Expression Analysis of Circulating microRNAs in Saliva and Plasma for the Identification of Clinically Relevant Biomarkers for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs.

Surgical outcomes of profunda artery perforator flap in head and neck reconstruction: A systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the efficacy of the profunda artery perforator (PAP) flap in head and neck reconstruction. METHODS: A single arm meta-analysis was performed for flap survival rate (primary outcome), reoperation for major complication, and overall complication rates (secondary outcomes). RESULTS: The search strategy yielded a total of 295 potentially relevant publications, of which 13 were included. A total of 305 patients (males: 80.8%, n = 232/281), with a median age of 56.1 years (n = 305/305; 95% CI 53.9-63), who underwent a total of 307 PAP flap reconstructions for head and neck defects were included. Flap survival rate was 100% (n = 306/307; 95% CI 99.6%-100%), with a reoperation rate for major complications of 3.7% (n = 15/307; 95% CI 1.85%-6.1%) and an overall complication rate of 26.5% (n = 92/307; 95% CI 15.7%-38.9%). Notable postoperative complications included wound dehiscence (n = 15/307, 4.9%), delayed healing (n = 14/307, 4.6%), and wound infection (n = 12/307, 3.9%). Partial flap necrosis and hematoma occurred in 2.6% of cases (n = 8/307), while arterial and venous thrombosis were documented in 0.7% (n = 2/307) and 1.3%, respectively (n = 4/307). CONCLUSION: The application of the PAP flap in head and neck reconstructions showed several favorable aspects, such as an exceptionally low flap failure rate, versatility in achieving variable dimensions, and a relatively low incidence of complications. PAP flap might be considered as a compelling alternative to the traditionally employed soft tissue free flaps in head and neck reconstruction.

The role of CD73 in predicting the response to immunotherapy in head and neck cancer patients.

Immunotherapy has a crucial role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a small percentage of patients achieve long-term benefit in terms of overall response and survival. It was shown that HNSCC has an immunosuppressive microenvironment due to high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. The aim of our study was to investigate if the expression of CD73 by neoplastic and immune cells could affect the efficacy of anti-PD-1 immunotherapy. We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We analysed the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. In 88 % of patients the primary tumour site was in the oral cavity or larynx. All patients received pembrolizumab associated in 40 % of cases to chemotherapy. CD73 was positive in 82 % and 96 % of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32 % for neoplastic cells and 10 % for the immune ones. We observed a significant association between the CD73 expression on neoplastic cells over the median value and EP disease. We didn't record a correlation between the expression of CD73 on immune cells and early progression. Our findings suggest that higher expression of CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select the patients primary resistant to anti-PD-1 immunotherapy.

Peri-implant diseases and systemic inflammation: A preliminary analysis from a cross-sectional survey of patients with hypertension.

BACKGROUND: The aim of this study was to investigate the association between peri-implant diseases and systemic inflammation assessed by serum C-reactive protein (CRP) levels in a sample of patients with hypertension. METHODS: A total of 151 participants with hypertension were included in a cross-sectional study. The population was divided into six groups according to their peri-implant and periodontal status (healthy controls, mucositis, peri-implantitis, periodontitis, periodontitis and mucositis, periodontitis, and peri-implantitis). Linear, logistic regression, and correlation analyses were performed. RESULTS: CRP levels were statistically significantly higher in participants with periodontitis alone (median 3.2 mg/L, interquartile range [IQR] 1.8, p = 0.012), combined with mucositis (3.10 mg/L, IQR 2.35, p < 0.001) or peri-implantitis (2.7 mg/L, IQR 2.53, p = 0.002) when compared to the healthy controls (1 mg/L, IQR 1.2). This association was independent of age, sex, smoking status, and adiposity differences. Participants with periodontitis with and without peri-implant diseases had the greatest odds of exhibiting CRP > 3 mg/L (odds ratio = 7.3, 95% confidence interval 1.6-33.9). CONCLUSIONS: Peri-implant diseases are associated with systemic inflammation, but the nature of the association should be further investigated.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

Nerve Growth Factor and the Role of Inflammation in Tumor Development.

Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

Computer-guided miniscrew insertion in the paramedian and parapalatal area of the palatal vault: low failure rate and no learning curve required to obtain predictable results?

