Background and Objectives: The SARS-CoV-2 pandemic disrupted oral and maxillofacial surgery (OMS) services worldwide because of the high aerosol-generating nature of head-and-neck procedures, restricted access to elective dental care, and systemic reallocation of hospital resources. Continuous longitudinal multi-year data covering both the pandemic and the post-pandemic phases from regional Romanian (and more broadly central and southeastern European) emergency centers remain scarce. We aimed to quantify the impact of the pandemic on OMS activity in a large Romanian regional referral center and to evaluate post-pandemic resilience. Materials and Methods: We conducted a retrospective single-center study of all inpatient admissions to the OMS Clinic of a tertiary emergency hospital in western Romania between 1 January 2018 and 31 December 2024. Three periods were pre-specified: pre-pandemic (2018-2019), pandemic (2020-2022) and post-pandemic (2023-2024). A Newey-West segmented interrupted-time-series (ITS) regression and a negative-binomial monthly count model with Fourier seasonality were fitted; length of hospital stay was further analyzed with a multivariable gamma-log generalized linear model adjusted for age, sex, county, primary ICD-10 chapter and total ICD-10 codes. Variables analyzed included case volume, demographics, primary and secondary ICD-10 diagnoses, length of hospital stay (LOS), case complexity (total ICD-10 codes per admission) and in-hospital mortality. Results: A total of 11,628 inpatient admissions corresponding to 8084 unique patients (56.5% male; mean age 52.2 ± 19.2 years) were analyzed. Compared with the pre-pandemic baseline (mean 2037 admissions/year), annual volume dropped by 45.1% in 2020, 44.0% in 2021 and 32.3% in 2022, with a nadir of -76% during the first state of emergency (April 2020; n = 34 admissions). Recovery was rapid; 2024 exceeded the pre-pandemic baseline by +10.1% on raw counts and by +16.2% on admissions per 100,000 catchment population using year-specific INS denominators. The segmented ITS regression confirmed an immediate level drop of -114.2 admissions/month in March 2020 (95% CI -133.1 to -95.3; p < 0.001) and a positive post-intervention slope of +2.06 admissions/month (95% CI 1.23-2.88; p < 0.001), with observed monthly volume returning to the counterfactual projection by October 2023. The case mix shifted significantly (χ2 = 406.9, p < 0.0001); elective benign neoplasm admissions were reduced from 7.2% to 2.0%, while neoplasms of uncertain behavior nearly doubled from 15.7% to 27.5%. Case complexity increased during the pandemic (mean ICD codes 4.08 ± 2.42 vs. 3.44 ± 2.30; p < 0.001); after exclusion of administrative codes (whole Z chapter and U07.x), the difference attenuated to 3.34 vs. 3.17 codes (still p < 0.001 by Kruskal-Wallis), indicating that the largest portion of the unadjusted increase was driven by the new mandatory pre-admission SARS-CoV-2 screening code Z11.5 rather than true clinical complexity. Notably, the clinically interpretable proxy R63.3 (feeding difficulty) independently rose from 41.5% to 53.1%. The crude median LOS did not differ between the pre-pandemic and pandemic periods (3.07 vs. 3.06 d; p = 0.19) and dropped significantly post-pandemic (2.22 d; p < 0.001); however, after multivariable adjustment for case mix, age, sex, county and code count, the LOS was 15.7% shorter during the pandemic (adjusted ratio 0.84, 95% CI 0.82-0.87; p < 0.001) and 22.8% shorter post-pandemic (adjusted ratio 0.77, 95% CI 0.75-0.80; p < 0.001) relative to baseline. Conclusions: The pandemic caused a severe but transient contraction of OMS activity accompanied by increased case complexity and a marked shift away from elective surgery. Inpatient volume returned to and exceeded the pre-pandemic baseline by 2024. These results support the value of standing pandemic-preparedness protocols, sustained access to preventive dental care, and integrated tele-triage pathways for future public-health crises.
