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The comparative effectiveness of transradial (TRA) compared with transfemoral (TFA) access in acute coronary syndrome (ACS) patients undergoing complex percutaneous coronary intervention (PCI) remains unclear.Among 8404 ACS patients in the Minimising Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX (MATRIX)-Access trial, 5233 underwent noncomplex (TRA: n = 2590; TFA: n = 2643) and 1491 complex (TRA: n = 777; TFA: n = 714) PCI. Co-primary outcomes were major adverse cardiovascular events (MACE, the composite of all-cause mortality, myocardial infarction, or stroke) and the composite of MACE and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding (net adverse cardiovascular events [NACE]) at 30 days.Rates of 30-day MACE (HR 0.94, 95% CI 0.72-1.22) or NACE (HR 0.89, 95% CI 0.69-1.14) did not significantly differ between groups in the complex PCI group, whereas both primary end points were lower (HR 0.84, 95% CI 0.70-1.00; HR 0.83, 95% CI 0.70-0.98; respectively) with TRA among noncomplex PCI patients, with negative interaction testing (PAmong ACS patients, PCI complexity did not affect the comparative efficacy and safety of TRA vs TFA, whereas the absolute risk reduction of access-site major bleeding was greater with TRA compared with TFA in complex as opposed to noncomplex PCI.

Background TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. Methods Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. Results Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . Conclusion The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

ObjectiveThe study was designed to: (1) confirm safety and feasibility of mini-invasive radial balloon aortic valvuloplasty (BAV); (2) assess its impact in terms of quality of life and frailty; and (3) evaluate whether changes in frailty after BAV are associated with death in patients undergoing transcatheter aortic valve implantation (TAVI).Methods330 patients undergoing BAV in 16 Italian centres were prospectively included. The primary endpoint was the occurrence of major and minor Valve Academic Research Consortium (VARC)-2 bleeding. Secondary endpoints were scales of quality of life, frailty, evaluated at baseline and 30 days, and their relationship with the occurrence of all-cause death.ResultsBAV was performed by radial access in 314 (95%) patients. No VARC-2 major and six (1.8%) VARC-2 minor bleedings occurred in the study population. Quality of life, as well as frailty status, significantly improved 30 days after BAV. At 1 year, patients undergoing TAVI with baseline essential frailty toolset (EFT) ConclusionsMini-invasive radial BAV is safe, feasible and associated with a low rate of vascular complications. Patients improving EFT 30 days after BAV showed a favourable outcome after TAVI.Trial registration numberNCT03087552.

Non-neoplastic jaw cyst (NJC) is one of the most common lesions in oral cavity, but there are only few detailed and extended epidemiological data based on the 2017 WHO classification. The aim of this study was to perform an epidemiological analysis of all NJCs treated from 1990 to 2019 at the Marche Polytechnic University, and to compare these data with those published in the literature. This retrospective study considered 2060 patients treated from 1990 to 2019. The NJCs were classified according to the 2017 WHO classification, and the main clinicopathological variables were analysed (sex, age, diagnosis, site of onset, size, and recurrences). Of 2150 total lesions, there were 2095 primary cysts and 55 recurrences; men are more frequently affected than women (M/F ratio of 1.73:1). The mean age of occurrence was 46.6 years, with a peak of frequency in the fifth decade. The mandible was more frequently involved than the maxilla, with a mean size of 1.9cm. Radicular cyst was the most frequently diagnosed cyst (56.6%), followed by dentigerous cyst (23.4%) and odontogenic keratocyst (12.9%). This is the first epidemiological study on NJCs in the Italian population according to 2017 WHO classification.

Nitric oxide (NO) produced in the oral cavity is a powerful resource for the human body, especially when NO-syntethase production is not adequate. The role of oral microbiome in determining blood pressure levels has been linked to the active role of some bacterial species involved in the nitro-reducing process. In the present study we investigated the correlation between selected oral microbiome characteristics, nitric oxide (NO) concentration in saliva and their association with hypertension.A case-control study including 48 (25 normotensive and 23 hypertensive subjects), subjects between 50 and 70 years old, was carried out at the dental clinic of an Italian teaching hospital. Characteristics of participants have been evaluated by means of a physical examination, and by an assisted interview. A real-time polymerase chain reaction in samples of saliva and plaque was used to detect Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola, Streptococcus mutans, Streptococcus sanguinis, Veillonella dispar and Neisseria subflava as well as total bacterial count. Nitric oxide in saliva was evaluated by the ELISA method.Normotensive subjects, compared with hypertensive subjects, had significantly higher concentration of NO (165.77 ± 61.7 vs 57.49 ± 19.61 μmol/l; p = 0.023), and higher bacterial concentration of the supragingival plaque (4.73E+07 ± 4.33+07 vs 4.02E+07 ± 4.00+07; p = 0.024). Bacterial species, usually associated to good oral health status, such as Neisseria subflava, were significantly more present in normotensive subjects than in hypertensive ones (9090.88 ± 5481.49 vs 4791.35 ± 4349.37; p 0.001). considering the concentration of bacteria as a biomarker of the development of hypertension.The results support the association between hypertension, oral microbiome and salivary nitric oxide, in fact do the results allow us to establish any biomarkers (microbial or biochemical, NO) that allow early therapeutic intervention.

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80–90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value P value

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.

