.
Oral squamous cell carcinoma (OSCC), the most prevalent histological subtype of oral cancer, is characterized by an immunosuppressive tumor microenvironment (TME) predominantly modulated by tumor-associated macrophages (TAMs). The CXCL9/SPP1 ratio (CS ratio) has been validated as a more reliable prognostic biomarker than the conventional M1/M2 classification. Although methyltransferase-like 14 (METTL14) participates in TAM polarization, its specific role in regulating the CS balance in OSCC remains elusive. This investigation elucidates the mechanism by which METTL14 modulates TAM CS polarization and affects OSCC growth and stemness. We utilized single-cell RNA sequencing (scRNA-seq) data for OSCC and normal samples from Gene Expression Omnibus (GEO) to characterize TAM CS polarization and screen critical regulatory molecules. To independently validate the expression of key candidate genes, we additionally analyzed three independent bulk transcriptomics cohorts from GEO, comprising 330 patient tissue samples. A METTL14-overexpressing TAM model was constructed to explore the effects of METTL14 on CS polarization and OSCC growth and stemness. The target gene of METTL14-mediated m6A modification was identified using the RM2Target database and validated by cellular experiments. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an m6A reader protein, mediates the downstream biological effects of this epigenetic modification. Finally, the impact of METTL14-driven TAM CS polarization on OSCC tumor growth and stemness was verified in vitro and in vivo in a macrophage-specific Mettl14 knockout mouse model. scRNA-seq re-analysis uncovered mutually exclusive CXCL9⁺ and SPP1⁺ TAM populations in OSCC. METTL14 was markedly enriched and co-expressed in CXCL9⁺ TAMs, where it showed a negative correlation with cancer stemness pathways. Independent validation in three bulk transcriptomics cohorts (n = 330) confirmed significant differential expression of CXCL9 and METTL14 between OSCC tumor and normal tissues. In vitro, METTL14 overexpression in TAMs promoted CXCL9⁺ TAM generation and suppressed OSCC cell growth and stemness, an effect attributed to METTL14-mediated m6A modification of CXCL9 mRNA, which was recognized and stabilized by the m6A reader protein IGF2BP3. Consistently, in vivo assays using macrophage-specific METTL14-knockout mice revealed that METTL14 knockdown reduced m6A modification levels of CXCL9 mRNA, promoted the polarization of TAMs toward the SPP1⁺ phenotype, and ultimately accelerated OSCC tumor growth and enhanced cancer stemness. Collectively, this study identifies a novel mechanism wherein METTL14 regulates TAM CS polarization by promoting m6A modification of CXCL9 mRNA, thereby driving TAMs towards a CXCL9⁺ phenotype and suppressing OSCC growth and stemness.
RATIONALE: Myelosuppression after autologous stem cell transplantation (ASCT) exposes patients with multiple myeloma to substantial infection and bleeding risks and may be accompanied by marked psychological distress during protective isolation. Although supportive care is central to posttransplant recovery, reports describing how narrative nursing can be integrated into routine transplantation care remain limited. PATIENT CONCERNS: A 46-year-old married man with multiple myeloma was admitted 7 months after ASCT because of fever for half a day and erosive oral-labial mucosal lesions. He presented with febrile neutropenia, oral mucositis, severe pancytopenia, anxiety, hopelessness, and concern about his family role as the main financial provider. DIAGNOSES: The patient was diagnosed with multiple myeloma after ASCT complicated by prolonged myelosuppression, febrile neutropenia, oral mucositis, and severe pancytopenia. Delayed hematopoietic reconstitution and infection, including possible fungal infection, were considered during the clinical course. INTERVENTIONS: The patient received protective isolation in a laminar airflow room, empiric broad-spectrum antimicrobial therapy, granulocyte colony-stimulating factor, hemostatic prophylaxis, blood component support, meticulous oral and skin-mucosal care, nutrition and hydration support, and dynamic monitoring. A supplemental infusion of autologous hematopoietic stem cells was administered on hospital day 2. Individualized narrative nursing was provided through repeated one-to-one conversations, emotional validation, misconception correction, achievable daily goal setting, family communication, and discharge planning. OUTCOMES: During the 16-day hospitalization, fever and mucositis resolved, leukocyte and neutrophil counts gradually recovered, inflammatory markers declined, and no new infection or major bleeding occurred. The patient reported reduced fear, improved sleep, and greater willingness to participate in care and follow-up. LESSONS: This case suggests that structured narrative nursing can be feasibly embedded in routine ASCT supportive care during prolonged myelosuppression and may support emotional adjustment, treatment engagement, and family-centered coping.