Informed consent is a core ethical and legal requirement in oral and maxillofacial surgery (OMFS). Traditional consent documents often lack adequate readability and comprehensive coverage of ethical and safety elements. Large language models (LLMs) may assist in drafting consent forms; however, their alignment with clinician expectations in OMFS remains insufficiently studied. This in silico descriptive evaluation study assessed AI-generated informed consent drafts using the QUEST (Quality, Utility, Ethics, Safety, and Transparency) framework. Consent drafts were generated for four representative OMFS procedures: third molar extraction, dental implant placement, open reduction and internal fixation of mandibular fracture, and soft tissue biopsy. One draft was produced per procedure. Two experienced oral and maxillofacial surgeons independently rated each draft across QUEST domains using a 5-point Likert scale (1 = poor, 3 = acceptable, 5 = excellent). Readability was evaluated using standard grade-level metrics. Inter-rater reliability was assessed using Cohen's kappa (κ), with significance set at p < 0.05. Four AI-generated consent drafts were evaluated. Readability scores ranged from grade 6.0 to 8.0 (mean 6.85 ± 0.85). Inter-rater reliability was substantial (κ = 0.78; p < 0.001). Among QUEST domains, Quality achieved the highest scores (mean 4.1 ± 0.4), while Ethics, Safety, and Transparency demonstrated comparatively lower ratings. AI-generated informed consent drafts showed acceptable readability and procedural descriptions but demonstrated limitations in ethical, safety, and transparency domains. These findings suggest that LLMs may assist in consent drafting; however, clinician oversight and further validation are required before routine clinical adoption. The online version contains supplementary material available at 10.1007/s12663-026-03085-7.
Oral squamous cell carcinoma (OSCC) is the predominant histological subtype of oral cavity cancers, with a 5-year survival rate of approximately 50%. The tumour microenvironment, particularly macrophage infiltration and polarization, plays a critical role in tumour progression and patient prognosis. Models describing macrophages as either M1 (pro-inflammatory) or M2 (anti-inflammatory) are increasingly recognized as oversimplified, given the functional heterogeneity and plasticity of tumour-associated macrophages (TAMs). This study aims to evaluate the expression of macrophage markers CD68, CD163, CD11c, and CD115 in OSCC compared to normal oral mucosa (NOM), to assess their diagnostic and prognostic value. A cross-sectional study of 179 tissue samples (111 OSCC, 68 controls) analysed macrophage markers (CD68, CD163, CD11c, CD115) via real-time qPCR. Statistical tests included Mann-Whitney U, ROC analysis for diagnostic utility, Spearman's ρ for correlations, and assessments of associations with prognosis and recurrence. Cut-offs for gene overexpression were based on ROC results and evaluated clinically. All four markers showed significantly higher expression in OSCC compared to NOM (p < 0.001 for CD68, CD163, CD11c; p = 0.001 for CD115). ROC analyses demonstrated diagnostic AUCs of 0.69 (CD68), 0.78 (CD163), 0.81 (CD11c), and 0.66 (CD115), indicating poor, fair and good discriminative capacity, respectively. Overexpression of the genes defined by COP was significantly associated with malignancy (p < 0.01). Elevated CD68 and CD163 levels correlated with higher tumour grading (G2/G3), while increased CD11c expression was linked to nodal metastasis (p = 0.04). Strong positive correlations existed between CD115 and the other markers (ρ > 0.61, p < 0.001), supporting a model of macrophage heterogeneity and plasticity. Concurrent upregulation of pro-inflammatory (CD11c) and M2-associated (CD163) markers suggests a complex, dynamic TAM landscape rather than a simple M1/M2 dichotomy. Altered RNA expression of the macrophage cell surface markers CD115, CD68, CD163 and CD11c in OSCC, and their respective association with tumour grading, N-status and perineural sheath infiltration, may serve as a basis for future single-cell sequencing or immunohistological - multiplex immunofluorescence - studies. Further investigation of these markers could lead to promising insights into the modulation of the tumour immune microenvironment.
To evaluate diagnostic ability of velscope for various oral potentially malignant disorders (OPMDs). Review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis - Diagnostic Test Accuracy (PRISMA- DTA) guidelines. Databases were searched till April 2025 to identify the diagnostic potential of velscope. Quality of selected studies was evaluated based on QUADAS (Quality assessment of diagnostic accuracy studies)- 2 tool. Pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR) and area under curve (AUC) was performed in Meta-Disc 1. software and Review Manager 5.3. Nine studies were included in review and for meta-analysis. Included studies evaluated the diagnostic accuracy of velscope for various OPMDs like oral leukoplakia (OL), oral lichen planus (OLP), oral submucous fibrosis (OSMF) and oral candidiasis in comparison with reference standard like toluidine blue test (TBT) and biopsy followed by histopathological investigation. Meta-analysis showed pooled sensitivity and specificity of 0.73 and 0.65 for OL, 0.70 and 0.80 for OLP, 0.72 and 0.84 for OSMF, 0.68 and 0.80 for candidiasis while an overall AUC of 0.75, 0.81, 0.80 and 0.50 was seen for OL, OLP, OSMF and candidiasis respectively. Velscope is a promising and valid tool and overall has good diagnostic potentiality in diagnosing the target condition and can be used as an alternative adjunct to histopathology. It can be undertaken for early diagnosis and prompt treatment under secondary level of prevention. The online version contains supplementary material available at 10.1007/s12663-025-02869-7.
