New perspectives in the differential diagnosis of jaw lesions: Machine learning and inflammatory biomarkers.

This study aimed to assess the diagnostic performance of a machine learning approach that utilized radiomic features extracted from Cone Beam Computer Tomography (CBCT) images and inflammatory biomarkers for distinguishing between Dentigerous Cysts (DCs), Odontogenic Keratocysts (OKCs), and Unicystic Ameloblastomas (UAs). This retrospective study involves 103 patients who underwent jaw lesion surgery in the Maxillofacial Surgery Unit of Federico II University Of Naples between January 2018 and January 2023. Nonparametric Wilcoxon-Mann-Whitney and Kruskal Wallis tests were used for continuous variables. Linear and non-logistic regression models (LRM and NLRM) were employed, along with machine learning techniques such as decision tree (DT), k-nearest neighbor (KNN), and support vector machine (SVM), to predict the outcomes. When individual inflammatory biomarkers were considered alone, their ability to differentiate between OKCs, UAs, and DCs was below 50 % accuracy. However, a linear regression model combining four inflammatory biomarkers achieved an accuracy of 95 % and an AUC of 0.96. The accuracy of single radiomics predictors was lower than that of inflammatory biomarkers, with an AUC of 0.83. The Fine Tree model, utilizing NLR, SII, and one radiomic feature, achieved an accuracy of 94.3 % (AUC = 0.95) on the training and testing sets, and a validation set accuracy of 100 %. The Fine Tree model demonstrated the capability to discriminate between OKCs, UAs, and DCs. However, the LRM utilizing four inflammatory biomarkers proved to be the most effective algorithm for distinguishing between OKCs, UAs, and DCs.

Reliability of magnetic resonance for temporomandibular joint disc perforation: A 12 years retrospective study.

The aim of this study was to evaluate the reliability of magnetic resonance imaging (MRI) in detecting disc perforations in the temporomandibular joint (TMJ), and to establish diagnostic criteria for this purpose. The retrospective analysis included patients who had undergone preoperative MRI and TMJ arthroscopy at the same hospital. Direct and indirect signs of disc abnormalities on MRI were compared with arthroscopic findings of disc perforation. Out of 355 joints evaluated in 185 patients, arthroscopy confirmed disc perforations in 14.7% of cases. Several MRI findings were significantly associated with disc perforation, including anterior disc displacement without reduction (ADDwoR), signal alterations in the mid-disc area, disc deformity (SAMD), retrocondylar disc fragments, osteophytes, condylar bone marrow degeneration (CBMD), and joint effusion in both joint spaces (ESJS-EIJS). Regression analysis revealed that SAMD, osteophytes, and CBDM were strongly associated with disc perforation. The ROC curve showed that MRI had an AUC = 0.791, with a sensitivity of 88.5% and a specificity of 61.5%. Two diagnostic methods, one based on three findings (osteophytes, ADDwoR, and SAMD) and one based on two direct signs (ADDwoR and SAMD), yielded high sensitivity and specificity values of 80.4% and 69.8%, and 84.3% and 62.5%, respectively. In conclusion, MRI demonstrated acceptable accuracy in the detection of TMJ disc perforations, with specific diagnostic criteria offering high sensitivity and specificity. Significant MRI indicators of disc perforation included SAMD, osteophytes, and CBDM. This study provides valuable information on the use of MRI as a diagnostic tool for TMJ disc perforations.

Epidemiological analysis of patients with isolated blowout fractures of orbital floor: Correlation between demographic characteristics and fracture area.

Isolated orbital floor fractures are more frequent due to low bone thickness (2 mm). The aim of this study was to conduct a retrospective epidemiological analysis on these fractures, investigating demographic variables and fractures' features and their statistical correlation. A total of 120 patients with isolated orbital floor fracture, admitted at the Maxillofacial Surgery Unit of University of Naples Federico II, from 2010 to 2022 were enrolled in the study. Patients were evaluated for age, sex, smoke, comorbidities, post-traumatic clinical manifestation,s and defect side and size. Statistical analysis was conducted using the Pearson regression coefficient (r). The fractures were more frequent in men (male:female 2.2:1) because of road accidents (30% of cases). The average age was 48 years. Enophthalmos, diplopia and ocular motility anomalies were observed in 31%, 23% and 21% of cases, respectively. Statistical analysis revealed that age was related to fracture area; in particular, older patients showed larger fractures (p < 0.001). Interpersonal violence and traffic accidents were related to younger age (p < 0.001). Data analysis revealed that isolated orbital floor fractures are more frequent in young men (<40 years) because of road accidents or interpersonal violence. There is a statistical correlation between fracture area and patient age; in particular, older age corresponds to larger defects.