Journal of medical Internet researchLaura Swinckels, Katharina Alves Rabelo, Eduardo L Delamare, Bruno G Loos, Pierre Lahoud, Harmen Bijwaard, Ander de Keijzer, Jinman Kim, Josef Bruers
BACKGROUND: Periodontitis is one of the most prevalent yet preventable oral diseases, as indicated by multiple clinical and radiographic factors. As these factors are recorded in electronic health records (EHRs), their reuse offers opportunities for personalized risk assessment and targeted prevention. Predictive AI and traditional machine learning models support fragmented detection tasks but lack the integration of textual and imaging predictors. Emerging multimodal large language models (M-LLMs) show promise in combining these data sources for clinical assessment. Evaluating the capabilities of M-LLMs and comparing them against the current clinical standard are therefore essential to determine their potential as digital assistants. OBJECTIVE: This study aimed to evaluate the ability of M-LLMs to assess periodontitis risk and suggest prevention strategies, based on EHR data and radiographic findings. Each M-LLM was individually evaluated by periodontal experts, benchmarked against other models, and compared with a periodontist as a reference. METHODS: A vignette study was conducted following TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines for the evaluation of LLMs. Ten periodontal vignettes were created, each including a panoramic radiograph and textual EHR data. Three LLMs capable of reasoning and handling multimodal data were compared to a periodontist who generated outputs manually, based on the same prompts and input data. Periodontal experts rated all outputs across 6 predefined criteria on a 5-point Likert scale. Statistical analyses evaluated overall performance per model and tested whether performance varied per model, scenario complexity, or rater. RESULTS: GPT o1 Pro and Claude Sonnet 4 showed strong performance, with 86.7% and 85.6% of ratings deemed acceptable-comparable to the periodontist's output (87.8%). Gemini 2.5 Pro was rated significantly lower than both the periodontist and the other models (59.4% acceptable; P<.002). Radiographic interpretation consistently received lower scores than other abilities across all models and the periodontist, with Gemini rated below the acceptable threshold. The time required for completion ranged from approximately 10 seconds for Claude to 37 seconds for Gemini; 3 minutes, 22 seconds, for GPT; and 5 minutes, 57 seconds, for the periodontist. CONCLUSIONS: M-LLMs demonstrated strong reasoning abilities in periodontal assessment. Across all models, unacceptable elements were consistently related to errors in radiographic interpretation, though refined prompting or newer model versions may improve this. Notably, even when radiographic findings were incorrect and plaque-retentive factors were absent, outputs were still rated well, indicating that EHR data alone provide a substantial basis. For clinical applicability, M-LLMs must at least perform comparably to a periodontist and meet the quality standards set by periodontal experts-a bar that GPT and Claude appear to approach.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical NeurophysiologyLeonardo Barbosa, Filipe Alves, Andreia Costa
BACKGROUND: Burning mouth syndrome (BMS) is a chronic orofacial neuropathic pain disorder, occurring in the absence of clinically evident mucosal lesions or identifiable oral pathology that can explain the symptoms. A significant proportion of patients experience uncontrolled symptoms despite multiple therapies. OnabotulinumtoxinA (onaBoNT/A) is used in neuropathic pain, as clinical trials have shown benefits in peripheral and central neuropathic pain management with its application. We present an exploratory case series of four patients with refractory BMS treated with intradermal onaBoNT/A injections. METHODS: Four patients with refractory BMS were included in this study. OnaBoNT/A intradermal injections were performed in the inner labial mucosae and tip of the tongue. We assessed pain intensity before the procedure and after 15 days, adverse effects, time to symptom recurrence, cumulative effects with multiple procedures, and patients' global impression of change. RESULTS: All patients reported the procedure was quick and well tolerated. No immediate adverse effects were identified. All patients had significant pain reduction at 15-day follow-up assessment. Regarding adverse effects, one patient reported transient lower lip asymmetry in one procedure, and another reported transient mild mouth closure impairment. Symptoms recurred between 2.5 and 3.0 months after the first procedure. Three patients desired to continue the treatment. One patient reported no symptom recurrence after four procedures with three-month intervals; after four procedures, the treatments were suspended, and she remained asymptomatic until the end of follow-up. One patient reported incremental benefit from repeated procedures. All patients reported the treatment had a meaningful impact on their daily life. CONCLUSIONS: Our results suggest that intradermal onaBoNT/A injections may constitute an effective and durable treatment option for patients with BMS refractory to conventional therapies. Despite these favourable outcomes, adverse events were noted in procedures targeting the labial mucosa. In future applications, we aim to examine technical variations between sessions associated with and without adverse effects, to optimise safety and refine the technique.