Background In patients with squamous cell carcinoma of the oral tongue (OTSCC), current tumor node metastasis staging system fails to identify at‐risk patients associated with early relapse and poor prognosis despite complete surgical resection. Given the importance of tumor‐infiltrating lymphocytes (TILs) in the development of cancers, here we investigated the prognostic significance of the immune phenotype in OTSCC. Methods Hematoxylin‐eosin stained sections of OTSCCs from 211 patients were evaluated. Cancers were classified as (a) immune‐inflamed when TILs were found next to tumor cell nests; (b) immune‐excluded when TILs were found in the stroma, outside the tumor; and (c) immune‐desert for tumors lacking lymphocyte infiltrate. The prognostic significance of these immune phenotypes classes was investigated. Data were further validated on an independent cohort from The Cancer Genome Atlas database. Results Immune‐desert phenotype was the least represented group of OTSCCs in our cohort (11.8%) and served as an independent prognostic factor. Patients with immune‐desert tumors exhibited worse disease‐specific survival (HR = 2.673; [CI: 95% 1.497‐4.773]; P = .001), overall survival (HR = 2.591; [CI: 95% 1.468‐4.572]; P = .001), and disease‐free survival (HR = 2.313; [CI: 95% 1.118‐4.786]; P = .024) at multivariate analysis. Conclusions We identified a specific subgroup of OTSCCs with poor prognosis. Tumor‐infiltrating lymphocytes density and localization could serve as an integrative parameter to the current staging system and inform the selection of most appropriate treatments. In particular, the tumor immune phenotype could improve the stratification of patients with more aggressive disease., In patients with squamous cell carcinoma of the oral tongue (OTSCC), current tumor node metastasis staging system fails to identify at‐risk patients associated with early relapse and poor prognosis despite complete surgical resection. Given the importance of tumor‐infiltrating lymphocytes in the development of cancers, here we investigated the prognostic significance of the immune phenotype in OTSCC.

Aims The purpose of this study was to verify the impact on the number and characteristics of coronary invasive procedures for acute coronary syndrome (ACS) of two hub centers with cardiac catheterization facilities, during the first month of lockdown following the COVID-19 pandemic. Materials and methods Procedural data of ACS patients admitted between 10 March and 10 April 2020 were compared with those of the same period of 2019. Results We observed a 23.4% reduction in ACS admissions during 2020, with a decrease for both ST-elevation myocardial infarction (STEMI) (-5.6%) and non-ST-elevation myocardial infarction (-34.5%), albeit not statistically significant (P = 0.2). During the first 15 days of the examined periods, the reduction in ACS admissions reached 52.5% (-25% for STEMI and -70.3% for non-ST-elevation myocardial infarction, P = 0.04). Among STEMI patients, the rate of those with a time delay from symptoms onset longer than 180 min was significantly higher during the lockdown period (P = 0.01). Radiograph exposure (P = 0.01) was higher in STEMI patients treated in 2020 with a slightly higher amount of contrast medium (P = 0.1) and number of stents implanted (P = 0.1), whereas the number of treated vessels was reduced (P = 0.03). Percutaneous coronary intervention procedural success and in-hospital mortality were not different between the two groups and in STEMI patients (P NS for all). Conclusion During the early phase, the COVID-19 outbreak was associated with a lower rate of admissions for ACS, with a substantial impact on the time delay presentation of STEMI patients, but apparently without affecting the in-hospital outcomes.

OBJECTIVES The frequency of oral squamous cell carcinoma in young adults has increased in the last decades, and there are conflicting results in literature about its prognosis in young subjects. The aim of this study was to analyse the clinical and pathological features of oral squamous cell carcinoma in a cohort of young adults in order to investigate the presence of new independent prognostic markers. MATERIALS AND METHODS Only HPV-negative young patients (under 40-year-old) affected by oral squamous cell carcinoma were considered in this study. Clinical and pathological data were collected. Patients were re-staged according to the 8th edition of AJCC. RESULTS Overall, 66 patients were considered in this study. Perineural invasion significant correlated with both 7th and 8th edition of AJCC, and lymphovascular invasion (p-value

Inferior alveolar nerve (IAN) block injections are commonly used in clinical practice, but they are not free from complications. The aim of the present systematic review is to assess the nerve-related adverse effects of IAN block anesthesia. A structured and systematic search was performed on the major electronic databases (PubMed, Cochrane Library, Web of Science, Scopus and CINAHL) for studies published in English until 30 September 2021. A total of 131 articles were identified through database searching using combinations of keywords. Fifteen papers were included and assessed for eligibility. Overall, nerve damage following an IAN block anesthesia injection is a rare occurrence, probably due to the direct nerve trauma of the needle, a neurotoxic effect of the used anesthetic solution and/or a combination of them. From a medico-legal point of view, a balanced discussion prior to nerve block anesthesia should be pursued in order to avoid patients’ reluctance to undergo necessary dental treatment due to the remote eventuality of nerve injury.

Background: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI).Methods/Design: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non–inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non–inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years.The PIONEER IV trial aims to demonstrate non–inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy.Clinical Trial Registration: ClinicalTrials.govUnique Identifier: NCT04923191Classifications: Interventional Cardiology

Background: COVID-19 disease first appeared in 2019 and quickly spread worldwide, causing a global pandemic. The oral cavity represents a target of SARS-CoV-2, and oral lesions are observed in both non-hospitalized and hospitalized patients. This systematic review aims to investigate the frequency of oral manifestations in COVID-19 hospitalized patients. Methods: An electronic search was conducted in PubMed, Scopus, and Web of Science databases, including articles published up to September 2021. The review protocol was based on PRISMA-P. The risk of bias of the studies was assessed using the Joana Briggs Institute. The certainty of evidence was assessed using the GRADE instrument. Results: Fifty-nine articles were included: 19 case reports, 17 case series, 2 case-control studies, 13 cross-sectional studies, 4 observational studies, and 4 retrospective studies. Oral ulcers, cheilitis, and tongue lesions were more common in patients before hospitalization, while perioral pressure ulcers, macroglossia, blisters, and oral candidiasis were more recurrent in patients during hospitalization. The first could be related directly to COVID-19, while the latter could be caused by medical devices, treatments, prone position, and immunological impairment. Conclusions: An accurate oral examination during the hospital admission of all confirmed COVID-19 cases is encouraged to recognize oral early manifestations and to apply appropriate treatments.