To determine dental students, dental practitioners and patients' knowledge about Human Papilloma Virus HPV) and HPV vaccination, HPV-related OPCs, and assess the acceptability of the HPV vaccine. A self-administered questionnaire consisted of four main sections. The questions were focused on demographic and personal information of the participants, knowledge about HPV, awareness of the link between HPV and Oral and Oropharyngeal cancers and the knowledge of the HPV vaccine and acceptance for vaccination. Chi-Square test was used to assess associations between the responses and the dependent variables. A significance level (p-value) of ≤ 0.05 was considered statistically significant. Overall knowledge shows that undergraduates were less aware about HPV (17.5%) than post graduates (85%, p < .001) and professionals (100%, p < .001), whereas patients had poor knowledge (0%). Undergraduates were not aware about vaccines available against and availability in India, whereas post graduates and professionals were quite aware about it. Almost all participants showed acceptance for vaccination in context of understanding that it reduces the risk of oral and oropharyngeal cancer and not completely offer prevention. The study concludes that there is a general lack of knowledge about HPV, the HPV vaccine, and HPV-related oropharyngeal cancers (OPCs) among the population is western Tamil Nadu. Addressing the identified knowledge gaps in terms of Targeted educational interventions in dental curricula and public health campaigns can potentially enhance students' readiness to contribute to public health awareness and recommend HPV vaccination.
Perioperative immune checkpoint blockade is rapidly moving into routine care for resectable head and neck squamous cell carcinoma (HNSCC), making timing of surgery after neoadjuvant immunotherapy (NAI) and neoadjuvant immunochemotherapy (NAIC) increasingly important clinical question rather than a purely theoretical one. Yet the literature remains dominated by studies that report feasibility or absence of delay, not by evidence that defines an optimal interval from treatment completion to surgery. Both immune-only and chemoimmunotherapy regimens are addressed, as their timing implications differ. To synthesize the current evidence regarding surgery timing after neoadjuvant immunotherapy and immunochemotherapy in HNSCC, with dedicated attention to oral squamous cell carcinoma (OSCC), and to propose a practical research-informed framework for current clinical use. This focused narrative review used targeted searches of PubMed/MEDLINE, Google Scholar, and reference lists of relevant reviews and primary studies through April 30, 2026. Priority was given to publications that explicitly reported interval to surgery, surgical delay, perioperative feasibility, pathologic response, complications, or OSCC-specific timing considerations. Consensus documents were included only to contextualize procedural guidance and were not treated as comparative timing evidence. We did not identify a systematic review whose primary aim was to define the optimal timing of surgery after neoadjuvant immunochemotherapy in HNSCC or OSCC. Previous reviews consistently show that neoadjuvant immunotherapy or chemoimmunotherapy is generally feasible and usually does not cause major surgical delay. Across prospective studies, surgery was commonly scheduled within approximately 1 to 4 weeks after the last neoadjuvant treatment, although interval definitions were heterogeneous. OSCC studies tend to use shorter intervals, often around 1 to 3 weeks. The strongest timing-specific evidence currently comes from a 2026 HNSCC study showing that surgery performed more than 3 weeks after neoadjuvant immunochemotherapy was associated with lower pathologic response, higher complication risk, and shorter disease-free survival. However, this finding remains observational and requires prospective validation. Current evidence supports surgical feasibility after neoadjuvant immunotherapy and immunochemotherapy in HNSCC but does not establish a universally validated optimal interval. For many PD-1-based immunochemotherapy regimens, avoiding unnecessary delay beyond 3 weeks after treatment completion appears evidence-aligned when toxicity recovery, wound-healing considerations, and operative logistics permit, but this position remains provisional and requires prospective validation. Immune-only regimens may permit earlier surgery in selected patients, whereas anti-angiogenic combinations require regimen-specific washout and wound-healing considerations. Future trials should prespecify timing strata, standardize interval definitions, and integrate surgical, pathological, and oncologic endpoints.