Unveiling the modulation of Pseudomonas aeruginosa virulence and biofilm formation by selective histone deacetylase 6 inhibitors.

Bacterial infections represent a key public health issue due to the occurrence of multidrug-resistant bacteria. Recently, the amount of data supporting the dynamic control of epigenetic pathways by environmental cues has triggered research efforts toward the clarification of their role in microbial infections. Among protein post-translational modifications, reversible acetylation is the most implicated in the feedback to environmental stimuli and in cellular homeostasis. Accordingly, the latest studies identified the histone deacetylase 6 (HDAC6) enzyme as a crucial player in the complex molecular machinery underlying bacterial clearance or killing. A very important milestone for the elucidation of the consequence of HDAC6 activity in bacterial infections is herein described, unveiling for the first time the role of a potent HDAC6 inhibitor in interfering with biofilm formation and modulating virulence factors of P. aeruginosa. We demonstrated that compound F2F-2020202 affected the production of some important virulence factors in P. aeruginosa, namely pyocyanin and rhamnolipids, clearly impairing its ability to form biofilm. Furthermore, evidence of possible QS involvement is supported by differential regulation of specific genes, namely RhlI, phAz1, and qsrO. The data herein obtained also complement and in part explain our previous results with selective HDAC6 inhibitors able to reduce inflammation and bacterial load in chronic infection models recapitulating the cystic fibrosis (CF) phenotype. This study fosters future in-depth investigation to allow the complete elucidation of the molecular mechanisms underlying HDAC6's role in bacterial infections.

Central giant cell granuloma: Off-label treatment with Denosumab in a patient with Noonan syndrome.

This study aims to describe the utilization of Denosumabࣨ, a human monoclonal antibody against the RANK-L receptor, in a mandibular giant cell granuloma (GCG) with a significant local aggressiveness component that was unresponsive to surgical treatment. We present a case of a 19-year-old male patient diagnosed with Noonan syndrome, who presented a multifocal giant cell granuloma with aggressive behaviour resistant to surgical treatment. Due to the functional and aesthetic implications associated with a surgical procedure, a decision was made to initiate medical treatment using Denosumabࣨ. Throughout the treatment, the patient presented excellent clinical and analytical tolerance, with no reported adverse effects. Surgical intervention remains the preferred approach for GCG. Denosumabࣨ emerges as an alternative, either as neoadjuvant treatment or as definitive therapy for unresectable or resectable tumors associated with significant morbidity. It leads to size stabilization and regression of the tumour stage.

Impact of Sarcopenia on Survival of Patients With Malignant Salivary Glands Tumors.

OBJECTIVE: Malignant salivary glands tumors (MSGTs) are a quite rare and heterogeneous group of tumors. Management of these lesions remains controversial and challenging. Thus, finding new prognostic factors that can help to guide the decision-making process, appears to be paramount. The aim of this study was to evaluate the prognostic performance of preoperative sarcopenia to stratify MSGTs patients at high risk of disease progression. STUDY DESIGN: Retrospective study. SETTING: A single-institution analysis (Maxillo-facial Surgery Unit, University of Naples Federico II). METHODS: The study consists of a retrospective analysis of 74 patients surgically treated for MSGTs. For all patients, the skeletal muscle index (SMI) was calculated and sarcopenia was defined as SMI < 41 in females and <43 in males. The correlation between sarcopenia and tumor variables was analyzed. The prognostic performance of sarcopenia was evaluated through survival Kaplan-Meier curves. RESULTS: Sarcopenia resulted statistically related to age (P < .001), tumor size (P < .001), lymph node metastases (P < .001), and American Joint Committee on Cancer tumor, node, metastasis stage (P < .001). Kaplan-Meier survival curves show that 47.3% of sarcopenic patients died before their final follow-up. CONCLUSION: Data obtained from our study seem to confirm the correlation between sarcopenia and other high-risk features. The early detection of sarcopenia in patients with negative prognostic factors could be used to implement the support therapeutic strategies aimed at restore the clinical conditions of the patients. Sarcopenia may be routinely investigated before surgery to suggest the implementation of precautionary therapeutic strategies to improve the standard treatment response, reducing possible complications.