Background Sebaceous carcinoma is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. Sebaceous carcinoma in the oral cavity is extremely rare, with only 14 cases reported in literature. We reported the fourth case of sebaceous carcinoma involving the lip Case presentation A 71-year-old Caucasian male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extraoral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation, and salivary gland neoplasms. Operation was performed under local anesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascular stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein and epithelial membrane antigen, but negative for carcinoembryonic antigen. Based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered. Conclusion The histogenesis, differential diagnosis, and clinicopathological conditions of this disease according to literature are reviewed. Sebaceous carcinoma should be distinguished from other tumors full of vacuolated clear cells. A periodic acid-Schiff stain and immunohistochemical stain for Ki-67, P53, cytokeratin, S-100, epithelial membrane antigen, and androgen receptor can be useful for the diagnosis.

Oral malignant melanoma (OMM) is an aggressive tumour, and shows deep tissue invasion at initial presentation. The prognosis is worse than that for cutaneous melanoma (CM), and the overall 5-year survival rate is 10-25%. A study of the molecular mechanisms involved in the development of OMM is necessary to identify new prognostic markers. In this study, we evaluated the possible role of nicotinamide N-methyltransferase (NNMT) in OMM. We carried out immunohistochemical analyses to evaluate the expression of NNMT in 15 OMM and 15 CM, measuring the percentage of positive cells and the value of NNMT expression intensity. Furthermore, we explored the relationship between NNMT levels and the prognostic parameters of patients with OMM. NNMT was significantly more expressed in CM compared with OMM, whereas higher staining intensity for NNMT was observed in OMM cases (P

The role of bruxism in children and adolescents with Down syndrome, the most often diagnosed congenital syndrome, is still unclear. Therefore, this study aims to conduct a narrative review of the literature about bruxism in children and adolescents with Down syndrome to identify the prevalence, risk factors, and possible treatments of this disorder. Although an accurate estimate of its prevalence could not be inferred, it appears that bruxism is more prevalent in Down syndrome individuals rather than in the general pediatric population. No gender difference was observed, but a reduction in its prevalence was described with increasing age (around 12 years). The variability in the diagnostic techniques contributed to the heterogeneity of the literature data. Clinicopathological features of Down syndrome, such as muscle spasticity, oral breathing, and a predisposition to obstructive sleep apnea, may suggest a higher prevalence of bruxism in this patient group. Finally, given the paucity of studies on the management of bruxism in this population, it was not possible to outline a standard protocol for the non-invasive treatment of cases in which an observational approach is not sufficient.

Oral cancer is the most common tumor of the head and neck region. Its management is based on surgical and systemic therapies. Taste disorders represent the most common side effect of these treatments; indeed, dysgeusia is noted by 70% of oral cancer patients. Despite survival remaining the primary endpoint of cancer patients, taste impairments can cause psychological distress. This comprehensive review describes the last decade’s knowledge from the literature regarding taste alterations in patients with oral and oropharyngeal squamous cell carcinoma. A total of 26 articles in English, including prospective, cross-sectional, and case–control studies, and clinical trials were evaluated. Literature analysis shows that anti-cancer treatments can destroy taste cells, decrease and alter their receptors, and interrupt nerve transmission. Furthermore, the tumour itself can destroy the oral mucosal lining, which encloses the taste buds. Dysgeusia typically occurs in 3–4 weeks of treatments, and usually taste sensation is recovered within 3–12 months. However, some patients exhibit incomplete or no recovery, even several years later. Thus, dysgeusia can become a chronic issue and negatively influence patients’ quality of life, worsening their dysphagia and their nutritional status. Physicians should be focused on preventing oncological treatment-related symptoms, offering the most suitable personalized support during therapy.

Background The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. Methods Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. Results DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. Conclusion These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

Aims One of the objectives of current research is to customise the treatment of cancer patients. The achievement of this objective requires stratification of patients based on the most significant prognostic factors. The aims of this study were to evaluate the prognostic value of the tumour-stroma ratio (TSR), defined as the proportion of tumour cells relative to surrounding stroma, in patients with oral tongue squamous cell carcinoma (OTSCC), and to develop a prognostic nomogram based on the most significant clinicopathological features. Methods and results Clinicopathological data of 211 patients treated at 'Ospedali Riuniti' General Hospital (Ancona, Italy) for OTSCC were collected. One hundred and thirty-nine patients were restaged according to the 8th edition American Joint Committee on Cancer (AJCC) staging system. Evaluation of the TSR was performed on haematoxylin and eosin-stained slides, and correlation with survival outcomes was evaluated. In addition, with the aim of integrating the independent value of the TSR with the 8th edition AJCC staging system, a prognostic nomogram for OTSCC has been developed. OTSCC with a low TSR (i.e. a high proportion of stroma and a low proportion of tumour cells) was shown to have negative prognostic value in terms of disease-specific survival, with a hazard ratio (HR) of 1.883 and a 95% confidence interval (CI) of 1.033-3.432 (P = 0.039), and overall survival (HR = 1.747, 95% CI 0.967-3.154;P = 0.044), independently of other histological and clinical parameters. For the cohort of 139 patients restaged according to the 8th edition AJCC staging system, variables correlating with a poor prognosis were: the TSR, perineural invasion, and sex. The nomogram built on these parameters showed good predictive capacity, outperforming the 8th edition AJCC staging system in stratifying disease-specific survival in OTSCC patients. Conclusions Including the TSR in the predictive model could improve risk stratification of OTSCC patients and aid in making treatment decisions.