To investigate the incidence, anatomical risk factors, and peri-operative determinants of surgical-site infection (SSI) after operative repair of maxillofacial fractures caused by E-scooter and E-bike trauma, a rapidly emerging cause of urban injuries. A retrospective cohort of 129 consecutive patients with micromobility-related facial fractures (2017-2022) was analyzed. Demographic, injury, operative, and pharmacologic variables were extracted from medical records. SSI was defined according to CDC/NHSN criteria and graded using the Clavien-Dindo classification. Comparative analyses employed Fisher's exact and Mann-Whitney U tests. SSI occurred in 3.1% (4/129; 95% CI 0.9-7.7%) of patients, all of whom were classified as Clavien-Dindo grade III and required reoperation or intravenous therapy. Infections were exclusively confined to sinus-bearing fractures (orbit, frontal, zygomatic), with significant clustering in orbital fractures (p = 0.023) and sparing of the mandible (p = 0.041). ORIF carried the highest burden, with an infection rate of 8.6%, while one case was managed with isolated soft-tissue repair. Neither operative duration, emergency status, steroids, nor antibiotic prophylaxis reduced the risk of infection. Infected patients had longer hospitalizations (7 vs. 5 days) and markedly prolonged surveillance periods (60 vs. 8 weeks; p = 0.053). Although uncommon, SSI in micromobility trauma occurs in 3.1% of patients and demonstrates an anatomical concentration within sinus-bearing fractures. These findings describe the occurrence and anatomical distribution of SSI within a micromobility-related facial trauma cohort and may inform future hypothesis-driven studies.
Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in the head and neck region. The standard therapeutic approach typically includes surgical intervention followed by adjuvant radiotherapy, which, although necessary, may significantly impair salivary gland function and disrupt redox homeostasis in the oral cavity. Aim: The aim of this study was to evaluate the effect of radiotherapy on the quantity and quality of saliva, assessed through salivary biomarkers FRAS, MDA, and SOD, in patients with oral squamous cell carcinoma who had undergone surgical treatment and subsequent head and neck radiotherapy. Materials and Methods: The study included 20 patients of both sexes, aged 41 to 76 years, who were surgically treated and subsequently underwent head and neck radiotherapy. Unstimulated saliva samples were collected at two time points: before and after completion of radiotherapy. Salivary flow rate was measured immediately after collection, and following sample processing, ferric reducing ability of saliva (FRAS), malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity were determined spectrophotometrically. Results: The salivary flow rate was significantly reduced after radiotherapy compared to the pre-treatment values. The post-radiotherapy FRAS levels were significantly lower, whereas MDA levels were significantly higher. SOD activity was slightly higher before radiotherapy compared to the post-radiotherapy values. Conclusion: Our findings confirm that radiotherapy is associated with increased oxidative stress and reduced antioxidant capacity in saliva. Although antioxidants may potentially mitigate radiotherapy-induced complications, their clinical application requires caution due to the possibility of protecting the tumor cells, thereby potentially compromising the oncologic treatment outcomes.
Breast cancer is one of the most common cancers among women, with improved therapies reducing mortality. Antiresorptive (AR) therapy is crucial for managing bone loss and skeletal complications in patients with cancer. However, high-dose AR therapy may carry a significant risk of medication-related osteonecrosis of the jaw (MRONJ). This study aimed to investigate the incidence of MRONJ and its risk factors in patients with diagnosed breast cancer undergoing either biannual postoperative bisphosphonate therapy or high-dose AR therapy. This study followed 220 female patients receiving AR therapy in Sweden, from 2015 to 2020. Oral health status was assessed before and during AR therapy, collecting data on MRONJ incidence, dental procedures, and data on breast cancer characteristics. Statistical analyses included Fisher's exact tests, and group differences in Kaplan-Meier curves were assessed using the log-rank test. p < 0.05 was considered statistically significant. The cohort comprised 119 patients on biannual AR therapy and 101 patients on high-dose AR therapy. Nine patients (4.0%) developed bone metastases and transitioned to high-dose AR therapy after a mean interval of 237 days; of these, 55.5% subsequently switched from bisphosphonates to denosumab. MRONJ cumulative incidence was 5.5% in the overall cohort and 11.9% in the high-dose group (p < 0.001); no MRONJ cases occurred in the biannual group. Tooth extractions (30.5%, p < 0.001), localisation to the mandible (83.3%, p = 0.039) and number of AR doses (p = 0.004) were significantly associated with the development of MRONJ. Notably, spontaneous MRONJ accounted for 41.7% of cases. Baseline DMFT did not differ, but MRONJ patients had a higher DMFT increment during follow-up. This study identifies a significant association between high-dose AR therapy and the development of MRONJ in breast cancer patients, with tooth extractions, mandibular localisation, and cumulative AR exposure identified as risk factors. MRONJ was not observed in the biannual AR therapy group. These findings underscore the importance of comprehensive dental assessments and early risk stratification.
Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic therapies, particularly following tooth extraction. Platelet-rich fibrin (PRF) has been proposed as a biologically active adjunct capable of enhancing tissue repair and potentially reducing the risk of MRONJ. This systematic review and meta-analysis evaluated the effectiveness of PRF in preventing MRONJ and improving postoperative healing in patients undergoing tooth extraction while receiving these medications. A comprehensive search of PubMed, EMBASE, and CENTRAL was conducted from inception to 1 June 2026. Studies comparing tooth extraction with PRF versus tooth extraction alone in patients receiving antiresorptive and/or antiangiogenic therapy were included. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. An exploratory subgroup analysis by PRF subtype (L-PRF versus A-PRF) was conducted for the healing outcome, and a sensitivity analysis restricted to studies with moderate risk of bias was performed for the MRONJ outcome. The certainty of evidence was assessed using the GRADE approach. The primary outcome was MRONJ occurrence, and the secondary outcome was postoperative healing. Seven studies were included in the qualitative synthesis, and seven contributed data to at least one meta-analysis. For MRONJ, six study cohorts involving 370 patients were analysed. PRF was associated with a significantly lower risk of MRONJ compared with extraction alone (RR = 0.29; 95% CI: 0.15-0.57; p = 0.0003; I² = 30%). A sensitivity analysis restricted to the two moderate-risk-of-bias studies yielded a consistent directional effect (RR = 0.13; 95% CI: 0.02-0.69; p = 0.02; I² = 0%), though based on very limited data. For postoperative healing, six studies involving 512 patients were included. PRF was associated with improved healing outcomes overall (RR = 1.31; 95% CI: 1.11-1.54; p = 0.001; I² = 69%). Subgroup analysis by PRF subtype demonstrated a significant effect for L-PRF (RR = 1.36; 95% CI: 1.07-1.73; p = 0.01; I² = 75%) but not for A-PRF (RR = 1.22; 95% CI: 0.99-1.52; p = 0.07; I² = 31%), with no statistically significant difference between subgroups (p = 0.51). The certainty of evidence was rated as Very Low for both outcomes according to GRADE. Current evidence suggests that adjunctive PRF may be associated with a reduced risk of MRONJ and improved healing following tooth extraction in patients receiving antiresorptive and/or antiangiogenic medications. However, these findings are based predominantly on observational studies with serious risk of bias and relatively small sample sizes, and the certainty of evidence is Very Low. Further well-designed randomised controlled trials are needed to confirm the magnitude and consistency of these potential benefits.
Artificial intelligence (AI) has emerged as a transformative tool in oral oncology, enabling earlier detection of oral potentially malignant disorders (OPMDs), prognostic modelling, and clinical decision support. This narrative review synthesizes the ethical, legal, and social implications (ELSI) of AI in oral oncology and highlights current evidence, regulatory frameworks, and governance practices. Literature and regulatory guidance (2018-2025) were reviewed, including WHO, FDA, EU AI Act, ADA guidelines, ISO/IEC standards, and systematic reviews in oral oncology. Key ethical issues include privacy, bias, and interpretability. Legal frameworks such as the EU AI Act and FDA guidance classify most AI medical tools as high-risk and subject them to lifecycle monitoring. Social considerations include equitable access, cultural factors, and trust-building. While AI can improve early oral cancer detection and outcomes, its safe and equitable deployment requires transparent governance, regulatory compliance, equity-focused design, and sustained human oversight.