AIM: To evaluate the failure rate of palatal computer-guided miniscrews, placed in paramedian and parapalatal regions for orthodontic purposes. In addition, to investigate the presence of a learning curve using computer guided miniscrew insertion, and to evaluate the peri-implant soft tissues response at 2-, 6- and 12- month follow-ups. MATERIALS AND METHODS: 202 palatal computer-guided miniscrews were inserted in 78 subjects for orthodontic purposes. A surgical guide was designed after planning the appropriate insertion sites on three-dimensional images created by the fusion of cone-beam computed tomography (CBCT) and digital dental model images. The devices were disassembled monthly to perform the percussion test and to evaluate the mobility of each miniscrew. To determine the presence of a learning curve, the time of miniscrew failures and the number of surgeries were evaluated. Bleeding on probing (BOP) and probing pocket depth (PPD) were recorded for each miniscrew, at 2- (T0), 6- (T1), and 12-month follow ups (T2). RESULTS: An immediate failure rate of 4.95%, due to lack of primary stability immediately following miniscrew insertion, was recorded, with statistically significant higher failure rate of parapalatal miniscrews (P= 0.00). Miniscrew failure occurred at random time, with an absence of a learning curve. The BOP (mean: 3.13%) and PPD (mean: 1.68mm) measurements remained stable over time. CONCLUSIONS: Computer-guided miniscrew insertion in the palatal vault showed a low failure rate without a determined learning curve to obtain predictable results and with long-term stability of peri-implant soft tissues indexes.

Oil Pulling and Polyphenols: Treatment of Gingivitis Patients with 'Itri Extra-Virgin Olive Oil'.

OBJECTIVES: The aim of the study was to evaluate the effectiveness of extra virgin olive (EVO) oil and fruity oil for the treatment of gingivitis. MATERIALS AND METHODS: A sample of 75 patients over 18 years of age with gingivitis induced by plaque bacteria was divided into three groups: study group A, with extra virgin olive oil; study group B, with fruity oil; and control group C. In the two study groups, EVO oil was administered as a mouthwash to patients with gingival inflammation. The protocol included a daily application of the product for 30 days, with three recalls 15 days apart. Clinical parameters of plaque formation and gingivitis, including plaque index (PI) and bleeding index (BI), were assessed at each recall and scored on a specific periodontal chart. The control group received no mouthwash treatment in addition to normal daily oral hygiene procedures, and the same clinical parameters as the study group were evaluated. Data were evaluated using SPSS 27.0 software for Windows (SPSS Inc., Chicago, IL, USA). Then, the pre- and post-treatment values of the groups were compared using Student's t-test, setting p < 0.05 as the significance level. RESULTS: Comparison of the three groups showed that extra-virgin olive oil was an adjuvant in the treatment of gingival inflammation, improving PI and BI. In group A, the mean plaque index showed a 48% reduction, and the bleeding index showed a 64% reduction after 30 days. In group B, the mean plaque index showed a 35% reduction and a bleeding index reduction of 43% after 30 days. CONCLUSIONS: The collected data showed significant improvements in the formation of bacterial plaque and gingivitis. The exact mechanism of such treatment is still to be elucidated. As a result of this, further studies with a different sample of patients than those used and a comparison with other products need to be addressed to verify and demonstrate the antibacterial and anti-inflammatory effects of the components of this natural product.

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793-63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182-16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464-138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661-31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

Endaural microscopic approach versus endoscopic transcanal approach in treatment of attic cholesteatomas.

PURPOSE: Compare the audiological results and postoperative outcomes of the endoscopic approach versus the endaural microscopic approach for treatment of attic cholesteatomas, using a randomized prospective model. MATERIALS AND METHODS: Eighty patients were consecutively enrolled in the study and randomized into two groups of treatment of 40 patients: Group A -tympanoplasty with a microscopic endaural approach; Group B -tympanoplasty with an exclusive trans-meatal endoscopic approach. Preoperative, intraoperative and postoperative outcomes were evaluated. Hearing was assessed preoperatively and at 1 month, 3 months and 6 months after surgery in both groups. RESULTS: There were no differences in the parameters analyzed (CT findings, patient age, disease duration, intraoperative cholesteatoma characteristics,) between the group A and B patients. No statistical difference between the two groups regarding hearing improvement, abnormal taste sensation, dizziness, post-operative pain and healing times emerged. Graft success rate was 94.5 % and 92.1 % for MES and ESS respectively. CONCLUSION: Both microscopic and exclusively endoscopic endaural approaches offer similar and excellent results in the surgical treatment of attic cholesteatomas.

Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2.