Oral cancer is the most common malignancy of the head and neck region, characterized by a poor prognosis. Novel prognostic markers are needed to better stratify these patients. Lymphovascular invasion (LVI) has been included in the eighth edition of the AJCC Cancer Staging Manual as an additional prognostic factor, but its influence on the recurrence risk and lymph node metastasis is relatively understudied. This is a comprehensive review of the literature on the clinical and prognostic role of LVI in oral cancer. A relevant search of the PubMed, Scopus, and Web of Science databases yielded 29 articles that satisfied the inclusion criteria. Findings indicated that LVI is an independent negative prognostic factor in oral cancer patients and appears to be associated with cervical lymph node metastasis and loco-regional recurrence. Notably, in oral tongue cancer, survival outcomes progressively worsen when LVI is associated with other adverse pathological features, especially in the early stages. Therefore, these patients could benefit from elective neck dissection and/or adjuvant therapy. The high variability of LVI prevalence hinders the comparison of literature results. Several methodological limitations were found to be present in the collected articles, including the lack of a rigorous definition for LVI, the difficult detection in routine histological section, the presence of potential confounders, the retrospective nature, and an inadequate sample size in most studies. Therefore, it is necessary to conduct prognostic studies using standardized methods to define and quantify LVI.

Although oral P2YThe purpose of this study was to compare downstream and upstream oral P2YWe performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit).We randomized 1,449 patients to downstream or upstream oral P2YDownstream and upstream oral P2Y

Tumor-associated macrophages (TAMs) are part of the tumor microenvironment, broadly divided into M1 and M2 phenotypes. M1 macrophages, commonly identified by staining the CD11c antigen, have an antitumour immunity role, while M2 macrophages, expressing the CD163 antigen, are involved in tumor progression. Little is known about M1 and M2 phenotypes in the context of the oral tongue squamous cell carcinomas (OTSCC), a subgroup of oral cancer with peculiar clinical behavior. This study evaluated the macrophage polarization in OTSCC specimens to examine their prognostic relevance. To this end, specimens from 71 OTSCC patients graded as G1 or G3 were investigated for CD11c and CD163 expression. Immunohistochemical staining of TAMs was evaluated in tumor nests, tumor inflammation area (TIA), and tumor stroma. To analyze the expression of CD11c and CD163, the percentage of positive cells was scored as 0 (negative), 1 (10%), 2 (11% to 50%), 3 (51% to 80%), and 4 (80%). The staining intensity was scored as 0 (negative), 1 (weak), 2 (moderate), and 3 (intense). Higher expression of both CD163+ and CD11c+ macrophages in inflammation area positively correlated with G3 grade, both in extension and intensity. Focusing on G3 tumors, survival curves showed better disease-free survival in patients with high CD11c expression in the TIA. Presence of CD163 expression in TIA was associated with worse disease-free survival. This study evaluated, for the first time, the distribution of M1 and M2 macrophages in relation to the pathologic grade in OTSCC, highlighting the prognostic relevance of analyzing the localization of TAMs.

Background The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors—ticagrelor and prasugrel—currently recommended by the guidelines. Study design DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. Conclusions The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. Trial registration ClinicalTrials.gov NCT02618837. Registered on 1 December 2015.

BACKGROUND Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long-term clinical and radiological follow-up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N-methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). MATERIALS AND METHODS A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. RESULTS NNMT expression was significantly higher in recurrent than primary AMs (P = .0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P = .0470). NNMT expression was significantly lower in recurrent than primary OKC (P = .0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P = .0276). CONCLUSIONS This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker.

Background and Objectives: Masticatory limitations on the dietary habits of edentulous subjects restrict their access to adequate nutrition, exposing them to a greater risk of protein energy malnutrition. The aim of this study is to verify the existence of an association between Masticatory Performance (MP) and nutritional changes in the elderly. Materials and Methods: 76 participants were enrolled. MP testing was performed using the two-color chewing gum mixing test. The system used reveals the extent to which the two differently colored chewing gums mix, and allows discrimination between different MPs. The assessment of the participants&rsquo, nutritional statuses was carried out through a food interview. Anthropometric parameters were collected, and bioimpedance analysis was performed. Results: Mean MP was 0.448 &plusmn, 0.188. No statistically significant differences were detected between male and female subjects (p &gt, 0.05). According to the Body Mass Index (BMI), obese patients had a lower MP than overweight and normal weight subjects (0.408 &plusmn, 0.225, 0.453 &plusmn, 0.169 and 0.486 &plusmn, 0.181, respectively). MP values were lower both in male and female subjects with a waist circumference above the threshold than those below it (0.455 &plusmn, 0.205 vs. 0.476 &plusmn, 0.110, respectively, in males and 0.447 &plusmn, 0.171 vs. 0.501 &plusmn, 0.138, respectively, in females). No relationship was noticed between MP and bioimpedance parameters (p &gt, 0.05). Conclusions: A statistically significant relation was observed between MP and the number of missing teeth. A reduced MP could worsen nutritional parameters. A reduced MP did not seem to negatively affect bioimpedance parameters.

Even if un to improve long-term prognosis, balloon aortic valvuloplasty (BAV) may be useful in selected patients with symptomatic severe aortic stenosis either as a bridge to surgical or transcatheter valve replacement (aortic valve replacement [AVR] or transcatheter aortic valve implantation [TAVI]) or as a triage strategy for patients with uncertain indications. International guidelines recommend BAV as: a "bridge" to AVR/TAVI, a "trial" in patients with undetermined symptoms, or a "bridge-to-decision" in case of comorbidities. However, in clinical practice, BAV is also used as a palliative measure to improve hemodynamics and quality of life in many patients who are excluded from AVR/TAVI. Finally, BAV is often performed during TAVI to facilitate prosthesis delivery, optimize frame expansion, or for bioprosthetic valve fracture in selected valve-in-valve procedures. Technical innovations, which allow for a mini-invasive approach via transradial access and pacing delivered through the wire, have led to a decrease in complications over time. This review focuses on contemporary BAV with a specific emphasis on new indications, innovative techniques, and specific complex patient subgroups.