Skin cancer is among the most common malignancies worldwide, mainly classified into malignant skin melanoma (MSM) and nonmelanoma skin cancer (NMSC). This study aimed to comprehensively analyze the global burden and temporal trends of skin cancer, focusing on the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Data on incidence, mortality, and disability-adjusted life years (DALYs) for skin cancer were obtained from the Global Burden of Disease 2021 database across 204 countries and territories. Both crude numbers and age-standardized rates (ASIR, ASMR, and ASDR) were analyzed. Temporal trends were evaluated using estimated annual percentage change, and autoregressive integrated moving average (ARIMA) models were applied to project age-standardized rates, rather than crude counts, through 2035. In 2021, there were 3,03,105 MSM cases, 18,99,907 squamous cell carcinoma cases, and 44,36,939 basal cell carcinoma cases globally. From 1990 to 2021, the global ASIR of MSM increased by 19.32% (95% UI: 13.60-23.62%), squamous cell carcinoma by 67.34% (95% UI: 42.13-95.42%), and basal cell carcinoma by 63.30% (95% UI: 52.54-77.53%). High-SDI regions showed the highest incidence levels, whereas middle-SDI regions bore relatively higher mortality and DALY burdens. Males consistently exhibited higher incidence, mortality, and DALYs than females, and the disease burden increased markedly with age, particularly among individuals aged ≥ 70 years. ARIMA projections suggest subtype-specific trends, with age-standardized incidence and DALY rates remaining stable or declining for most skin cancer subtypes through 2035. Significant regional disparities persist in the burden of skin cancer. While high-income regions report higher incidence, low-income regions face greater challenges in early detection and treatment. Strengthening UV protection awareness, promoting early screening, and improving healthcare access are essential to reduce the future global burden of skin cancer.
Acute mucositis and dermatitis frequently occur during radiotherapy for head and neck malignancies and can impair oral intake and quality of life (QOL). Nutritional supplementation using β-hydroxy-β-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) may support tissue repair and protein metabolism. This prospective single-arm exploratory study evaluated the feasibility of continuous oral HMB-Arg-Gln supplementation during carbon-ion radiotherapy (CIRT). Sixteen consecutive patients with head and neck tumors who underwent CIRT were enrolled. Patients received oral HMB-Arg-Gln supplementation twice daily from the start of CIRT until 2 weeks after treatment completion. The primary endpoint was feasibility, defined as completion of CIRT with continuous supplementation without grade ≥4 acute toxicity or the need for enteral or parenteral nutritional support. Acute mucositis and radiation dermatitis were graded weekly using Common Terminology Criteria for Adverse Events v4.03 and Radiation Therapy Oncology Group criteria. Health-related QOL was assessed using Short Form-8 (SF-8) questionnaires before CIRT, at completion of 16 fractions, and 2 months after treatment. All patients completed the CIRT course with supplementation, meeting the predefined feasibility criteria. No grade ≥4 acute toxicities occurred. Temporal mucositis and dermatitis patterns were consistent with those typically reported during radiotherapy, with peak severity near the end of treatment. SF-8 physical component summary scores had decreased at CIRT completion but had partially recovered by 2 months, whereas mental component summary scores remained relatively stable. Continuous oral HMB-Arg-Gln supplementation during CIRT for head and neck tumors was feasible and well tolerated. Treatment was completed without severe acute toxicity, and QOL was largely maintained during and after therapy. Nutritional supplementation may support patients undergoing particle therapy.
Reconstruction following tongue carcinoma resection is critical for restoring speech, swallowing, and overall quality of life. Among the available reconstructive options, the radial forearm free flap (RFF) and pectoralis major myocutaneous flap (PMMF) are commonly used techniques. However, uncertainty remains regarding their comparative effectiveness, particularly in hemi- and total glossectomy defects. To systematically evaluate and compare the effectiveness of RFF and PMMF in tongue cancer reconstruction with respect to functional outcomes, complications, and quality of life (QOL). This systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO. Electronic databases were searched till April 2025. Comparative studies evaluating RFF and PMMF in tongue carcinoma patients (T1-T4) were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random-effects model, with standardized mean difference (SMD) as the summary measure. Six retrospective studies comprising 380 patients were included for qualitative synthesis, and four studies were eligible for meta-analysis. Pooled analysis demonstrated a trend toward improved speech (SMD = 0.35) and swallowing outcomes (SMD = 0.18) in the RFF group, although statistical significance was not achieved. Combined speech and swallowing outcomes in hemi-glossectomy patients demonstrated a statistically significant trend favouring RFF (SMD = 1.63, p < 0.05); however, substantial heterogeneity among studies limits the reliability and generalizability of this finding. Complication rates, including dehiscence and fistula formation, were generally lower with RFF. Quality-of-life parameters also demonstrated favourable trends in the RFF group. Also, as fewer studies were included, funnel plot assessment is underpowered, and publication bias could not be reliably determined. RFF showed a trend toward improved functional outcomes and lower complication rates compared with PMMF, particularly in hemi-glossectomy defects; however, several pooled outcomes did not achieve statistical significance. Flap selection should consider tumor extent, patient comorbidities, and anticipated adjuvant therapy. High-quality prospective studies are required to strengthen the current evidence base. The online version contains supplementary material available at 10.1007/s12663-026-03123-4.