BACKGROUND: Genetic-based COVID-19 vaccines have proved to be highly effective in reducing the risk of hospitalization and death. Because they were first distributed in a large-scale population, the adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome, and the interplay between platelets and vaccinations increasingly gained attention. OBJECTIVES: The objective of this article was to study the crosstalk between platelets and the vaccine-induced immune response. METHODS: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n = 15), or the adenovirus-based vaccine, AZD1222 (n = 25) and studied their short-term platelet and immune response before and after vaccine injections. In a separate cohort, we retrospectively analyzed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. RESULTS: Here, we show that a faster antibody response to either vaccine is associated with the formation of platelet aggregates with marginal zone-like B cells, a subset geared to bridge the temporal gap between innate and adaptive immunities. However, although the mRNA-based vaccine is associated with a more gradual and tolerogenic response that fosters the crosstalk between platelets and adaptive immunity, the adenovirus-based vaccine, the less immunogenic of the 2, evokes an antiviral-like response during which the platelets are cleared and less likely to cooperate with B cells. Moreover, subjects taking aspirin (n = 56) display lower antibody levels after BNT162b2 vaccination compared with matched individuals. CONCLUSION: Platelets are a component of the innate immune pathways that promote the B-cell response after vaccination. Future studies on the platelet-immune crosstalk post-immunization will improve the safety, efficacy, and strategic administration of next-generation vaccines.

Hemorrhagic Complications in Implant Surgery: A Scoping Review on Etiology, Prevention, and Management.

This article seeks to provide the most relevant aspects of the etiology, prevention, and management of bleeding in routine implant surgery. A comprehensive and systematic electronic search was conducted in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews databases until June 2021. Further references of interest were retrieved from bibliographic lists of the selected articles and the "Related Articles" feature of PubMed. Eligibility criteria were papers about bleeding, hemorrhage, or hematoma associated with routine implant surgery on human subjects. Twenty reviews and 41 case reports fulfilled eligibility criteria and were included in the scoping review. Involved implants were mandibular in 37 and maxillary in 4 cases. The major number of bleeding complications was in the mandibular canine region. The most injured vessels were sublingual and submental arteries, due mainly to perforation of the lingual cortical plate. Time to bleeding occurred intraoperatively, at suturing, or postoperatively. The most reported clinical manifestations were swelling and elevation of the mouth floor and the tongue with partial or complete airway obstructions. First aid to manage airway obstruction was intubation and tracheostomy. For active bleeding control, gauze tamponade, manual or digital compression, hemostatic agents, and cauterization were applied. When conservative procedures failed, hemorrhage was controlled by intra- or extraoral surgical approaches to ligate injured vessels or by angiographic embolization. The present scoping review provides knowledge and evidence on the most relevant aspects of the etiology, prevention, and management of implant surgery bleeding complications.

Association between subclinical atherosclerosis and oral inflammation: A cross-sectional study.

BACKGROUND: The aim of this cross-sectional study was to investigate the association between carotid intima-media thickness (c-IMT) values and periodontal and peri-implant diseases in a sample of patients with hypertension. METHODS: A total of 151 participants with presence of at least one dental implant in function for >5 years were recruited. Anthropometric measurements, 24-h ambulatory blood pressure monitoring, ultrasound assessment of carotid arteries (c-IMT and presence of plaque) were recorded and venous blood samples obtained. An oral examination was performed by calibrated examiners to ascertain prevalence and severity of periodontal and peri-implant diseases. Binomial logistic regression was performed to investigate the potential association between various measures of exposure of dental diseases and predictors of cardiovascular risk (c-IMT > 0.9 mm and presence of plaque or their combination). RESULTS: Diagnosis of periodontitis (OR 6.71, 95% CI: 2.68-16.76, P < 0.001), cumulative mucosal/gingival inflammation (Periodontal Screening and Recording score) (OR 1.25, 95% CI:1.12-1.41, P < 0.001), and mucositis (OR 3.34, 95% CI:1.13-9.85, P < 0.05) were associated with c-IMT > 0.9 mm and/or plaque presence independent of age, sex, smoking, 24 h systolic blood pressure and body mass index differences. No statistically significant results were noted for peri-implantitis. Linear regression models confirmed a positive association of cumulative mucosal/gingival inflammation (ß = 0.011, SE 0.002, P < 0.001), diagnosis of periodontitis (ß = 0.114, SE 0.020, P < 0.001), and peri-implant diseases (ß = 0.011, SE 0.002, P < 0.001) with increased c-IMT values. CONCLUSIONS: This study confirms a positive association between mucosal/gingival inflammation and subclinical atherosclerosis assessed by c-IMT values and the presence of carotid plaque in patients with hypertension, independent of traditional cardiovascular risk factors. Future studies are needed to further characterize this relationship.

Characteristic Hallmarks of Aging and the Impact on Carcinogenesis.