Background Myocardial infarction (MI) in elderly patients is associated with unfavorable prognosis, and it is becoming an increasingly prevalent condition. The prognosis of elderly patients is equally impaired in ST-segment elevation (STE) or non-STE (NSTE), and it is markedly worsened by the common presence of multivessel disease (MVD). Given the limited evidence available for elderly patients, it has not yet been established whether, as for younger patients, a complete revascularization strategy in MI patients with MVD should be advocated. We present the design of a dedicated study that will address this research gap. Methods and design The FIRE trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients aged 75years and older, with MI (either STE or NSTE), MVD at coronary artery angiography and a clear culprit lesion will be randomized to culprit-only treatment or to physiology-guided complete revascularization. The primary endpoint will be the patient-oriented composite endpoint (POCE) of all cause death, any MI, any stroke, any revascularization at one year. The key secondary endpoint will be the composite of cardiovascular death and MI. Quality of life and physical performance will be evaluated as well. All components of the primary and key secondary outcome will be tested also at 3 and 5years. The sample size for the study is 1400 patients. Implications The FIRE trial will provide evidence on whether a specific revascularization strategy should be applied to elderly patients presenting MI and MVD in order to improve their clinical outcomes.

BackgroundThe role of planned angiographic control (PAC) over a conservative management driven by symptoms and ischaemia following percutaneous coronary intervention (PCI) of the unprotected left main (ULM) with second-generation drug-eluting stents remains controversial. PAC may timely detect intrastent restenosis, but it is still unclear if this translated into improved prognosis.Methods and analysisPULSE is a prospective, multicentre, open-label, randomised controlled trial. Consecutive patients treated with PCI on ULM will be included, and after the index revascularisation patients will be randomised to PAC strategy performed with CT coronary after 6 months versus a conservative symptoms and ischaemia-driven follow-up management. Follow-up will be for at least 18 months from randomisation. Major adverse cardiovascular events at 18 months (a composite endpoint including death, cardiovascular death, myocardial infarction (MI) (excluding periprocedural MI), unstable angina, stent thrombosis) will be the primary efficacy outcome. Secondary outcomes will include any unplanned target lesion revascularisation (TLR) and TLR driven by PAC. Safety endpoints embrace worsening of renal failure and bleeding events. A sample size of 550 patients (275 per group) is required to have a 80% chance of detecting, as significant at the 5% level, a 7.5% relative reduction in the primary outcome.Trial registration numberNCT04144881

Aims The aim of this work was to investigate the prognostic impact of revascularization of non-culprit lesions in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease by performing a meta-analysis of available randomized clinical trials (RCTs). Methods and results Data from six RCTs comparing complete vs. culprit-only revascularization in STEMI patients with multivessel disease were analysed with random effect generic inverse variance method meta-analysis. The endpoints were expressed as hazard ratio (HR) with 95% confidence interval (CI). The primary outcome was cardiovascular death. Main secondary outcomes of interest were all-cause death, myocardial infarction (MI), and repeated coronary revascularization. Overall, 6528 patients were included (3139 complete group, 3389 culprit-only group). After a follow-up ranging between 1 and 3 years (median 2 years), cardiovascular death was significantly reduced in the group receiving complete revascularization (HR 0.62, 95% CI 0.39–0.97, I 2 = 29%). The number needed to treat to prevent one cardiovascular death was 70 (95% CI 36–150). The secondary endpoints MI and revascularization were also significantly reduced (HR 0.68, 95% CI 0.55–0.84, I 2 = 0% and HR 0.29, 95% CI 0.22–0.38, I 2 = 36%, respectively). Needed to treats were 45 (95% CI 37–55) for MI and 8 (95% CI 5–13) for revascularization. All-cause death (HR 0.81, 95% CI 0.56–1.16, I 2 = 27%) was not affected by the revascularization strategy. Conclusion In a selected study population of STEMI patients with multivessel disease, a complete revascularization strategy is associated with a reduction in cardiovascular death. This reduction is concomitant with that of MI and the need of repeated revascularization.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.

Oral squamous-cell carcinoma (OSCC) and most human tumors are characterized by an imbalance of regulatory mechanisms controlling cell processes such as apoptosis. Survivin, a member of the inhibitor of apoptosis family, is overexpressed in most solid and hematological malignancies and correlates with a reduced overall survival rate. Thus, the aim of this study was to find a correlation between nuclear Survivin expression and clinicopathologic data and the prognosis in OSCC patients. A total of 152 OSCC samples were investigated by immunohistochemistry for nuclear Survivin expression. Then, Survivin was scored semiquantitatively using an immunoreactivity score (IRS), calculated by multiplying the percentage of positive cells with the staining intensity. Using a digital image analysis software, OSCC patients were stratified into 4 groups. Results showed that patients with a lower IRS score displayed better survival rates than patients with a higher IRS score, reaching statistical significance. As the expression of Survivin at the nuclear level seems to suggest a poor prognosis in OSCC patients, the evaluation of nuclear Survivin IRS may be a useful tool to identify patients with more aggressive and disseminated disease, influencing follow-up and therapeutic protocols.

Objective The aim of this study was to perform an epidemiologic analysis of cases of jaw cysts treated from 1973 to 2012 at the Dentistry and Maxillofacial Surgery Unit of the Verona Hospital, Italy, and to compare the data obtained with those published in the literature. Study Design A retrospective survey of 2030 patients treated for jaw cysts from 1973 to 2012 was performed. The lesions were classified according to the 2005 World Health Organization histologic classification, and the following variables were analyzed: age, gender, histopathologic diagnosis, and site of onset. Results Of 2030 total lesions, there were 1970 odontogenic cysts (97.04%), 50 nonodontogenic cysts (2.46%), and 10 pseudocysts (0.49%). Of the patients, 314 were children (15.47%), and 1716 were adults (84.53%). Mean age was 37.24 years, with a male/female ratio of 1.71:1. Conclusions There is a wide variety of cysts, some of which are subject to variations according to gender, localization, and age.