Submental intubation in complex maxillofacial trauma: Pilot balloon protection.

AIMS: This study aims to describe our refined technique of submental intubation to avoid the recorded intraoperative complications related to tube passage and pilot balloon rupture. CASE SERIES: This is a retrospective case series of 21 patients with complex maxillofacial trauma who underwent submental intubation from January 2019 to January 2023. All the patients underwent to the same procedure with a new technique of pilot balloon protection: the pilot balloon was not deflated because, once the connector was removed, only the tube was curved and passed through the incision extraorally while the cuff remained inflated. The wire of the pilot balloon was passed behind the last tooth so as not to interfere with the maxillary-mandibular fixation, remaining extraorally under the anesthetist's view. DISCUSSION: Only 2 patients (9.5%) reported complications related to submental intubation: in particular a patient (4.8%) reported oral floor infection, and in another patient (4.8%) an unesthetic skin scar was observed. No patients reported intraoperative complications related to the procedure. CONCLUSION: The technique of pilot balloon protection that we have proposed seems to be effective in reducing the intraoperative complications related to the passage of the pilot balloon, such as rupture, damage or early extubation.

Is There a Correlation between Endoscopic Sinus Surgery and Improvement in Erectile Dysfunction?

BACKGROUND: In recent years, the focus on respiratory disorders has increased, notably on chronic rhinosinusitis (CRS), an inflammatory condition of the upper airway that can significantly impact one's quality of life. Interestingly, CRS has emerged as a potential comorbidity in erectile dysfunction (ED). This study aims to assess the impact of endoscopic sinus surgery for CRS on sexual function. MATERIALS AND METHODS: The authors conducted a prospective study of patients who visited their clinics for chronic rhinosinusitis between June 2018 and June 2022. The study involved 53 patients aged between 40 and 70 years who were treated for CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Preoperative and postoperative assessments were performed using the Nasal Obstruction Symptoms Evaluation Score (NOSE score) and the 5th International Index of Erectile Function Score (IIEF-5 score) to evaluate potential improvements in sexual function following endoscopic sinus surgery. RESULTS: Before surgery, the average NOSE score was 72.6, which decreased to 24.9 postoperatively. The average preoperative IIEF-5 score was 16.35, while the postoperative average increased to 19.52. Statistical analysis revealed a significant improvement in erectile function for penetration (p-value = 0.024) and overall satisfaction after intercourse (p-value < 0.001) regarding the degree of nasal obstruction. CONCLUSION: This study underscores the potential benefits of treating chronic obstructive upper airway diseases such as sinusitis in improving the sexual outcomes of patients clinically diagnosed with erectile dysfunction.

Diagnostic performance of inflammatory biomarkers and cytological analysis in salivary gland tumors.

BACKGROUND: This study aimed to evaluate the diagnostic performance of serum inflammatory biomarkers in salivary gland tumors with dubious results following cytological analysis. METHODS: A retrospective analysis of 239 cases following surgery between January 2011 and June 2022 was performed. Receiver Operating Characteristic curves were drawn and areas under the curves were computed to evaluate the diagnostic performance of the inflammatory biomarkers (SII, SIRI, PLR, and NLR). Optimal cut-offs for each marker were determined by maximizing the Youden index. RESULTS: Analysis showed that among the major biomarkers examined, SIRI performed an AUC of 0.77. The best SIRI cut-off was 0.94 with an accuracy of 79.9%. The accuracy, sensitivity, and specificity of cytological analysis were 77.8%, 59.6%, and 90.7% respectively. By combining SIRI with cytological analysis we demonstrated an increase in sensitivity to 82.8%. CONCLUSIONS: Inflammatory biomarkers could be evaluated to support the diagnosis and treatment of salivary gland tumors in difficult cases.

Minimally Invasive Harvesting Technique for Costal Cartilage Graft: Donor Site, Morbidity and Aesthetic Outcomes.