It has previously been demonstrated that the nuclear factor of activated T cells (NFAT) is crucial for the development of tumors. Given OSCC's drug resistance and poor outcomes, identifying NFAT-associated prognostic genes is urgent for better treatment. The TCGA-OSCC and GSE41613 datasets were utilized to identify differentially expressed genes (DEGs) between oral squamous cell carcinoma (OSCC) and controls. Specifically, differentially expressed genes related to NFAT (DEG-NFATs) were further screened for NFAT scores in OSCC versus control. The intersection of DEGs and DEG-NFATs was taken to identify differentially expressed NFAT-related genes (DE-NFATRGs). Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were employed to identify prognostic genes. A risk score was developed based solely on the expression levels of the seven-gene signature. Subsequently, independent prognostic analyses incorporating clinicopathological variables were performed using univariate and multivariate Cox regression to evaluate whether the risk score served as an independent predictor of survival. Lastly, targeted therapeutic agents for OSCC were predicted. In addition, prognostic gene expression was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Totally 4463 DEGs obtained were intersected with 310 DEG-NFATs to obtain 263 DE-NFATRGs. A risk model can be built using the seven prognostic genes associated with NFAT (ALB, PDK4, SERPINA5, SPINK6, SERPINA9, CGNL1 and IL17F). The risk score accurately predicts survival in OSCC patients. Finally, a total of 31 drugs with significant differences were predicted between risk groups. The most significant of these were AG.014699, Midostaurin, Gefitinib, and LFM.A13. Besides, the expression levels of ALB, PDK4, and SERPINA5 were significantly higher in tumors, while the expression levels of CGNL1 and IL17F were significantly lower in tumors. The identification of new prognostic genes (ALB, PDK4, SERPINA5, SPINK6, SERPINA9, CGNL1, and IL17F) was provided for the prognosis and treatment of OSCC.
Radiotherapy for head and neck cancer frequently results in radiation-induced xerostomia, a chronic symptom that can persist long-term and compromise oral function and survivorship. A cross-sectional, non-interventional survey was conducted using a mixed recruitment approach (department-based and nationwide online dissemination). Xerostomia prevalence, symptom characteristics, coping strategies, and oral health-related quality of life (OHRQoL) were assessed using a study-specific xerostomia questionnaire and the validated OHIP-G14 instrument. Overall, 253 questionnaires were returned (202 complete and 51 partial), including 163 completed online via LimeSurvey and 39 completed on paper during routine follow-up visits at the tumour clinic of the department. Xerostomia was reported by 90% of respondents; 53.1% described the daily burden as strong/very strong. Patients with xerostomia had significantly worse OHRQoL than those without (mean OHIP-G14 26.7 vs. 17.3; p < 0.001), corresponding to a clinically relevant mean difference of 9.4 points. In multivariable linear regression, xerostomia remained independently associated with worse OHRQoL (B = 8.86, p < 0.001). Functional impairment and oral pain were more pronounced than psychosocial or aesthetic domains, and perceived xerostomia severity correlated with OHIP scores. Commonly used coping strategies included frequent water intake (81%), sugar-free gum/lozenges (46%), saliva substitutes (43%), and home remedies (e.g., oil or tea) (33%); prescription sialogogues were infrequently used (15%) and perceived as less effective. Post-radiotherapy xerostomia is highly prevalent and independently associated with clinically meaningful OHRQoL impairment, underscoring the need for optimized counselling and structured supportive care. Management was dominated by low-threshold behavioural strategies, while prescription sialogogues were used by only a minority of respondents and were rated less effective in terms of perceived benefit.
The global incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, and the failure rate of current treatments remains substantially high. Therefore, there is an urgent need to find effective targets and formulate precise personalized treatment strategies. HNSCC is characterized by an immunosuppressive environment, and the accumulation of senescent cells can promote aging by reshaping immune system function. However, in the context of HNSCC, the understanding of aging-related immunosuppressive genes (ARIS) remains limited. In this study, we identified 13 prognosis-associated ARIS and, using machine learning, pinpointed Fibroblast Activation Protein (FAP) as a key ARIS. In vitro experiments confirmed functional inhibition of FAP via siRNA-mediated silencing and pharmacological blockade with UMAC-1110 significantly suppressed the proliferation, migration, and invasion of CAL-27 cells. Furthermore, FAP was predominantly enriched in the FAP-positive myofibroblastic cancer-associated fibroblast (FAP + myCAF) subpopulation and was associated with altered inferred FAP + myCAF-neutrophil communication, consistent with a potential contribution to an immunosuppressive tumor microenvironment (TME). We subsequently performed in silico knockout analyses in FAP + myCAFs and constructed a FAP-centered regulatory network, thereby identifying candidate FAP-associated signaling modules for further functional validation. Notably, FAP expression increased following anti-programmed death-ligand 1 (PD-L1) treatment. We also identified three FAP targeting inhibitors, Pazopanib, Talazoparib and Ursodiol. And Pazopanib that exhibited a more stable binding affinity with FAP was selected for further in vitro validation. Collectively, these findings may offer new avenues for clinical intervention and precision therapy in HNSCC.