An altered oral microbiota has been linked with the development of several oral diseases, such as dental caries, periodontal disease, and oral stomatitis. Moreover, poor oral health has been linked to head and neck cancer, particularly oral cancer. In recent years a growing number of studies indicate that oral microbiota could be involved in the development of primary tumours outside of head and neck region. The aim of this article is to review the recent studies based on high-throughput technology to present evidences of a relationship between oral microbiota and “non-head and neck tumours.” Oral dysbiosis seem to be more pronounced in patients with tumours of gastrointestinal tract, in particular oesophageal, gastric, pancreatic, and colorectal cancers, paving the way for developing specific oral microbiota test to allow early cancer detection. Regarding other tumour types, the results are promising but highly preliminary and still debated. Currently, there are several factors that limit the generalization of the results, such as the small sample size, the lack of adequate clinical information about patients, the different sequencing techniques used, and biological sample heterogeneity. Although only at the beginning, the analysis of oral microbiota could be the next step in the evolution of cancer therapy and will help clinicians to develop individualised approaches to cancer prevention and treatment.

Epidemiological data of odontogenic tumours (OT) are conflicting, with significant differences among the countries. This study aims to evaluate incidence and prevalence of OTs in the Marche population in a period of 25 years, according to 4th Edition of WHO Classification. In this study, only patients of Marche region treated for OTs were considered. Data were retrieved from Institute of Pathology, Marche Polytechnic University, Italy. Because this is the only tertiary referral centre for Head and Neck pathology within Marche region, the patient sample could be considered well representative of this area. From each case, age, sex, site, diagnosis and relapses were recorded. Overall, 100 patients were treated for OTs from 1994 to 2018 in Marche region. The annual incidence rate ranged from 0.13 to 0.39 per 100,000, while life prevalence was 6.50 per 100,000. Mean age of onset for primary OTs was 49.7 ± 20.1 years. Twenty-seven patients developed recurrences, showing a mean age of 54 ± 19.7 years and a mean recurrence time of 51.2 ± 34 months. This is the first epidemiological study on OTs in Italian population according to 4th Edition of WHO Classification. Although limited in their retrospective nature, these findings could accurately estimate epidemiology of OTs in Italy.

The present study investigated the immunohistochemical expression of p53, p63, and p73 in different types of odontogenic cysts (OC), a group of common intraosseous jaw lesions, to provide a better understanding of p53-family functions in odontogenic lesions. We carried out immunohistochemical analysis to evaluate the expression of p53, p63, and p73 in 60 samples of OC, including dentigerous cysts, radicular cysts, orthokeratinized OC, and odontogenic keratocysts (OKC). The epithelial expression of p53-family members was evaluated both in the basal-parabasal and in the superficial layers, measuring the percentage of positive cells and the value of expression intensity. The expression of p53-family members showed a significant difference between the "OKC" and "non-OKC" groups. In particular, p53 positivity in the basal-parabasal layers, as well as p63 positivity in the superficial layers, were more common in OKC (P

A high level of unmet oral health needs is very common among elderly people. In a society that is getting older and that has been hit so hard by the coronavirus pandemic, the development of new strategies aimed at enhancing general and oral health status should be crucial in order to promote healthy aging. The aim of this systematic review is to assess the feasibility of Teledentistry in communities or in a domiciliary setting where elderly people live. A structured and systematic research was performed on the major electronic databases for studies published in English until 30 June 2020: the PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL databases. A total of 13 articles were identified through database searching using combinations of keywords. Out of 13 papers, eight abstracts were reviewed to assess if they were coherent with the aim of the study, and full texts were retrieved. After abstract reviews, seven articles were selected for closer inspection. Of these, six were assessed for eligibility. Four papers were aimed at assessing patients and health practitioners experiences about Teledentistry, three studies reported a cost analysis and cost description of Teledentistry in residential aged care facilities, and two studies investigated the feasibility and accuracy of Teledentistry for diagnosis dental pathology. The implementation of Teledentistry in residential aged care facilities and in home-assistance programs could be a viable tool for the management of oral care in people who cannot access dental care.

BACKGROUND The value of prolonged bivalirudin infusion after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients with or without ST-segment elevation remains unclear. OBJECTIVES The purpose of this study was to assess efficacy and safety of a full or low post-PCI bivalirudin regimen in ACS patients with or without ST-segment elevation. METHODS The MATRIX program assigned bivalirudin to patients without or with a post-PCI infusion at either a full (1.75 mg/kg/h for #4 h) or reduced (0.25 mg/kg/h for #6 h) regimen at the operator's discretion. The primary endpoint was the 30-day composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (composite of all-cause death, myocardial infarction, or stroke, or major bleeding). RESULTS Among 3,610 patients assigned to bivalirudin, 1,799 were randomized to receive and 1,811 not to receive a post-PCI bivalirudin infusion. Post-PCI full bivalirudin was administered in 612 (ST-segment elevation myocardial infarction [STEMI], n = 399; non-ST-segment elevation acute coronary syndromes [NSTE-ACS], n = 213), whereas the low-dose regimen was administered in 1,068 (STEMI, n = 519; NSTE-ACS, n = 549) patients. The primary outcome did not differ in STEMI or NSTE-ACS patients who received or did not receive post-PCI bivalirudin. However, full compared with low bivalirudin regimen remained associated with a significant reduction of the primary endpoint after multivariable (rate ratio: 0.21; 95% CI: 0.12 to 0.35; p < 0.001) or propensity score (rate ratio: 0.16; 95% CI: 0.09 to 0.26; p < 0.001) adjustment. Full post-PCI bivalirudin was associated with improved outcomes consistently across ACS types compared with the no post-PCI infusion or heparin groups. CONCLUSIONS In ACS patients with or without ST-segment elevation, the primary endpoint did not differ with or without post-PCI bivalirudin infusion but a post-PCI full dose was associated with improved outcomes when compared with no or low-dose post-PCI infusion or heparin (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627). (J Am Coll Cardiol 2019; 73: 758-74) (c) 2019 by the American College of Cardiology Foundation. The trial was sponsored by the Societa Italiana di Cardiologia Invasiva (GISE, a nonprofit organization), which received grant support from The Medicines Company and TERUMO. This substudy did not receive any direct or indirect funding. Dr. Gargiulo has received research grant support from the Cardiopath PhD program. Dr. Vranckx has received consulting fees from AstraZeneca and The Medicines Company during the study; and has received speaking or consulting fees from Bayer HealthCare, Terumo, and Daiichi-Sankyo outside of the submitted work. Dr. Campo has received research grants from AstraZeneca, Boston Scientific, and Abbott Vascular outside of this work. Dr. Varbella has received personal fees from AstraZeneca, Eli Lilly, and Bayer; has received other support from Biosensors; has received grants from Medtronic, Kardia SRL, and Boston Scientific outside of the submitted work; and has received lecture fees for Advisory Board participation from AstraZeneca, Daichi-Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Servier, Amgen, Novartis, Sanofi, and Biotronik. Dr. Ando has received nonfinancial support from Terumo during the conduct of the study; has received personal fees from Daiichi-Sankyo, AstraZeneca, Menarini, Pfizer, Philips, and Bayer; and has received nonfinancial support from Bayer, Boehringer Ingelheim, Chiesi, and Philips outside of the submitted work. Dr. Limbruno has received personal fees from The Medicines Company, AstraZeneca, Lilly, Boston Scientific, Biotronik, and Merck outside of the submitted work. Dr. Windecker's institution has received research contracts from Abbott, Amgen, Boston Scientific, Biotronik, Medtronic, Edwards Lifesciences, St. Jude, and Terumo. Dr. Valgimigli has received grants from The Medicines Company and Terumo during the conduct of the study; has received grants and personal fees from AstraZeneca; has received nonfinancial support from The Medicines Company; and has received personal fees from The Medicines Company, Terumo, St. Jude Vascular, Alvimedica, Abbott Vascular, and Correvio outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