Cartilage grafts are well-known as being reliable in reconstructive surgery for craniofacial pathologies. The aim of this study is to describe a new technique which requires an incision smaller than 1.5 cm but is still effective for harvesting cartilage graft. Thirty-six patients who underwent costal cartilage harvesting for septorhinoplasty have been included in this study, admitted from January 2018 to December 2021. Out of 36 patients, 34 have not reported any major complications, and two cases were followed up for pneumothorax. There were no infections and no chest wall deformities. All patients reported minimal pain at the donor site. The Vancouver Scar Scale was used to evaluate the entity of the postoperative scarring phenomena. This scale total ranges from 0 (representing normal skin) to a maximum score of 13 (representing worst scar imaginable). The results were 1.53 SD ± 0.64 (on average) 1 week after the surgical procedure and 1.28 SD ± 0.45 (on average) at the 6 months follow-up. This minimally invasive method provided a valid and effective surgical technique for cartilage graft. Despite the limitations of the case series, it seems that this procedure might be comparable to other and well-established traditional procedures and could be even preferred when the minimal invasiveness is mandatory.

Support Tools in the Differential Diagnosis of Salivary Gland Tumors through Inflammatory Biomarkers and Radiomics Metrics: A Preliminary Study.

BACKGROUND: The purpose of this study was to investigate how the systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), and radiomic metrics (quantitative descriptors of image content) extracted from MRI sequences by machine learning increase the efficacy of proper presurgical differentiation between benign and malignant salivary gland tumors. METHODS: A retrospective study of 117 patients with salivary gland tumors was conducted between January 2015 and November 2022. Univariate analyses with nonparametric tests and multivariate analyses with machine learning approaches were used. RESULTS: Inflammatory biomarkers showed statistically significant differences (p < 0.05) in the Kruskal-Wallis test based on median values in discriminating Warthin tumors from pleomorphic adenoma and malignancies. The accuracy of NLR, PLR, SII, and SIRI was 0.88, 0.74, 0.76, and 0.83, respectively. Analysis of radiomic metrics to discriminate Warthin tumors from pleomorphic adenoma and malignancies showed statistically significant differences (p < 0.05) in nine radiomic features. The best multivariate analysis result was obtained from an SVM model with 86% accuracy, 68% sensitivity, and 91% specificity for six features. CONCLUSIONS: Inflammatory biomarkers and radiomic features can comparably support a pre-surgical differential diagnosis.

Facial soft tissue thickness measurement method and relationship with BMI, age and sex.

INTRODUCTION: Facial aesthetics results from the harmony of various components of the craniofacial region, a structure whose physiognomy and topography are determined by a set of hard and soft tissues. Few works in the literature have investigated the relationship between the variables of sex, age, BMI and soft tissue thickness and have considered how these variables may influence operative outcomes. The purpose of this study is to increase the pre-operative knowledge of the thickness of the soft tissues of the face through an analysis of their measurement conducted on cone beam computed tomography (CBCT) and to investigate the impact that the variables of gender, age and BMI have on their determination. MATERIALS AND METHODS: For this study 82 patients were recruited between January 2020 and January 2021 in the Department of Maxillofacial Surgery of the University of Naples "Federico II". A descriptive analysis of the sample was carried out on the selected sample, calculating averages and standard deviations for the individual variables analyzed. RESULTS: BMI has a predominant role on some craniometric points while age and sex have a more marginal role. Our analysis shows that some points are affected by only one variable, BMI (G' N' PR' ID' SM' GN' PG' MIO' ACP' GO' ZY' SC' IC' ECMS' and MMB'); some points are affected by both BMI and gender (MP' and MR'); while only two (RHI' and MSO') are influenced by all the three variables. CONCLUSION: A priori knowledge through CBCT of the thickness of the soft tissues of the face and a comparison with the data we propose could provide the surgeon with advance notice of the characteristics of the tissues which she/he will encounter.

Management of Orbital Floor Fractures: Our Experience in 10 Years.