Clinical oral investigationsLauriina Soiniemi, Eelis Hyvärinen, Jopi Mikkonen, Heli Jäsberg, Bina Kashyap, Arja Kullaa
OBJECTIVES: Oral Potential Malignant Lesions (OPMDs), including oral leukoplakia (OLK) and lichen planus (OLP), as well as Oral Squamous Cell Carcinoma (OSCC) are influenced by oral dysbiosis and might represent a disease continuum. Our hypothesis was that the oral salivary metabolomic reflects the association of those diseases. Hence, we aimed to study and compare salivary metabolites and metabolic pathways in OPMDs and OSCC. MATERIAL AND METHODS: Unstimulated saliva samples were collected from 60 participants: OLK (n = 15), OLP (n = 15), OSCC (n = 15), and healthy controls (HCs; n = 15). Metabolites were quantified using NMR spectroscopy, and pathway analyses were performed with MetaboAnalyst 6.0. RESULTS: Four metabolites (acetate, taurine, pyruvate, methylamine) were elevated, while proline was consistently decreased in all disease groups relative to HCs. Four key pathways were altered: pyruvate metabolism (in all disease groups), glutamate metabolism (in OLK and OSCC), taurine and hypotaurine metabolism (in OLP and OLK), and the glucose-alanine cycle. OLK shared more metabolic features with OSCC than with OLP. CONCLUSIONS: Salivary metabolomic profiling reveals distinct metabolic alterations across OPMDs and OSCC, supporting their potential continuum and reflecting disease-related biochemical reprogramming. These findings highlight salivary metabolomics as a promising, non-invasive tool for understanding pathogenesis and for future development of biomarkers. CLINICAL RELEVANCE: Divergent metabolic pathways in OLP and OLK may relate to their different pathogenesis and malignant transformation risks. Improved understanding of these pathways may support early diagnostics and targeted therapeutic strategies.
The international journal of medical robotics + computer assisted surgery : MRCASShiling Dong, Jingjing Cheng, Shuanfeng Xing, Guangwen Yang
BACKGROUND: Oral squamous cell carcinoma (OSCC) remains a clinically heterogeneous malignancy with unsatisfactory long-term outcomes, particularly in patients with advanced disease and treatment resistance. Conventional clinicopathologic parameters incompletely capture the biological diversity of OSCC and provide limited guidance for individualised therapeutic stratification. METHODS: We performed an integrated transcriptomic analysis of TCGA-derived OSCC data to construct and evaluate an immune-associated prognostic signature. Associations with survival, clinicopathologic features, immune infiltration, somatic mutation profiles and pathway-level biological programs were assessed. The manuscript-specified ten-gene equation was additionally evaluated without refitting in an independent CPTAC oral-cavity SCC cohort using overall survival, Harrell's C-index and time-dependent ROC analysis. Amphiregulin (AREG) was selected for functional investigation using siRNA-mediated knockdown, proliferation assays, cisplatin sensitivity testing, IC50 estimation and apoptosis analysis in OSCC cells. RESULTS: The original TCGA analysis separated survival groups and reported 1-, 3- and 5-year AUCs of 0.701, 0.693 and 0.623. In 42 independent CPTAC patients with 14 deaths, however, the fixed score was not significantly associated with overall survival (HR per SD, 1.181; 95% CI, 0.674-2.069; p = 0.561). The C-index was 0.521, and the 1- and 3-year AUCs were 0.369 and 0.550; 5-year evaluation was unsupported by follow-up. The supplied AREG experiments suggested reduced proliferation and increased cisplatin sensitivity after knockdown. CONCLUSIONS: This study identifies an exploratory immune-associated score and AREG-associated cellular phenotypes in OSCC.