In this study, we evaluated the 8th edition of American Joint Committee on Cancer (AJCC) staging criteria and lymph node ratio (LNR) to identify patients affected by squamous cell carcinoma of the tongue (SCCT) with a poor prognosis.Seventy-three cases of SCCT were analyzed retrospectively. Tumor staging was revised according to the 7th and 8th editions of the AJCC criteria. Depth of invasion (DOI), extranodal extension (ENE), and LNR were evaluated.Twenty-five cases were reclassified: 17 patients received an upstage in the staging score, and in 8 cases in the same stage group, pT or pN was changed. In the pT-upstaged group, 7 patients experienced recurrence, and 8 died. In the pN-upstaged group, 9 patients developed recurrence, and 10 died. The number of disease recurrence or death was higher in the groups of patients who received an upstage in pN and in the staging score (P.05). The pN-upstaged group showed worse disease-free survival (DFS) and overall survival (OS) (P.05). LNR was higher in patients with recurrence, and among these, LNR was lower in patients with ENE (P.05).The 8th edition of the AJCC criteria allows for better stratification of patients with SCCT. The implementation of ENE and LNR to pN classification seems to identify patients with worse DFS and OS.

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge.

Objectives To define the incidence of vascular complications (VC) after balloon aortic valvuloplasty (BAV) in recent years, and to compare the performance of two vascular closure devices (VCD). Background VC remain the most frequent drawback of BAV and are associated with adverse clinical outcomes. Methods All BAV procedures performed at 2 high-volume centers over a 6-year period (n = 930) were collected in prospective registries and investigated to assess the incidence of Valve Academic Research Consortium-2 (VARC-2) defined VC. Incidence of life-threatening, major and minor bleeding was also assessed. In-hospital major adverse cardiac and cerebrovascular events (MACCE) rate (composite of in-hospital death, myocardial infarction, TIA/stroke, and life-threatening bleeding) as well as 30-day survival was compared between a suture-mediated closure system and a collagen plug hemostatic device. Results A 9 Fr arterial sheath was used in most of the patients (84.1%). Vascular closure was obtained with the Angio-Seal in 643 patients (69.1%) and the ProGlide in 287 (30.9%). The overall incidence of major VC was 2.7%, and minor VC 6.6%, without significant differences between groups. The Angio-Seal group was associated with a higher rate of small hematomas (6.9% vs. 3.5%, P = 0.042), whilst blood transfusions were more frequent in the ProGlide group (6.6% vs. 3.5%, P = 0.034). Rates of in-hospital MACCE and 30-day survival were similar. Use of either VCD was not independently associated with major VC. Conclusions VC rate after BAV is fairly low in experienced centers without major differences between the 2 most used VCD.

Summary Background The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. Methods MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70–100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50–70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. Findings Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80–1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78–0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83–1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81–1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84–1·16; p=0·90). Interpretation In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. Funding Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

Objectives Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. Materials and Methods We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Results Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. Conclusion This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis.

The bioresorbable vascular scaffold (BRS) technology constitutes the new revolution of the coronary artery disease interventional treatment. Currently, three distinct types of BRSs are available but only one, the Absorb BVS, was on the market in 2013 when the Regional Commission for Medical Devices and the Cardiology and Cardiac Surgery Commission of the Emilia-Romagna Region drew up a technical and scientific essay to provide guidance for the introduction of BRS in public and affiliated health facilities. Five preferential indications were given for use: long coronary lesions (28 mm), ostial lesions (left main stem excluded), complete revascularization in patients aged50 years, diffuse disease (40 mm) or involving the mid/distal left anterior descending (LAD) branch in patients70 years, spontaneous coronary artery dissection.This survey analyzed data from all the catheterization laboratories in the Emilia-Romagna Region, merged in a unified database.In a 3-year study period, 546 BRS were implanted in 328 patients, corresponding to 1.5% of the drug-eluting stents (DES) used, with a trend towards a progressive increase over time. Initial indications were followed in 200/328 (61.0%) patients (about one third fitting more indications), mainly for treatment of long lesions in vessels2.5 mm (67%), young patients (31.5%) and mid/distal LAD (28%). In 22.6% of cases the clinical scenario was a ST-segment elevation myocardial infarction, in 39.3% a non-ST-segment elevation acute coronary syndrome. Intracoronary imaging was infrequently used (intravascular ultrasound in 24.7% of cases). In 85 patients (25.9%) a hybrid procedure (BVS/DES) was performed.BRS use has resulted lower than expected, with discrete variability among centers, but according to the initial indications of the Emilia-Romagna Region in the majority of cases. The underuse might have been due to operators' caution in their initial experience. However, the increasing trend may reveal a greater confidence in the implantation technique and the whole amount of safety and efficacy data.