Purpose: Orbital floor Fractures are the most common fractures involving the facial skeleton and usually occurs after traumatic events. The reconstruction of the orbital floor can be performed with different biocompatible materials. The aim of our retrospective study is to analyze the short- and long-term outcomes of surgically treated patients based on the material used to repair the orbital floor. Methods: We enrolled 146 patients hospitalized for orbital floor fractures in the Maxillofacial Surgery Unit of the Federico II University of Naples from 1 to 2010 to July 2020. All the fractured orbital floors were reconstructed with non-resorbable (Titanium Mesh, SynPor, SuPor and MedPor implants) or resorbable (collagen membrane, bovinum pericardium membrane, autologous bone graft) materials. Results: We utilized non-resorbable materials in 56% (82 cases) and resorbable implants in 44% (64 cases). An improvement of the preoperative symptomatology and an aesthetical good outcome was achieved in most cases. Conclusions: Data obtained supports that both resorbable and non-resorbable materials for orbital floor reconstruction are a safe and effective alternatives and offer satisfactory results in functional and aesthetic evaluations.

The Combination of Inflammatory Biomarkers as Prognostic Indicator in Salivary Gland Malignancy.

Background: The aim of this study was to investigate how the systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), taken individually and combined, are associated with overall survival (OS) in patients surgically treated for malignant salivary gland tumors (MSGTs). Methods: A retrospective analysis of 74 cases following surgery at our department between January 2011 and June 2018 was performed. The Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR. Survival curves of different groups at 1−3−5 years were estimated using the Kaplan−Meier method. Results: The optimal thresholds with the highest sensitivity and specificity were 3.95 for NLR, 187.6 for PLR, 917.585 for SII, and 2.045 for SIRI. The ROC curves revealed that the best combination with AUC = 0.884 was SII + SIRI. The estimated 5-year OS probability in patients with SII+ SIRI scores of 0, 1, and 2 was 96%, 87.5% and 12.5%, respectively (p < 0.001). Conclusion: SII+ SIRI can independently predict the OS of patients after MSGT surgery. The prognostic score system based on SII+ SIRI may be good clinical practice as a reference for clinical decision-making.

Efficacy of selective histone deacetylase 6 inhibition in mouse models of Pseudomonas aeruginosa infection: A new glimpse for reducing inflammation and infection in cystic fibrosis.

The latest studies identified the histone deacetylase (HDAC) class of enzymes as strategic components of the complex molecular machinery underlying inflammation in cystic fibrosis (CF). Compelling new support has been provided for HDAC6 isoform as a key player in the generation of the dysregulated proinflammatory phenotype in CF, as well as in the immune response to the persistent bacterial infection accompanying CF patients. We herein provide in vivo proof-of-concept (PoC) of the efficacy of selective HDAC6 inhibition in contrasting the pro-inflammatory phenotype in a mouse model of chronic P. aeruginosa respiratory infection. Upon careful selection and in-house re-profiling (in vitro and cell-based assessment of acetylated tubulin level through Western blot analysis) of three potent and selective HDAC6 inhibitors as putative candidates for the PoC, we engaged the best performing compound 2 for pre-clinical studies. Compound 2 demonstrated no toxicity and robust anti-inflammatory profile in a mouse model of chronic P. aeruginosa respiratory infection upon repeated aerosol administration. A significant reduction of leukocyte recruitment in the airways, in particular neutrophils, was observed in compound 2-treated mice in comparison with the vehicle; moreover, quantitative immunoassays confirmed a significant reduction of chemokines and cytokines in lung homogenate. This effect was also associated with a modest reduced bacterial load after compound 2-treatment in mice compared to the vehicle. Our study is of particular significance since it demonstrates for the first time the utility of selective drug-like HDAC6 inhibitors in a relevant in vivo model of chronic P. aeruginosa infection, thus supporting their potential application for reverting CF phenotype.

Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology.

Compelling new support has been provided for histone deacetylase isoform 6 (HDAC6) as a common thread in the generation of the dysregulated proinflammatory and fibrotic phenotype in cystic fibrosis (CF). HDAC6 also plays a crucial role in bacterial clearance or killing as a direct consequence of its effects on CF immune responses. Inhibiting HDAC6 functions thus eventually represents an innovative and effective strategy to tackle multiple aspects of CF-associated lung disease. In this Perspective, we not only showcase the latest evidence linking HDAC(6) activity and expression with CF phenotype but also track the new dawn of HDAC(6) modulators in CF and explore potentialities and future perspectives in the field.