Evidence shows that there is a synergistic, bidirectional association between cancer and aging with many shared traits. Age itself is a risk factor for the onset of most cancers, while evidence suggests that cancer and its treatments might accelerate aging by causing genotoxic and cytotoxic insults. Aging has been associated with a series of alterations that can be linked to cancer: i) genomic instability caused by DNA damage or epigenetic alterations coupled with repair errors, which lead to progressive accumulation of mutations; ii) telomere attrition with possible impairment of telomerase, shelterin complex, or the trimeric complex (Cdc13, Stn1 and Ten1 - CST) activities associated with abnormalities in DNA replication and repair; iii) altered proteostasis, especially when leading to an augmented proteasome, chaperon and autophagy-lysosome activity; iv) mitochondrial dysfunction causing oxidative stress; v) cellular senescence; vi) stem cells exhaustion, intercellular altered communication and deregulated nutrient sensing which are associated with microenvironmental modifications which may facilitate the subsequential role of cancer stem cells. Nowadays, anti-growth factor agents and epigenetic therapies seem to assume an increasing role in fighting aging-related diseases, especially cancer. This report aims to discuss the impact of age on cancer growth.

Effects of an amino acid buffered hypochlorite solution as an adjunctive to air-powder abrasion in open-flap surface decontamination of implants failed for peri-implantitis: an ex vivo randomized clinical trial.

OBJECTIVES: To evaluate ex vivo the efficacy of an amino acid buffered hypochlorite solution supplemented to surface debridement with air-powder abrasion in removing bacterial biofilm following open-flap decontamination of implants failed due to peri-implantitis. MATERIALS AND METHODS: This study was an ex vivo, single-blind, randomized, intra-subject investigation. Study population consisted of 20 subjects with at least three implants failed for peri-implantitis (in function for > 12 months and progressive bone loss exceeding 50%) to be explanted. For each patient, implants were randomly assigned to surface decontamination with sodium bicarbonate air-powder abrasion (test-group 1) or sodium bicarbonate air-powder abrasion supplemented by amino acid buffered hypochlorite solution (test-group 2) or untreated control group. Following open-flap surgery, untreated implants (control group) were explanted. Afterwards, test implants were decontaminated according to allocation and explanted. Microbiological analysis was expressed in colony-forming units (CFU/ml). RESULTS: A statistically significant difference in the concentrations of CFU/ml was found between implants of test-group 1 (63,018.18 ± 228,599.36) (p = 0.007) and implants of test-group 2 (260.00 ± 375.80) (p < 0.001) compared to untreated implants (control group) (86,846.15 ± 266,689.44). The concentration of CFU/ml on implant surfaces was lower in test-group 2 than in test-group 1, with a statistically significant difference (p < 0.001). CONCLUSION: The additional application of amino acid buffered hypochlorite solution seemed to improve the effectiveness of implant surface decontamination with air-powder abrasion following open-flap surgery. CLINICAL RELEVANCE: Lacking evidence on the most effective method for biofilm removal from contaminated implant surfaces, the present experimental study provides further information for clinicians and researchers.

Management of transverse root fractures in dental trauma.

The management of complex dental trauma can be modulated according to the emergencies that may arise over time. Clinical management of transverse root fractures may require different therapies based on situations, such as delay and error in the treatment of an avulsion trauma associated with apical third root fracture, patient's poor compliance, or external and internal root resorption. The primary aim of this article was to review studies regarding root fractures in the permanent dentition and root fracture management. The secondary aim was to present the inflammatory reaction and the complications (i.e., infections) that may occur if the International Association for Dental Traumatology (IADT) guidelines are not followed. In addition, a scenario is devised in which endodontic surgery, despite the baseline patient's conditions and negative prognosis, can help to inhibit the inflammatory root resorption and allow the preservation of soft and hard tissues within a long follow-up from the injury, for the purpose of demonstrating the next possible implant-prosthetic rehabilitation.

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile.

INTRODUCTION: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. METHODS: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. RESULTS: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value ≤ 0.05) correlation with alive status was evidenced for sE-selectin at T1. CONCLUSIONS: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.

Characteristics, Diagnosis and Treatment of Compound Odontoma Associated with Impacted Teeth.

Compound odontoma is a malformation typical of young adults below the age of 20, with a slight preference for the male gender and the anterior region of the maxilla. Clinically asymptomatic, it can be detected during a radiological investigation in connection with the persistence of deciduous dental elements and the impaction of definitive ones. The treatment of choice is excisional surgery and recurrence is a rare event. The need for orthodontic therapy for impacted elements is usually not necessary because in most cases, odontomas are small, circumscribed lesions the size of a permanent tooth. In this article, the diagnostic and therapeutic surgical excision procedure is presented in three patients at developmental age with large compound odontomas associated with at least one retained canine, and in two of the cases, with serious transmigration to the impacted tooth elements.