Since raloxifene, a drug used in osteoporosis therapy, inhibits osteoclast, but not osteoblast functions, it has been suggested to improve recovery during implant surgery. The present paper describes an effective method to link raloxifene, through a covalent bond, to a nano-Hydroxyapatite-based biomaterial by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by Infra Red-Fourier Transformed (IR-FT) spectroscopy and Scanning Electron Microscope (SEM). To evaluate the safety of this modified new material, the vitality of osteoblast-like cells cultured with the new biomaterial was then investigated. Raloxifene-conjugated HA-biomaterial has been shown to be a safe material easy to obtain which could be an interesting starting point for the use of a new functional biomaterial suitable in bone regeneration procedures.

Early invasive management and the use of combined antithrombotic therapies have decreased the risk of recurrent ischaemia in patients with acute coronary syndrome (ACS) but have also increased the bleeding risk. Transradial intervention (TRI) and bivalirudin infusion compared to transfemoral intervention (TFI) or unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decrease bleeding complications in patients with ACS. To what extent, a bleeding preventive strategy incorporating at least one of these two treatment options translates into improved outcomes is a matter of debate. The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX study is a large-scale, multicenter, prospective, open-label trial, conducted at approximately 100 sites in Europe aiming to primarily assess whether TRI and bivalirudin infusion, as compared to TFI and UFH plus provisional GPI, decrease the 30-day incidence of death, myocardial infarction or stroke across the whole spectrum of ACS patients.

Odontogenic tumors are a group of lesions arising from the odontogenic apparatus. Although the mechanism of oncogenesis and tumor progression in these lesions remains unknown, certain proteins, such as those involved in apoptosis, seem to be involved in the differentiation and proliferation of odontogenic epithelial cells. The aim of this study was to analyze the expression of p73 and TNF-related apoptosis-inducing ligand (TRAIL) in odontogenic tumors and cysts, and to clarify changes in the expression of these proteins. Immunohistochemical analysis was performed on 21 ameloblastomas, 15 keratocystic odontogenic tumors and 15 dentigerous cysts. We carried out quantitative assessment of p73 and TRAIL expression by determining the percentages of positive cells on a continuous scale. Five cases of orthokeratinized odontogenic cyst were also examined. The percentages of cells immunohistochemically positive for p73 were 52.6 ± 25.4% in ameloblastomas, 76.0 ± 13.1% in keratocystic odontogenic tumors, and 26.7 ± 30.7% in odontogenic cysts, whereas the corresponding figures for TRAIL were 57.6 ± 16.1%, 8.9 ± 10.0%, and 1.5 ± 0.5%, respectively. Imbalance of the apoptosis pathway, with dysregulation of p73 and TRAIL, seems to play a role in the oncogenesis of odontogenic tumors.(J Oral Sci 58, 459-464, 2016).

We assessed the prevalence of superior semicircular canal dehiscence (SSCD) through examination of ultrahigh-resolution computed tomography (CT) scans of the temporal bone and attempted to verify the correspondence between a radiologic diagnosis of SSCD and clinical signs of SSCD syndrome.A prospective study was carried out on 191 consecutive patients who underwent temporal bone ultrahigh-resolution CT scans. Cases that matched the radiologic diagnosis of SSCD were subsequently referred for a comprehensive audiological evaluation that might enable a final diagnosis of SSCD syndrome.Among the 191 patients, 17 had a radiologic diagnosis of SSCD, which was bilateral in 5 cases, for a total of 22 SSCD cases, with a prevalence rate of 5.8%. In 2 of the 17 patients, the audiological examination revealed signs and symptoms indicative of SSCD syndrome, with a total prevalence rate of 0.5%.Our data confirm that the radiologic diagnosis of SSCD, performed by mean thin-section CT scans reformatted in the plane of the superior semicircular canal, is not necessarily related to the clinical presentation of SSCD syndrome. Our study also showed a prevalence rate of SSCD syndrome that was similar to the prevalence of SSCD reported from studies of histologic specimens.

Objective To present a retrospective analysis of multicentre case series of oral syphilis and a review of relevant literature. Subjects and Methods A PUBMED search was carried out from 1950 to 2011. Clinical records of patients with exclusive/prevalent oral manifestations of syphilis were collected and examined in three independent hospitals. Results Of 23 reports describing 34 patients were detected through the review (35% primary, 56% secondary, and 9% tertiary disease), describing unspecific ulcers (59%), mucosal patches (23%), keratosis (6%), pseudomembranes (3%), and gumma (9%). Multicentre case series revealed 12 patients with oral syphilis, of which 17%, 58%, and 25% with, respectively, primary, secondary, and tertiary lesions. Clinically, patients showed white patches (17%), blistering mucositis (8%), chronic unspecific ulcers with/without skin lesions (50%), gumma (17%), and necrosis of the dorsum of the tongue (8%). Oral bullae and tongue necrosis are never described in the current review. Conclusions Diagnosis of syphilis remains a challenge because of the multiform and polymorphous clinical pattern at onset and its ability to imitate different diseases. It is mandatory to include syphilis in the differential diagnosis of unusual oral lesions. Diagnosis of oral lesions of syphilis is often difficult, and biopsy is required in controversial cases.