MicrobiologyOpenNils Werner, Marie Schöffel, Annette Wittmer, Klaus Pelz, Kirstin Vach, Cornelia Frese, Christiane von Ohle, Diana Wolff, Fabian Cieplik, Ali Al-Ahmad
This study aimed to analyse antimicrobial resistance (AMR) in bacterial isolates from subgingival biofilms of patients with periodontitis and supragingival biofilms of orally healthy individuals, and to explore the association between biofilm-forming capacity and AMR. Three hundred and forty-seven bacterial isolates from 44 patients were analysed. Bacterial isolates were obtained from subgingival/supragingival biofilm and identified using MALDI-TOF mass spectrometry. Antibiotic susceptibility was evaluated by the Kirby-Bauer test, the E-test, and a β-lactamase activity assay, and biofilm formation capacity was assessed using the gentian violet assay. The 44 participants (median age 28.0 [25.0; 55.0]) were stratified into untreated generalised stage III/IV periodontitis (n = 21) and orally healthy (n = 23) groups. Among 347 isolates, 74.4% formed biofilms. AMR was generally higher in isolates from orally healthy subjects (77.7% vs. 59.1% in periodontitis patients, p < 0.001) and females (73.2% vs. 60.6% in males, p = 0.026). Multivariate binary logistic mixed models linked biofilm formation to AMR (OR: 1.66 CI: [1.12, 2.49]; p = 0.045 for severe biofilm formers and OR: 1.93 CI: [1.31, 2.83]; p = 0.004 for moderate biofilm formers). Phenotypic antimicrobial resistance was thus commonly detected throughout the cohort and was at least as frequent in orally healthy participants as in patients with periodontitis. Because the orally healthy group was substantially younger, this contrast is confounded by age and smoking and cannot be interpreted as an independent effect of periodontal status. Furthermore, this study might indicate that biofilm-forming isolates may exhibit increased antibiotic resistance.
Clinical and experimental dental researchDavid C Johnsen, Lauren A G Erickson, Derek Smith, Carlos Garaicoa-Pazmino
BACKGROUND: Scarce scientific evidence is available on the association of cumulative coping challenges and periodontitis. The present retrospective cross-sectional exploratory study explored a new method to depict the association between periodontal disease (extent/severity/rate of progression) and cumulative coping challenges. METHODS: A population sample was identified with an array of periodontal disease levels and coping challenges within an academic setting. In January 2026, a total of 39 student-led patient presentations were recorded using an ordinal scale based on the 2017 American Academy of Periodontology/European Federation of Periodontology framework of staging/grading and a cumulative coping challenges score, including biologic, sociologic, behavioral, demographic, and oral disability-related factors. Spearman's correlation analysis was used to correlate periodontal disease level and cumulative coping challenges. RESULTS: A distinct and significant association was found between level of periodontal disease and cumulative coping challenges (Spearman's ρ = 0.77, 95% CI, p < 0.01). Clusters of patients depicted that those with mild forms of periodontal disease (Stages I-II) had few coping challenges and another group with severe forms of periodontal disease (Stages III-IV) harbored higher cumulative coping challenges. No person appeared with high disease and low cumulative coping challenges, and only one person appeared with low disease and high coping challenges. CONCLUSIONS: This retrospective cross-sectional exploratory study quantified risk factors from a series of cumulative coping challenges resulting in a single metric to be correlated with disease level based on the current staging/grading system for periodontal diseases. Periodontitis was observed among individuals with minimal disease and few coping challenges, and another group with severe stages and extensive coping challenges. Despite the theoretical limitation of the proposed scale, the present model has a practical use in an educational setting as an exploratory composite index.
Mymensingh medical journal : MMJM I Ali, R Banik, A Jabeer, B Nowreen, M D H Bhuiyan, N Hossain
Squamous cell carcinoma (SCC) is the most frequent type of oral cancer in the globe. Despite breakthroughs in overall treatment modalities, survival rates of individuals with oral squamous cell carcinoma (OSCC) have not improved appreciably. One of the reasons for OSCC's poor survival rate is late diagnosis. The majority of patients arrive at the hospital in advanced stages of the disease (stage-3 and stage-4). This cross-sectional comparative study was carried out in the Department of Oral and Maxillofacial Surgery of former Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from September 2022 to August 2023. And aimed to find out the association of hypercalcemia with advanced oral squamous cell carcinoma (stage-3 and stage-4). The study was comprised of 84 subjects in which 42 were selected as case group with advanced Oral Squamous Cell Carcinoma (OSCC), reporting to the Department of Oral and Maxillofacial Surgery, BSMMU; fulfilling the inclusion and exclusion criteria. The control group of subjects was consisted with 42 healthy attendants of patients after fulfilling the inclusion and exclusion criteria. All these participants were assessed clinically and their detailed history was recorded, 5 ml of intravenous blood was collected using standard aseptic conditions. These samples were centrifuged and serum was seen separated as the top transparent layer. This separated serum was used immediately for quantitative determination of serum calcium by biochemistry automated analyzer: Alinity ci. Serum calcium level was calculated and expressed in mg/dl. The collected data was sorted, tabulated and statistically analyzed. Hypercalcemia (>10.50 mg/dl) was found in 10(23.8%) patients of case group and no one in control group. The mean serum calcium level was found 9.48±0.71 mg/dl in case group and 9.07±0.56 mg/dl in control group. The difference was statistically significant (p<0.05) between two groups. The findings of the study showed that mean serum calcium levels in OSCC patients were substantially higher than in healthy people in Bangladesh.
