Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Objective:To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN).Methods:A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ 2 test was used for difference analysis. Results:Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions:The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient′s occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

The RASopathies are a group of syndromes that have in common germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway and have been a focus of study to understand the role of this pathway in development and disease. These syndromes include Noonan syndrome (NS), NS with multiple lentigines (NSML), neu-rofibromatosis type 1 (NF1), Costello syndrome (CS), cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type 1-like syndrome (NFLS) and capillary malformation-arteriovenous malformation syndrome (CM-AVM). These disorders affect multiple systems, including the craniofacial complex. Although the crani-ofacial features have been well described and can aid in clinical diagnosis, the dental phenotypes have not been analysed in detail for each of the RASopathies. In this review, we summarize the clinical features of the RASopathies, highlighting the reported craniofacial and dental findings.