Achieving profound local anesthesia during mandibular third molar extraction can be challenging because of dense cortical bone and anatomical variations. Articaine has gained increasing attention due to its superior tissue penetration, faster onset, and longer duration of action, but concerns regarding its potential neurotoxic effects when used in mandibular nerve blocks, remain controversial. Fifty patients aged 18-60 years were enrolled following strict inclusion and exclusion criteria, ensuring the absence of radiographic proximity of the third molar to the inferior alveolar nerve and the absence of periapical pathology. Clinical parameters, including onset and duration of anesthesia, intra-operative pain assessed using the Visual Analog Scale (VAS), and postoperative neurosensory responses, were evaluated using standardized tests (brush stroke directional discrimination, two-point discrimination, and pin-prick nociception) on days 1, 3, and 5 post-operatively. The mean onset and duration of anesthesia were 1.30 ± 0.33 min and 4.22 ± 1.09 h, respectively, and the mean intra-operative pain score was 1.10 ± 0.78. No neurosensory deficits were observed during the 5-day follow-up period; however, long-term complications cannot be excluded. Within the limitations of this single-arm study without a comparator group and involving low-risk, non-surgical extractions, 4% Articaine with 1:100,000 epinephrine demonstrated effective anesthesia with no clinically detectable neurosensory impairment.
Kinesio taping is a simple, non-invasive technique that may reduce postoperative discomfort. This study aimed to evaluate the effectiveness of Kinesio taping in reducing pain, swelling, and trismus after mandibular third molar surgery. A split-mouth, randomized, placebo-controlled clinical trial was conducted involving 17 patients requiring bilateral mandibular third molar surgery. Kinesio tape was applied to one surgical side, while placebo tape was applied to the contralateral side. Postoperative pain was assessed using a 10-point Visual Analog Scale (VAS), facial swelling was measured using predefined anatomical landmarks, and mouth opening was evaluated by measuring the interincisal distance. Data were collected preoperatively and on postoperative days 1, 2, and 3. The Kinesio group showed significantly lower pain intensity and greater mouth opening at all postoperative time points compared with the control group. Vertical and oblique facial swelling were significantly lower at most early postoperative time points, whereas no significant differences were observed for horizontal swelling at any time point. Kinesio taping may help reduce early postoperative pain, swelling, and trismus after mandibular third molar surgery. However, these findings are limited to short-term outcomes and should be further validated in larger multicenter studies. The study was registered at ClinicalTrials.gov (NCT06967246). The online version contains supplementary material available at 10.1007/s12663-026-03156-9.
Orofacial clefts (OFCs) are common congenital anomalies with substantial health and social consequences, particularly where access to surgery and longitudinal care is limited. Burden varies across regions and socioeconomic strata. Using Global Burden of Disease 2021 estimates, we analyzed OFC incidence, prevalence, mortality, years of life lost, years lived with disability, and disability-adjusted life years (DALYs) from 1990 to 2021 at global, regional, and national levels. Analyses were stratified by Socio-demographic Index (SDI) quintiles and World Bank regions. We applied autoregressive integrated moving average models to project prevalence and DALY trends to 2035. In 2021, OFCs affected an estimated 4.12 million individuals worldwide, with an age-standardized DALY rate of 5.18 per 100,000 population. The highest burdens were observed in Oceania, Western sub-Saharan Africa, and South Asia - regions predominantly in the lower SDI strata. Projections indicate gradual global reductions in prevalence and DALY rates through 2035; however, declines are expected to proceed more slowly in high-SDI regions than in low-SDI regions. OFCs remain a notable global health burden with marked geographic and socioeconomic disparities. Priorities include expanding access to timely surgical repair and multidisciplinary follow-up, strengthening public health outreach, and embedding psychosocial support - particularly in low-SDI settings.