Clinical and experimental dental researchGrace Wong, Sarah Glastras, Sarah Brennan, Marija Saponja, Anna Cheng, Jami Walk, Kyle Cheng, Wenpeng You
BACKGROUND: Periodontal disease is common among adults with diabetes, yet periodontal screening is rarely incorporated into routine outpatient diabetes care. The Oral Health Assessment Tool (OHAT) is a structured observational tool designed for non-dental healthcare professionals; however, its relationship with periodontal screening findings remains unclear. OBJECTIVES: To examine the association between OHAT findings and periodontal screening outcomes in adults attending diabetes outpatient clinics. METHODS: This cross-sectional study included adults with type 1 or type 2 diabetes at a tertiary hospital in Sydney, Australia. Periodontal screening was performed using the Periodontal Screening and Recording (PSR) system, and oral health was assessed using OHAT. Periodontal status was dichotomized as no/mild (PSR 0-2) versus moderate-to-severe (PSR ≥ 3). Logistic regression examined associations of OHAT domains and total OHAT burden with periodontal status. Covariate-adjusted models assessed robustness. Screening performance was evaluated using sensitivity, specificity, and predictive values. RESULTS: Among 120 participants (mean age 61.5 years, 64.2% with type 2 diabetes), 71.4% demonstrated moderate-to-severe periodontal findings. Mean OHAT score was 4.99 (SD 2.02). Change/unhealthy ratings for tongue (OR 3.23, 95% CI 1.30-8.02), gums and oral tissues (OR 4.59, 95% CI 1.78-11.85), and increasing categories of decayed teeth (OR 2.06, 95% CI 1.05-4.05) were associated with moderate-to-severe findings. Higher total OHAT score (> 5 vs. ≤ 5) was strongly associated with moderate-to-severe periodontal findings (OR 7.00, 95% CI 2.25-21.76), with consistent results. This threshold showed high specificity (87.5%) and positive predictive value (90.9%), but moderate sensitivity (50.0%). CONCLUSION: OHAT findings were associated with moderate-to-severe periodontal screening findings among adults with diabetes, supporting further evaluation of OHAT as a pragmatic screening and referral aid in settings where formal periodontal assessment is not routinely available. Its performance when administered by non-dental clinicians requires further investigation.
Clinical and experimental dental researchAnna Liisa Suominen, Tuomas Saxlin, Marja-Leena Lamidi, Virva Vänttinen, Johanna Pasanen, Tiina Laatikainen
OBJECTIVES: The aim was to evaluate how treatment supplied in public oral health care services is associated with the prevalence and incidence of periodontitis. METHODS: The data for this study comprised patients aged 20 years or older who had visited publicly funded oral health care services in the Wellbeing Services County of North Karelia (Siun sote) during the years 2021-2022 (N = 50,469). These patients were retrospectively followed in the patient register starting from 2014. Associations of treatments received during the follow-up period (years 2014-2020) with ICD-10 diagnoses of chronic and acute periodontitis at follow-up (in 2021-2022) were analyzed by logistic regressions. RESULTS: The prevalence of diagnoses of both chronic and acute periodontitis in 2021-2022 was quite low. The number of years of having received different treatments in 2014-2020 was associated with the odds of being diagnosed with periodontitis in 2021-2022. In the case of chronic periodontitis, an increasing number of years with preventive and restorative treatments was particularly associated with lower prevalence and incidence. Conversely, an increasing number of years with periodontal treatments and tooth extractions, in addition to earlier diagnosis, were associated with higher prevalence and incidence. For acute periodontitis, in contrast, an increasing number of years with preventive care among all participants and periodontal treatment in incident cases appeared to slightly increase the odds, whereas more years of examinations and tooth extractions were associated with reduced odds. In addition, smoking and diagnosis of diabetes mellitus were associated with higher odds of periodontitis diagnosis. CONCLUSIONS: While the association of treatments was similar for prevalence and incidence, it differed between chronic and acute periodontitis, highlighting their distinct pathophysiological profiles. Although preventive care is offered less frequently than other treatments and often for reasons unrelated to periodontal health, it shows a positive impact in reducing the risk of chronic but not acute periodontitis.